Blood purification for removal of pfas

Abstract

Provided herein are methods of removing PFAS from the blood or the body of a subject, including one or more tissues of the subject, by extracorporeal blood purification (EBP), including by plasmapheresis, such as double-filtration plasmapheresis (DFPP). In other aspects are provided methods of treating medical conditions and methods of improving healthspan and lifespan using extracorporeal blood purification, including plasmapheresis, such as DFPP, for example by filtering PFAS from the blood, and otherwise removing PFAS from the tissues or body of a subject, such as a human subject.

Description

[0001] 2025-09-12

[0002] BLOOD PURIFICATION FOR REMOVAL OF PFAS

[0003] INVENTORS: Karin Voit-Bak, Richard Straube, Michael Petegorsky, and Carlos Schuster

[0004] CROSS-REFERENCE

[0005]

[0001] Priority is claimed under PCT Art. 8(1) and Rule 4.10 to U.S. Provisional Application No. 63 / 693,912, filed September 12, 2024, and hereby incorporated by reference in its entirety for all purposes.

[0006] FIELD OF THE INVENTION

[0007]

[0002] The disclosure relates to the removal of PFAS from the blood or body using blood purification, including plasmapheresis, such as double-filtration plasmapheresis (DFPP). In some aspects, it relates to methods of treating medical conditions and improving healthspan and lifespan by the removal of PFAS.

[0008] BACKGROUND OF THE INVENTION

[0009]

[0003] Per- and polyfluoroalkyl substances (PFAS) are a class of organic compounds first made in the 1940s.

[0004] Different types of PFAS have different fluorinated alkyl chains, the composition of which contributes to differences in physicochemical properties such as hydrophobicity, lipophobicity, and thermal tolerance. All PFAS however share in having carbon-fluorine (C-F) bonds, one of the strongest single bonds in chemistry.

[0010]

[0005] As a result of the C-F bonds, PFAS exhibit very high chemical and thermal stability. This stability, along with other desirable properties, has led to PFAS being widely used in numerous industries (Guelfo et al. Environ Toxicol Chem. 2021 ;40(12):3234-3260). Applications include non-stick cookware, water-repellent fabrics, stain-resistant carpets, food packaging, construction materials, electronics, and firefighting foam.

[0011]

[0006] PFAS are also resistant to degradation under environmental conditions, causing them to be referred to as “forever chemicals.” Because of this and their diverse industrial applications, PFAS is ubiquitous in our water, food supply, and bodies (Brennan et al. Int J Environ Res Public Health. 2021 ; 18(20): 10900).

[0012]

[0007] Studies have established the adverse health impacts of PFAS, and have demonstrated that PFAS accumulate in human tissues, fluids, and organs, including in the blood, brain, breast milk, and umbilical cord (Calafat et al. Environ Health Perspect. 2007;115(11):1596-1602; Cao et al. Environ Sci Process Impacts. 2021 ;23(11): 1623-1640; Zheng et al. Environ Sci Technol. 2021 ;55(11):7510-7520; Dai et al. Environ Int. 2023; 180: 108238). The presence of PFAS in the human body has been linked to cancers, developmental disorders, neurological disorders, metabolic disorders, heart disease, chronic inflammation, and immune disorders (Messmer et al. Environ Health Insights. 2022; 16: 11786302221139359; Rappazzo et al. Int J Environ Res Public Health. 2017;14(7):691 ; Brown-Leung et al. Chem Res Toxicol. 2022;35(8):1312-1333; Liu et al. Environ Health Perspect. 2023;131 (6):67001 ; Min et al. Occup Environ Med. 2012;69(9):658-662; Zhang et al. Environ Res. 2023;220: 115188; Ehrlich et al. Environ Health. 2023;22(1):19).

[0013]

[0008] Although the health risks of PFAS are widely appreciated, medical guidelines for reducing such risks are typically limited to minimizing exposure to PFAS and PFAS-containing products. However, due to the 2025-09-12 ubiquity and magnitude of PFAS environmental contamination, simply minimizing exposure may not be enough to meaningfully decrease the accumulation of PFAS in the body or the concomitant consequences.

[0014]

[0009] Accordingly, there is an important and growing unmet need for methods to remove PFAS directly from the body, including methods that treat the health issues resulting from the presence of PFAS in the body. Provided herein are devices, systems, and methods to meet this need and others, having such advantages and improvements as will become apparent through the disclosure below.

[0015] INCORPORATION BY REFERENCE

[0016]

[0010] Each cited patent, publication, and non-patent literature is hereby incorporated by reference in its entirety, as if each was manual individually, and as if each is fully set forth herein. No such citation should however be construed as an admission that a cited reference comes from an area that is analogous or directly applicable to the invention, nor should any citation be construed as an admission that a document or any underlying information, in any jurisdiction, is prior art or part of the common general knowledge in the art.

[0017] BRIEF SUMMARY OF THE INVENTION

[0018]

[0011] The following presents a simplified summary of some aspects and embodiments of the disclosure in order to provide a basic understanding thereof. It is not an extensive overview, nor intended to identify every key or critical element of the invention or to delineate the complete scope thereof. Its purpose is to present some exemplary aspects and embodiments in a simplified form as a prelude to the detailed description below.

[0019]

[0012] In some aspects are provided methods for removing per- and polyfluoroalkyl substances (PFAS) from a subject, such as comprising: selecting the subject for treatment; and administering an extracorporeal blood purification (EBP) treatment; wherein the EBP treatment is effective to remove an amount of PFAS from the body of the subject. Other methods comprise creating a blood circuit via vascular access to the subject; separating whole blood of the subject into a plasma portion and a blood cell portion using a first filter; removing one or both of albumin-bound PFAS and microplastics from the plasma portion using a second filter to yield purified plasma; returning the blood cell portion to the subject; and providing the purified plasma for allogeneic or autologous therapeutic use, storage, or further processing. Further methods will be understood as below.

[0020]

[0013] In further aspects are provided such methods, devices, and systems as described and enabled herein.

[0021]

[0014] The foregoing has outlined broadly and in summary certain pertinent features of the disclosure so that the detailed description of the invention that follows may be better understood, and so that the present contribution to the art can be more fully appreciated. Hence, this summary is to be considered as a brief and general synopsis of only some of the aspects and embodiments disclosed herein, is provided solely for the benefit and convenience of the reader, and is not intended to limit in any manner the scope, or range of equivalents, to which the claims are lawfully entitled. Additional features of the invention are described hereinafter. It should be appreciated by those in the art that all disclosed specific devices, systems, and methods are only exemplary, and may be readily utilized as a basis for modifying or designing other devices, systems, and methods for carrying out the same purposes. Such equivalent compositions and methods will be 2025-09-12 appreciated to be also within the scope and spirit of the invention as claimed.

[0022]

[0015] The headings are only for ease of review, and should not be used to limit the invention in any manner.

[0023] BRIEF DESCRIPTION OF THE FIGURES

[0024]

[0016] To further clarify various aspects of the invention, certain exemplary embodiments are illustrated in the figures. The figures depict only illustrated embodiments of the invention and should not be considered limiting of its scope. Certain aspects of the invention are thus further described and explained with additional specificity and detail, but still by way of example only, with reference to the accompanying figures in which:

[0025]

[0017] FIG. 1 illustrates an exemplary treatment regimen, according to some disclosed embodiments;

[0026]

[0018] FIG. 2 illustrates an exemplary EBP circuit, according to some disclosed embodiments;

[0027]

[0019] FIG. 3 illustrates an exemplary EBP circuit that includes an electrostatic binding mechanism, according to some disclosed embodiments;

[0028]

[0020] FIG. 4 illustrates an exemplary EBP circuit that includes an adsorbent media, according to some disclosed embodiments; and

[0029]

[0021] FIG. 5 illustrates a flow diagram of an exemplary EBP treatment regimen.

[0030] DETAILED DESCRIPTION OF THE INVENTION

[0031]

[0022] While various features of certain aspects and embodiments are summarized above, the detailed description illustrates exemplary aspects and embodiments in further detail to enable one of skill in the art to practice such aspects and embodiments, and in so doing to make and use the full scope of the invention.

[0032]

[0023] The described examples are provided for illustrative purposes and are not intended to limit the scope of the invention or its applications. It will be understood that many modifications, substitutions, changes, and variations in the described aspects, embodiments, applications, examples, and details can be made by one of skill without departing from the spirit of the invention, or the scope of the invention as described in the appended claims, and the general principles defined herein may be applied to a wide range of aspects. Thus, the invention should not be limited to the aspects and embodiments presented, but should be accorded the widest scope consistent with the principles and novel features disclosed, including their equivalents. The disclosure will make such aspects and embodiments apparent to one of skill, and readily cognizable and creatable without undue experimentation, solely using the teachings herein and general knowledge in the art.

[0033]

[0024] While the disclosed methods may include particular steps, it will be apparent that other methods including fewer, more, or different steps than those described are also within the spirit and scope of the invention. The methods and uses of any disclosed device, machine, or apparatus, including combinations thereof (equivalently as shorthand, unless context indicates otherwise, each a “device”), and any associated steps shown herein, therefore should be understood as being provided for purposes of illustration, not limitation. The specific order or hierarchy of steps in the methods and uses of a device are exemplary. The disclosed methods may be performed in any suitable order unless context clearly indicates otherwise. The specific order or hierarchy of steps in a method thus may be rearranged according to ordinary skill, while 2025-09-12 remaining within the spirit and scope of the disclosure. The presented claims also may present elements or steps in a sample and exemplary order, but will not be meant to be limited to the specific order presented.

[0034]

[0025] Unless otherwise stated, all measurements, values, ratings, positions, dimensions, magnitudes, sizes, locations, orientations, configurations, and other specifications that are set forth (either expressly or impliedly) in this specification, including in the figures and in the claims, are approximate, and not exact. They are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain. The recitation of ranges of values is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated, each individual value is incorporated into the specification as if it were individually recited herein.

[0035]

[0026] The use of any and all examples, or exemplary language provided with respect to an embodiment, is intended merely to better illuminate certain non-limiting aspects of the invention and does not pose a limitation on the scope of the invention as otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[0036]

[0027] While the invention is described in terms of particular aspects and embodiments, it is not intended that these descriptions in any way limit its scope to any such aspects and embodiments, and it will be understood that many modifications, substitutions, changes, and variations in the described aspects, embodiments, and details of the invention illustrated herein can be made by those skilled in the art without departing from the spirit of the invention, or the scope of the invention as described in the claims.

[0037] A. General Definitions and Terms

[0038]

[0028] The singular forms “a,” “an,” and “the” include plural referents unless context clearly dictates otherwise. The term “one or more” may be used, but its absence (or the use of the singular) does not signify the singular only, as the term simply underscores that there may be more than one in some embodiments.

[0039]

[0029] The terms “comprising,” “including,” “such as,” and “having” are inclusive and not exclusive (i.e. , there may be other elements in addition to the recited elements). Thus, the term “including” as used herein means, and is used interchangeably with, the phrase “including but not limited to.” Similarly, the term “include” as used herein means, and is used interchangeably with, the phrase “include, for example.” The term “or” is used to mean, and is used interchangeably with, the term “and / or,” unless context clearly indicates otherwise.

[0040]

[0030] Numerical parameters in the description and claims may be approximations and can vary, such as depending upon the desired properties sought to be obtained by a particular embodiment. Unless otherwise indicated, all numbers, for example numbers expressing quantities, properties, parameters, conditions, and so forth, such as used to describe and claim certain embodiments, will be understood as being modified in some instances by the term “about,” even where not stated explicitly. For each such embodiment, there is disclosed an alternative embodiment, where such numbers are not modified by the term “about.” In embodiments, “about” refers to plus or minus zero point five percent (±0.5%) of the recited unit of measure. In embodiments, “about” refers to plus or minus one percent (±1 %) of the recited unit of measure. In embodiments, “about” 2025-09-12 refers to plus or minus two point five percent (±2.5%) of the recited unit of measure. In embodiments, “about” refers to plus or minus five percent (±5%) of the recited unit of measure. In embodiments, “about” refers to plus or minus 10 percent (±10%) of the recited unit of measure. Where “about” is used to modify one number in a series or range, it is understood to modify all numbers in the series or range, including, for a range, both the upper and lower bounds of the range; thus the term “about 1, 2, or 3” is understood to mean “about 1, about 2, or about 3”; the term “about 1 to 10” means “about 1 to about 10.”

[0041]

[0031] The term “substantially,” where it is applied to modify a parameter or characteristic herein, will be read in the context of the invention and in light of the knowledge in the art to provide certainty, e.g., by using a standard that is recognized in the art for measuring the meaning of substantially as a term of degree, or by ascertaining the scope as would one of skill in the art. Where no such certainty can be established from context, the term may be understood as meaning “about,” e.g., within ±0.5%, ±1 %, ±2.5%, ±5%, or ±10%.

[0042]

[0032] In some embodiments, numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that numerical ranges and parameters setting forth the broad scope of some embodiments are approximations, the numerical values set forth in specific examples are reported as precisely as practicable. Such values may however contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0043]

[0033] The term “in embodiments” is equivalent to, and is simply shorthand for, the term “in some embodiments.” “Embodiments” refers to disclosed embodiments and their equivalents.

[0044]

[0034] A “disclosed method” refers to any described or claimed method of the invention, including methods understood as equivalents by one of skill in view of the disclosure and the general knowledge of the art.

[0045]

[0035] Unless described otherwise, disclosed techniques and procedures will be those that are standard and known in the art, and will be those performed according to conventional methods in the art. If no techniques or procedures are expressly disclosed, one may infer that standard technique(s) or procedure(s) are performed.

[0046]

[0036] Unless defined otherwise, all technical and scientific terms herein have the meaning that the term would have to a person of ordinary skill in the art in question at the time of the invention, who simply as shorthand may be referred to simply as “one of skill” or equivalently in the plural as “those of skill.”

[0047]

[0037] Generally, the nomenclature herein is known by one of skill in fields relating to one or more aspects of the invention, such as medicine, hematology, toxicology, epidemiology, environmental health sciences, pathology, biomedical engineering, analytical chemistry, material science, polymer science, nanomaterials, and the like, and will be well known and commonly employed in such fields. Standard techniques and procedures will be those generally performed according to conventional methods in the art in such fields.

[0048]

[0038] Where definitions are provided herein, they are for purposes of assisting the reader in understanding the disclosed embodiments; however, any such definitions are not intended to limit the scope of the invention, which shall be properly interpreted and understood by reference to the full specification (as well as any plain meaning known to one of skill) in view of the language used in the claims. Terminology is chosen for the 2025-09-12 purpose of describing particular embodiments and is not intended to be limiting.

[0049]

[0039] Further definitions follow, to assist a reader in understanding the embodiments.

[0050]

[0040] “Blood purification” refers to a process in which blood is subjected to physical, chemical, or adsorptive treatment, such as via extracorporeal circulation, for the purpose of removing, separating, or reducing specific components or contaminants, such as PFAS. Blood purification may be performed using one or more filtration, adsorption, or separation modalities, including extracorporeal blood purification (EBP) modalities.

[0051]

[0041] “Extracorporeal blood purification” or “EBP” refers to a procedure in which the blood of a subject is withdrawn, processed externally to remove, separate, or modify one or more specific components (e.g., via filtration, adsorption, and / or separation), and returned to the subject. EBP includes plasmapheresis (e.g., TPE, DFPP, PP), dialysis-based therapies (e.g., hemodialysis, hemofiltration, hemodiafiltration, ultrafiltration), adsorption-based therapies (e.g., hemoperfusion, immunoadsorption), and hybrid systems (e.g., CPFA).

[0052]

[0042] “Extracorporeal blood purification treatment” or “EBP treatment” refers to the administration of an extracorporeal blood purification (EBP) procedure to a subject for the reduction or removal of PFAS and / or for a therapeutic or prophylactic purpose. EBP treatment may involve the reduction or removal of circulating substances or particulates (e.g., PFAS) using any disclosed EBP modality.

[0053]

[0043] In general, “treat,” “treated,” “treating,” “treatment,” and like terms refer to treating a condition in a subject, such as a mammalian subject, and including a human, and include causing a desired biological or pharmacological effect, such as: (a) preventing a condition from occurring in a subject who may be predisposed to the disorder but has not yet been diagnosed with it; (b) inhibiting a condition, i.e., arresting its development; (c) relieving a condition, i.e., causing regression thereof; (d) protecting from or relieving a symptom or pathology caused by or related to a condition; (e) reducing, decreasing, inhibiting, ameliorating, or preventing the onset, severity, duration, progression, frequency or probability of one or more symptoms or pathologies associated with a condition; and (f) preventing or inhibiting of a worsening or progression of symptoms or pathologies associated with a condition or comorbid with a condition. In embodiments, treatment includes prevention. In other embodiments, treatment does not include prevention. In embodiments, treatment will be determined by the presence of at least one objective indicium of improvement, wherein the improvement may be prophylactic in terms of completely or partially reducing, decreasing, inhibiting, ameliorating, or preventing a condition or a symptom thereof. In embodiments, treatment may be therapeutic, such as in terms of a partial or complete cure for a condition, an adverse effect attributable to a condition, and / or a comorbidity simultaneously present with a condition. Other such measurements, benefits, and surrogate or clinical endpoints, alone or in combination, will be understood to those of skill in view of the teachings herein and knowledge in the art, and may be used to determine or measure a treatment.

[0054]

[0044] A “condition,” in different disclosed embodiments, and unless context clearly indicates otherwise, should be broadly understood to include any disease, disorder, illness, injury, disability, symptom, set of symptoms, or other medical or health condition that the disclosed methods are useful to treat. Where the terms 2025-09-12 “disease” and “disorder” are used herein, such terms should be interpreted broadly unless context clearly indicates otherwise to include conditions, symptoms, and clusters of symptoms that may not result or may not yet have resulted in a diagnosis of a disease or disorder, or a diagnosable disease or disorder. In some embodiments, the condition is diagnosed, such as by a medical professional. In embodiments, the condition is diagnosable, such as by a medical professional, but has not been diagnosed. In embodiments, the condition is not diagnosed nor diagnosable, such as by a medical professional, or not diagnosable at the time of treatment.

[0055]

[0045] “Plasmapheresis” refers to a method by which plasma is separated from the cellular fraction of blood of a subject for treatment and / or replacement. In some embodiments, plasmapheresis refers to a method comprising double-filtration plasmapheresis (DFPP). In some embodiments, plasmapheresis refers to a method comprising plasma exchange (PE, PEX, PLEX) or therapeutic plasma exchange (TPE). In some embodiments, plasmapheresis refers to a method comprising plasma perfusion (PP). In some embodiments, plasmapheresis refers to a method comprising adsorption, such as plasma adsorption (PA), immunoadsorption (IAS), immunoapheresis (IA), coupled plasma filtration and adsorption (CPFA), or immunoadsorption plasmapheresis (IAPP). “Plasmapheresis” also may refer to a combination of such methods. Other plasmapheresis methods useful in the disclosed methods will be appreciated by those of skill in view of the disclosure.

[0056]

[0046] “Double-filtration plasmapheresis” or “DFPP” refers to a “two-step” procedure to remove substances from plasma, generally where membrane plasma separation is followed by plasma filtration (see, e.g., Am Soc’y Apheresis (ASFA) Guidelines). In some embodiments, centrifugal plasma separation is followed by plasma filtration. DFPP is generally used to remove pathogenic substances, such as autoantibodies, immune complexes, and lipoproteins. DFPP can also be used for “rheopheresis,” the removal of high molecular weight proteins from the blood, such as to lower blood viscosity and improve micro-circulation. DFPP refers, in some embodiments, to a method of plasmapheresis comprising the separation of whole blood into a cellular fraction and a plasma fraction by a first filter, such as a first membrane filter; a second separation of solutes in plasma from the plasma fraction by a second filter, such as a second membrane filter; and a subsequent recombining of the cellular fraction and filtered plasma fraction before re-entry into a subject.

[0057]

[0047] Although DFPP is referred to or used in some embodiments as an exemplary blood purification procedure, or as an exemplary plasmapheresis procedure, reference to DFPP in such embodiments should not be understood as limiting on the scope of the disclosure, and alternate embodiments will be appreciated by one of skill in view of the context, using other blood purification procedures such as disclosed herein. Methods and devices for performing such other blood purification procedures will be readily appreciated by those of skill in view of the disclosure, and reference to a specific type of method or device is not intended to be limiting where the method or device in general is understood, unless context demands otherwise, such as in claims.

[0058]

[0048] “Therapeutic plasma exchange” or “TPE” refers to methods of plasmapheresis comprising separation of whole blood into a cellular fraction and a plasma fraction by a first membrane filter or by centrifugation, disposal of the plasma fraction, and subsequent combining of the cellular fraction with a plasma substitution 2025-09-12 fluid before re-entry into a subject. TPE may refer to methods comprising plasma exchange.

[0059]

[0049] “Plasma perfusion” or “PP” refers to methods of plasmapheresis comprising the separation of whole blood into a cellular fraction and a plasma fraction by a first membrane filter or by centrifugation, the separation of solutes in plasma from the plasma fraction by an adsorption filter, and a subsequent recombining of the cellular fraction and filtered plasma fraction before re-entry into a subject. In some embodiments, PP refers to methods comprising adsorption, such as plasma adsorption (PA), immunoadsorption (IAS), immunoapheresis (IA), or immunoadsorption plasmapheresis (IAPP).

[0060]

[0050] “Coupled plasma filtration adsorption” or “CPFA” refers to methods of plasmapheresis comprising the separation of whole blood into a cellular fraction and a plasma fraction by a first membrane filter or by centrifugation, the separation of excess fluids and / or solutes from the cellular fraction across a semipermeable membrane, the separation of solutes in plasma from the plasma fraction by an adsorption filter, and a subsequent recombining of the filtered cellular fraction and filtered plasma fraction before re-entry into a subject. In some embodiments, CPFA refers to a method comprising adsorption, such as plasma adsorption (PA), immunoadsorption (IAS), immunoapheresis (IA), or immunoadsorption plasmapheresis (IAPP).

[0061]

[0051] “Hemodialysis” refers to methods comprising the separation of excess water and solutes from a subject’s blood by a dialyzer.

[0062]

[0052] “Hemofiltration” refers to methods comprising the extraction of excess water and solutes from a subject's blood using a hemofilter. In some embodiments, the hemofilter comprises a semipermeable membrane through which excess water and solutes are filtered via convection.

[0063]

[0053] “Hemoperfusion” refers to methods comprising the extraction of solutes from a subject’s blood by passing a subject's blood through an adsorbent filter.

[0064]

[0054] “Ultrafiltration” refers to methods comprising the extraction of water from a subject’s blood across a semipermeable membrane having a molecular weight cutoff of between about 10,000 Da and about 100,000 Da. In some embodiments, the semipermeable membrane allows small molecules (such as water) to pass through while retaining larger molecules (such as proteins).

[0065]

[0055] Although EBP treatments and procedures are defined above by reference to exemplary methods, those of skill also will understand such treatments and procedures by reference to the plain meaning in the art.

[0066]

[0056] The term “cellular fraction” as used herein can refer to or comprise red blood cells, white blood cells, and platelets. The terms “plasma fraction” or “plasma” as used herein can refer to or comprise a liquid portion of whole blood which contains, among other things, proteins, electrolytes, vitamins, and hormones.

[0067]

[0057] The terms “withdraw,” “withdrawal,” “withdrawn,” and “withdrawing” (or any other conjugation of “withdraw”) means to draw blood out (actively or passively) from the vascular system of an individual receiving plasmapheresis (or other type of apheresis procedure) which may be achieved using any suitable vascular access, which includes peripheral intravenous lines and central lines.

[0068]

[0058] The terms “return” or “returning” (or any other conjugation of “return”) or “infuse,” or “infusing” (or any 2025-09-12 other conjugation of “infuse”) means to return blood back (actively or passively) to the vascular system of a subject receiving plasmapheresis (or other procedure), be achieved using any suitable vascular access.

[0069]

[0059] The terms “separate,” “separated,” or “separating” (or any other conjugation of “separate”) means to separate components of blood and / or plasma from one another. For example, in DFPP, whole blood is withdrawn and plasma is separated from the cellular fraction of the withdrawn whole blood.

[0070]

[0060] The terms “purify,” “purified,” or “purifying,” (or any other conjugation of “purify”) means to reduce the amount of a contaminant, such as PFAS, from a plasma fraction, cellular fraction, or whole blood. For example, DFPP comprises passing a separated plasma fraction through a filter to produce a filter product or “eluate” (containing one or more contaminants removed by filtration) and a purified plasma fraction.

[0071]

[0061] “Per- and polyfluoroalkyl substances” (i.e., perfluoroalkyl and polyfluoroalkyl substances) or “PFAS” refers to a class of organic compounds comprising a completely or partially fluorinated alkyl chain. In some embodiments, a PFAS molecule comprises an acid moiety or its conjugate base (e.g., carboxylic acid, carboxylate, sulfonic acid, sulfonate). PFAS include perfluorinated compounds (PFCs) comprising a perfluoroalkyl moiety CnF2n+i, where n is an integer typically between 3 and 10, where all hydrogens have been replaced by fluorine atoms; and polyfluorinated compounds in which only some of the hydrogens replaced by fluorines. Exemplary PFAS, including perfluorinated and polyfluorinated compounds, are known to one of skill.

[0072]

[0062] Some common exemplary PFAS include perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorobutane sulfonate (PFBS), perfluoroundecanoic acid (PFUnDA), perfluorohexanoic acid (PFHxA), perfluorododecanoic acid (PFDoA), hexafluoropropylene oxide dimer acid (HFPO-DA), perfluorobutanoic acid (PFBA), perfluoropentanoic acid (PFPeA), perfluoroheptanoic acid (PFHpA), perfluorononanoic sulfonate (PFNS), perfluorodecane sulfonate (PFDS), perfluorooctane sulfonamide (PFOSA), perfluoropentane sulfonate (PFPeS), perfluoroheptane sulfonate (PFHpS), perfluoroundecane sulfonate (PFUnDS), perfluorotridecanoic acid (PFTrDA). Additional PFAS are known to those of skill, such as described in Buck et al. Integr Environ Assess Manag. 2011 ;7:513-541 ; U.S. Environmental Protection Agency. § 8(a)(7) Rule List of Chemicals (V3). Apr 24, 2024. https: / / comptox.epa.gov / dashboard / chemical-lists / PFAS8a7V3 (accessed Aug 29, 2024); each of which is incorporated by reference as if fully set forth herein.

[0073]

[0063] The composition of PFAS in a sample may be determined. The “composition” of PFAS refers to one or more characteristics of PFAS present in the sample, such as the chemical makeup (e.g., polymer type), physical properties (e.g., size distribution, shape, surface morphology), associated substances (e.g., adsorbed toxins, metals, or biofilms), and complexed endogenous or exogenous carriers.

[0074]

[0064] In embodiments, PFAS refers to one or more individual PFAS molecules. In embodiments, PFAS refers to an agglomerate of PFAS, such as that formed by coagulation or flocculation (Lin et al. Environ Sci Technol. 2015;49:10562-10569; Hubert et al. Water Res. 2024;249: 120888). In embodiments, PFAS refers to PFAS molecules bound to a blood or plasma constituent, such as red blood cells, albumin, globulins, 2025-09-12 fibrinogen, lipoproteins, or other plasma or serum proteins (Forsthuber et al. Environ Int. 2020; 137:105324).

[0075]

[0065] “Particle size” herein (e.g., to describe the size of PFAS) refers to a linear dimension of a particle (e.g., diameter, radius, length, width). For a PFAS molecule, particle size refers to the molecular hydrodynamic diameter of the molecule in the fluid medium. Where PFAS are bound to carrier macromolecules (e.g., serum albumin, lipoproteins, microplastics, liposomes, exosomes) or otherwise immobilized or aggregated (e.g., on a resin bead, within a precipitate), “particle size” refers to the effective hydrodynamic diameter (complex size) of the PFAS complex in the fluid medium. Depending on context, “particle size” accordingly may refer to molecular-level dimensions (e.g., the hydrodynamic diameter of a PFAS molecule) or particulate-level dimensions (e.g., the effective hydrodynamic diameter of a PFAS complex). A “particle” therefore may include individual PFAS molecules as well as PFAS-containing complexes or aggregates. Accordingly, the meaning of “particle size” will be understood in light of the context of the sample source. For example, in blood, plasma, or serum, PFAS are predominantly present in association with carrier macromolecules such as albumin or lipoproteins, and particle size therefore generally refers to the hydrodynamic diameter of the resulting PFAS-macromolecule complex; whereas in purified aqueous solution, particle size generally refers to the molecular hydrodynamic diameter of the unbound PFAS molecule.

[0076]

[0066] Herein, unless context indicates otherwise, ‘“PFAS molecule” refers to an individual per- and polyfluoroalkyl substance; ‘“PFAS complex” refers to a PFAS molecule bound to or encapsulated by one or more endogenous or exogenous carriers (e.g., albumin, lipoproteins, fibrinogen, micelles, vesicles, exosomes, and the like), including aggregates thereof. In embodiments, “‘PFAS particle” (or simply, “PFAS”) refers to a PFAS molecule and / or to a PFAS complex. In embodiments, PFAS are PFAS molecules. In embodiments, PFAS are PFAS complexes. In embodiments, PFAS comprises both PFAS molecules and PFAS complexes.

[0077]

[0067] Where PFAS comprises both PFAS molecules and PFAS complexes, or where PFAS is otherwise present as a distribution of two or more sizes, “particle size” refers to a statistical average of the distribution, such as mean hydrodynamic diameter, median hydrodynamic diameter, or number-weighted average.

[0078]

[0068] In embodiments, “particle size” refers to a particle size range centered on the mean particle size, plus or minus a number of standard deviations (e.g., ± 1, ± 2, ± 3, ± 4, ± 5 standard deviations). In embodiments, “particle size” refers to a particle size range centered on the mean particle size, plus or minus a percentage value (e.g., ± 1%, ± 5%, ± 10%, ± 20%, ± 30%, ± 40%, ± 50%). In embodiments, “particle size” refers to the median particle size of a distribution of particle sizes, and may include for example the D50, DV50, D(V,0.5), or x50. In embodiments, “particle size distribution” refers to any of the D10, D 50, D90, and D99.

[0079]

[0069] Techniques to measure particle size and particle size distribution are known in the art, and include sieve analysis, light scattering techniques (e.g., static light scattering, dynamic light scattering, nanoparticle tracking analysis), laser diffraction analysis, spectroscopic techniques (e.g., vibrational spectroscopy methods such as IR spectroscopy and Raman spectroscopy, including microFTIR and microRaman spectroscopy), flow cytometry, microscopic techniques (e.g., optical microscopy, electron microscopy), optofluidic force induction 2025-09-12 (0F2i) (see Neuper et al. Anal Chem. 2024 May 28;96(21):8291-8299), electrical sensing zone techniques (e.g., Coulter counter), acoustic spectroscopy, analytical ultracentrifugation, atomic force microscopy (AFM), small-angle X-ray scattering (SAXS), and resistive pulse sensing (RPS).

[0080]

[0070] “Pore size” refers to the size of the openings (i.e., pores) in a membrane, such as the membranes used in a plasmapheresis (e.g., DFPP) device. Definitions of “pore size” vary in the art, as do methods commonly used to measure pore size (see, e.g., Zhao et al. Desalination. 2000; 129(2): 107-123); all such definitions as are appreciated to be applicable may be used to understand the scope of “pore size” herein.

[0081]

[0071] Membranes may have non-uniform pore sizes and shapes, on the surface of the membrane and / or within the membrane, i.e., not on the membrane surface. In embodiments, pore size may be characterized according to the distribution of pore sizes on the surface of the membrane. In embodiments, pore size may be characterized according to the distribution of pore sizes not on the surface of the membrane (i.e., within the membrane). In embodiments, a membrane has a Gaussian distribution of pore sizes (e.g., as measured on the surface of the membrane and / or within the membrane). In embodiments, “pore size” refers to the mean diameter of pores on a membrane surface. In embodiments, “pore size” refers to the mean diameter of pores within a membrane. In embodiments, “pore size” refers to the median diameter of pores on a membrane surface. In embodiments, “pore size” refers to the median diameter of pores within a membrane. In embodiments, wherein “pore size” refers to the diameter of pores on a membrane surface, or within a membrane, pore size can be measured by microscopy (e.g., using optical or electron microscopy techniques), among other known techniques. In embodiments, “pore size” refers to the average or median pore size determined by a technique that measures pore properties over the entire membrane, including the internal pore structure. Techniques include gas sorption experiments (e.g., using the Brunauer-Emmett-Teller (BET) method), used to calculate pore size and pore size distribution. Pore size may also be defined or measured by a porosimetry technique, such as mercury intrusion porosimetry, which comprises measuring the pressure-driven intrusion of mercury into a membrane, and estimating pore size based on the pressure needed to force the mercury into the membrane pores against the opposing force of the mercury’s surface tension. Pore size and pore size distribution may also be defined or measured by membrane performance, e.g., by challenging the membrane with a series of solutes of increasing molecular size to characterize the membrane’s performance as a function of solute size (e.g., by measuring solute retention in the feed, and / or solute rejection in the filtrate). In embodiments, pore size is determined by the molecular weight cutoff (“MWCO”) of a membrane, such as determined using techniques known in the art. The MWCO of a membrane may be conventionally defined as being equal to the molecular weight of a solute of known size that is 90% retained by the membrane, and can be determined by methods that measure membrane performance (e.g., retention) as a function of solute molecular weight.

[0082]

[0072] In embodiments, the pore size of a plasma filter is selected to differentially target components in one or more specific portions of plasma, such as determined by molecular weight and three-dimensional structure. 2025-09-12

[0083]

[0073] In embodiments, administering a DFPP, plasmapheresis, or other EBP treatment reduces an amount of PFAS in a subject’s blood. Techniques to assess the amount of PFAS, such as the amount of PFAS in a subject’s blood, include those known in the art, as well as exemplary techniques in disclosed embodiments.

[0084]

[0074] In embodiments, PFAS, including PFAS present in a biological matrix of a subject or removed from the biological matrix by a disclosed method (e.g., in an eluate from the subject), have a particle size of less than about 1 pm. In embodiments, PFAS have a particle size in the submicron range, such as less than about 500 nm, less than about 200 nm, or less than about 100 nm. In embodiments, PFAS have a particle size of of between about 1 mm and about 1 pm, including about 5 mm, about 4 mm, about 3 mm, about 2 mm, about 1 mm, about 900 pm, about 800 pm, about 700 pm, about 600 pm, about 500 pm, about 400 pm, about 300 pm, about 200 pm, or about 100 pm. In embodiments, PFAS have a particle size of between about 100 pm and about 100 nm, including about 90 pm, about 80 pm, about 70 pm, about 60 pm, about 50 pm, about 40 pm, about 30 pm, about 20 pm, about 10 pm, about 9 pm, about 8 pm, about 7 pm, about 6 pm, about 5 pm, about 4 pm, about 3 pm, about 2 pm, about 1 pm, about 900 nm, about 800 nm, about 700 nm, about 600 nm, about 500 nm, about 400 nm, about 300 nm, or about 200 nm. In embodiments, PFAS have a particle size in the tens of nanometers range, including about 50 nm, about 30 nm, or about 20 nm, such as when associated with carrier macromolecules (e.g., albumin, lipoproteins) or contained within vesicles (e.g., liposomes, exosomes). In embodiments, PFAS have a particle size of less than about 100 nm, including about 90 nm, about 80 nm, about 70 nm, about 60 nm, about 50 nm, about 40 nm, about 30 nm, or about 20 nm. In embodiments, PFAS have a particle size in the low nanometer range, including about 10 nm, about 5 nm, or about 2-3 nm, such as when bound to proteins or small complexes. In embodiments, PFAS have a particle size of about 10 nm, about 9 nm, about 8 nm, about 7 nm, about 6 nm, about 5 nm, about 4 nm, about 3 nm, or about 2 nm, such as in small complexes or oligomers. In embodiments, PFAS comprises PFAS molecules, which for example may have a hydrodynamic diameter of about 1-2 nm in a fluid medium.

[0085]

[0075] “Biological matrix” refers to any material of biological origin obtained from a subject or derived therefrom, in which an analyte (e.g., PFAS, co-contaminants) may be present and measured, and / or that may be processed, filtered, exchanged, or otherwise treated by the disclosed devices and methods. The biological matrix may comprise, may consist essentially of, may consist of, or may be any of, including any combination of: blood and blood derivatives, such as whole blood, plasma, serum, peripheral blood mononuclear cells, red blood cells, and platelets; body fluids, such as interstitial fluid, lymph, cerebrospinal fluid, synovial fluid, bile, urine, feces, stool homogenate, saliva, sweat, tears, breast milk, semen, vaginal fluid, follicular fluid, amniotic fluid, cord blood, and bronchoalveolar lavage fluid; tissues and organs, such as liver, kidney, adipose, muscle, skin, brain, and their homogenates or lysates; cellular and extracellular components, such as extracellular vesicles (e.g., exosomes), lipoprotein fractions (e.g., VLDL, LDL, HDL), and protein fractions (e.g., albumin-containing fractions); and processed fractions, such as any supernatant, pellet, isolate, eluate, retentate, adsorbate, ultrafiltrate, or dialysate produced from any of the foregoing. 2025-09-12

[0086]

[0076] In embodiments, “in” or “from” “the biological matrix of a subject” include “in” or “from” “a tissue of a subject,” “in” or “from” “the blood of a subject and / or the tissue of a subject,” “in” or “from” “the blood, fluid, and / or tissue of a subject,” “in” or “from” “a fluid of a subject,” and the like, as context permits. In embodiments, “in” or “from” “the blood of a subject” include “in” or “from” “a tissue of a subject” and may be interpreted to mean “in” or “from” “the blood of a subject and / or the tissue of a subject,” as context permits. In embodiments, “in” or “from” “a tissue of a subject” include “in” or “from” “the blood of a subject” and may be interpreted to mean “in” or “from” “the blood of a subject and / or the tissue of a subject,” as context permits.

[0087]

[0077] In embodiments, PFAS present as complexes with carriers or assemblies in the biological matrix of a subject, or removed therefrom using a disclosed method, including complexes with proteins, peptides, lipoproteins, globulins, micelles, fibrinogen, complement components, vesicles, liposomes, polymeric carriers, colloids, exosomes, or other plasma constituents, have an effective complex size expressed as a hydrodynamic diameter within the nanometer range. In embodiments, the hydrodynamic diameter is between about 1 nm and 100 nm, including sub-ranges of about 1-10 nm, about 10-20 nm, about 20-30 nm, about 30-40 nm, about 40-50 nm, about 50-60 nm, about 60-70 nm, about 70-80 nm, about 80-90 nm, or about 90-100 nm. In embodiments, the hydrodynamic diameter is between about 100 nm and 1,000 nm, including sub-ranges of about 100-200 nm, about 200-300 nm, about 300-400 nm, about 400-500 nm, about 500-600 nm, about 600-700 nm, about 700-800 nm, about 800-900 nm, or about 900-1 ,000 nm. In embodiments, the effective complex size is greater than about 1,000 nm, including about 1,100 nm, about 1 ,200 nm, about 1 ,300 nm, about 1 ,400 nm, about 1 ,500 nm, about 1 ,600 nm, about 1,700 nm, about 1,800 nm, about 1 ,900 nm, or about 2,000 nm. In some embodiments, either the lower bound, the upper bound, or both bounds of a recited range are preceded by the term “about,” while in other embodiments neither bound is preceded by “about.” Further embodiments include ranges defined by any combination of the above lower and upper bounds.

[0088]

[0078] In embodiments, PFAS bound to microplastic particles in the biological matrix of a subject, or removed therefrom using a disclosed method, have an effective complex size that, depending on the size of the microplastic particle, is between about 1 pm and 5 mm, such as a size between about 1 pm and 1 mm, about 10 pm and 500 pm, about 50 pm and 500 pm, about 100 pm and 1 mm, or about 0.5 mm and 5 mm; in embodiments, PFAS bound to nanoplastic particles in the biological matrix of a subject, or removed therefrom using a disclosed method, have an effective complex size expressed as a hydrodynamic diameter between about 10 nm and about 1 ,000 nm, such as a size between about 10 nm and 50 nm, about 20 nm and 200 nm, about 50 nm and 200 nm, about 100 nm and 500 nm, or about 200 nm and 800 nm, wherein each range is inclusive, and each size is preceded in embodiments by “about” and in other embodiments not by “about.”

[0089]

[0079] In embodiments, PFAS bound to microplastic particles in the biological matrix of a subject, or removed therefrom using a disclosed method, have a molecular weight, e.g., a molecular (formula-average) mass, of about 0.2 kDa to about 1.0 kDa, such as between about 0.2-0.3 kDa, 0.3-0.4 kDa, 0.4— 0.5 kDa, 0.5-0.6 kDa, 0.6-0.7 kDa, 0.7-0.8 kDa, 0.8-0.9 kDa, or 0.9-1.0 kDa, wherein each range is inclusive. Further 2025-09-12 embodiments include ranges defined by any combination of the foregoing bounds (e.g., 0.25-0.8 kDa, or 0.3-0.7 kDa). In embodiments, PFAS have a molecular weight of less than about 1.0 kDa, less than about 0.9 kDa, less than about 0.8 kDa, less than about 0.7 kDa, less than about 0.6 kDa, less than about 0.5 kDa, or less than about 0.4 kDa. In embodiments, such as directed to polymeric PFAS (e.g., side-chain fluorinated polymers), the polymer has a number-average molecular weight (Mn) and / or weight-average molecular weight (Mw) in the range of about 10 kDa to about 10,000 kDa, including sub-ranges of about 10-100 kDa, 100-1 ,000 kDa, 1,000-5,000 kDa, or 5,000-10,000 kDa. In embodiments, PFAS-carrier complexes (e.g., PFAS bound to albumin, lipoproteins, vesicles, or colloids) exhibit an apparent or effective molecular weight (e.g., as determined by size-exclusion chromatography) greater than about 50 kDa, including about 50-100 kDa, about 100-500 kDa, about 500-1,000 kDa, or greater than about 1 ,000 kDa.

[0090]

[0080] In embodiments, PFAS circulate in the blood or plasma bound to carrier macromolecules, thereby forming PFAS-carrier complexes. In such embodiments, the mass or effective molecular weight of a PFAS-carrier complex corresponds approximately to the combined mass of the carrier macromolecule and the bound PFAS, or to the sum of the molecular weight of the carrier macromolecule and the molecular weight of the bound PFAS, where “effective molecular weight” refers to the apparent or measured molecular weight of a PFAS-containing complex, as determined by techniques such as size-exclusion chromatography, light scattering, or similar methods. For example, in embodiments, albumin-bound PFAS complexes have an effective molecular weight of about 65-70 kDa (e.g., about 66-67 kDa for human serum albumin plus about 0.1-1.0 kDa for PFAS). In embodiments, fibrinogen-bound PFAS complexes have an effective molecular weight of about 305-350 kDa (e.g., about 340 kDa for standard fibrinogen or about 305 kDa for fibrinogen with partial alpha-chain degradation). In embodiments, immunoglobulin G (IgG)-bound PFAS complexes have an effective molecular weight of about 150-152 kDa (e.g., about 150 kDa for IgG plus the bound PFAS). In embodiments, PFAS bound to multiprotein complexes have an effective molecular weight corresponding to the combined mass of the multiprotein complex and the PFAS. In embodiments, PFAS bound to extracellular vesicles have an effective molecular weight corresponding to the combined mass of the vesicle and the PFAS.

[0091]

[0081] In embodiments, the size of PFAS-carrier complexes is expressed as a hydrodynamic diameter in a fluid medium. For example, albumin-bound PFAS complexes may have a hydrodynamic diameter of about 6-8 nm, IgG-bound PFAS complexes about 9-11 nm, and fibrinogen-bound PFAS complexes about 40-50 nm. In embodiments, as will be appreciated, PFAS bound to multiprotein complexes or extracellular vesicles may have hydrodynamic diameters ranging from tens to hundreds of nm, depending on the size of the assembly.

[0092]

[0082] In embodiments, PFAS are bound (i.e., a PFAS complex) in the biological matrix of a subject such that the bound fraction is at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99%.

[0093]

[0083] In some embodiments, administration of a DFPP, plasmapheresis, or other EBP treatment reduces the amount of PFAS in a subject’s biological matrix by at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99%, relative to the amount present prior to 2025-09-12 treatment. In embodiments, administration of the treatment reduces the amount of PFAS to below a detectable level, as determined by a measurement technique described herein or otherwise known to one of skill.

[0094]

[0084] In embodiments, the amount of PFAS in a subject’s biological matrix is assessed by measuring PFAS concentration. A “concentration” of PFAS may refer to (i) a mass concentration (e.g., ng / mL, pg / L), (ii) a molar concentration (e.g., nM), or (iii) a calibrated instrument response (e.g., area ratio converted to ng / mL) of a PFAS analyte, a sum of PFAS analytes, and / or PFAS complexes in a biological matrix or in a process stream (e.g., permeate / filtrate, retentate, or eluate).

[0095]

[0085] In embodiments, the amount of PFAS in a subject’s biological matrix is assessed by measuring PFAS concentration on a mass / volume basis (e.g., pg / mL or ng / mL). In embodiments, a disclosed method reduces the PFAS concentration by at least about 0.01 ng / mL, 0.05 ng / mL, 0.1 ng / mL, 0.5 ng / mL, 1 ng / mL, 2 ng / mL, 5 ng / mL, 10 ng / mL, 20 ng / mL, or 50 ng / mL, compared to the concentration prior to treatment. In some embodiments, measuring an amount (e.g., an absolute amount), such as a ng or pg amount removed, or measuring a concentration, such as a ng / mL or pg / mL concentration reduction, of PFAS in a subject’s biological matrix is performed directly on a sample of the subject’s biological matrix. In embodiments, measuring the concentration of PFAS is performed directly on a blood sample from a subject.

[0096]

[0086] In embodiments, administration of a DFPP, plasmapheresis, or other EBP treatment increases the clearance rate of PFAS from a subject’s biological matrix relative to the subject’s natural clearance rate. In embodiments, the clearance rate is increased by at least about 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 75-fold, 100-fold, 200-fold, 500-fold, or 1 ,000-fold, compared to the clearance rate of PFAS in the absence of treatment. In embodiments, the treatment increases the clearance rate of PFAS to a level sufficient to reduce the effective half-life of PFAS in plasma or serum from years to weeks, days, or hours. In embodiments, clearance rate is expressed as the apparent volume of biological fluid (e.g., plasma, serum, or whole blood) cleared of PFAS per unit time. In embodiments, administration of a DFPP, plasmapheresis, or other EBP treatment increases the clearance of PFAS by at least about 1 mL / min, 2 mL / min, 5 mL / min, 10 mL / min, 20 mL / min, 50 mL / min, or 100 mL / min, compared to baseline clearance. In embodiments, clearance rate is expressed as an apparent systemic clearance (e.g., L / hour), and treatment increases systemic clearance of PFAS by at least about 0.1 L / hour, 0.5 L / hour, 1 L / hour, 2 L / hour, 5 L / hour, or 10 L / hour, relative to baseline.

[0097]

[0087] Clearance rate may be determined by measuring plasma PFAS concentrations before and after treatment and calculating elimination kinetics according to standard pharmacokinetic models.

[0098]

[0088] As provided in various aspects and embodiments of the disclosure, methods include any one or more of the steps of: identifying a subject, including a subject who has or is at risk of a condition; administering to the subject a DFPP, plasmapheresis, or other EBP treatment; and measuring an amount of PFAS, such as a concentration of PFAS in the biological matrix of the subject, which may be before and / or after a treatment, or an amount, such as a concentration, of PFAS in an eluate from the subject. In embodiments, administering a disclosed EBP treatment to a subject treats a condition, which in embodiments includes preventing a condition 2025-09-12 or reducing the risk of a condition, such as a disease or disorder, and which in embodiments provides an improvement, such as an improvement to health, to healthspan, or to lifespan.

[0099] B. Selection of Subjects For Treatment

[0100]

[0089] Disclosed devices and methods for EBP to remove PFAS are useful for subjects, such as human subjects. In some aspects, the selection of subjects for treatment using such devices and methods is provided.

[0101]

[0090] In some embodiments, a subject is selected to undergo treatment according to a disclosed method. In some embodiments, a subject is selected for treatment if the subject meets certain specified inclusion criteria, does not meet certain specified exclusion criteria, does not meet any specified withdrawal criteria before or during the course of the treatment, and otherwise satisfies the disclosed or claimed requirements. In some embodiments, a subject is selected to undergo a specific disclosed treatment or set of disclosed treatments.

[0102]

[0091] Disclosed devices and methods are useful for a subject having a measurable amount of PFAS in a biological matrix, including a fluid (e.g., blood), a tissue, an eluate obtained from the subject, a plasma fraction removed from the subject (e.g., plasma isolated during an extracorporeal blood purification treatment), or an adsorbate recovered from an adsorption column or other adsorbent material of an extracorporeal circuit. In embodiments, a subject is selected for treatment based on the presence of a measurable amount of PFAS. In embodiments, the subject is selected for treatment based on the measurable amount of PFAS in the biological matrix. In embodiments, a subject is selected for treatment based on an eluate containing a measurable amount of PFAS obtained from the subject. In embodiments, a subject is selected for treatment based on a plasma fraction containing a measurable amount of PFAS removed from the subject (e.g., plasma isolated during another EBP treatment). In embodiments, a subject is selected for treatment based on an adsorbate containing a measurable amount of PFAS recovered from an adsorption column or other adsorbent material of an extracorporeal circuit after an EBP treatment administered to the subject. Measurement of PFAS in such biological matrices can be performed using methods disclosed herein or otherwise known in the art.

[0103]

[0092] In embodiments, selecting a subject for treatment comprises measuring an amount of PFAS in a fluid of the subject, such as a sample of the fluid. Measuring an amount of PFAS “in a fluid of a subject” or “in a subject’s fluid” includes, in embodiments, measuring the amount of PFAS while the fluid is in the body of the subject. In other embodiments, it refers to measuring the amount of PFAS after the fluid is obtained from the body of the subject. Fluids may be obtained using known methods. In embodiments, fluids may comprise, may consist essentially of, may consist of, or may be a biological fluid, a non-blood fluid, a non-blood biological fluid, or a specific fluid, including blood, plasma, serum, urine, saliva, sweat, tears, cerebrospinal fluid, interstitial fluid, synovial fluid, peritoneal fluid, pleural fluid, pericardial fluid, amniotic fluid, seminal fluid, vaginal secretions, breast milk, bile, gastric fluid, bronchoalveolar lavage fluid, fecal extract, lymph, menstrual fluid, nasopharyngeal mucus, sputum, wound exudate, dialysate, eluate, apheresis eluate, or lavage fluid.

[0104]

[0093] In embodiments, selecting a subject for treatment comprises measuring an amount of PFAS in a biological matrix of the subject. Measuring an amount of PFAS “in a biological matrix of the subject” 2025-09-12 (equivalently stated as “in a subject’s biological matrix”) includes measuring the amount of PFAS in the biological matrix of the subject whether the biological matrix is in the body of the subject or withdrawn from the body of the subject, including withdrawn by any known means (e.g., biopsy). In embodiments, selecting a subject for treatment comprises measuring the concentration of PFAS in the biological matrix of the subject.

[0105]

[0094] In embodiments, a subject is selected for treatment if the concentration of PFAS in a biological matrix of the subject is greater than about 0.01 ng / mL to about 100 ng / mL. Herein, “greater than about 0.01 ng / mL to about 100 ng / mL” includes a concentration greater than any of 0.01 , 0.02, 0.05, 0.1 , 0.2, 0.5, 1, 2, 3, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100 ng / mL, as well as sub-ranges bounded by these values, and also includes higher concentrations, such as greater than about 200, 500, and 1000 ng / mL, and sub-ranges therebetween.

[0106]

[0095] In embodiments, selecting a subject for treatment comprises measuring the concentration of PFAS in a fluid of the subject. In embodiments, a subject is selected for treatment if the concentration of PFAS in the fluid of the subject is greater than about 0.01 ng / mL to about 100 ng / mL. In embodiments, selecting a subject for treatment comprises measuring an amount of PFAS in the blood of the subject, such as a sample of blood of the subject. Measuring an amount of PFAS in the blood of a subject includes in embodiments measuring the amount of PFAS in the subject’s blood when the blood is in the body of the subject. In embodiments, it refers to measuring the amount of PFAS in the subject’s blood when the blood is withdrawn from the body of the subject. Blood may be withdrawn according to known methods. In some embodiments, selecting a subject for treatment comprises measuring the concentration of PFAS in the blood of the subject. In embodiments, a subject is selected for treatment if the concentration of PFAS in the blood of the subject is greater than about 0.01 ng / mL to about 100 ng / mL. In embodiments, selecting a subject for treatment comprises measuring an amount of PFAS in an eluate from the subject (e.g., an eluate from a DFPP treatment). Measuring an amount of PFAS in an eluate from the subject includes embodiments that are independent of how the eluate of the subject is obtained, and independent of whether the eluate is obtained using a disclosed method or a disclosed device. In some embodiments, the eluate of the subject is obtained using a disclosed method or using a disclosed device. In embodiments, selecting a subject for treatment comprises measuring the concentration of PFAS in an eluate of the subject. In embodiments, a subject is selected for treatment if the concentration of PFAS in an eluate of the subject is greater than about 0.01 ng / mL to about 100 ng / mL. In embodiments, selecting a subject for treatment comprises measuring an amount of PFAS in a tissue of the subject. Measuring an amount of PFAS in a tissue of the subject includes measuring the amount of PFAS in the tissue of the subject whether the tissue is in the body of the subject or withdrawn from the body of the subject, including withdrawn by any known means (e.g., biopsy). In embodiments, selecting a subject for treatment comprises measuring the concentration of PFAS in the tissue of the subject. In embodiments, a subject is selected for treatment if the concentration of PFAS in the tissue of the subject is greater than about 0.01 ng / mL to about 100 ng / mL.

[0107]

[0096] In embodiments, selecting a subject for treatment comprises an assessment. An “assessment” refers 2025-09-12 to any means or method used with a subject, whether before, during, after, or unrelated in time to administration of a disclosed treatment, to measure, estimate, or evaluate a nature, ability, symptom, disorder, or other characteristic, trait, or behavior of the subject, whether qualitatively or quantitatively, and whether performed by a clinician (e.g., an interview), by the subject his or herself (e.g., a self-reported questionnaire), by a third-party, or by a computer, including a medical device (e.g., as such as defined by FDA or other regulatory body) or other device (e.g., medical sensor, biosensor, smartphone, watch, fitness tracker, “wearable”), and whether graded by a human decision-maker or by an artificial intelligence (Al), machine learning (ML), or computer algorithm. An assessment may be computer-assisted, including an assessment comprising the use of a computer, device, and / or electronic tool such as an online tool or an app, such as a health app, and including any assessment contributing to or comprising the use of a digital phenotype.

[0108]

[0097] An assessment may be a clinical assessment conducted by a medical professional, and / or a subject’s self-assessment of symptoms they wish to reduce (e.g., where a subject has a diagnosed or diagnosable medical condition) or aspects of their general health and wellbeing they wish to improve or preserve. In embodiments, a subject is selected for treatment if an assessment indicates the subject would benefit from a disclosed treatment. Assessments may vary depending on the health status of the subject, and any specific medical condition(s) sought to be treated, or particular aspects of health and wellbeing sought to be improved or preserved, e.g., by reducing the amount of PFAS in the subject’s biological matrix. An assessment (e.g., a pre-treatment assessment) may be any of a general consultation, one or more blood panels, a gut microbiome test, an environmental toxin test, one or more biomarker tests (e.g., aging biomarkers), a medical history evaluation, a health examination, a physical examination, a cognitive examination, a fitness or strength test, a fertility health test, a heart scan, and such other assessments as disclosed herein and known to one of skill.

[0109]

[0098] In embodiments, a subject is selected for treatment if the subject has a condition, for example which a disclosed method is useful to treat. In embodiments, a subject is selected for treatment if the subject is at risk of a condition, for example which a disclosed method is useful to treat. A subject “at risk of’ a condition, such as a disease or a disorder, includes a subject with an increased risk of developing the condition, such as a 5%, 10%, 15%, 20% 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, 1 ,000%, or greater than 1,000% increased risk, such as an increased relative risk, of developing the condition, of developing symptoms of the condition, or of being diagnosed with the condition. In embodiments, a subject “at risk of’ a condition includes a subject having a statistically significant increased relative risk (e.g., greater than or equal to a certain percentage when compared to a control group) of developing the condition, of developing symptoms of the condition, or of being diagnosed with the condition. Exemplary methods of determining an increased risk, such as an increased relative risk, will be known to those of skill in view of the teachings herein and the general knowledge in the art as they relate to a specific condition, such as a disclosed condition for which the disclosed methods are useful.

[0110]

[0099] In embodiments, a subject is selected for treatment if the subject has a reproductive or fertility 2025-09-12 condition, including a reproductive or fertility disease or disorder (e.g., male factor infertility (such as decreased sperm count or sperm quality), female factor infertility (such as low estrogen levels, endometriosis, or polycystic ovary syndrome (PCOS)), erectile dysfunction, hormone imbalance, preterm birth, preeclampsia, low birth weight, and developmental delays in children associated with maternal reproductive conditions; as well as endocrine disorders that may impact reproductive health, such as hypothyroidism, hyperthyroidism, or adrenal disruption). In embodiments, a subject is selected for treatment if the subject is at risk of a reproductive or fertility condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a reproductive or fertility condition and the subject has a measurable amount of PFAS in a biological matrix, which here and elsewhere shall be understood to mean any of the definitions provided below.

[0111]

[0100] As used herein, including as used for the selection of a subject for treatment, the phrase “a measurable amount of PFAS in a biological matrix” refers in embodiments to a concentration of PFAS in a biological matrix of the subject that is detectable by an analytical method, such as a method disclosed herein or known in the art (e.g., LC-MS / MS, ELISA, fluorine NMR, or other quantitative assays). In embodiments, a measurable amount refers to a concentration above the limit of detection or quantitation of the analytical method employed. In embodiments, a “measurable amount” refers to a concentration greater than about 0.005 ng / mL, 0.01 ng / mL, 0.05 ng / mL, 0.1 ng / mL, 0.5 ng / mL, 1 ng / mL, 2 ng / mL, 5 ng / mL, 10 ng / mL, 20 ng / mL, 50 ng / mL, or 100 ng / mL. In embodiments, a measurable amount refers to an amount greater than the concentration of PFAS commonly observed in an equivalent general population, environmentally exposed population, or occupationally exposed population. In embodiments, a measurable amount refers to an amount approximately equal to or greater than a concentration associated with clinical or toxicological effects.

[0112]

[0101] Hormonal imbalances and conditions: In some embodiments, a subject is selected for treatment if the subject has a hormonal imbalance or condition, including a hormonal disease or disorder. In embodiments, a subject is selected for treatment if the subject is at risk of a hormonal imbalance or disorder. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a hormonal imbalance or condition and the subject has a measurable amount of PFAS in a biological matrix.

[0113]

[0102] Mitochondrial dysfunctions and conditions: In some embodiments, a subject is selected for treatment if the subject has a mitochondrial dysfunction or condition, including a mitochondrial disease or disorder. In embodiments, a subject is selected for treatment if the subject is at risk of a mitochondrial dysfunction or condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a mitochondrial dysfunction or condition and the subject has a measurable amount of PFAS in a biological matrix.

[0114]

[0103] Fatigue-related conditions: In some embodiments, a subject is selected for treatment if the subject has a fatigue-related condition, including a fatigue-related disease or disorder (e.g., chronic fatigue syndrome). In embodiments, a subject is selected for treatment if the subject is at risk of developing a fatigue-related condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a fatigue-related condition and the subject has a measurable amount of PFAS in a biological matrix. 2025-09-12

[0115]

[0104] Gastrointestinal (Gl) conditions: In some embodiments, a subject is selected for treatment if the subject has a Gl condition, including a Gl disease or disorder, or a hepatic condition, including a hepatic disease or disorder (e.g., liver fibrosis, non-alcoholic fatty liver disease, gut-microbiome disruption, intestinal inflammation, digestive dysfunction, Irritable bowel syndrome (IBS), inflammatory bowel disease (IBD)). In embodiments, a subject is selected for treatment if the subject is at risk of developing a Gl condition or a hepatic condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a Gl condition or a hepatic condition and the subject has a measurable amount of PFAS in a biological matrix.

[0116]

[0105] Cardiovascular conditions: In embodiments, a subject is selected for treatment if the subject has a cardiovascular condition, including a cardiovascular disease (CVD) or disorder, or a cardiometabolic condition, including a cardiometabolic disease or disorder (e.g., atherosclerosis, hypertension, dyslipidemia, hypertension, atherosclerotic plaque, thrombosis, arrhythmias, insulin resistance, obesity, diabetes, metabolic syndrome). In embodiments, a subject is selected for treatment if the subject is at risk of a CVD or a cardiometabolic condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a CVD or a cardiometabolic condition, and the subject has a measurable amount of PFAS in a biological matrix.

[0117]

[0106] Stroke-related conditions: In some embodiments, a subject is selected for treatment if the subject has a stroke-related condition, including a stroke-related disease or disorder. In embodiments, a subject is selected for treatment if the subject is at risk of a stroke-related condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a stroke-related condition and the subject has a measurable amount of PFAS in a biological matrix.

[0118]

[0107] Thrombosis: In some embodiments, a subject is selected for treatment if the subject has thrombosis. In embodiments, a subject is selected for treatment if the subject is at risk of thrombosis. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, thrombosis and the subject has a measurable amount of PFAS in a biological matrix.

[0119]

[0108] Respiratory conditions: In some embodiments, a subject is selected for treatment if the subject has a respiratory condition, including a respiratory disease or disorder (e.g., asthma, lung fibrosis). In embodiments, a subject is selected for treatment if the subject is at risk of a respiratory condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a respiratory condition and the subject has a measurable amount of PFAS in a biological matrix.

[0120]

[0109] Inflammation: In embodiments, a subject is selected for treatment if the subject has acute or chronic inflammation, an inflammatory condition such as a chronic inflammatory condition, or an inflammatory disease or disorder. In embodiments, a subject is selected for treatment if the subject is at risk of inflammation or an inflammatory condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, inflammation or an inflammatory condition and has a measurable amount of PFAS in a biological matrix.

[0121]

[0110] Immunological conditions: In some embodiments, a subject is selected for treatment if the subject has an immunological condition, including an immunological disease or disorder (e.g., an autoimmune disease 2025-09-12 such as rheumatoid arthritis, multiple sclerosis, lupus, Hashimoto’s Thyroiditis, psoriasis, an allergic disorder, an immunodeficiency disorder, a hypersensitivity reaction). In embodiments, the immunological condition is an autoimmune disease. In embodiments, the immunological condition is an allergic disorder. In embodiments, the immunological condition is an immunodeficiency disorder. In embodiments, the immunological condition is a hypersensitivity reaction. In embodiments, a subject is selected for treatment if the subject is at risk of an immunological condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, an immunological condition and the subject has a measurable amount of PFAS in a biological matrix.

[0122]

[0111] Cancer: In embodiments, a subject is selected for treatment if the subject has cancer (e.g., breast, testicular, kidney, renal cell carcinoma, thyroid, lung, colorectal, liver). In embodiments, a subject is selected for treatment if the subject is at risk of cancer. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, cancer and the subject has a measurable amount of PFAS in a biological matrix.

[0123]

[0112] Mental health conditions: In some embodiments, a subject is selected for treatment if the subject has a mental health condition, including a mental health disease or disorder (e.g., depression, anxiety, post-traumatic stress disorder (PTSD), a cognitive or behavioral impairment, or another disclosed mental health disorder). In embodiments, a subject is selected for treatment if the subject is at risk of a mental health condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a mental health condition and the subject has a measurable amount of PFAS in a biological matrix.

[0124]

[0113] Neurodeaenerative conditions: In some embodiments, a subject is selected for treatment if the subject has a neurodegenerative condition, including a neurodegenerative disease or disorder. In embodiments, a subject is selected for treatment if the subject is at risk of a neurodegenerative condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a neurodegenerative condition and the subject has a measurable amount of PFAS in a biological matrix.

[0125]

[0114] Pain and pain conditions: In some embodiments, a subject is selected for treatment if the subject has pain or a pain condition, including a pain disease or disorder (e.g., chronic inflammation, neuropathic pain, musculoskeletal pain, gastrointestinal pain, cluster headaches, migraines, chronic headaches, fibromyalgia). In embodiments, a subject is selected for treatment if the subject is at risk of pain or a pain condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, pain or a pain condition and the subject has a measurable amount of PFAS in a biological matrix.

[0126]

[0115] Blood conditions: In some embodiments, a subject is selected for treatment if the subject has a blood condition, including a blood disease or disorder. In embodiments, a subject is selected for treatment if the subject is at risk of a blood condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a blood condition and the subject has a measurable amount of PFAS in a biological matrix.

[0127]

[0116] Erectile dysfunction: In some embodiments, a subject is selected for treatment if the subject has erectile dysfunction (ED). In embodiments, a subject is selected for treatment if the subject is at risk of ED. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, ED and the subject has a 2025-09-12 measurable amount of PFAS in a biological matrix.

[0128]

[0117] Dermatological conditions: I n some embodiments, a subject is selected for treatment if the subject has a dermatological condition. In embodiments, a subject is selected for treatment if the subject is at risk of a dermatological condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a dermatological condition and the subject has a measurable amount of PFAS in a biological matrix.

[0129]

[0118] Hair loss conditions: In some embodiments, a subject is selected for treatment if the subject has a hair loss condition. In embodiments, a subject is selected for treatment if the subject is at risk of a hair loss condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a hair loss condition and the subject has a measurable amount of PFAS in a biological matrix.

[0130]

[0119] Skin conditions: In some embodiments, a subject is selected for treatment if the subject has a skin condition, including a skin disease or disorder. In embodiments, a subject is selected for treatment if the subject is at risk of a skin condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a skin condition and the subject has a measurable amount of PFAS in a biological matrix.

[0131]

[0120] Excretory system conditions: In some embodiments, a subject is selected for treatment if the subject has an excretory system condition, including an excretory system disease or disorder. In embodiments, a subject is selected for treatment if the subject is at risk of an excretory system condition. In embodiments, an excretory system disorder comprises a liver condition, a kidney condition, or a urinary tract condition. In embodiments, an excretory system condition reduces the subject's ability to eliminate PFAS from their body. In some embodiments, dialysis, such as intermittent or continuous hemodialysis, introduces PFAS into the bloodstream through dialysate, tubing, and / or membrane components, and contributes to an excretory system condition of a subject (see, e.g., Passos et al. Environ Toxicol Pharmacol. 2023 Sep;102:104253). In some embodiments, a subject is selected for treatment to remove PFAS introduced through dialysis. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, an excretory system condition and the subject has a measurable amount of PFAS in a biological matrix.

[0132]

[0121] Prostate conditions: In embodiments, a subject is selected for treatment if the subject has a prostate condition, including a prostate disease or disorder. In embodiments, a subject is selected for treatment if the subject is at risk of a prostate condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a prostate condition and the subject has a measurable amount of PFAS in a biological matrix.

[0133]

[0122] Metabolic conditions: In embodiments, a subject is selected for treatment if the subject has a metabolic condition, including a metabolic disease or disorder. In embodiments, a subject is selected for treatment if the subject is at risk of a metabolic condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a metabolic condition and has a measurable amount of PFAS in a biological matrix.

[0134]

[0123] Endocrine conditions: In some embodiments, a subject is selected for treatment if the subject has an endocrine condition, including an endocrine disease or disorder. In embodiments, a subject is selected for treatment if the subject is at risk of an endocrine condition. In embodiments, the endocrine condition is a 2025-09-12 thyroid disorder. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, an endocrine condition and the subject has a measurable amount of PFAS in a biological matrix.

[0135]

[0124] Vaccine-associated conditions: In some embodiments, a subject is selected for treatment if the subject has a vaccine-associated condition, including a vaccine-associated disease or disorder. In embodiments, a subject is selected for treatment if the subject is at risk of a vaccine-associated condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a vaccine-associated condition and the subject has a measurable amount of PFAS in a biological matrix.

[0136]

[0125] Cholesterol-related conditions: I n some embodiments, a subject is selected for treatment if the subject has a cholesterol-related condition, including a cholesterol-related disease or disorder. In embodiments, a subject is selected for treatment if the subject is at risk of a cholesterol-related condition. In embodiments, the cholesterol-related condition comprises hyperlipidemia, including familial hyperlipidemia. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a cholesterol-related condition and the subject has a measurable amount of PFAS in a biological matrix.

[0137]

[0126] Complications from cholesterol crystals: In embodiments, a subject is selected for treatment if the subject has a complication from cholesterol crystals in a biological matrix. In embodiments, a subject is selected for treatment if the subject is at risk of a complication from cholesterol crystals in a biological matrix. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a complication from cholesterol crystals in a biological matrix and has a measurable amount of PFAS in a biological matrix.

[0138]

[0127] Wound, injury, and surgery recovery: In embodiments, a subject is selected for treatment to promote wound, injury, or surgery recovery. In embodiments, a subject is selected for treatment if the subject is recovering from a wound, injury, or surgery and has a measurable amount of PFAS in a biological matrix.

[0139]

[0128] Conditions not etiologically linked to PFAS: In some embodiments, a subject is selected for treatment if the subject has a diagnosed or diagnosable condition that is not etiologically linked to PFAS (e.g., a monogenic disorder (cystic fibrosis), an acute or chronic infectious disease (malaria, Epstein-Barr virus reactivation), an autoimmune flare (systemic lupus erythematosus), or a hereditary cardiomyopathy). In embodiments, a subject is selected for treatment if the subject is at risk of such a condition or at risk of worsened outcomes from such a condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, the condition and the subject has a measurable amount of PFAS in a biological matrix.

[0140]

[0129] Athletic performance: In some embodiments, a subject is selected for treatment to improve athletic performance. In embodiments, a subject is selected for treatment if the subject desires to improve their athletic performance and the subject has a measurable amount of PFAS in a biological matrix.

[0141]

[0130] Musculoskeletal health: In some embodiments, a subject is selected for treatment to improve musculoskeletal health, such as promoting muscle hypertrophy or increasing bone density. In embodiments, a subject is selected for treatment if the subject desires to improve their musculoskeletal health and the subject has a measurable amount of PFAS in a biological matrix. 2025-09-12

[0142]

[0131] Skin rejuvenation: In some embodiments, a subject is selected for treatment for skin rejuvenation. In embodiments, a subject is selected for treatment if the subject desires to rejuvenate their skin and the subject has a measurable amount of PFAS in a biological matrix.

[0143]

[0132] Cognitive functioning: In some embodiments, a subject is selected for treatment to improve a subject’s cognitive functioning. In embodiments, a subject is selected for treatment if the subject desires to improve their cognitive functioning and the subject has a measurable amount of PFAS in a biological matrix.

[0144]

[0133] Efficacy of other therapeutic interventions: In some embodiments, a subject is selected for treatment to increase the efficacy of another therapeutic intervention (e.g., an allogeneic or autologous organ transplant, a stem-cell or exosome therapy, a gene-editing or gene-replacement therapy (including CRISPR-based, viral-vector, mRNA delivery), or a comparable regenerative or cell-based procedure). In embodiments, a subject is selected for treatment before the other therapeutic intervention to, for example, reduce PFAS-induced symptoms, and / or after the other therapeutic intervention to, for example, remove residual inflammatory mediators and toxicants mobilized by the procedure. In embodiments, a subject is selected for treatment if the subject desires to increase the efficacy of another therapeutic intervention and the subject has a measurable amount of PFAS in a biological matrix.

[0145]

[0134] Efficacy of fertility treatments: In some embodiments, a subject is selected for treatment to increase the efficacy of a fertility treatment, such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), intrauterine insemination (IUI), controlled ovarian stimulation, oocyte retrieval, embryo transfer, cryopreservation or thawing of gametes or embryos, pre-implantation genetic testing, sperm preparation or capacitation, hormone replacement therapy, luteal-phase support, general male and / or female pregnancy preparation (including, for example, optimization of semen parameters, endometrial receptivity, or oocyte quality. In embodiments, a subject is selected for treatment if the subject desires to increase the efficacy of a fertility treatment and the subject has a measurable amount of PFAS in a biological matrix.

[0146]

[0135] Progression of aging: In some embodiments, a subject is selected for treatment to reduce the progression of aging in the subject, such as slowing the biological processes that drive functional decline, maintaining cellular repair, mitigating DNA damage, or keeping tissues resilient. In embodiments, a subject is selected for treatment if the subject desires to reduce their progression of aging and the subject has a measurable amount of PFAS in a biological matrix.

[0147]

[0136] Longevity: In some embodiments, a subject is selected for treatment to promote, improve, enhance, or extend longevity in the subject, such as by increasing mean or maximum lifespan, extending health span, delaying the onset or progression of age-related diseases, delaying morbidity, maintaining or improving functional capacity, improving one or more biomarkers or physiological indicators associated with longevity, extending the subject’s expected remaining years of life, or otherwise positively affecting longevity-related outcomes. In embodiments, a subject is selected for treatment if the subject desires to promote, improve, enhance, or extend longevity and the subject has a measurable amount of PFAS in a biological matrix. 2025-09-12

[0148]

[0137] Weight loss and weight maintenance: In some embodiments, a subject is selected for treatment to support weight loss or weight maintenance objectives, such as reducing excess adiposity, maintaining a target body-mass index (BMI), or improving metabolic health markers e.g., insulin sensitivity and lipid profiles. In embodiments, a subject is selected for treatment if the subject desires to lose weight or maintain weight, or the subject is undergoing, or is scheduled to undergo, a weight-management intervention (e.g., caloric-restriction program, pharmacologic weight-loss therapy, bariatric procedure, or structured exercise regimen) and the subject has a measurable amount of PFAS in a biological matrix.

[0149]

[0138] Closed-habitat environments: In some embodiments, a subject is selected for treatment to mitigate PFAS exposure encountered in closed-habitat environments, such as spaceflight vehicles, orbital or lunar stations, submarines, isolated research facilities, or off-planet colonization missions (e.g., long-duration voyages to, or settlements on, Mars). In embodiments, a subject is selected for treatment if the subject is scheduled for, currently engaged in, or has returned from spaceflight or another closed-habitat mission and the subject has a measurable amount of PFAS in a biological matrix.

[0150]

[0139] Exposure to environmental sources of PFAS: In some embodiments, a subject is selected for treatment if the subject was exposed to one or more environmental sources of PFAS. In embodiments, an environmental source of PFAS is any feature of a subject’s environment that is made from, contaminated by, or otherwise contains PFAS, or any other source of PFAS exogenous to the subject’s body, and which may introduce PFAS into the subject’s body. Examples of environmental sources of PFAS include drinking water, food items, food packaging, construction materials, cosmetic products, construction materials, non-stick cookware, water repellent fabrics, stain resistant carpets, electronics, and firefighting foam. Determining “exposure” to an environmental source of PFAS will be appreciated by those of skill in view of the disclosure and the art. In embodiments, a subject is selected for treatment if the subject was exposed to one or more environmental sources of PFAS, or the subject desires to reduce PFAS from one or more environmental sources in their body. In embodiments, a subject is selected for treatment if the subject was exposed to one or more environmental sources of PFAS, or if the subject desires to reduce PFAS from one or more environmental sources in their body, and the subject has a measurable amount of PFAS in a biological matrix.

[0151]

[0140] Increased risk based on PFAS exposure: In some embodiments, a subject is selected for treatment if the subject was exposed to one or more environmental sources of PFAS, and the subject is at risk of having PFAS in a biological matrix, as a result of that exposure. In embodiments, a subject is selected for treatment if the subject was exposed to one or more environmental sources of PFAS, and the subject is at an increased risk of having PFAS in a biological matrix, as a result of that exposure. In embodiments, a subject is selected for treatment if the subject was exposed to one or more environmental sources of PFAS, and the subject is at risk, or at an increased risk, of exposure to an environmental source of PFAS.

[0152]

[0141] Exposure to environmental sources of PFAS will be as understood in view of the disclosure and the general knowledge in the art. In non-limiting exemplary embodiments, exposure to environmental sources of 2025-09-12 PFAS comprises living within a distance of a water source with elevated PFAS contamination known to increase risk; using furniture or clothes made of synthetic fabrics; having an occupation requiring the handling of PFAS-containing materials; and other such risks, including increased risks. Occupational exposure to PFAS includes working in, or working in proximity to, activities that generate high particulate plastic loads, for example: structural or wildland firefighting; emergency response, demolition, or cleanup at plastic-rich fire scenes; plastic manufacturing, recycling, or extrusion facilities; textile, carpet, or synthetic fiber production; construction or renovation involving composite panels and insulation foams; commercial fishing or aquaculture using polymeric nets and ropes; agricultural operations employing plastic mulches or greenhouses; landfill, incineration, or waste-sorting sites; and automotive, aviation, or 3-D printing shops where polymer dust is airborne. In embodiments, exposure arises from indoor PFAS accumulation in offices, gyms, or industrial kitchens, or from residing near waterways, runoff zones, or atmospheric downwind plumes with elevated PFAS contamination. In embodiments, the subject at risk, or at an increased risk, of exposure to an environmental source of PFAS has a concentration of PFAS in a biological matrix greater than about 0.01 to 100 ng / mL.

[0153]

[0142] PFAS-related symptoms, conditions, and complications: In some embodiments, a subject is selected for treatment if the subject has a symptom, condition, or complication caused by or associated with PFAS alone or in combination with co-contaminants (e.g., heavy metals, microplastics, phthalates) present in the subject’s biological matrix. In embodiments, a subject is selected for treatment if the subject is at risk of a symptom, condition, or complication caused by or associated with PFAS alone or in combination with co-contaminants in a biological matrix. Other than examples disclosed herein, a symptom, condition, or complication caused by or associated with PFAS alone or in combination with co-contaminants in the biological matrix may be any such symptom, condition, or complication known in the art. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a symptom, condition, or complication caused by or associated with PFAS alone or in combination with co-contaminants in a biological matrix and the subject has a measurable amount of PFAS in a biological matrix.

[0154]

[0143] Disclosed methods provide therapeutic benefit from removal of PFAS in at least two ways. In some embodiments, PFAS directly contribute to the onset or progression of disease, and EBP treatment removes an amount PFAS in the body of a subject, thereby treating or ameliorating the PFAS-associated disease. In other embodiments, PFAS induce chronic inflammation and immune dysregulation, which impairs a subject’s capacity to mount effective responses to unrelated illnesses. By reducing the PFAS burden, disclosed EBP treatments decrease systemic inflammatory load and improve, for example, immune, metabolic, and physiological resilience, enabling a subject to respond more effectively to infectious diseases, neoplastic processes, and other conditions not directly caused by PFAS. In embodiments, removing PFAS by plasmapheresis directly treats a PFAS-associated condition in which PFAS accumulation is a causal or aggravating factor. In embodiments, EBP treatment improves immune competence by reducing PFAS-induced systemic inflammation, thereby enhancing a subject’s ability to resist or recover from unrelated illnesses.ln 2025-09-12 embodiments, reducing PFAS burden decreases chronic inflammatory signaling, resulting in improved metabolic function, mitochondrial activity, and vascular health. In embodiments, the treatment improves responsiveness to other medical therapies by lowering toxic and inflammatory burden prior to or during such therapy. In embodiments, removing PFAS indirectly improves healthspan and resilience by enabling endogenous repair processes and immune surveillance mechanisms otherwise impaired by PFAS exposure.

[0155]

[0144] In embodiments, the subject is selected for treatment if an elevated PFAS load may increase the relative risk of developing the condition, heighten its severity, reduce responsiveness to conventional therapies typically used to treat the condition, or hinder durable remission after otherwise adequate treatment.

[0156]

[0145] In embodiments, a method comprises: (i) determining a difference between the PFAS concentration in the biological matrix of the subject before administering a DFPP, plasmapheresis, or other EBP treatment and the PFAS concentration in the biological matrix of the subject after administering the DFPP, plasmapheresis, or other EBP treatment; and (ii) repeating the EBP treatment when the difference is greater than an amount or less than an amount. In embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the difference is “greater than an amount” meaning greater than about 0.005, 0.01 , 0.02, 0.05, 0.1 , 0.2, 0.5, 1, 2, 3, 5, 10, 20, 50, or 100 ng / mL. In embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the difference is “less than an amount” meaning less than about 0.005, 0.01, 0.02, 0.05, 0.1, 0.2, 0.5, 1 , 2, 3, 5, 10, 20, 50, or 100 ng / mL.

[0157]

[0146] In some embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the difference is greater than an amount, or when the difference is less than an amount. In some embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the difference is greater than an amount, and the concentration in the biological matrix of the subject before the treatment is greater than an amount. In embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the difference is greater than an amount, and the concentration in the biological matrix of the subject before the treatment is less than an amount. In embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the difference is less than an amount, and the concentration in the biological matrix of the subject before the treatment is greater than an amount. In embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the difference is less than an amount, and the concentration in the biological matrix of the subject before the treatment is less than an amount. In some embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the difference is greater than an amount, and the concentration in the biological matrix of the subject after the treatment is greater than an amount. In embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the difference is greater than an amount, and the concentration in the biological matrix of the subject after the treatment is less than an amount. In embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the difference is less than an amount, and the concentration in the biological matrix of the subject after 2025-09-12 the treatment is greater than an amount. In embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the difference is less than an amount, and the concentration in the biological matrix of the subject after the treatment is less than an amount.

[0158]

[0147] In embodiments, a method comprises: (i) determining a percent difference between a PFAS concentration in a biological matrix of a subject before administering a DFPP, plasmapheresis, or other EBP treatment and a PFAS concentration in the biological matrix of the subject after administering the treatment; and (ii) repeating the EBP treatment when the percent difference is greater than a percent amount or less than a percent amount. In some embodiments, a method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the percent difference is greater than a percent amount, or when the percent difference is less than a percent amount. In embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the percent difference is “greater than a percent amount” meaning greater than about 0.5%, 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, or 99%. In embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the percent difference is “less than a percent amount” meaning less than about 0.5%, 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, or 99%.

[0159]

[0148] In embodiments, the method comprises repeating a DFPP, plasmapheresis, or other EBP treatment when the percent difference is greater than a percent amount, and the concentration in a biological matrix of the subject before the treatment is greater than an amount. In embodiments, the method comprises repeating the treatment when the percent difference is greater than a percent amount, and the concentration in the biological matrix of the subject before the treatment is less than an amount. In embodiments, the method comprises repeating the treatment when the percent difference is less than a percent amount, and the concentration in the biological matrix of the subject before the treatment is greater than an amount. In embodiments, the method comprises repeating the treatment when the percent difference is less than a percent amount, and the concentration in the biological matrix of the subject before the treatment is less than an amount. In embodiments, a method comprises repeating a DFPP, plasmapheresis, or other EBP treatment when the percent difference fails to meet a target on two or more consecutive measurements separated by a rest interval (e.g., about 12 hours, 24 hours, 48 hours, 72 hours, 1 week, 2 weeks, 1 month, or 3 months).

[0160]

[0149] In some embodiments, disclosed methods are useful for treating a subject, such as treating a condition in the subject, or symptoms of the subject. In embodiments, the subject is a human subject with a condition or with one or more symptoms. In embodiments, the condition or the one or more of the symptoms is PFAS-related, wherein “PFAS-related” means caused by or associated with the presence of PFAS in the biological matrix of the subject. In embodiments, the subject has a measurable amount of PFAS in a biological matrix, but does not have a PFAS-related condition. In embodiments, the subject has a measurable amount of PFAS in a biological matrix, but does not have a PFAS-related symptom. 2025-09-12

[0161] C. Extracorporeal Blood Purification Devices and Systems Configured to Remove PFAS

[0162]

[0150] In some aspects are provided extracorporeal blood purification (EBP) devices and systems configured to remove PFAS from a biological matrix of a human or animal subject, including when used in the disclosed methods. EBP devices and systems include apparatuses and configurations configured to remove PFAS from the blood or plasma of a subject, operating through filtration, adsorption, plasma separation, or combinations thereof. EBP devices and systems include those for plasmapheresis, hemodialysis, and hemoperfusion.

[0163]

[0151] Herein, the terms “device” and “system” are intended to cover a range of extracorporeal blood purification technologies and configurations, including individual components (e.g., filters, columns, cartridges) as well as complete assemblies incorporating pumps, sensors, fluid circuits, control units, and related hardware. Unless context indicates otherwise, “device” and “system” are used interchangeably to refer to any apparatus, or combination of apparatuses, for plasmapheresis, hemodialysis, hemoperfusion, or a related EBP method. Exemplary modalities are described without referring to and repeating both terms in each instance.

[0164]

[0152] Devices and systems for plasmapheresis include membrane-based or centrifugation-based plasma separation apparatuses configured to isolate plasma from whole blood, as well as optional components for plasma discard, replacement, recirculation, or downstream treatment. Such devices and systems may include plasma filters, pumps, anticoagulation circuits, fluid balancing modules, and associated software or control elements. In embodiments, the separated plasma may be subjected to further filtration or adsorption for the removal of PFAS or other targeted substances, either within the same circuit or via a coupled module. Plasmapheresis devices and systems may operate in a continuous or intermittent mode. Plasmapheresis devices and systems may include, or be adapted for, modalities such as double-filtration plasmapheresis (DFPP), therapeutic plasma exchange (TPE), plasma perfusion (PP), and plasma adsorption (PA).

[0165]

[0153] Devices and systems for hemodialysis include extracorporeal blood circuits configured to remove solutes and contaminants from the blood through diffusion across a semipermeable membrane. Such systems may include a dialyzer unit (e.g., hollow-fiber cartridge), arterial and venous tubing lines, blood and dialysate pumps, anticoagulant infusion controls, and sensors or control software to regulate ultrafiltration, conductivity, and flow rates. Hemodialysis systems may include fluid replacement circuits and may be used in conjunction with hemofiltration or hemodiafiltration modalities. For removal of PFAS according to the disclosed methods, hemodialysis systems may be adapted by modifying membrane pore size, surface chemistry, and / or filtration architecture to enhance capture of contaminants.

[0166]

[0154] Devices and systems for hemoperfusion include extracorporeal blood circuits in which blood is passed directly through an adsorbent-containing cartridge or column designed to remove targeted substances via surface adsorption. Hemoperfusion devices and systems may include components such as resin- or charcoal-based adsorption columns, blood pumps, tubing circuits, anticoagulation control, and pressure monitors. Such systems may operate as standalone therapies or in conjunction with hemodialysis, hemofiltration, or plasmapheresis. For removal of PFAS according to the disclosed methods, the adsorption 2025-09-12 media or column structure may be tailored to retain particles within a defined size range or based on hydrophobic, charge-based, or chemical affinity interactions.

[0167]

[0155] EBP devices and systems also include hybrid systems, such as plasma perfusion (PP) and coupled plasma filtration adsorption (CPFA) systems, which integrate plasma separation and adsorption within a single treatment pathway. Components of such devices and systems may include plasma filters, dialyzers, adsorbent columns, fluid circuits, pumps, anticoagulation controls, and software configured to regulate flow, pressure, and treatment duration. These may be configured or adapted to selectively remove PFAS based on size exclusion, charge, hydrophobic interactions, or other engineered binding or capture mechanisms.

[0168]

[0156] In embodiments, a DFPP, plasmapheresis, or EBP device comprises: (1) a means for removing a subject’s blood; (2) a means for returning a subject’s blood; (3) a blood circuit; (4) a means for supplying force to a subject’s blood / plasma in a blood circuit; (5) a means for separating whole blood into a cellular fraction and a plasma fraction; (6) a means for separating an eluate (e.g., containing PFAS) from a plasma fraction; (7) a means for rinsing or flushing an eluate from the blood circuit; and (8) a means for collecting waste.

[0169]

[0157] In some embodiments, the plasmapheresis or EBP device is configured to perform a plasmapheresis method (herein, a “device configuration”). In embodiments, a device configuration refers to the precise order and arrangement of the components that comprise the device (i.e., filters, blood circuit, etc.). In embodiments, a device configuration is any of a DFPP configuration, a TPE configuration, a PP configuration, a PA configuration, or a CPFA configuration. In embodiments, a plasmapheresis device may comprise one device configuration, e.g., may perform one plasmapheresis method. In embodiments, a plasmapheresis device may comprise more than one device configuration, e.g., may perform more than one blood filtration method.

[0170]

[0158] In some embodiments, the DFPP or other EBP device comprises a means for removing a subject’s blood. In some embodiments, the DFPP or other EBP device comprises a means for returning a subject’s blood. Such means, for example, include an intravenous catheter inserted into a site of vascular access, and tubing in fluid connection to a blood circuit. In some embodiments, the vascular site of access is a central or peripheral site. In some embodiments, the vascular site of access is an artery or a vein. In some embodiments, a means for removing a subject’s blood and returning a subject’s blood are placed at different vascular sites of access. Examples of these and other suitable means are known in the art.

[0171]

[0159] In some embodiments, the DFPP or other EBP device comprises an extracorporeal blood circuit. In embodiments, the blood circuit comprises medical-grade tubing, for example, polyvinyl-chloride (PVC) tubing, configured to convey whole blood or plasma (i) from the subject to the plasmapheresis device, (ii) between individual modules or components of the device, and (iii) back to the subject. In embodiments, the blood circuit further comprises ancillary components such as any one or more of, including combinations comprising more than one of, a pump, a flow sensor, a pressure monitor, an arterial-access line, and a venous-access line. Examples of suitable tubing materials and circuit configurations will be known in the art.

[0172]

[0160] In some embodiments, the DFPP or other EBP device comprises one or more means for supplying 2025-09-12 force to a blood circuit. Such means, for example, comprise one or more peristaltic roller pumps, which sequentially compress a segment of tubing against a curved rigid track, forcing blood / plasma through the blood circuit. Such means also include centrifugal pumps, which pass on kinetic energy to the blood / plasma via a rotating impeller and diaphragm (membrane) pumps to displace fluid through an oscillating flexible membrane. Such means further generate a transmembrane pressure gradient across the filters of the DFPP or other EBP device. Examples of these and other suitable means are known in the art.

[0173]

[0161] In embodiments, the DFPP or other EBP device comprises a means for separating whole blood into a cellular fraction and a plasma fraction. Such means include passing whole blood through a first membrane filter. Such means also include a centrifugation module (e.g., a continuous-flow or bowl-type centrifuge) configured to separate whole blood into plasma and cellular fractions by differential density. In one example, the first membrane filter is permeable to a plasma fraction and impermeable to a cellular fraction. In one example, the first membrane filter diverts the cellular fraction and plasma fraction into separate lines of a blood circuit. Examples of these and other suitable means are known in the art.

[0174]

[0162] In some embodiments, the DFPP or other EBP device comprises a means for rinsing or flushing the eluate from the blood circuit. Such means include closing a blood circuit, opening a waste line, pumping a rinsing or flushing fluid into a second membrane filter, and collecting the eluate-containing rinsing or flushing fluid in a waste bag. Examples of these and other suitable means are known in the art, and examples of rinsing and flushing fluids will be known in the art, suitable for use in disclosed embodiments.

[0175]

[0163] In some embodiments, the DFPP or other EBP device comprises a means for collecting waste. Such means include diverting the eluate from the second filter into a waste line leading to a waste bag.

[0176]

[0164] DFPP and other plasmapheresis devices suitable for use in disclosed methods may comprise one or more additional components known to those of skill including, for example, a bubble trap, a blood leak detector, a warming unit, security clamps, and a monitoring system.

[0177]

[0165] In some embodiments, the DFPP or other EBP device comprises a second filter configured to capture PFAS and other co-transported toxicants from the plasma fraction. Such means include, for example, passing the plasma fraction through a second filter having a median pore size of about 10 nm, the filter being permeable to dissolved plasma components while retaining particles greater than about 10 nm in diameter.

[0178]

[0166] In some embodiments, PFAS are filtered from the blood of a subject using double-filtration plasmapheresis (DFPP), such as by using a DFPP device. In some embodiments, PFAS are filtered from the blood of a subject using a DFPP device.

[0179]

[0167] Examples of DFPP devices, which may be adapted or configured for use in the disclosed methods, including as taught by and appreciated in view of the disclosure, include the Inuspheresis® IN300 (Ayus Medical Devices AG (formerly INUS Medical Devices AG), Zug, Switzerland). Aspects of the operation of the Inuspheresis® device are described in the IN300 Operator Manual, From software 3.2.5 R, INUS Medical Devices, Infomed SA, Meineir, Switz., fully incorporated by reference herein, as if expressly set forth herein. 2025-09-12

[0180]

[0168] In one example of the operation of an exemplary DFPP device, a subject is connected intravenously to an Inuspheresis® device by a blood supply line and a blood return line, thereby creating a blood circuit.

[0181]

[0169] Whole blood is withdrawn from the subject into the blood supply line, under pressure by a blood pump, then pumped to a plasma separation filter. The plasma separation filter is a hollow fiber membrane filter structured to separate whole blood into a plasma fraction and a cellular fraction. The cellular fraction is pumped toward the blood return line. The plasma fraction is pumped into a plasma circuit by a plasma supply pump, then pumped into a plasma fractionation filter. The plasma fractionation filter comprises a hollow fiber membrane. The plasma fractionation filters PFAS from the plasma (thereby producing a DFPP eluate containing PFAS) to produce a purified plasma fraction. The DFPP eluate is collected in a waste bag. The purified plasma fraction is pumped into a plasma return line. The plasma return line is heated to raise the temperature of a purified plasma fraction to a desired temperature (e.g., the subject’s body temperature). The plasma return line leads to the blood return line, where the cellular fraction and purified plasma fraction are recombined to produce a purified whole blood mixture, which is then pumped back into the subject.

[0182]

[0170] In some embodiments, the DFPP device comprises: (1) a means for removing a subject’s blood; (2) a means for returning a subject’s blood; (3) a blood circuit; (4) a means for supplying force to a subject’s blood / plasma in a blood circuit; (5) a means for separating whole blood into a cellular fraction and a plasma fraction; (6) a means for separating a DFPP eluate (e.g., that contains PFAS) from a plasma fraction; (7) a means for rinsing or flushing the DFPP eluate from the blood circuit; and (8) a means for collecting waste. Exemplary such DFPP devices are generally known in the art, and include, e.g., those disclosed in US4,397,747; US7,291 ,269; and US5, 108,612; each incorporated by reference as if fully set forth herein.

[0183]

[0171] In some embodiments, the DFPP device comprises a means for separating a DFPP eluate from a plasma fraction. Such means include passing plasma through a second membrane filter. In some embodiments, the second membrane filter is permeable to plasma components up to a certain size. In embodiments, the second membrane filter is permeable to plasma components up to a certain molecular weight. In embodiments, the second membrane filter diverts the permeable plasma fraction and the DFPP eluate into separate lines of a blood circuit. Examples of these and other suitable means are known in the art.

[0184]

[0172] In some embodiments, the DFPP plasmapheresis, or other EBP device comprises a means for plasma adsorption (PA). Such means include passing plasma, either before or after filtration through a second membrane filter, through an adsorbent material that selectively binds one or more plasma adsorbates (e.g., pathogenic antibodies, cytokines, immune complexes). In embodiments, the binding affinity of the adsorbent material for the target adsorbate may fall within a range of approximately 10“4to 10“9M, depending on the specificity and application. For example, adsorbents designed to capture pathogenic IgG antibodies may exhibit binding affinities in the range of approximately 10“6to 10“8M. In embodiments, the plasma adsorbate is separated from the plasma fraction through adsorption. In embodiments, the processed plasma may be subsequently recombined with cellular components or directed along a separate line of the blood circuit. 2025-09-12

[0185]

[0173] In some embodiments, the DFPP or other EBP device comprises one or more adsorption columns as a means for plasma adsorption. In embodiments, adsorption columns may be configured to remove selected plasma components from biological matrix circulation. Such columns may include devices or cartridges containing adsorbent materials suitable for extracorporeal plasma treatment. In embodiments, adsorbent materials include, as non-limiting examples, polymeric resins, AmberLite , AmberCrom , Depuro (e.g., D2000), activated charcoal and / or activated carbon, ion exchange resins, affinity ligand-functionalized media, and glass and / or silica beads. In embodiments, the adsorption column may be selected based on the physicochemical properties of the target adsorbate, flow rate requirements, and / or clinical objectives.

[0186]

[0174] In embodiments, the DFPP adsorption column is configured for electrostatic removal of PFAS. A wide range of PFAS compounds, including perfluoroalkyl carboxylates (PFCAs, e.g., PFOA) and perfluoroalkyl sulfonates (PFSAs, e.g., PFOS), are anions at physiological pH due to acidic head groups. Removal of PFAS can be affected by electrostatic attraction to positively charged functional groups on an adsorption medium.

[0187]

[0175] In embodiments, the adsorption medium is a strong-base anion-exchange resin. The resin may include a polymeric backbone (e.g., styrene-divinylbenzene, polyacrylate, or cellulose) functionalized with quaternary ammonium groups (e.g., — N+(CH3)3). In embodiments, the resin is in chloride (Cl ) form for initial equilibration. When plasma containing anionic PFAS passes through the resin, the PFAS anions can displace chloride ions and can be bound to the positively charged quaternary ammonium sites. In embodiments, the electrostatic adsorption medium is a weak-base anion-exchange resin. The resin may include a polymeric backbone functionalized with primary, secondary, or tertiary amine groups (e.g., -NH2, -NHCH3, — N(CH3)2), which can be protonated and thus positively charged at physiological pH. The binding capacity and kinetics for PFAS can be influenced by one or more of the ionic strength of the plasma, the presence of competing anions (e.g., chloride, bicarbonate, phosphate, albumin-bound fatty acids), the density and accessibility of the positively charged functional groups on the resin, the specific PFAS analyte (e.g., sulfonate vs. carboxylate head group, chain length), the flow rate of plasma through the column, and the temperature.

[0188]

[0176] In embodiments, operational parameters are selected to optimize electrostatic adsorption. A lower plasma flow rate may be used to increase residence time and binding efficiency for PFAS. In embodiments, the ionic strength of the plasma is adjusted within a physiologically acceptable range (e.g., by minimal dilution or buffer addition) to reduce competition from native anions and enhance PFAS binding affinity. In embodiments, the adsorption column is preconditioned with a solution of relatively low ionic strength to enhance the electrostatic potential of the functional groups prior to contact with plasma of the subject.

[0189]

[0177] In some embodiments, PFAS are filtered from the biological matrix of a subject using TPE, such as by using a TPE device. Exemplary TPE devices, which may be adapted or configured for use in the disclosed methods, including as taught by and will be appreciated in view of the disclosure, include the HF440 (Infomed SA, Switzerland), the Spectra Optia (Terumo BCT, Japan), the Amicus (Fresenius, Germany), the System One / TPE Cartridge (NxStage Med., U.S.), the Prismaflex (Baxter Int’l, U.S.), and the PrisMax (Baxter Int’l, U.S.). 2025-09-12

[0190]

[0178] In some embodiments, the TPE device comprises: (1) a means for removing a subject’s blood; (2) a means for returning a subject’s blood; (3) a blood circuit; (4) a means for supplying force to a subject’s blood / plasma in a blood circuit; (5) a means for separating whole blood into a cellular fraction and a plasma fraction; (6) a plasma substitution fluid container; (7) a means for combining a plasma substitution fluid with a cellular fraction; (8) a means for rinsing or flushing a plasma fraction from the blood circuit; and (9) a means for collecting waste. Exemplary such devices will be appreciated by those of skill and include, e.g., those disclosed in US4,954, 128 and US2021 / 0128811, both incorporated by reference as if fully set forth herein.

[0191]

[0179] In embodiments, the TPE device comprises a plasma substitution fluid container. In embodiments, the TPE device comprises a means for combining a plasma substitution fluid with a cellular fraction. Such means include directing plasma substitution fluid and the cellular fraction from the first filter into a return line leading to the subject. Examples of these and other suitable means are known in the art, and examples of plasma substitution fluids suitable for use in the disclosed methods will be appreciated by those of skill.

[0192]

[0180] In some embodiments, the TPE device comprises a means for rinsing or flushing a plasma fraction from the blood circuit. Such means include closing a blood circuit, opening a waste line, pumping a rinsing or flushing fluid into a first membrane filter, and collecting the plasma fraction-containing rinsing or flushing fluid in a waste bag. Examples of these and other suitable means will be appreciated by those of skill, and examples of rinsing and flushing fluids will be known in the art, suitable for use in disclosed embodiments.

[0193]

[0181] In embodiments, the TPE device comprises a means for replacing a removed plasma fraction with a physiologically acceptable replacement fluid. Such means include a replenishment pump and reservoir, albumin solution, or colloid / crustalloid having a PFAS content below a predefined threshold relative to the subject’s plasma. Examples of these and other suitable replacement-fluid delivery systems will be appreciated by those of skill. In some embodiments, the TPE device comprises a means for collecting waste. Such means include diverting a plasma fraction from the first filter into a waste line leading to a waste bag.

[0194]

[0182] In embodiments, PFAS are filtered from the biological matrix of a subject using PP (e.g., PA), such as by using a PP (e.g., PA) device. Examples of PP and PA devices, which may be adapted or configured for use in the methods by one of skill in view of the disclosure, include the HF440 (Infomed SA, Switzerland), and those taught in US6, 960,178 and US4, 215,688, both incorporated by reference as if fully set forth herein.

[0195]

[0183] In some embodiments, the PP device comprises: (1) a means for removing a subject’s blood; (2) a means for returning a subject’s blood; (3) a blood circuit; (4) a means for supplying force to a subject’s blood / plasma in a blood circuit; (5) a means for separating whole blood into a cellular fraction and a plasma fraction; (6) a means for separating a target substance (e.g., PFAS) from a plasma fraction; (8) a means for rinsing or flushing waste from the blood circuit; and (9) a means for collecting waste.

[0196]

[0184] In some embodiments, the PP device comprises a means for separating whole blood into a cellular fraction and a plasma fraction. Such means include separating whole blood by centrifugation or by passing whole blood through a first membrane filter. Examples of these and other suitable means are known in the art. 2025-09-12

[0197]

[0185] In some embodiments, the PP device comprises a means for separating a target substance (e.g., PFAS) from a plasma fraction. Such means include directing a plasma fraction through an adsorption filter designed to bind and capture a target substance. Exemplary adsorption columns include affinity columns, ion-exchange columns, activated charcoal columns, polymeric adsorbent columns, and immunoadsorption columns. Examples of these and other suitable means are known in the art, and examples of adsorption filters suitable for use in disclosed methods will be appreciated by those of skill.

[0198]

[0186] In some embodiments, PFAS are filtered from the biological matrix of a subject using CPFA, such as by using a CPFA device. Examples of CPFA devices, which may be adapted or configured for use in the disclosed methods, including as taught by and will be appreciated in view of the disclosure, include the HF440 (Infomed SA, Switzerland) the PDS-2™ System (HDL Therapeutics, U.S.), and those disclosed in Abdul Cader et al. Nephrourol Mon. 2013;5(4):891 -6, incorporated by reference as if fully set forth herein.

[0199]

[0187] In some embodiments, the CPFA device comprises: (1) a means for removing a subject’s blood; (2) a means for returning a subject’s blood; (3) a blood circuit; (4) a means for supplying force to a subject’s blood / plasma in a blood circuit; (5) a means for separating whole blood into a cellular fraction and a plasma fraction; (6) optionally, a means for separating an ultrafiltrate from the plasma fraction across a semi-permeable membrane; (7) a means for separating a target substance (e.g., PFAS) from a plasma fraction or the ultrafiltrate; (8) a plasma substitution fluid container; (9) a means for combining a plasma substitution fluid with a cellular fraction; (10) a means for rinsing or flushing waste from the the blood circuit; and (11) a means for collecting waste. In some embodiments, the optional means for separating an ultrafiltrate (6) may be positioned and operated prior to, subsequent to, or in parallel with the means for separating a target substance (7).

[0200]

[0188] In embodiments, the CPFA device comprises a means for separating whole blood into a cellular fraction and a plasma fraction, such as by using centrifugation or by passing whole blood through a membrane filter. Examples of these and other suitable means will be appreciated by those of skill. In embodiments, the CPFA device comprises a means for separating an ultrafiltrate from a cellular fraction. Such means include those for directing a cellular fraction through a hemofilter configured to allow water and other low molecular weight molecules (e.g., an ultrafiltrate) to pass while retaining blood cells and large molecules.

[0201]

[0189] In some embodiments, the CPFA device comprises a means for separating a target substance (e.g., PFAS) from a plasma fraction. Such means include directing a plasma fraction through an adsorption filter designed to bind and capture a target substance. Exemplary adsorption columns include affinity columns, ion-exchange columns, activated charcoal columns, and immunoadsorption columns. Examples of these and other suitable means are known in the art, and examples of adsorption filters suitable for use in the disclosed methods will be known in the art.

[0202]

[0190] In some embodiments, the CPFA device comprises a plasma substitution fluid container. In some embodiments, the CPFA device comprises a means for combining a plasma substitution fluid with a cellular 2025-09-12 fraction. Such means include directing plasma substitution fluid and the cellular fraction from the first filter into a return line leading to the subject. Examples of these and other suitable means are known in the art, and examples of plasma substitution fluids suitable for use in the disclosed methods will be known in the art.

[0203]

[0191] In some embodiments, PFAS are filtered from the biological matrix of a subject using plasma adsorption (PA), such as by using a PA device. Examples of PA devices, which may be adapted or configured for use in the disclosed methods, including as taught by and will be appreciated in view of the disclosure, include Immusorba® TR-350 / PH-350 immunoadsorption columns (Asahi Kasei Medical, Japan); TheraSorb® immunoadsorption columns (e.g., TheraSorb Ig flex); GLOBAFFIN® immunoadsorption system; Liposorber® LA-15 / LA-40 dextran-sulfate cellulose columns; and BS-series plasma adsorption cartridges (e.g., BS330 bilirubin adsorber), as well as other resin-, charcoal-, ion-exchange-, or affinity-ligand columns suitable for PA.

[0204]

[0192] In some embodiments, the PA device comprises a means for passing a plasma fraction of a subject through an adsorption column comprising one or more binding agents configured to adsorb PFAS by anion-exchange, hydrophobic, and / or fluorophilic interactions to produce processed plasma. In embodiments, the adsorption media comprises activated carbon, a strong-base anion-exchange resin, a fluorophilic polymer, a molecularly imprinted medium, cyclodextrin, or a combination thereof. Strong-base anion-exchange resins operate via electrostatic attraction, exchanging counter-ions (e.g., Cl ) for anionic PFAS molecules due to the strong positive charge of their quaternary ammonium functional groups. In embodiments, the adsorption column housing and wetted components are formed from materials selected to minimize PFAS leaching and nonspecific protein adsorption, such as medical-grade stainless steel. Examples of these and other suitable means, and examples of plasma substitution fluids suitable for use in disclosed methods, will be appreciated.

[0205]

[0193] In some embodiments, the adsorption media comprises cyclodextrin moieties (e.g., p-cyclodextrin) immobilized or crosslinked into a polymeric sorbent (e.g., p-cyclodextrin polymer (P-CDP)). In embodiments, the cyclodextrin sorbet removes PFAS from a separated plasma stream by inclusion-complex formation and / or hydrophobic interactions.

[0206]

[0194] In some embodiments, the adsorption media comprises a metal-organic framework (MOF) sorbent. In some embodiments, the MOF is any of a Ze-based framework (e.g., UiO-, MIL- families), an Al-based framework, a zeolitic imidazolate framework (ZIF), HKUST-type framework, or a functionalized derivative or equivalent.

[0207]

[0195] In embodiments, the PA device has a means for obtaining a plasma fraction upstream by membrane or centrifugation-based plasma separation and, optionally, plasma fractionation. In embodiments, the plasma fraction contains albumin, albumin-bound PFAS, and other PFAS complexes and is directed to the adsorption column. In some embodiments, the PA device comprises an adsorption column. In embodiments, the adsorption column has a packed media volume between about 20 mL and 500 mL, between about 50 mL and 250 mL, or between about 100 mL and 200 mL. In embodiments, media particle size is between about 1 pm and 1000 pm, between about 100 pm and 500 pm, or between about 150 pm and 300 pm. In embodiments, 2025-09-12 plasma flow through the column is between about 5 mL / min and 120 mL / min, between about 10 mL / min and 80 mL / min, or between about 20 mL / min and 60 mL / min, wherein each range is inclusive.

[0208]

[0196] In embodiments, strong base anion-exchange media comprises quaternary ammonium functional groups on a crosslinked polymer backbone (e.g., styrene-divinylbenzene or polyacrylate). Such resins can operate via electrostatic attraction by exchanging counter-ions (e.g., Cl“) for anionic PFAS molecules. In embodiments, the binding strength is influenced by the hydration energy and size of the PFAS anion, with longer-chain PFAS sometimes exhibiting higher affinity. The capacity of the resin for PFAS in plasma may be a function of the resin's total ion-exchange capacity, the concentration of competing anions in plasma, and the flow dynamics within the column (see, e.g., Passos et al. Environ Toxicol Pharmacol. 2023; 102: 104253).

[0209]

[0197] In embodiments utilizing electrostatic adsorption, the efficacy of the process can be monitored by measuring the breakthrough of PFAS. The point of breakthrough is detected by a rise in the post-column PFAS concentration relative to the inlet concentration. A ratio of post-column to inlet concentration (C_out / CJn) exceeding a predefined threshold (e.g., 0.10, 0.20, or 0.30) can indicate saturation of the adsorption media's electrostatic binding sites and may trigger a column changeover or regeneration cycle. Breakthrough can be monitored in real-time using inline sensors (e.g., UV absorbance, fluorescence) or by periodically collecting samples for analytical quantification (e.g., LC-MS / MS).

[0210]

[0198] In some embodiments, two or more adsorption columns are arranged in series, wherein a first column functions as a guard bed and a second column provides primary removal, and toxin (e.g., PFAS) breakthrough is monitored between columns. In embodiments, the adsorption system monitors one or more of pre-column PFAS concentration, post-column PFAS concentration, differential pressure across the column, flow rate, and processed plasma volume. In embodiments, an adsorption column may be changed when any of the following occur: post-column PFAS concentration exceeds a predefined threshold of the column’s inlet concentration (e.g., when concentration out / concentration in is greater than or equal to 0.10, 0.20, or 0.30), differential pressure exceeds a threshold (e.g., greater than about 80 mmHg), or a capacity-based processed plasma volume target is reached (e.g., about 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, or 3.5 plasma volumes).

[0211]

[0199] In some embodiments, PFAS are filtered from the biological matrix of a subject using albumin dialysis, such as by using an albumin dialysis device. Examples of albumin dialysis devices, which may be adapted or configured for use in the disclosed methods, including as taught by and will be appreciated in view of the disclosure, include the Molecular Adsorbent Recirculating System (MARS®; Baxter International, U.S., originally Teraklin / Gambro), the Prometheus® fractionated plasma separation and adsorption system (Fresenius Medical Care, Germany), the ADVOS multi® albumin dialysis platform (ADVITOS GmbH, Germany), the DIALIVE® system (Yaqrit Ltd., U.K.), and single-pass albumin dialysis (SPAD) implementations on continuous renal replacement therapy platforms such as Prismaflex® / PrisMax® (Baxter International, U.S.) and MultiFiltrate® / MultiFiltrate Pro® (Fresenius Medical Care, Germany).

[0212]

[0200] In some embodiments, the albumin dialysis device comprises: (1) a means for removing a subject’s 2025-09-12 blood; (2) a means for returning the subject’s blood; (3) an extracorporeal blood circuit; (4) a dialyzer comprising a semi-permeable membrane; (5) an albumin-containing dialysate reservoir; (6) a dialysate circuit; (7) one or more adsorption modules in fluid communication with the dialysate circuit; (8) one or more pumps configured to drive blood and dialysate flows; and (9) a controller configured to regulate flows, pressures, and alarms. Such means include, for example, venous and / or arterial catheters, medical grade low-sorption tubing, a high-flux or high-cutoff hollow fiber dialyzer, an HSA dialysate reservoir (e.g., about 1-5% human serum albumin), dialysate pumps, pressure and flow sensors, air detectors, bubble traps, anticoagulation infusion (e.g., heparin or citrate), temperature control, and leak / protein sensors. Examples of these and other suitable means are known in the art.

[0213]

[0201] In some embodiments, the albumin dialysis device comprises a single-pass albumin dialysis (SPAD) configuration in which albumin containing dialysate flows once through the dialysate side of the dialyzer and is discarded. Such means include an HSA reservoir, a dialysate pump delivering fresh albumin dialysate to the dialyzer counter-current to blood flow, and a waste collection container. In embodiments, HSA dialysate is prescreened or pretreated to meet a predefined PFAS content threshold and is supplied in glass or low-sorption containers with low-sorption fluid paths. In embodiments, the device controller maintains dialysate flow, conductivity, and TMP within predefined ranges to promote removal of albumin bound toxicants while maintaining serum proteins within safety limits. Examples of these and other suitable means are known in the art.

[0214]

[0202] In some embodiments, the albumin dialysis device comprises a recirculating albumin dialysate configuration in which the albumin dialysate is regenerated continuously through one or more adsorption modules and then returned to the dialyzer. Such means include a dialysate loop with a circulation pump and adsorber cartridges positioned downstream of the dialyzer, the adsorber cartridges comprising one or more binding media (e.g., activated carbon, strong-base anion-exchange resin, fluorophilic polymer, or molecularly imprinted media) configured to capture PFAS and other protein-bound toxicants from the albumin dialysate. In embodiments, the device further comprises sensors across each adsorber (e.g., pressure drop, pre / post cartridge PFAS sampling ports) and a controller that triggers cartridge change out based on saturation thresholds. Examples of these and other suitable means are known in the art.

[0215]

[0203] In some embodiments, the albumin dialysis device comprises a fractionated plasma separation and adsorption (FPSA) configuration. Such means include a plasma-separation module (e.g., a first membrane fractionator) that yields an albumin rich plasma fraction, one or more adsorption columns through which the albumin fraction is passed to remove PFAS, and a recombination junction where the processed albumin fraction is returned to the cellular / blood stream prior to return to the subject. Examples of these and other suitable means are known in the art.

[0216]

[0204] In some embodiments, the albumin dialysis device further comprises an albumin management module configured to monitor and modulate albumin concentration. Such means include sensors to estimate an albumin sieving coefficient across the dialyzer, real time or per-session serum albumin measurements, and a 2025-09-12 replacement fluid subsystem for administration of HSA when predefined thresholds are reached.

[0217]

[0205] In some embodiments, the EBP device comprises a first membrane filter. In some embodiments, the plasmapheresis device comprises a first membrane filter and a second membrane filter.

[0218]

[0206] In some embodiments, the first and second membrane filters comprise hollow fiber membrane filter cartridges or hollow fiber membrane filter columns. Hollow fiber membrane filter cartridges or columns may comprise a series of parallel, hollow fibers comprising a polymeric material. The hollow fibers of a hollow fiber membrane filter cartridge or column configuration may comprise a median pore diameter enabling the selective filtering of fluids by particle size or by molecular weight. In some embodiments, the hollow fiber membrane is a thermoplastic hollow fiber membrane, e.g., a polyethersulfone (PES) hollow fiber membrane.

[0219]

[0207] In embodiments, the hollow fiber membrane is a plasma separation filter. In embodiments, the hollow fiber plasma separation filter and has a median pore size selected for use with a disclosed EBP device or in a disclosed method, such as a median pore size of 1000 nm or less, 900 nm or less, 800 nm or less, 700 nm or less, 600 nm or less, 500 nm or less, 400 nm or less, 300 nm or less, 200 nm or less, or 100 nm or less. In embodiments, the hollow fiber plasma separation filter has a median pore size of 300-600 nm. In embodiments, the hollow fiber plasma separation filter has a median pore size of about 450 nm.

[0220]

[0208] In embodiments, the hollow fiber membrane is a plasma fractionation filter. In embodiments, the hollow fiber plasma fractionation filter and has a median pore size selected for use with a disclosed EBP device or in a disclosed method, such as a median pore size of 100 nm or less, 90 nm or less, 80 nm or less, 70 nm or less, 60 nm or less, 50 nm or less, 40 nm or less, 30 nm or less, 20 nm or less, or 10 nm or less. In embodiments, the hollow fiber plasma fractionation filter has a median pore size of 10 nm or less.

[0221]

[0209] In embodiments, the hollow fiber membrane has a membrane area selected for use with a disclosed device or in a disclosed method. In embodiments, the hollow fiber membrane has a membrane area of 0.1 to 1 .0 m2, 0.2 to 0.8 m2, 0.3 to 0.6 m2, or 0.4 to 0.5 m2. In embodiments, the membrane area is 0.3-0.6 m2.

[0222]

[0210] In configurations where hollow fiber membrane filter columns are employed, the fibers may be arranged in a housing having a variety of configurations, for example, a vertically or horizontally oriented housing, allowing for alternative flow dynamics compared to traditional cartridge-based systems. The column-based design may facilitate enhanced scalability, modular assembly, or improved fluid distribution across the fiber bundle. In contrast, cartridge-based configurations may allow for improved compactness or ease of replacement. The selection between cartridges and / or columns may depend on factors such as system footprint, desired filtration efficiency, or maintenance requirements.

[0223]

[0211] Suitable membranes for use in disclosed devices and systems, such as DFPP and other plasmapheresis devices, may comprise a polymeric material, such as any one or more of polyethylene, polyacrylonitrile, polypropylene, polyamide, polysulfone, polyvinyldifluoride, and polyethersulfone. In some embodiments, a membrane used in a DFPP or other plasmapheresis device comprises any one or more of polyethylene, polyacrylonitrile, polypropylene, polyamide, polysulfone, polyvinyldifluoride, or polyethersulfone. 2025-09-12

[0224]

[0212] In embodiments, a DFPP or other plasmapheresis device comprises a membrane filter, such as a first membrane filter, useful for separating a plasma fraction from a cellular fraction of whole blood. In some embodiments, the membrane filter, such as the first membrane filter, is structured to be, or is adapted to be, permeable to plasma while rejecting erythrocytes, leukocytes, and thrombocytes. In some embodiments, the first membrane exhibits a rejection of at least about 90%, 95%, 99%, 99.9%, 99.99%, or 99.999% for erythrocytes and leukocytes, and at least about 90%, 95%, 99%, or 99.9% for thrombocytes.

[0225]

[0213] In some embodiments, a first membrane filter has a pore size of about 300 nm. In embodiments, a first membrane filter has a pore size of about 400 nm. In embodiments, a first membrane filter has a pore size of about 450 nm. In embodiments, a first membrane filter has a pore size of about 500 nm. In embodiments, a first membrane filter has a pore size of about 600 nm. In embodiments, a first membrane filter has a pore size of about 700 nm. In embodiments, a first membrane filter has a pore size of about 800 nm. In embodiments, a first membrane filter has a pore size of about 900 nm. In embodiments, a first membrane filter has a pore size of about 1000 nm. In embodiments, a first membrane filter has a pore size of greater than 1000 nm.

[0226]

[0214] In embodiments, a first membrane filter has a pore size of between about 300 nm and about 1000 nm.

[0227] In embodiments, a first membrane filter has a pore size of between about 400 nm and about 1000 nm. In embodiments, a first membrane filter has a pore size of between about 500 nm and about 1000 nm. In embodiments, a first membrane filter has a pore size of between about 600 nm and about 1000 nm. In embodiments, a first membrane filter has a pore size of between about 700 nm and about 1000 nm. In embodiments, a first membrane filter has a pore size of between about 800 nm and about 1000 nm. In embodiments, a first membrane filter has a pore size of between about 900 nm and about 1000 nm.

[0228]

[0215] In some embodiments, a first membrane filter has a pore size of between about 300 nm and about

[0229] 400 nm. In embodiments, a first membrane filter has a pore size of between about 400 nm and about 500 nm. In embodiments, a first membrane filter has a pore size of between about 500 nm and about 600 nm. In embodiments, a first membrane filter has a pore size of between about 600 nm and about 700 nm. In embodiments, a first membrane filter has a pore size of between about 700 nm and about 800 nm. In embodiments, a first membrane filter has a pore size of between about 800 nm and about 900 nm. In embodiments, a first membrane filter has a pore size of between about 900 nm and about 1000 nm.

[0230]

[0216] In embodiments, a first membrane filter has a pore size of less than 1000 nm. In embodiments, a first membrane filter has a pore size of less than 900 nm. In embodiments, a first membrane filter has a pore size of less than 800 nm. In embodiments, a first membrane filter has a pore size of less than 700 nm. In embodiments, a first membrane filter has a pore size of less than 600 nm. In embodiments, a first membrane filter has a pore size of less than 500 nm. In embodiments, a first membrane filter has a pore size of less than 400 nm. In embodiments, a first membrane filter has a pore size of less than 300 nm.

[0231]

[0217] In some embodiments, a first membrane filter is structured or selected to separate whole blood into a cellular fraction and a plasma fraction by retaining formed elements (e.g., erythrocytes, leukocytes, platelets) 2025-09-12 while permitting passage of plasma and dissolved or colloidal macromolecules. In some embodiments, the first membrane has a nominal pore size of about 0.2— 0.6 pm and is configured to achieve plasma recovery with minimal hemolysis or cellular leakage. In some embodiments, a second membrane filter is structured or selected to be permeable to molecules having a molecular weight less than about 30, 50, 70, 100, 150, 300, or 500 kDa, and to substantially retain molecules having a molecular weight greater than about 100, 150, 300, 500, or 1,000 kDa. In some embodiments, the second membrane exhibits an albumin sieving coefficient of about 0.5-0.9 and an IgG sieving coefficient of less than about 0.1 .

[0232]

[0218] In embodiments, a first membrane filter is structured or selected to separate whole blood into a cellular fraction and a plasma fraction by retaining formed elements (e.g., erythrocytes, leukocytes, platelets) while permitting passage of plasma and dissolved or colloidal macromolecules. In embodiments, a first membrane filter is structured or selected to be permeable to particles (e.g., PFAS, PFAS-bound molecules) having a molecular weight (MW) greater than a specified MW. In embodiments, a first membrane filter is structured or selected to be permeable to particles (e.g., PFAS, PFAS-bound molecules) having a MW less than a specified MW. In embodiments, a first membrane filter is structured or selected to be impermeable (i.e., to substantially reject or retain) particles (e.g., PFAS) having a MW higher than a specified MW. In embodiments, a first membrane filter is structured or selected to be permeable to particles having a MW of less than about 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 mDa. In embodiments, a first membrane filter is structured or selected to be permeable to particles having a MW of less than about 4 mDa.

[0233]

[0219] In embodiments, a first membrane (plasma separator) is a microporous membrane having a nominal pore size of about 0.2-0.6 pm, configured to pass plasma while retaining cellular components. In embodiments, a second membrane (fractionation membrane) is an ultrafiltration membrane characterized by a molecular-weight cut-off (MWCO) within about 10-1 ,000 kDa, as calibrated for globular proteins. In other embodiments, the first membrane filter is structured or selected to be permeable to particles having a MW less than about, or impermeable to particles having a MW greater than about, 100, 250, 500, 750, 1,000, 1 ,500, 2,000, 3,000, 4,000, 5,000, 7,500, or 10,000 kDa, or in embodiments, 20,000, 50,000, or 100,000 kDa.

[0234]

[0220] In embodiments, the second membrane is structured or selected to be permeable to solutes having a molecular weight less than about 30, 50, 70, 100, 150, 300, or 500 kDa, and substantially impermeable to solutes greater than about 100, 150, 300, 500, or 1 ,000 kDa. In embodiments, the second membrane exhibits an albumin sieving coefficient of about 0.5-0.9, an IgG sieving coefficient of less than about 0.1 , and a fibrinogen sieving coefficient of less than about 0.05. In embodiments, the second membrane is selected or operated to be permeable to PFAS molecules and PFAS-albumin complexes that present an effective hydrodynamic diameter less than about 3-10 nm, while retaining larger PFAS-containing macromolecular complexes, such as PFAS bound to lipoproteins, that present an effective hydrodynamic diameter greater than about 10-20 nm. In embodiments, selectivity is further influenced by charge effects, such as Donnan exclusion, and by operating conditions such as transmembrane pressure and cross-flow rate. 2025-09-12

[0235]

[0221] In some embodiments, a second membrane filter has a pore size of about 1 nm. In embodiments, a second membrane filter has a pore size of about 5 nm. In embodiments, a second membrane filter has a pore size of about 10 nm. In embodiments, a second membrane filter has a pore size of about 20 nm. In embodiments, a second membrane filter has a pore size of about 30 nm. In embodiments, a second membrane filter has a pore size of about 40 nm. In embodiments, a second membrane filter has a pore size of about 50 nm. In embodiments, a second membrane filter has a pore size of about 60 nm. In embodiments, a second membrane filter has a pore size of about 70 nm. In embodiments, a second membrane filter has a pore size of about 80 nm. In embodiments, a second membrane filter has a pore size of about 90 nm. In embodiments, a second membrane filter has a pore size of about 100 nm. In embodiments, a second membrane filter has a pore size of greater than 100 nm.

[0236]

[0222] In some embodiments, a second membrane filter has a pore size of about 1 nm. In embodiments, a second membrane filter has a pore size of about 2 nm. In embodiments, a second membrane filter has a pore size of about 3 nm. In embodiments, a second membrane filter has a pore size of about 4 nm. In embodiments, a second membrane filter has a pore size of about 5 nm. In embodiments, a second membrane filter has a pore size of about 6 nm. In embodiments, a second membrane filter has a pore size of about 7 nm. In embodiments, a second membrane filter has a pore size of about 8 nm. In embodiments, a second membrane filter has a pore size of about 9 nm. In embodiments, a second membrane filter has a pore size of about 10 nm. In embodiments, a second membrane filter has a pore size of about 11 nm. In embodiments, a second membrane filter has a pore size of about 12 nm. In embodiments, a second membrane filter has a pore size of about 13 nm. In embodiments, a second membrane filter has a pore size of about 14 nm. In embodiments, a second membrane filter has a pore size of about 15 nm.

[0237]

[0223] In some embodiments, a second membrane filter has a pore size of between about 1 nm and about 30 nm. In embodiments, a second membrane filter has a pore size of between about 2 nm and about 25 nm. In embodiments, a second membrane filter has a pore size of between about 3 nm and about 20 nm. In embodiments, a second membrane filter has a pore size of between about 4 nm and about 20 nm. In embodiments, a second membrane filter has a pore size of between about 5 nm and about 10 nm.

[0238]

[0224] In embodiments, the pore size is selected to control plasma protein transmission. In embodiments, unbound PFAS (i.e., as dissolved small molecules) traverse the membrane and are removed by a downstream adsorption or albumin-dialysis module rather than by size exclusion at the membrane.

[0239]

[0225] In embodiments, a second membrane filter has a pore size of between about 1 nm and 100 nm. In embodiments, a second membrane filter has a pore size of between about 5 nm and 100 nm. In embodiments, a second membrane filter has a pore size of between about 10 nm and 100 nm. In embodiments, a second membrane filter has a pore size of between about 20 nm and 100 nm. In embodiments, a second membrane filter has a pore size of between about 30 nm and 100 nm. In embodiments, a second membrane filter has a pore size of between about 40 nm and 100 nm. In embodiments, a second membrane filter has a pore size of 2025-09-12 between about 50 nm and 100 nm. In embodiments, a second membrane filter has a pore size of between about 60 nm and 100 nm. In embodiments, a second membrane filter has a pore size of between about 70 nm and 100 nm. In embodiments, a second membrane filter has a pore size of between about 80 nm and 100 nm. In embodiments, a second membrane filter has a pore size of between about 90 nm and 100 nm.

[0240]

[0226] In embodiments, a second membrane filter has a pore size of less than 50 nm. In embodiments, a second membrane filter has a pore size of less than 40 nm. In embodiments, a second membrane filter has a pore size of less than 30 nm. In embodiments, a second membrane filter has a pore size of less than 20 nm. In embodiments, a second membrane filter has a pore size of less than 10 nm. In embodiments, a second membrane filter has a pore size of less than 5 nm. In embodiments, a second membrane filter has a pore size of less than 1 nm.

[0241]

[0227] In some embodiments, a second membrane filter is structured or selected to be permeable to particles (e.g., PFAS) having a molecular weight (MW) less than a specified MW. In embodiments, a second membrane filter is structured or selected to be impermeable (i.e., to substantially reject or retain) particles (e.g., PFAS) having a MW higher than a specified MW. In embodiments, a second membrane filter is structured or selected to be permeable to particles having a MW less than about 1 kDa, 2 kDa, 3 kDa, 4 kDa, 5 kDa, 6 kDa, 7 kDa, 8 kDa, 9 kDa, 10 kDa, 11 kDa, 12 kDa, 13 kDa, 14 kDa, 15 kDa, 16 kDa, 17 kDa, 18 kDa, 19 kDa, 20 kDa, 25 kDa, 30 kDa, 35 kDa, 40 kDa, 45 kDa, 50 kDa, 55 kDa, 60 kDa, 65 kDa, 70 kDa, 75 kDa, 80 kDa, 85 kDa, 90 kDa, 95 kDa, or 100 kDa. In embodiments, a second membrane filter is structured or selected to be impermeable to particles having a MW greater than about 1 kDa, 2 kDa, 3 kDa, 4 kDa, 5 kDa, 6 kDa, 7 kDa, 8 kDa, 9 kDa, 10 kDa, 11 kDa, 12 kDa, 13 kDa, 14 kDa, 15 kDa, 16 kDa, 17 kDa, 18 kDa, 19 kDa, 20 kDa, 25 kDa, 30 kDa, 35 kDa, 40 kDa, 45 kDa, 50 kDa, 55 kDa, 60 kDa, 65 kDa, 70 kDa, 75 kDa, 80 kDa, 85 kDa, 90 kDa, 95 kDa, 100 kDa, 110 kDa, 120 kDa, 130 kDa, 140 kDa, 150 kDa, 160 kDa, 170 kDa, 180 kDa, 190 kDa, 200 kDa, 225 kDa, 250 kDa, 275 kDa, or 300 kDa, including values and ranges in between.

[0242]

[0228] In some embodiments, a membrane filter (e.g., a first and / or second membrane filter) has a membrane area of between about 0.1 and 5.0 m2. In embodiments, a membrane filter has a membrane area of between about 0.1 and 4.0 m2. In embodiments, a membrane filter has a membrane area of between about 0.1 and 3.0 m2. In embodiments, a membrane filter has a membrane area of between about 0.1 and 2.0 m2. In embodiments, a membrane filter has a membrane area of between about 0.1 and 1.0 m2. In embodiments, a membrane filter has a membrane area of between about 0.1 and 0.9 m2. In embodiments, a membrane filter has a membrane area of between about 0.1 and 0.8 m2. In embodiments, a membrane filter has a membrane area of between about 0.1 and 0.7 m2. In embodiments, a membrane filter has a membrane area of between about 0.1 and 0.6 m2. In embodiments, a membrane filter has a membrane area of between about 0.1 and 0.5 m2. In embodiments, a membrane filter has a membrane area of between about 0.2 and 0.5 m2. In embodiments, a membrane filter has a membrane area of between about 0.2 and 0.6 m2. In embodiments, a membrane filter has a membrane area of between about 0.3 and 0.6 m2. 2025-09-12

[0243]

[0229] In some embodiments, a membrane for use in a DFPP or other plasmapheresis device is structured or selected according to a selected transmembrane pressure (TMP). In embodiments, the TMP is selected to enable filtration or to enable improved or optimized filtration of PFAS according to a disclosed method. In embodiments, the membrane structured or selected according to a selected TMP is a first membrane filter or a second membrane filter. In embodiments, the TMP, when using a plasmapheresis device according to a disclosed method, such as a DFPP device, is selected to enable filtration or to enable improved or optimized filtration of PFAS according to the disclosed method. In embodiments, the TMP is the TMP of a membrane, such as a first membrane filter or a second membrane filter. In embodiments, the TMP is selected prior to administration of a DFPP treatment, such as selected on or using a DFPP or other plasmapheresis device. In embodiments, the TMP is selected during the administration of a DFPP treatment to a subject, such as selected on or using a DFPP or other plasmapheresis device. In embodiments, the TMP is selected after the administration of a DFPP treatment, such as selected on or using a DFPP or other plasmapheresis device. In embodiments, the TMP is selected in view of a membrane, including a selected membrane, and including a first membrane filter or a second membrane filter.

[0244]

[0230] In some embodiments, the TMP (e.g., the TMP of a membrane filter, such as the first and / or second membrane filter) is controlled by one or more pumps in a DFPP or other plasmapheresis device. In embodiments, the TMP is controlled by a pump upstream and / or downstream of a membrane. In embodiments, the TMP is controlled by a pump upstream of a membrane. In embodiments, the TMP is controlled by a pump downstream of a membrane. In embodiments, the TMP of a membrane (e.g., the first and / or second membrane filter) increases as PFAS (e.g., those impermeable to the membrane filter) are rejected or retained by the membrane. For example, particles accumulating within a membrane and / or on the surface of a membrane block the filter pores, restricting fluid flow through the membrane and increasing the TMP required to maintain fluid transport through the membrane. In embodiments, a method comprises increasing the TMP as a means for rinsing or flushing an eluate (e.g., a DFPP eluate) from a blood circuit.

[0245]

[0231] In embodiments, a DFPP, plasmapheresis, or other EBP treatment is conducted at a specified TMP. In embodiments, an EBP treatment is conducted at a TMP (e.g., at the first and / or second membrane filter) between about 10 mmHg and about 200 mmHg. In embodiments, an EBP treatment is conducted at a TMP between about 40 mmHg and about 100 mmHg. In embodiments, an EBP treatment is conducted at a TMP less than about 200 mmHg. In embodiments, an EBP treatment is conducted at a TMP between about 20 and about 200 mmHg, between about 30 and about 150 mmHg, or between about 40 and about 100 mmHg.

[0246]

[0232] In embodiments, an EBP treatment is conducted at a TMP between about 30 and about 150 mmHg.

[0247] In embodiments, an EBP treatment is conducted at a TMP between about 40 and about 100 mmHg. In embodiments, an EBP treatment is conducted at a TMP between about 100 and about 300 mmHg. In embodiments, an EBP treatment is conducted at a TMP between about 100 and about 200 mmHg. In embodiments, an EBP treatment is conducted at a TMP between about 200 and about 300 mmHg. In 2025-09-12 embodiments, an EBP treatment is conducted at a TMP greater than about 300 mmHg.

[0248]

[0233] In embodiments, a DFPP, plasmapheresis, or other EBP treatment is conducted at a TMP of a first membrane filter above about 250 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a first membrane filter above about 300 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a first membrane filter above about 350 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a first membrane filter above about 400 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a first membrane filter below about 400 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a first membrane filter below about 350 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a first membrane filter below about 300 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a first membrane filter below about 250 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a first membrane filter below about 200 mmHg.

[0249]

[0234] In some embodiments, a DFPP, plasmapheresis, or other EBP treatment is conducted at a TMP of a second membrane filter below about 200 mmHg. In some embodiments, an EBP treatment is conducted at a TMP of a second membrane filter below about 150 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a second membrane filter below about 125 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a second membrane filter below about 100 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a second membrane filter below about 50 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a second membrane filter below about 25 mmHg.

[0250]

[0235] In embodiments, an EBP treatment is conducted at a TMP of a second membrane filter above about 25 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a second membrane filter above about 50 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a second membrane filter above about 100 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a second membrane filter above about 125 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a second membrane filter above about 150 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a second membrane filter above about 200 mmHg.

[0251]

[0236] In some embodiments, a DFPP, plasmapheresis, or other EBP treatment is conducted at a TMP below a specified maximum TMP. In embodiments, wherein TMP increases as the treatment progresses, when the TMP reaches the maximum TMP, a suitable means for controlling or decreasing the TMP is activated, such as by opening a waste line, thereby diverting fluid (e.g., through a waste line to a waste blag). In embodiments, the specified maximum TMP of an EBP treatment is about 100 mmHg. In embodiments, the specified maximum TMP of an EBP treatment is about 110 mmHg. In embodiments, the specified maximum TMP of an EBP treatment is about 120 mmHg. In embodiments, the specified maximum TMP of an EBP treatment is about 130 mmHg. In embodiments, the specified maximum TMP of an EBP treatment is about 140 mmHg. In embodiments, the specified maximum TMP of an EBP treatment is about 150 mmHg.

[0252]

[0237] In some embodiments, TMP is selected and controlled to achieve a target sieving coefficient for 2025-09-12 albumin at a second membrane. In embodiments, a target albumin sieving coefficient is at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, or 0.7. In embodiments, a target albumin sieving coefficient is 0.6.

[0253]

[0238] In some embodiments, TMP is managed by a controller that adjusts one or more pump speeds (e.g., blood pump, plasma pump, permeate pump) and / or a throttle or bypass valve to maintain TMP within a predefined setpoint window.

[0254]

[0239] In some embodiments, a critical-flux protocol is used to limit fouling, wherein TMP is incrementally increased at fixed crossflow until a non-linear rise in TMP per unit flux is observed, and subsequent operation is maintained below this critical flux. Operation below critical flux may reduce filter fouling, stabilize albumin sieving, and decrease session-to-session variability.

[0255]

[0240] In some embodiments, a rise in TMP at the first membrane is used as an indicator of cellular or protein fouling, clot formation, lipid accumulation, or air entrapment. In such embodiments, corrective actions include reducing blood or plasma flow, increasing anticoagulation within predefined safety limits, performing a saline rinse or back-flush, or replacing the membrane module.

[0256]

[0241] In some embodiments, TMP at the second membrane is selected to permit albumin passage while minimizing shear-induced hemolysis, and PFAS removal is effected primarily by an adsorption module placed downstream of the second membrane. In embodiments, a pressure drop across the adsorption module is monitored independently of TMP to detect fouling or saturation of the adsorbent.

[0257]

[0242] In some embodiments, alarms are generated when TMP falls below a minimum threshold (e.g., line disconnect, leak, or sensor failure) or exceeds a maximum threshold (e.g., occlusion or fouling), and the system automatically pauses flow, opens a bypass, or diverts to waste.

[0258]

[0243] In embodiments, PFAS are filtered from the biological matrix of a subject with an EBP device, or using an EBP treatment, such as by using an EBP device.

[0259]

[0244] In embodiments, an EBP device is a hemodialysis device, a hemofiltration device, a hemodiafiltration device, a hemoperfusion device, or an ultrafiltration device.

[0260]

[0245] In some embodiments, an EBP device is used together with an additional EBP treatment. In embodiments, the additional EBP treatment is a plasmapheresis treatment, such as using a plasmapheresis device. In embodiments, the additional EBP treatment is a DFPP treatment, such as using a DFPP device. In embodiments, the additional EBP treatment is a TPE treatment, such as using a TPE device. In embodiments, the additional EBP treatment is a PP treatment, such as using a PP device. In embodiments, the additional EBP treatment is a PA treatment, such as using a PA device. In embodiments, the additional EBP treatment is a CPFA treatment, such as using a CPFA device.

[0261]

[0246] Herein, in all such embodiments unless context demands otherwise, an EBP device “used together with” another device or treatment may mean the EBP device is used before, is used at the same time as, or is used after the other device or treatment. In embodiments, “before” and “after” refer to a period of time separating the two treatments of about 1 hour, about 2 hours, about 4 hours, about 8 hours, about 12 hours, 2025-09-12 about 24 hours, about 48 hours, about 72 hours, and about 1 week, including periods in between. In embodiments, “before” and “after” refer to a period of time separating the two treatments of about 1 week, about 2 weeks, about 3 weeks, about 1 month, about 2 months, about 3 months, and about 6 months, including periods in between. In embodiments, “before” and “after” refer to a period of time separating the two treatments of about 6 months, about 9 months, about 1 year, about 18 months, about 3 years, and about 5 years, including periods in between. In embodiments, “before” and “after” refer to a period of time separating the two treatments of greater than 5 years. “At the same time as” will include two treatments provided where the period of time separating the two treatments is less than 1 hour, such as less than 45 minutes apart, less than 30 minutes apart, less than 15 minutes apart, and times in between (e.g., where two treatments are provided in a single treatment session). In embodiments, “at the same time as” means the two treatments are provided on the same day. In embodiments, “at the same time as” means the two treatments are provided during the same treatment session, such as during the same treatment center visit. In embodiments, “at the same time as” means the two treatments are provided concurrently.

[0262]

[0247] In some embodiments, PFAS are filtered from the blood of a subject using a hemodialysis device. Examples of hemodialysis devices are known in the art, and include those disclosed in, e.g., US10,322,220 and EP2280748B1 (Wallenborg et al.). In embodiments, PFAS are filtered from the blood of a subject using a hemodialysis device together with an additional EBP treatment.

[0263]

[0248] In some embodiments, PFAS are filtered from the blood of a subject using a hemofiltration device. Examples of hemofiltration devices are known in the art, and include those disclosed in, e.g., US2005 / 0082210. In embodiments, PFAS are filtered from the blood of a subject using a hemofiltration device together with an additional EBP treatment.

[0264]

[0249] In some embodiments, PFAS are filtered from the blood of a subject using a hemodiafiltration device. Examples of hemodiafiltration devices are known in the art, and include those disclosed in, e.g., US10,322,220 and EP2280748B1 (Wallenborg et al.). In embodiments, PFAS are filtered from the blood of a subject using a hemodiafiltration device together with an additional EBP treatment.

[0265]

[0250] In some embodiments, PFAS are filtered from the blood of a subject using a hemoperfusion device. Examples of hemoperfusion devices are known in the art, and include those disclosed in, e.g., US7,625,351. In embodiments, PFAS are filtered from the blood of a subject using a hemoperfusion device together with an additional EBP treatment.

[0266]

[0251] In some embodiments, PFAS are filtered from the blood of a subject using an ultrafiltration device. Examples of ultrafiltration devices are known in the art, and include those disclosed in, e.g., US8,956,317. In embodiments, PFAS are filtered from the blood of a subject using an ultrafiltration device together with an additional EBP treatment.

[0267]

[0252] In some embodiments, PFAS are filtered from the blood of a subject using a hemoadsorption device. Examples of hemoadsorption devices and tools are known in the art, and include CYTOSORB® porous 2025-09-12 polymer bead adsorber, HA330 / HA380 resin hemoperfusion cartridges (JAFRON); ADSORBA® 300C activated-carbon hemoperfusion cartridge; SERAPH® 100 MICROBINDS® affinity blood filter; TORAYMYXIN™, ALTECO® LPS ADSORBER, OXIRIS®, and LIXELLE® p2-microglobulin hemoadsorption column. In embodiments, PFAS are filtered from the blood of a subject using a hemoadsorption device together with an additional EBP treatment.

[0268]

[0253] In embodiments, an EBP device comprises: (1) a means for removing a subject’s blood; (2) a means for returning a subject’s blood; (3) a blood circuit; (4) a means for supplying force to a subject’s blood / plasma in a blood circuit; and (5) a means for separating an eluate (e.g., containing PFAS) from whole blood.

[0269]

[0254] Other exemplary EBP devices will be as disclosed herein or as known in the art. Exemplary EBP devices, as examples, include double filtration plasmapheresis (DFPP) devices, such as the INUSpheresis (INUS Medical Devices AG), H.E.L.P (B Braun), PURE SELECT® (Meise Medical Technology), Evaflux (BREU GmbH), Rheofilter ER-4000 and Lipidfiltration (DIAMED), Medopen (Infomed), Fractiosmart (Medica Spa); other plasmapheresis devices such as the Trackpore (Hemafenix); plasma perfusion (PP) devices, such as the MTx.100 (Marker Health), Liposorber (Kaneka Medical America LLC), DALI (Fresenius Medical Care), BS Series (Jafron), XGal-3® Device (Eliaz Therapeutics), Immusorba TR-350 (DIAMED); hemo-perfusion (HP) devices, such as the Seraph 100 and Oncobind (ExThera Medical), Cytosorb (CytoSorbent), Hemopurifier for Infectious Disease and Hemopurifier for Cancer (Aethlon Medical), GLOBAFFIN (Fresenius Medical Care), Infectious Disease, ImmunePrep, ChemoPrep, and ChemoPure (Sigyn Therapeutics), HA Series (Jafron), LA25 (Medica Spa); and therapeutic plasma exchange (TPE) devices, such as the Spectra Optia (Terumo BCT), NxStage and COM.TEC (Fresenius Medical Care), Amicus (Fresenius Kabi), Prismaflex (Baxter), PrisMax (Baxter), Plasmat Futura (B Braun), Plasmafilter SepaPlas® 06 (Meise Medical Tech.), Evaclio (BREU GmbH), Plasmaflo OP (DIAMED), Granopen (Infomed), and Plasmart (Medica Spa).

[0270]

[0255] In some embodiments, an EBP device configuration includes any of a hemodialysis configuration, a hemofiltration configuration, a hemodiafiltration configuration, a hemoperfusion configuration, or an ultrafiltration configuration. In embodiments, an EBP device comprises one device configuration, or performs one blood filtration method. In embodiments, an EBP device comprises more than one device configuration, or performs more than one blood filtration method.

[0271]

[0256] In some embodiments, an EBP device is used for chronic care, such as for one or more sessions daily over a period of time. In embodiments, an EBP device is used for acute care, such as for continuous renal replacement therapy (CRRT). Additional examples of EBP devices suitable for administering EBP treatments (e.g., hemodialysis, hemodiafiltration, ultrafiltration) according to disclosed methods, and include, e.g., DIMI (Infomed SA, Switzerland) and SAMI (Infomed SA, Switzerland).

[0272] D. Measuring PFAS In or From the Biological Matrix of Subjects

[0273]

[0257] In some aspects are provided methods which comprise measuring an amount of PFAS. In some embodiments, a method comprises measuring an amount of PFAS in a biological matrix of a subject, such as 2025-09-12 a subject administered a disclosed treatment (e.g., using a disclosed device, system, or method).

[0274]

[0258] In embodiments, measuring an amount of PFAS in a subject comprises measuring the amount of PFAS in a biological matrix of the subject (i.e., any biological matrix of the subject described herein, including a fluid; blood; a fluid other than blood, i.e., a non-blood fluid, including a non-blood biological fluid, such as an interstitial fluid; and further including an eluate derived from the subject, such as a DFPP eluate obtained during a DFPP treatment administered to the subject). In embodiments, the amount of PFAS in the biological matrix of the subject is measured prior to administering a DFPP, plasmapheresis, or other EBP treatment. In embodiments, the amount of PFAS is measured after administering the EBP treatment. In embodiments, the amount of PFAS is measured both prior to and after administering the EBP treatment. In embodiments, the amount of PFAS is measured during administration of the EBP treatment. In embodiments, the amount of PFAS is measured prior to, during, and after administering the EBP treatment.

[0275]

[0259] In embodiments, measuring an amount of PFAS comprises measuring a concentration of PFAS.

[0276]

[0260] In some embodiments, measuring an amount of PFAS comprises measuring a composition of PFAS.

[0277]

[0261] Numerous analytical techniques are suitable for measuring PFAS concentrations, such as in biological matrices and in fluids; exemplary such techniques are described, and others are known to those of skill.

[0278]

[0262] In embodiments, measuring an amount of PFAS in a biological matrix of a subject comprises a chromatography technique, such as gas chromatography (GC), pyrolysis gas chromatography (Py-GC), gas chromatography / electron capture negative ion (GC / ECNI), liquid chromatography (LC), high performance liquid chromatography (HPLC), ultra high performance liquid chromatography (UHPLC), capillary electrophoresis (CE), nanoscale capillary electrophoresis (NCE), ion mobility spectrometry (IMS), sonication (ACN), and Ion-Pair Extraction (MTBE). In embodiments, measuring an amount of PFAS in a biological matrix of a subject comprises a mass spectrometry technique, such as mass spectrometry (MS), tandem mass spectrometry (MS / MS), high resolution mass spectrometry (HRMS), time-of-flight mass spectrometry (TOF-MS), and quadrupole time-of-flight mass spectrometry (QTOF-MS). In embodiments, a measuring an amount of PFAS in a biological matrix of a subject comprises a combination of a chromatography technique and a mass spectrometry technique, such as gas chromatography-mass spectrometry (GC-MS), gas chromatography tandem mass spectrometry (GC-MS / MS), liquid chromatography-mass spectrometry (LC-MS), liquid chromatography tandem mass spectrometry (LC-MS / MS), high-performance liquid chromatography-mass spectrometry (HPLC-MS), high-performance liquid chromatography tandem mass spectrometry (HPLC-MS / MS), ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS), ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS / MS), Mass Spectrometry Imaging with Nanoscale Capillary Electrophoresis and Mass Spectrometry (MSI-NACE-MS), Mass Spectrometry Imaging with Nanoscale Capillary Electrophoresis and Tandem Mass Spectrometry (MSI-NACE-MS / MS), Capillary Electrophoresis-Mass Spectrometry (CE-MS), and Capillary Electrophoresis- Tandem Mass Spectrometry (CE-MS / MS) (Jimenez-Skrzypek et al. J Chromatography Open. 2023;4: 100089; 2025-09-12 Comito et al. Chemosphere. 2023;345: 140433; Perera et al. Trends Enviro Analytical Chem. 2024;41 :e00224; Analytical methods for PFAS in products and the environment. Norden.org. Accessed August 9, 2024).

[0279]

[0263] In embodiments, measuring a concentration of PFAS in a sample (e.g., of a biological matrix of a subject, such as a blood sample, a serum sample, an eluate sample, or a tissue sample) comprises analyzing the sample using LC-MS / MS (see, e.g., Pan et al. Environ Toxicol Chem. 2010;29(12):2695-2701 ; Frigerio et al. Anal Bioanal Chem. 2022;414(3): 1259-1278; Wu et al. Chemosphere. 2017;168:100-105); UHPLC-MS / MS (see, e.g., Salihovic et al. Anal Bioanal Chem. 2020;412(10):2251 -2259), MSI-NACE-MS / MS (see, e.g., Azab et al. Anal Sci Adv. 2020; 1 (3): 173-182), or solid-phase extraction coupled to isotope dilution-HPLC-MS / MS (see, e.g., Calafat et al. Environ Health Perspect. 2007;115(11):1596-1602), or another disclosed or known such technique. In embodiments, determining the composition and concentration of PFAS in the sample, comprises analysis with LC-MS / MS, UHPLC-MS / MS, MSI-NACE-MS / MS, solid-phase extraction coupled to isotope dilution-HPLC-MS / MS, or another disclosed or known such technique.

[0280]

[0264] In embodiments, measuring a composition and / or concentration of PFAS in a sample comprises the use of one or more fluorescent dyes in combination with microscopy. In embodiments, fluorescent dyes are selected to preferentially bind to or adsorb onto PFAS, enhancing optical visibility and enabling discrimination from background biological material. In embodiments, the sample is stained with a hydrophobic fluorescent dye (e.g., Nile Red or other lipophilic dyes), followed by imaging using fluorescence microscopy, a fluorescence-assisted detection technique, confocal microscopy, or another suitable optical modality. Resulting images may be analyzed manually or using automated or Al-based image processing to determine the presence, identity, and / or abundance of PFAS in the sample. Compositional analysis may be performed based on dye affinity profiles or quantitative assessment based on particle counts or relative fluorescence intensity.

[0281]

[0265] In embodiments, measuring an amount of PFAS comprises characterizing the anionic nature or charge state of PFAS analytes. Where PFAS species (e.g., PFOA, PFOS) exist as anions in solution at physiological pH, analytical techniques are selected or optimized to take advantage of this property (see, e.g., Winchell et al. Sci Total Environ. 2021 ;774: 145257). Chromatographic methods may utilize anion-exchange columns designed to separate analytes based on ionic charge and hydrophobicity. Detection and quantification may be refined by targeting the mass-to-charge ratio of the deprotonated [M-H]“ ions, characteristic of anionic PFAS compounds in mass spectrometry. Measuring the ratio of protein-bound to free (unbound) PFAS may involve techniques sensitive to charge or size, such as equilibrium dialysis or capillary electrophoresis.

[0282] E. Administering Extracorporeal Blood Purification Treatments to Subjects

[0283]

[0266] In some aspects are provided methods of administering an extracorporeal blood purification (EBP) treatment to a subject, such as a human subject, using an EBP device.

[0284]

[0267] In some embodiments, EBP treatments are administered to a subject using a plasmapheresis device, a DFPP device, a TPE device, a PP device, a PA device, or a CPFA device. In embodiments, the EBP treatment is administered to a subject using a plasmapheresis device. In embodiments, the EBP treatment is 2025-09-12 administered using a DFPP device. In embodiments, the EBP treatment is administered using a TPE device. In embodiments, the EBP treatment is administered using a PP device. In embodiments, the EBP treatment is administered using a PA device. In embodiments, the EBP treatment is administered using a CPFA device. In embodiments, the EBP treatment is administered using an albumin-dialysis device.

[0285]

[0268] In some embodiments, EBP treatments are administered using a hemodialysis device, a hemofiltration device, a hemodiafiltration device, a hemoperfusion device, or an ultrafiltration device. In embodiments, the EBP treatment is administered using a hemodialysis device. In embodiments, the EBP treatment is administered using a hemofiltration device. In embodiments, the EBP treatment is administered using a hemoperfusion device. In embodiments, the EBP treatment is administered using an ultrafiltration device.

[0286]

[0269] FIG. 1 illustrates an exemplary EBP circuit 100. In some implementations, the EBP circuit 100 is used as part of an EBP treatment such as DFPP. Whole blood is received from a subject 102. The whole blood passes through a first filter 104. The first filter 104 separates the whole blood into a cellular fraction and a plasma fraction. The plasma fraction passes through a second filter 106. The second filter 106 removes PFAS from the plasma fraction to provide a filtered plasma fraction. In some implementations, the second filter 106 is a fractionation filter (e.g., a membrane with a defined molecular weight cut-off). The filtered plasma fraction is combined with the cellular fraction, and the filtered blood is provided to the subject 102. In some implementations, an optional third filter 108 filters the whole blood before the whole blood is separated into the cellular fraction and the plasma fraction. In some implementations, the filtered blood may not be returned to the subject, but may instead be stored or used for another purpose. Characteristics of the first filter 104, the second filter 106, and the optional third filter 108 are described in more detail herein with respect to the various examples.

[0287]

[0270] In implementations, the second filter 106 or a subsequent in-line adsorption module can be configured to remove PFAS based on their physicochemical properties, including size exclusion, hydrophobicity, or electrostatic charge. For example, the module may contain a medium functionalized with positively charged groups to adsorb anionic PFAS compounds via electrostatic attraction

[0288]

[0271] FIG. 2 illustrates an exemplary EBP circuit 200 configured for enhanced PFAS removal using integrated electrostatic binding mechanisms. In some implementations, the EBP circuit 200 is used as part of a DFPP treatment. Whole blood is received from a subject 202. The whole blood passes through a plasma separator 204 that is configured to separate the whole blood into a cellular fraction and a plasma fraction.

[0289]

[0272] The plasma fraction is directed to an electrostatic adsorption unit 206. As in the example related to FIG. 1, an optional third filter 208 (e.g., an initial filter) may also be provided.

[0290]

[0273] The electrostatic adsorption unit 206 is configured to remove PFAS from the plasma fraction through a charge-based binding mechanism. In some implementations, the electrostatic adsorption unit 206 is an integrated system that includes an electrostatic pre-charging unit configured to ionize the plasma and enhance the polarity of PFAS compounds, an anion exchange adsorption cartridge including a substrate functionalized 2025-09-12 with cationic ligands such as a strong-base anion-exchange resin to electrostatically bind anionic PFAS molecules, and an electrostatic precipitation chamber configured to capture any remaining charged particulates. The electrostatic adsorption unit 206 can be powered by a high voltage generator and controlled by a field strength controller that is configured to modulate electrical parameters of the electrostatic adsorption unit 206 to optimize PFAS capture efficiency. The plasma fraction flows through the electrostatic adsorption unit 206, which yields a filtered plasma fraction. The filtered plasma fraction exiting the electrostatic adsorption unit 206 is then combined with the cellular fraction to yield filtered whole blood, and the filtered whole blood is returned to the subject 202. In some implementations, the circuit may include one or more sensors to monitor parameters such as plasma conductivity, pH, or real-time PFAS concentration to provide feedback to the field strength controller. Feedback information can be used for data collection, monitoring, and / or dynamic control of the treatment. In some implementations, the filtered whole blood may not be returned to the subject but may instead be stored or used for another purpose.

[0291]

[0274] FIG. 3 illustrates an exemplary EBP circuit 300 configured for enhanced PFAS removal using an adsorbent media. In some implementations, the EBP circuit 300 is used as part of a DFPP treatment.

[0292]

[0275] Whole blood is received from a subject 302. The whole blood passes through a first filter 304 (e.g., a plasma separator) that is configured to separate the whole blood into a cellular fraction and a plasma fraction. The plasma fraction is directed to a second filter 306 that is configured to separate PFAS from the plasma fraction and provide a filtered plasma fraction. In some implementations, the second filter 306 is a fractionation filter (e.g., a membrane with a defined molecular weight cut-off). An optional third filter 308 may also be provided upstream to remove larger aggregates or particulates.

[0293]

[0276] The filtered plasma fraction from the second filter 306 is directed to an adsorbent media unit 310. The adsorbent media unit 310 is configured to remove PFAS from the plasma fraction, through a physiochemical binding mechanism. In some implementations, the adsorbent media unit 310 is a cartridge or column that includes adsorbent particles tailored for high-affinity PFAS binding, such as activated carbon, strong-base anion-exchange resin, fluorophilic polymer, or molecularly imprinted polymer. The adsorbent media can provide a relatively high surface area with functional groups configured to sequester PFAS molecules via mechanisms including hydrophobic interaction, anion exchange, and fluorocarbon-fluorocarbon affinity. The adsorbent media unit 310 can be equipped with a flow controller and pressure sensors that are configured to modulate plasma flow rate and residence time to optimize contact with the adsorbent media and prevent channeling. The plasma fraction flows through the adsorbent media unit 310, which yields purified plasma.

[0294]

[0277] The purified plasma exiting the adsorbent media unit 310 is combined with the cellular fraction from the first filter 304 to yield filtered whole blood, and the filtered whole blood is returned to the subject 302. In some implementations, the circuit may include one or more sensors to monitor parameters such as pre- and post-adsorption PFAS concentration, pressure drop across the media bed, or plasma flow rate to provide feedback for determining media saturation and treatment efficacy. This feedback information can be used for 2025-09-12 data collection, monitoring, and / or dynamic control of the treatment. In some implementations, the filtered whole blood may not be returned to the subject but may instead be stored or used for another purpose.

[0295]

[0278] A “treatment,” such as a DFPP, plasmapheresis, or other EBP treatment, refers to a single session or procedure administered to a subject using the DFPP, plasmapheresis, or other EBP device, such as a single session or procedure in which the subject is connected to the DFPP, plasmapheresis, or other EBP device, the blood of the subject is filtered using the device, and the subject is disconnected from the device. In embodiments, PFAS are filtered from a biological matrix of a subject by administering to the subject a DFPP, plasmapheresis, or other EBP treatment, such as using a DFPP, plasmapheresis, or other EBP device.

[0296]

[0279] An exemplary DFPP treatment administered using a DFPP device is described in the Examples.

[0297]

[0280] In embodiments, an amount of PFAS in a biological matrix of a subject is reduced by administering to the subject an EBP treatment, such as using an EBP device, according to a disclosed method. Exemplary such treatments affecting an amount of PFAS in different biological matrices, include the following (likewise for each EBP treatment). In embodiments, an amount of PFAS in a tissue of a subject is reduced by administering to the subject an EBP treatment, such as using an EBP device, according to a disclosed method. In embodiments, an amount of PFAS in an organ of a subject is reduced by administering to the subject an EBP treatment, using an EBP device, according to a disclosed method. In embodiments, an amount of PFAS in the blood of a subject is reduced by administering to the subject an EBP treatment, using an EBP device, according to a disclosed method. In embodiments, an amount of PFAS in the body of a subject is reduced by administering to the subject an EBP treatment, using an EBP device, according to a disclosed method.

[0298]

[0281] In embodiments, an amount of PFAS in a biological matrix of a subject is reduced by administering to the subject a plasmapheresis treatment, such as using a plasmapheresis device, according to a disclosed method. In embodiments, an amount of PFAS in a biological matrix of a subject is reduced by administering to the subject a TPE treatment, such as using a TPE device, according to a disclosed method. In embodiments, an amount of PFAS in a biological matrix of a subject is reduced by administering to the subject a PP treatment, such as using a PP device, according to a disclosed method. In embodiments, an amount of PFAS in a biological matrix of a subject is reduced by administering to the subject a PA treatment, such as using a PA device, according to a disclosed method. In embodiments, an amount of PFAS in a biological matrix of a subject is reduced by administering to the subject a CPFA treatment, such as using a CPFA device, according to a disclosed method. In embodiments, an amount of PFAS in a biological matrix of a subject is reduced by administering to the subject an albumin dialysis treatment, such as using an albumin dialysis device, according to a disclosed method. In embodiments, an amount of PFAS in a biological matrix of a subject is reduced by administering to the subject a hemodialysis treatment, such as using a hemodialysis device, according to a disclosed method. In embodiments, an amount of PFAS in a biological matrix of a subject is reduced by administering to the subject a hemofiltration treatment, such as using a hemofiltration device, according to a disclosed method. In embodiments, an amount of PFAS in a biological matrix of a subject is reduced by 2025-09-12 administering to the subject a hemodiafiltration treatment, such as using a hemodiafiltration device, according to a disclosed method. In embodiments, an amount of PFAS in a biological matrix of a subject is reduced by administering to the subject a hemoperfusion treatment, such as using a hemoperfusion device, according to a disclosed method. In embodiments, an amount of PFAS in a biological matrix of a subject is reduced by administering to the subject an ultrafiltration treatment, such as using an ultrafiltration device, according to a disclosed method. Other such treatments, useful according to disclosure, will be appreciated in view hereof.

[0299]

[0282] Without dedication to a particular theory, PFAS are believed to exist in a dynamic equilibrium between those accumulated in tissues and solid organs and those circulating in the blood. In embodiments, the removal of circulating PFAS by a DFPP, plasmapheresis, or other EBP treatment creates a diffusion gradient between the blood and the tissues and solid organs of the subject, whereby PFAS are pulled from the tissues and solid organs to the blood, and in embodiments, filtered from the blood according to disclosed methods (i.e., PFAS rebound). In embodiments, EBP treatments, including second and subsequent treatments administered according to a disclosed regimen, filter PFAS that have diffused from tissues and solid organs into the blood of the subject. As a result, the overall PFAS burden in the subject, including both blood and tissues, is reduced, and in embodiments is progressively reduced with successive EBP treatments administered in the regimen.

[0300]

[0283] In embodiments, a method comprises administering a DFPP, plasmapheresis, or other EBP treatment for a specified treatment duration. In embodiments, the treatment duration refers to the time from which a subject administered the EBP treatment is connected to the EBP device, until the time upon which the subject is disconnected from the EBP device. In other embodiments, the treatment duration may refer to the time during which a subject’s blood is filtered using an EBP device, the time an EBP device is run during administration, or a time interval set by or programmed into the EBP device as the treatment duration.

[0301]

[0284] In embodiments, the treatment duration of a DFPP, plasmapheresis, or other EBP treatment, is about 0.5 hours, about 0.75 hours, about 1 hour, about 1.25 hours, about 1.5 hours, about 1.75 hours, about 2 hours, about 2.25 hours, about 2.5 hours, about 2.75 hours, about 3 hours, about 3.25 hours, about 3.5 hours, about 3.75 hours, about 4 hours, or greater than 4.0 hours, including durations in between these values.

[0302]

[0285] In embodiments, a method comprises administering an EBP treatment at a specified temperature. In embodiments, the temperature of a treatment refers to a temperature set by the EBP device as the treatment temperature. In embodiments, the temperature of a treatment refers to the temperature set by the EBP device as the temperature of a heating element (used, e.g., to heat plasma, blood, one or more membranes, or any other fluid or device component in contact with a heating element) to a specified temperature. In embodiments, the EBP device comprises a heater that can be set to a temperature of between about 35 °C and about 38 °C. In embodiments, the temperature of a treatment refers to the temperature of the subject. In embodiments, the temperature is about 35.0 °C, 35.1 °C, 35.2 °C, 35.3 °C, 35.4 °C, 35.5 °C, 35.6 °C, 35.7 °C, 35.8 °C, 35.9 °C, 36.0 °C, 36.1 °C, 36.2 °C, 36.3 °C, 36.4 °C, 36.5 °C, 36.6 °C, 36.7 °C, 36.8 °C, 36.9 °C, 37.0 °C, 37.1 °C, 37.2 °C, 37.3 °C, 37.4 °C, 37.5 °C, 37.6 °C, 37.7 °C, 37.8 °C, 37.9 °C, or 38.0 °C. In embodiments, 2025-09-12 the temperature is less than about 35.0 °C. In embodiments, the temperature is greater than about 38.0 °C.

[0303] F. Treatment Regimens for Extracorporeal Blood Purification

[0304]

[0286] In some aspects are provided treatment regimens comprising EBP treatments administered to a subject, such as a human subject, including to reduce an amount of PFAS in a biological matrix of the subject (i.e., an “EBP treatment regimen” or simply a “treatment regimen” or a “regimen,” as will be known by context).

[0305]

[0287] FIG. 4 illustrates an exemplary treatment regimen. At block 402, a subject is selected for therapy on the basis of a pre-treatment assessment (e.g., toxin panel, clinical history, physical exam). At block 404, a specific plasmapheresis protocol, such as double-filtration plasmapheresis (DFPP), therapeutic plasma exchange (TPE), or another extracorporeal blood-purification (EBP) modality, is chosen for the subject. At block 406, the plasmapheresis treatment is administered to reduce the subject’s PFAS burden. The dashed blocks represent optional feedback operations: block 408 comprises measuring one or more treatment- associated metrics (e.g., post-session PFAS load, inflammatory markers, hemodynamic parameters); block 410 comprises dynamically adjusting one or more treatment variables (e.g., flow rate, session length, replacement-fluid composition) in view of those measurements, after which the method may loop back to block 406 for a modified session. At block 412, the disclosed method may include performing one or more additional therapies, such as repeat plasmapheresis sessions, adjunct detoxification strategies, or regenerative interventions, either immediately or in a staged regimen.

[0306]

[0288] In embodiments, a treatment regimen comprises a DFPP, plasmapheresis, or other EBP treatment.

[0307]

[0289] FIG. 5 is a flow diagram of an example EBP treatment regimen. The process begins at A [Start] and proceeds as follows:

[0308]

[0290] (Pre-treatment assessment): At B, a subject is evaluated for treatment suitability, including medical history, treatment consent, vital signs, and baseline laboratory testing (e.g., albumin, electrolytes, hematocrit, hemoglobin, one or more PFAS analytes, and optionally one or more co-contaminants). (Eligible for EBP?): At C, A decision point determines whether the subject is eligible for EBP, such as DFPP or plasmapheresis, under protocol criteria (e.g., clinical status, contraindications). C1 (Optimize status; alternative therapy): If eligibility criteria is not met at C, supportive measures are undertaken (e.g., optimize hemodynamics, prescribe one or more supplements). The process may then re-enter C to reassess eligibility or direct the subject to an alternative therapy. (Plan treatment session count; start any pre-treatment regiments): At D, if the subject is eligible, a plan is established specifying the intended number of sessions and treatment regimen stopping criteria. Based on the findings at B, a protocol establishes an initial rest-interval window and any pre-session measures. For example, if the subject’s albumin is low (e.g., less than about 3.5 g / mL), the protocol may initiate a pre-session albumin regimen to raise albumin, set a longer first rest interval of about 48-72 hours between treatments, and / or reduce the processed plasma volume cap for each treatment. Optional pre-treatment measures may be initiated (e.g., hydration, oral chelation supplement, oral adjunct therapy, albumin management plan, medication holds). (EBP session): At E, an EBP treatment session is performed 2025-09-12 according to protocol (e.g., selected membranes / filters, target processed plasma volume, blood / plasma flow rates, anticoagulation, TMP limits). (Adverse event?): At F, a decision point determines whether an adverse event or alarm indication occurs, such as symptomatic hypocalcemia, hypotension, excessive TMP, access malfunction). (Pause, mitigate): At F1, if F is “yes,” the session is paused and corrective actions are taken (e.g., calcium administration, rate adjustments, circuit troubleshooting, backflush, or abort per safety rules). Upon stabilization, the process may resume the current session or proceed to G for a post-treatment assessment. (Post-treatment assessment): At G, after an EBP treatment, clinical status and laboratories are reassessed. PFAS measurements are obtained and may be compared with pre-session values (e.g., absolute difference, percentage difference, fold change). Albumin and electrolytes are measured to guide replenishment. (Albumin replacement needed?): At H, a decision point determines whether albumin replacement is indicated (e.g., albumin below a threshold and / or a drop from baseline exceeding a threshold). (Administer one or more albumin-replenishment strategies): At H1, if H is a “yes,” an albumin product may be administered (e.g., 5% HSA), or the subject’s treatment regimen may be adjusted (e.g., if there is a subsequent EBP treatment, add a rest interval of about 24-72 hours to allow for natural albumin replenishment). (Criteria met to end treatment regimen?): At I, a decision point evaluates whether regimen-termination criteria are satisfied, such as meeting PFAS reduction targets on one or more consecutive measurements, reaching a maximum EBP treatment count, or encountering intolerance / safety limits.

[0309]

[0291] In embodiments, a treatment regimen comprises two or more DFPP, plasmapheresis, or other EBP treatments, including 3 treatments, 4 treatments, 5 treatments, 6 treatments, 7 treatments, 8 treatments, 9 treatments, 10 treatments, and more than 10 EBP treatments. If I is “yes,” the regimen concludes at J [End] and follow-up is scheduled. If I is “no,” additional sessions are performed by returning to E, optionally updating the treatment regimen at D, and observing a rest interval between treatments as specified by protocol).

[0310]

[0292] In embodiments, a treatment regimen comprises at least two DFPP, plasmapheresis, or other EBP treatments, including at least 3 treatments, at least 4 treatments, at least 5 treatments, at least 6 treatments, at least 7 treatments, at least 8 treatments, at least 9 treatments, and at least 10 treatments.

[0311]

[0293] In embodiments, a treatment regimen comprises more than two EBP treatments, including more than 3 treatments, more than 4 treatments, more than 5 treatments, more than 6 treatments, more than 7 treatments, more than 8 treatments, more than 9 treatments, and more than 10 treatments.

[0312]

[0294] In embodiments, a treatment regimen comprises two or more EBP treatments, at least two EBP treatments, or more than two EBP treatments, wherein all of the EBP treatments are the same type of treatments, such as using the same EBP device, such as two or more, at least two, or more than two DFPP treatments, or two or more, at least two, or more than two plasmapheresis treatments.

[0313]

[0295] In embodiments, a treatment regimen comprises a combination of EBP treatments. In embodiments, the regimen comprises one or more DFPP treatments and one or more other EBP treatments. In embodiments, the regimen comprises one or more DFPP treatments and one or more other plasmapheresis 2025-09-12 treatments. In embodiments, the regimen comprises administering one or more DFPP treatments and one or more TPE treatments. In embodiments, the regimen comprises administering one or more DFPP treatments and one or more PP treatments. In embodiments, the regimen comprises administering one or more DFPP treatments and one or more PA treatments. In embodiments, the regimen comprises administering one or more DFPP treatments and one or more CPFA treatments. In embodiments, the regimen comprises administering one or more DFPP treatments and one or more hemodialysis treatments. In embodiments, the regimen comprises administering one or more DFPP treatments and one or more hemofiltration treatments. In embodiments, the regimen comprises administering one or more DFPP treatments and one or more hemodiafiltration treatments. In embodiments, the regimen comprises administering one or more DFPP treatments and one or more hemoperfusion treatments. In embodiments, the regimen comprises administering one or more DFPP treatments and one or more ultrafiltration treatments.

[0314]

[0296] Where a treatment regimen comprises two or more EBP treatments, such as two or more DFPP treatments, each treatment may be administered after a period of time following the previous treatment, such as a period of at least one day, at least a number of days from 2-6 days, at least one week, at least 2 weeks, at least 3 weeks, at least one month, at least a number of months from 3-11 days, at least one year, and at least two years, including at least 3, 4, 5, and more than 5 years, and times in between.

[0315]

[0297] Where a treatment regimen comprises two different EBP treatments, such as a DFPP treatment and another EBP treatment, such as a TPE treatment, the DFPP treatment may be administered before or after the other EBP treatment. In embodiments, the DFPP treatment is before the other EBP treatment. In embodiments, the DFPP treatment is after the other EBP treatment. In embodiments where a regimen has three or more EBP treatments, a DFPP treatment may be between two other EBP treatments in the regimen, or two DFPP treatments may be before and after another EBP treatment, and the like.

[0316]

[0298] In embodiments where a treatment regimen comprises three or more treatments, each treatment may be administered after about the same period of time (i.e., with about the same length of time in between).

[0317]

[0299] In other embodiments where a treatment regimen comprises three or more treatments, the treatments may have different lengths of time in between administration. In embodiments, the length of time between treatments is preselected, i.e., selected in advance of the first treatment. In other embodiments, the length of time between treatments is determined after the first treatment, such as based on a measurement of an amount of PFAS in a biological matrix of the subject. In other embodiments, the length of time between treatments is determined after each treatment, such as based on a measurement of an amount of PFAS in a biological matrix of the subject. In such embodiments, the length of time may be selected in view of one or more previous measurement(s), and / or in view of a reference table for similarly situated subjects.

[0318]

[0300] In embodiments, a treatment regimen comprises one or more EBP treatments administered in an inpatient setting, for example, in an intensive-care unit, step-down unit, or dedicated apheresis suite with integrated monitoring and continuous nursing oversight. 2025-09-12

[0319]

[0301] In embodiments, a treatment regimen comprises one or more EBP treatments administered in an outpatient or ambulatory setting, such as a hospital-based infusion center, a stand-alone dialysis or apheresis clinic, or a mobile medical unit, such as using a compact cart-mounted device.

[0320]

[0302] In embodiments, a treatment regimen comprises one or more EBP treatments administered in an in-home setting, for example where a portable or wearable EBP device (e.g., equipped with automated priming, closed-loop anticoagulation, remote telemetry, and single use disposable circuits) is operated by, e.g., any of the subject, a live-in caregiver, or a visiting healthcare professional under telemedical supervision.

[0321]

[0303] Depending on the treatment environment for the EBP treatment, one will appreciate that different ancillary equipment (e.g., pumps, filters, adsorbent columns, replacement-fluid reservoirs) and procedural protocols may be selected, for example to match the scale of the environment, to ensure safety, promote efficacy, and comply with regulatory differences across inpatient, outpatient, and in-home use cases.

[0322]

[0304] Some exemplary treatment regimen embodiments follow, which will be understood to be illustrative and not limiting, and which will provide sufficient description for those of ordinary skill to determine additional embodiments for the practice of the disclosure. In embodiments, a treatment regimen comprises bi-weekly treatments, such as by administering one EBP treatment approximately every two weeks. In embodiments, a treatment regimen comprises semi-annual treatments, such as by administering two EBP treatments per year. In embodiments, a treatment regimen comprises quarterly treatments, such as by administering one EBP treatment approximately every quarter, for example one EBP treatment about every 90 days, such as for two, three, four, or more than four consecutive quarters. In embodiments, a treatment regimen comprises monthly treatments, such as by administering one EBP treatment approximately every month, for example, for two, three, four, five, six, seven, eight, nine, 10, or for more than 10 consecutive months. In embodiments, a treatment regimen comprises a “treatment-rest-treatment” regimen, such as by administering two sets of EBP treatments annually, each set comprising an EBP treatment, a rest period, and a second EBP treatment, for example where the first set is administered in the first half of the year and the second set is administered in the second half of the year. In embodiments, a treatment regimen comprises a “loading and maintenance” regimen, such as comprising a loading phase followed by a maintenance phase. In embodiments, for example, the loading phase comprises two bi-weekly EBP treatments, followed by a maintenance (“maint.”) phase comprising quarterly EBP treatments for the remainder of the year. In embodiments, the loading phase comprises one EBP treatment each month for two consecutive months, followed by quarterly EBP treatments.

[0323]

[0305] In embodiments, a treatment regimen comprises measuring an amount of PFAS in a biological matrix of a subject. In embodiments, a treatment regimen comprises measuring an amount of PFAS in an eluate of a subject. In embodiments, a treatment regimen comprises measuring the amount of PFAS in a biological matrix of a subject prior to a DFPP, plasmapheresis, or other EBP treatment. In embodiments, a method comprises assessing an amount of PFAS in a blood purification waste eluate, such as from a DFPP or other plasmapheresis eluate from a subject. In embodiments, a method comprises measuring an amount of PFAS in 2025-09-12 a biological matrix of a subject after a DFPP, plasmapheresis, or other EBP treatment.

[0324]

[0306] In embodiments, a method comprises (i) measuring an amount of PFAS in a biological matrix of a subject; and (ii) administering to the subject an EBP treatment. In embodiments, the method further comprises (iii) measuring an amount of PFAS in a blood purification eluate from the subject. In embodiments, the method further comprises (iv) measuring an amount of PFAS in a biological matrix of the subject post-treatment, such as after an EBP treatment, such as after a first EBP treatment, or after a subsequent EBP treatment.

[0325]

[0307] In embodiments, a method comprises (i) measuring an amount of PFAS in a biological matrix of a subject; and (ii) administering to the subject a DFPP treatment. In embodiments, the method further comprises (iii) measuring an amount of PFAS in a DFPP eluate from the subject. In embodiments, the method further comprises (iv) measuring an amount of PFAS in a biological matrix of the subject post-treatment, such as after a DFPP treatment, such as after a first DFPP treatment, or after another DFPP treatment.

[0326]

[0308] In embodiments, a treatment regimen is determined prior to the subject’s first DFPP, plasmapheresis, or other EBP treatment. In embodiments, a treatment regimen is determined by a measurement of a PFAS concentration in a blood purification (e.g., DFPP) eluate after the DFPP, plasmapheresis, or other EBP treatment. In embodiments, a treatment regimen is determined by a measurement of a PFAS concentration in a blood sample from a subject taken after a DFPP, plasmapheresis, or other EBP treatment.

[0327]

[0309] In embodiments, a treatment regimen comprises a diagnostic step (e.g., a clinical assessment of the subject). In embodiments, a treatment regimen comprises measuring PFAS concentrations in a pre-treatment blood sample, an eluate, and a post-treatment blood sample. In embodiments, a treatment regimen is determined by a subject’s progress towards a target level of PFAS amounts (e.g., a maximum concentration in the subject’s blood or eluate). In embodiments, a treatment regimen is updated after a subject’s EBP treatment, such as after the subject’s first DFPP treatment, or after a subsequent DFPP treatment.

[0328]

[0310] In embodiments, a treatment regimen comprises administering to a subject an anticoagulant during the subject’s DFPP, plasmapheresis, or other EBP treatment. Examples of suitable anticoagulants include citrate, heparin, argatroban, bivalirudin, fondaparinux, and danaparoid.

[0329]

[0311] In embodiments, a treatment regimen comprises an additional health treatment, i.e., a health treatment provided with the EBP treatment. In embodiments, the additional health treatment comprises a lifestyle intervention, a supplement, an adjunct oral therapy intervention or adjuvant therapeutic intervention, a pharmacological intervention (e.g., an oral therapy agent or other agent), a biologic or regenerative intervention, a nervous system or nervous system regulation intervention, a metabolic or endocrine adjunct intervention, an antimicrobial intervention, a detox-pathway support intervention or detoxification support intervention, a supportive health modality, a systemic bioenhancement therapy, a bioenergetic or conditioning intervention, or a carrier modulating intervention (e.g., an albumin modulating intervention).

[0330]

[0312] An additional health treatment, depending on the embodiment, may be provided before an EBP treatment; provided concurrently with an EBP treatment; provided after an EBP treatment; or provided in 2025-09-12 between EBP treatments (i.e., in a regimen comprising more than one treatment); or any combination thereof.

[0331]

[0313] In embodiments, the additional health treatment is a supplement. “Supplements” include compositions, formulations, and active ingredients thereof that support, enhance, or modulate one or more benefits of an EBP treatment, reduce one or more adverse effects of an EBP treatment, or provide one or more adjunct therapeutic, physiological, or symptomatic benefits with an EBP treatment, including to a condition comorbid with a PFAS-related condition because of which the EBP treatment is administered.

[0332]

[0314] In embodiments, the supplement is provided to the subject. “Providing” a supplement to a subject includes administering the supplement to the subject, instructing the subject to self-administer the supplement, choosing or selecting the supplement for the subject, directing the subject to obtain or acquire the supplement, giving the supplement to the subject, making the supplement available to the subject, and the like.

[0333]

[0315] In embodiments, the supplement is provided to the subject to reduce or to help reduce the amount of PFAS in a biological matrix of the subject, such as to enhance the reduction of the amount of PFAS by an EBP treatment. In embodiments, the supplement is effective to reduce the amount of PFAS.

[0334]

[0316] In embodiments, the supplement comprises a detoxification enzyme or an inducer, precursor, or cofactor thereof. In embodiments, the inducer is a phase II detoxification enzyme inducer, such as sulforaphane. In embodiments, the supplement comprises any of a cytochrome P450 enzyme, a flavin-containing monooxygenase, a sulfotransferase, a UDP-glucuronosyltransferase, an N-acetyltransferase, or a methyltransferase. In embodiments, the supplement comprises glutathione or a glutathione precursor.

[0335]

[0317] In embodiments, the additional health treatment is an oral binding agent (e.g., a chelation agent, ion-exchange resin, or bile acid sequestrant). In embodiments, the oral binding agent binds PFAS or a carrier molecule to which PFAS is bound, thereby forming a complex that can be excreted. In embodiments, the oral binding agent is an ion-exchange resin or a cyclodextrin, which acts as an oral sequestrant by binding PFAS in the gut and preventing reabsorption. In embodiments, the oral binding agent is a bile acid sequestrant such as cholestyramine which enhances PFAS elimination via feces by binding in the intestine.

[0336]

[0318] In embodiments, the additional health treatment is selected to reduce the amount of PFAS absorbed from the gastrointestinal tract, or to reduce the transport of PFAS across the gut lining. In embodiments, the additional health treatment is selected to improve the functioning of the immune system. In embodiments, the additional health treatment is selected to improve the functioning of a subject’s kidney or liver. In embodiments, the additional health treatment is selected to improve the ability to excrete PFAS.

[0337]

[0319] In embodiments, the supplement is any one or more of activated charcoal (i.e., activated carbon), zeolite, humic acid, chlorella, algae, pectin, a probiotic supplement, a Lactobacillus supplement, a Bifidobacterium supplement, L-glutamine, an amino acid, an amino acid with glutathione, taurine, L-carnitine, acetyl-L-carnitine, a neurotrophic peptide, a nootropic, nicotinamide adenine dinucleotide (NAD+), nicotinamide adenine dinucleotide hydride (NADH), coenzyme Q10 (CoQ10), N-acetyl-L-cysteine (NAC), reduced glutathione, alpha-lipoic acid (ALA), magnesium, selenium, zinc, vitamin C, vitamin D, vitamin E, a 2025-09-12 B-complex vitamin, an omega-3 fatty acid (EPA / DHA), tauroursodeoxycholic acid (TUDCA), ox bile, bitters, ginger, lion’s mane, bacopa, coriander, curcumin, quercetin, resveratrol, epigallocatechin gallate (EGCG), sulforaphane, astaxanthin, boswellia extract, an anti-inflammatory, an antioxidant, a prokinetic, or melatonin.

[0338]

[0320] In embodiments, the additional health treatment is an adjunct oral therapy intervention. Examples include dietary fiber, gel-forming fiber, oat B-glucan, pectin, acacia fiber, psyllium, bile-acid sequestrant, holestyramine, colesevelam, colestipol, activated carbon, zeolite, bentonite, chitosan, calcium alginate, sodium alginate, inulin, fructo-oligosaccharides, galacto-oligo- saccharides, resistant starch, phosphatidylcholine, and tauroursodeoxycholic acid.

[0339]

[0321] In embodiments, a treatment regimen comprises a lifestyle intervention. In embodiments, the lifestyle intervention comprises guidance for limiting exposure to PFAS. Lifestyle interventions include lifestyle changes, dietary changes, product choice changes, supplement choice changes and the like, for example to reduce or limit PFAS exposure in the environment or limit PFAS ingestion, such as through food or beverages. Examples include filtering water (e.g., portably, or by installing a whole-house water filter), restricting certain foods from the diet (e.g., seafood known to be high in PFAS), avoiding food and beverage containers made from plastic, avoiding certain uses of food and beverage implements made from plastic in cooking, limiting the use of clothing and home textiles made from plastic fibers, using a rebounder, and the like. Lifestyle interventions include methods and procedures recognized as promoting bodily detoxification, such as dry brushing, lymphatic drainage massage, vagal stimulation, intermittent hypoxia therapy, and intravenous (IV) infusion therapy. Lifestyle interventions include bioenergetic or conditioning interventions, such as sauna use, infrared sauna use, ozone therapy, hyperbaric oxygen therapy, red-light photobiomodulation (red light) therapy, pulsed-electromagnetic-field (PEMF) therapy, and structured exercise guided by heart-rate-variability (HRV) or similar metrics. Lifestyle interventions include nervous system regulation interventions, such as which optimize autonomic balance and stress resilience. Examples include structured breath-work (e.g., timed paced diaphragmatic breathing at about 4-6 breaths / minute), vagus nerve stimulation (e.g., auricular stimulation or a vagal neuromodulation device), HRV biofeedback sessions, sleep hygiene protocols, and craniosacral therapy.

[0340]

[0322] In embodiments, a treatment regimen comprises a metabolic or endocrine adjunct intervention. The metabolic or endocrine adjunct intervention may be hormone-replacement or modulation therapy (e.g., thyroid, sex steroids, estrogen / progesterone balancing adrenal support), nicotinamide adenine dinucleotide (NAD+) replenishment (e.g., IV NAD+infusions or precursors such as NMN), glucagon-like peptide- 1 receptor agonists (GLP-1s) administered at clinically approved or sub-therapeutic doses, mitochondrial optimization (e.g., CoQ10, PQQ, L-carnitine, ribose, magnesium), cell membrane stabilization (e.g., phosphatidylcholine, omega-3 fatty acids, vitamin E, sphingomyelin), and peptide therapeutics (e.g., BPC-157, thymosin 04, LL-37) such as delivered according to protocols that will be appreciated by those of skill.

[0341]

[0323] In embodiments, a treatment regimen comprises a biologic or regenerative intervention. Such interventions include autologous or allogeneic stem-cell therapy (e.g., mesenchymal stromal cells), 2025-09-12 platelet-rich plasma (PRP) therapy, and exosome-based therapy derived from conditioned media or purified extracellular vesicles. In embodiments, biologic or regenerative interventions enhance bodily repair efficacy.

[0342]

[0324] In embodiments, a treatment regimen comprises an anti-microbial intervention, such as to reduce systemic bioburden that synergizes with or exacerbates PFAS-related toxicities. Anti-microbial interventions include botanical and nutraceutical anti-microbial protocols (e.g., broad spectrum herbal antimicrobials such as berberine-containing extracts, allicin-rich garlic preparations, or oregano oil blends), targeted antifungal agents (e.g., caprylic-acid complexes or botanical terpenes), and antiviral botanicals (e.g., elderberry, Andrographis, or standardized polyphenol formulations).

[0343]

[0325] In embodiments, a treatment regimen comprises dental care, such as surgical or laser debridement of jaw-bone cavitations, or revision or removal of problematic root canal treated teeth.

[0344]

[0326] In embodiments, a treatment regimen comprises a gastrointestinal “cleanup” measure, such as an eradication protocol for small-intestinal bacterial overgrowth (SIBO) or dysbiosis, such as a combined herbal and low FODMAP approaches. It will be readily appreciated that additional health treatments may be in multiple categories, for example a low FODMAP diet also could be considered a lifestyle intervention.

[0345]

[0327] In embodiments, a treatment regimen comprises a detoxification pathway support intervention. Such support interventions include gut health support, bowel movement support and motility aids, lymphatic drainage support (e.g., manual techniques, rebound exercise), hepatic support (e.g., choleretics, methylation cofactors), and renal detoxification support (e.g., hydration protocols, nephron safe diuresis strategies).

[0346]

[0328] In embodiments, a treatment regimen comprises a detoxification therapy. Herein, “detoxification” or “detox” therapy refers to therapeutic interventions to reduce, remove, neutralize, sequester, or otherwise lessen the physiological burden of one or more toxicants in a subject’s body. Toxicants may be endogenous or exogenous and include PFAS and their adsorbed contaminants, heavy metals, persistent organic pollutants (e.g., phthalates), pathogenic metabolites, pro-inflammatory cytokines, oxidized lipids, metabolic waste products, and pharmacologic or environmental chemicals. In embodiments, a treatment regimen comprises a detoxification therapy to reduce the level of an endogenous toxicant. In embodiments, a treatment regimen comprises a detoxification therapy to reduce the level of an exogenous toxicant. In embodiments, a treatment regimen comprises a detoxification therapy to reduce the level of an exogenous toxicant other than PFAS.

[0347]

[0329] In embodiments, a treatment regimen comprises a carrier modulating intervention. PFAS may circulate in association with one or more carrier molecules in the biological matrix of a subject, including plasma proteins (e.g., albumin, cH-acid glycoprotein, transthyretin, sex hormone-binding globulin, thyroxine-binding globulin, fibrinogen, complement proteins), lipoprotein particles (e.g., HDL, LDL, VLDL, chylomicrons), and non-protein carriers (e.g., phospholipid micelles, extracellular vesicles such as exosomes and microvesicles, cellular membranes, microplastics, and surfactant complexes). A carrier modulating intervention refers to any process that affects PFAS binding, release, transport, partitioning, and / or bioavailability from a carrier before, during, or after an EBP session (e.g., DFPP, TPE, PA / PP, CPFA), such as 2025-09-12 by adjusting the concentration or turnover of carrier pools (e.g., protein or lipoprotein pools) within physiologic safety limits, introducing reversible competitor ligands to transiently occupy PFAS-interactive sites on carrier proteins, providing an alternative hydrophobic phase (e.g., a lipid emulsion) to promote PFAS partitioning prior to downstream capture, and modulating electrostatic environment (e.g., ionic strength, buffer composition, pH).

[0348]

[0330] In embodiments, the carrier modulating intervention is an albumin modulating intervention to influence the binding, release, transport, and / or availability of PFAS before, during, or after an EBP session (e.g., DFPP, TPE, PA / PP, CPFA). Herein, an “albumin-modulating intervention” refers to any process that (i) increases circulating albumin concentration, (ii) transiently and reversibly competes with PFAS for albumin binding sites to promote PFAS dissociation (“unloading”), (iii) provides an alternative hydrophobic phase to partition PFAS prior to capture, and / or (iv) tunes electrostatic conditions that affect albumin-PFAS interactions, while maintaining physiologic safety parameters. In embodiments, the albumin modulating intervention comprises a treatment schedule with a rest interval between two EBP treatments of about 24 hours to 72 hours, about 72 hours to 1 week, about 1 week to 2 weeks, about 2 weeks to 3 weeks, or about 3 weeks to 4 weeks to allow PFAS re-equilibration and natural albumin replenishment. In embodiments, the albumin modulating intervention comprises a treatment schedule with a rest interval between two EBP treatments of about 24 hours to 72 hours to allow PFAS re-equilibration and natural albumin replenishment.

[0349]

[0331] In embodiments, the albumin modulating intervention comprises an adjunct oral therapy. In embodiments, the adjunct oral therapy comprises one or more of dietary fiber, gel-forming fiber, oat B-glucan, pectin, acacia fiber, psyllium, bile-acid sequestrant, cholestyramine, colesevelam, colestipol, activated carbon, zeolite, bentonite, chitosan, calcium alginate, sodium alginate, inulin, fructo-oligosaccharide, galacto-oligosaccharide, resistant starch, phosphatidylcholine, and tauroursodeoxycholic acid.

[0350]

[0332] In embodiments, the albumin modulating intervention comprises a plasma albumin dialysis (e.g., single pass albumin dialysis) device in an EBP circuit to facilitate redistribution of PFAS from tissue stores to the intravascular compartment, to increase overall PFAS removal with EBP treatment. In embodiments, a plasma albumin dialysis module (e.g., Molecular Adsorbent Recirculating System (MARS®) is used, and plasma is dialyzed across a permeable membrane against a recirculating albumin dialysate (e.g., 5-25% HSA), with dialysate being regenerated continuously or intermittently by adsorbent beds configured to remove PFAS (see, e.g., Boyle et al. Grit Care. 2004;8(4):280-6; Schaefer et al. Nephrol Dial Transplant. 2011 ;26(11): 3633-9). In embodiments, albumin dialysate flow, residence time, and adsorbent bed capacity are selected to maintain a low PFAS activity in the dialysate, to enhance PFAS flux out of the plasma and into the dialysate. In embodiments, the albumin dialysate loop includes temperature control, pressure sensing, and bypass valving to maintain stability and to permit adsorbent exchange when saturation or breakthrough is detected.

[0351]

[0333] In embodiments, the albumin modulating intervention comprises exogenous human serum albumin (HSA) administration, such as administering a sterile HSA solution (e.g., 5%, 10%, 15%, 20%, 25% albumin) pre-, post-, and / or during an EBP treatment to maintain oncotic pressure and target albumin levels (e.g., 2025-09-12 greater than about 3.2— 3.5 g / dL) and / or provide an albumin “sink” that facilitates PFAS carriage toward a downstream capture step, such as an adsorption cartridge in a disclosed DFPP configuration. In embodiments, the HSA is a 5% albumin solution. In embodiments, the HSA is supplied in glass containers and delivered via low-sorption tubing. In embodiments, albumin lots are pre-screened to meet a PFAS content threshold prior to use, for example, using Liquid Chromatography / Tandem Mass Spectrometry (LC-MS / MS).

[0352]

[0334] In embodiments, the albumin modulating intervention comprises a reversible albumin binding competitor formulated and dosed to transiently occupy one or more albumin binding sites. In embodiments, the competitor increases an unbound fraction of PFAS for extracorporeal capture. The intervention may include administering, upstream of an adsorption module or other capture step, a competitor having reversible albumin affinity, and a short or controllable exposure window. Non-limiting classes include salicylates, short-chain fatty acids, aromatic amino acids, and other reversible ligands selected for any of safety, reversibility, dialyzability and removability by adsorption. In embodiments, the competitor is infused prior to or during an EBP treatment, and is removed during the same EBP treatment by adsorption, hemoperfusion, and / or dialytic clearance.

[0353]

[0335] In embodiments, the albumin modulating intervention comprises a lipid emulsion configured to partition hydrophobic or amphiphilic PFAS species prior to extracorporeal capture. The intervention may include administering a pharmacopeial lipid emulsion (e.g., 10-20%) at about 0.25-1.5 mL / kg, pre-EBP treatment or between EBP treatments, with capture accomplished by an adsorption cartridge and / or a hemoperfusion module placed downstream of an emulsion mixing point. In embodiments, packaging and fluid path are selected to minimize exogenous PFAS introduction.

[0354]

[0336] In embodiments, the albumin modulating intervention comprises adjustment of ionic strength within physiologic limits to tune electrostatic interactions between PFAS and albumin (see Bangma et al. Environ I nt. 2022; 159:107037). In embodiments, buffers (e.g., bicarbonate, phosphate), chloride concentration, and / or divalent cations (e.g., Ca2+, Mg2+) are controlled to promote PFAS dissociation while preserving coagulation and cell integrity. In embodiments, ionic strength adjustments are performed in a plasma line upstream of an adsorption module and are monitored by conductivity and pH sensors integrated into the circuit.

[0355]

[0337] In embodiments, the albumin modulating intervention comprises any of a plasma albumin dialysis module, an exogenous HSA, a reversible albumin binding competitor, a lipid emulsion, or an adjustment of ionic strength are administered pre-, post-, or during an EBP treatment. In embodiments, the albumin modulating interventions are staged relative to a second membrane so that, for example, bound and unbound PFAS enter an adsorption media prior to recombination with a cellular fraction.

[0356]

[0338] In embodiments, albumin safety is monitored and controlled by targeting serum albumin at or above about 3.0 g / dL, 3.2 g / dL, 3.5 g / dL, or 4.0 g / dL during and / or following one or more EBP treatments. In embodiments, where donor plasma is used, ABO compatibility and infectious disease screening is observed according to clinical standards. In embodiments, the albumin modulating intervention comprises assessing and optimizing the albumin status of a subject prior to an EBP treatment, including correcting hypoalbuminemia to 2025-09-12 at least about 3.0 g / dL, 3.2 g / dL, or 3.5 g / dL via nutrition, providing a rest interval between two or more EBP treatments, treating a smaller plasma volume (e.g., 0.75 plasma volume) and / or administering HSA.

[0357]

[0339] In embodiments, an albumin concentration of a subject is measured using a dye binding clinical chemistry assay (e.g., bromocresol green (BCG), bromocresol purple (BCP), an immunoturbidimetric assay, an immunonephelometric assay, an enzyme linked immunosorbent assay (ELISA), UV absorbance, serum protein electrophoresis (SPEP), high-performance liquid chromatography, or mass spectrometry (see. e.g., Choi et al. Clin Chim Acta. 2004 Jan;339(1 -2):147-56; Doumas et al. Clinica Chimica Acta. 1971 ;31 (1):87-96).

[0358]

[0340] In embodiments, co-ligands (e.g., free fatty acids, bilirubin, drugs that bind to albumin sites) are managed to reduce competitive displacement of PFAS during treatment. In embodiments, management includes a standardized pre-treatment window (e.g., fasting or controlled lipid intake), temporary adjustment of albumin dialysate concentration, or timing of concomitant medications.

[0359]

[0341] In embodiments, PFAS-laden waste (e.g., adsorber cartridges, eluates, dialysate regenerant) is captured, contained, and disposed or regenerated according to a compliant waste protocol. In embodiments, waste handling is regulated to prevent secondary PFAS release to the environment.

[0360]

[0342] In embodiments, metrics associated with the subject, such as functional health metrics, are assessed before and / or after a treatment, as well as, where applicable, between one or more lifestyle interventions, nervous system regulation interventions, metabolic or endocrine adjunct interventions, biologic or regenerative interventions, albumin modulating interventions, and anti-microbial interventions. In embodiments, the pre-, peri- and / or post-intervention values of the metrics, such as functional health metrics, are recorded, and are used to quantify treatment efficacy or determine further treatment, according to methods known in view hereof.

[0361]

[0343] In embodiments, “metrics associated with a treatment regimen” comprise one or more measurements obtained in a pre-treatment assessment or a post-treatment assessment, and where applicable, between treatment assessments. Such metrics (e.g., functional health metrics) may be assessed before and / or after one or more lifestyle interventions, nervous system regulation interventions, metabolic or endocrine adjunct interventions, biologic or regenerative interventions, albumin modulating interventions, detoxification pathway interventions, bioenergetic or conditioning interventions, carrier modulating interventions, and anti-microbial interventions. In embodiments, the values of the metrics are recorded and used to quantify treatment efficacy and / or to or determine further treatment, e.g., adjust one or more parameters of the EBP treatment regimen.

[0362]

[0344] In embodiments, a treatment regimen comprises a health status examination. A health status examination may comprise any one or more of a medical history review, a physical health examination (e.g., a fitness test, a strength test), a gut microbiome test, an environmental toxin test, a mental health examination, a cognitive examination, and a measurement of vital signs (e.g., blood pressure, heart rate, respiratory rate, and temperature). A health status examination may comprise an assessment.

[0363]

[0345] In embodiments, a health status examination comprises an exogenous toxin assessment. An exogenous toxin assessment may include measuring a concentration of PFAS or co-transported toxicants that 2025-09-12 adsorb to or are carried by PFAS, including heavy metals (e.g., lead, mercury, cadmium, arsenic), phthalate metabolites, and other persistent organic pollutants.

[0364]

[0346] In embodiments, a health status examination comprises a blood panel. Blood panels may comprise any one or more of a complete blood count, basic metabolic panel, comprehensive metabolic panel, lipid panel, thyroid function test, hemoglobin A1 C, C-reactive protein panel, and erythrocyte sedimentation rate test. A blood panel may comprise a small blood count. A small blood count may comprise measuring the levels of any one or more of haematocrit, coagulation, fibrinogen, and electrolytes. A small blood count may comprise a PT / INR (prothrombin time / international normalized ratio) test or a PTT (partial thromboplastin time) test.

[0365]

[0347] In embodiments, a health status examination comprises a cardiovascular health panel. A cardiovascular health panel may comprise any of a 12-channel electrocardiogram, an echocardiogram, an exercise stress test, a carotid ultrasound, an ankle-brachial index measurement, a cardiac MRI, a CT angiography, a tilt test, and a pulse wave velocity test.

[0366]

[0348] In embodiments, a health status examination comprises a renal health panel. A renal health panel may comprise an analysis of serum creatine, blood urea nitrogen, glomerular filtration rate, blood electrolyte concentration, blood calcium and phosphorus concentration, and blood albumin. A renal health panel may comprise a urinalysis, proteinuria analysis, or urine albumin-to-creatinine ratio analysis. A renal health panel may comprise an analysis of urine collected over a 24-hours. A renal health panel may comprise a renal scan.

[0367]

[0349] In embodiments, a health status examination comprises an aging biomarker panel. In embodiments, disclosed EBP treatments can slow, halt, or reverse biological aging progresses in cells, tissues, organs, or systems, in manners specific thereto, addressing and reflecting the distinct environments, stresses, and genetic and regulatory architectures of individuals. Aging biomarkers include measurable indicators of an aging state or condition, including specific to an organ or system. Biological age assessments may be made with one or with a plurality of aging biomarkers, including with an increased number of biomarkers to increase the accuracy of the biological age assessment. An aging biomarker panel may comprise any of an antibody assay, an antinuclear antibody (ANA) screen (IFA) with reflex to titer assay, a rheumatoid factor assay, a thyroid peroxidase antibody (anti-TPO) assay, a quantitative immunoglobulin assay, a proteomic assay, a fibrinogen assay, a creatinine kinase assay, a hemoglobin A1 C assay, a metabolomic assay, a direct LDL assay, a HDL cholesterol assay, a total cholesterol assay, a blood glucose assay, and urine analyses.

[0368]

[0350] In embodiments, a health status examination comprises a fertility health panel. In embodiments, a fertility health panel is a male fertility health panel. A male fertility health panel may comprise any of an erectile dysfunction analysis, a semen analysis, sperm function analysis, a scrotal ultrasound, and a male fertility blood hormone test. A semen analysis may comprise any of an assessment of sperm count, sperm motility, sperm morphology, semen composition, and volume. A sperm function analysis may comprise a sperm penetration assay, an acrosome reaction test, or a DNA fragmentation test. A male fertility hormone test may assess circulating levels of testosterone, follicle-stimulating hormone (FSH), luteinizing hormone, prolactin, or estradiol. 2025-09-12

[0369]

[0351] In embodiments, a fertility health panel is a female fertility health panel. A female fertility health panel may comprise any of an ovarian reserve test, a female fertility blood hormone test, and a pelvic ultrasound. An ovarian reserve test may comprise any of an antral follicle count and a clomiphene citrate challenge test. A female fertility blood hormone test may comprise assessing circulating levels of FSH, luteinizing hormone, estradiol, progesterone, prolactin, thyroid-stimulating hormone, and anti-Mullerian hormone.

[0370]

[0352] In embodiments, a health status examination comprises an assessment of erectile dysfunction (ED). An erectile dysfunction assessment may comprise any of ED-related blood tests, erectile function tests, and an ED-related psychological assessment. An ED-related blood test may comprise any one or more of testosterone level, lipid profile, blood glucose levels, thyroid hormone levels, and prolactin levels. An erectile function test may comprise any one or more of a nocturnal penile tumescence (NPT) test, an intracavernosal injection test, a doppler ultrasound of penile arteries and veins, dynamic infusion cavernosometry and cavernosography, and a penile biothesiometry test. An ED-related psychological assessment may comprise the International Index of Erectile Function (IIEF).

[0371]

[0353] In some embodiments, a health status examination comprises an endocrine health panel. An endocrine health assessment may comprise any one or more of a thyroid function test, an adrenal function test, a pituitary function test, a reproductive hormone test, a pancreatic function test, and a bone metabolism test. A thyroid function test may comprise any one or more of assessing circulating levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine, and a thyroid antibody test (e.g., thyroid peroxidase antibodies and thyroglobulin antibodies). An adrenal function test may comprise any one or more of assessing circulating levels of cortisol, adrenocorticotropic hormone, and aldosterone. A pituitary function test may comprise any one or more of assessing circulating levels of prolactin, growth hormone, and insulin-like growth factor 1. A reproductive hormone test may comprise any one or more of assessing circulating levels of testosterone follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, prolactin, thyroid-stimulating hormone, and anti-Mullerian hormone. A pancreatic function test may comprise any one or more of assessing circulating levels of insulin, c-peptide, and hemoglobin A1c. A bone metabolism test may comprise any one or more of assessing circulating levels of parathyroid hormone, calcium, and vitamin D.

[0372]

[0354] In some embodiments, a health status examination comprises a mental health assessment. A mental health assessment may comprise any one or more of the Generalized Anxiety Disorder Scale-7 (GAD-7), the Montgomery-Asberg Depression Rating Scale (MADRS), the Global Assessment of Functioning (GAF) Scale, the Clinical Global Impression (CGI), the Substance Abuse Questionnaire (SAQ), the Mini International Neuropsychiatric Interview 5 (MINI 5), the Columbia Suicide Severity Rating Scale (C-SSRS), the Patient Health Questionnaire (PHQ-9), the Pittsburgh Sleep Quality Index (PSQI), the Interpersonal Reactivity Index (IRI), the Short Form (36) Health Survey (SF-36), the Self-Compassion Scale (SCS), the Trauma History Questionnaire (THQ), the Beck Depression Index (BDI), and related subject- or observer-reported measures.

[0373]

[0355] Exemplary treatment regimens are provided. Further regimens will be readily appreciated by one of 2025-09-12 skill in view of the disclosure, such as by combining individual aspects and features of the exemplary treatment regimens to provide further treatment regimens, with combinations made according to the disclosure. 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12 2025-09-12

[0374]

[0356] Further treatment regimens according to the disclosure will be appreciated in view of the exemplary regimens, such as by combining individual aspects and features of the exemplary regimens to provide further such treatment regimens, with such combinations made according to ordinary skill and the teachings herein.

[0375]

[0357] For example, for each of the exemplary treatment regimens, in some alternative treatment regimens, rather than a DFPP treatment, another EBP treatment is provided, such as disclosed.

[0376]

[0358] For further example, for each of the exemplary treatment regimens, in some alternative treatment regimens, the post-treatment measurement of PFAS concentration after the first treatment, such as in a subject’s blood sample or in DFPP eluate, is not provided. In some alternative embodiments, only the posttreatment measurement of PFAS concentration after the last treatment is provided, such as after the second treatment where there are 2 treatments, after the third treatment where there are 3 treatments, and the like. In embodiments, where 3 or more treatments are provided, only the post-treatment measurement of PFAS concentration after the first treatment is not provided. In other embodiments, where 3 or more treatments are provided, the post-treatment measurement of PFAS concentration after the first treatment is provided, but no post-treatment measurement of PFAS concentration is provided again until after the last treatment.

[0377]

[0359] For each of the exemplary treatment regimens where “and / or” is used, in some embodiments “and / or” 2025-09-12 should be understood to mean “and.” In other such embodiments, “and / or” should be understood to mean “or.”

[0378]

[0360] For each of the exemplary treatment regimens where “any one or more of’ is used, in some embodiments “any one or more of’ should be understood to mean “one.” In other embodiments, “any one or more of’ should be understood to mean each integer between one and the total number of listed items, including the total number of listed items (i.e., the term will mean “all of the following”). In yet other embodiments, more than one of at least one listed item is intended, and the lists also shall be inclusive (i.e., the term will mean “comprising any one or more of”). In some embodiments, such lists will be exclusive (e.g., the term will mean “consisting of” or “consisting essentially of’ an integer number of items from the list).

[0379]

[0361] In embodiments, including each of the exemplary treatment regimens, a regimen may be dynamically adjusted for a subject in response to real-time or periodic assessments of one or more parameters, for example, biological matrix concentrations of PFAS and co-transported toxicants (e.g., heavy metals, PFAS, phthalates); inflammatory or immune biomarkers (e.g., CRP, IL-6, TNF-a); metabolic or endocrine markers (e.g., fasting glucose, thyroid panel, sex-steroid levels); physiologic metrics (e.g., heart-rate variability, blood pressure, renal function); validated symptom or performance scores; and the speciation of PFAS (e.g., the relative concentration and binding affinity of anionic carboxylates vs. sulfonates). In embodiments, any aspect of the regimen, including the number, sequence, timing, duration, and flow parameters of one or more DFPP or other EBP treatments; the selection, dose, or frequency of one or more agents, such as a supplement; the selection, dose, or frequency of lifestyle, nervous system, metabolic, endocrine, detox, and antimicrobial interventions; and the interval between successive interventions may be modified to optimize efficacy, minimize adverse effects, and achieve a target reduction in toxin load or a predefined clinical endpoint.

[0380]

[0362] In embodiments, including each of the exemplary treatment regimens, a regimen may be structured in sequential categories, such as: (1) prepare, (2) clear, (3) stabilize, and (4) improve, wherein each category comprises one or more interventions that are administered before, after, or between EBP treatments.

[0381]

[0363] In embodiments, a treatment regimen comprises a “prepare” phase, such as designed to optimize detoxification and immune readiness prior to systemic mobilization of toxicants, for example by addressing blocked elimination pathways (e.g., gut, liver, kidney, and lymphatic drainage), hidden inflammatory drivers (e.g., occult infections, mold exposure, dental cavitations), mitochondrial insufficiency, and autonomic dysregulation. Suitable therapeutics for the “prepare” phase may include drainage-support agents such as activated-carbon or zeolite binders, chlorella, agents that enhance bile flow (e.g., ox bile, TUDCA, bitters, phosphatidylcholine), and gastrointestinal-motility adjuncts (e.g., ginger, magnesium, pro- kinetic peptides); mitochondrial-priming agents; targeted anti-microbial programs; lymphatic- and circulatory- activation measures (e.g., sauna, dry-brushing, rebound exercise, manual lymph drainage, IV ozone, or hyperbaric-oxygen sessions); and nervous-system-regulation techniques (e.g., structured breath-work, transcutaneous vagus-nerve stimulation, HRV biofeedback, or craniosacral therapy). The “prepare” phase may be performed over a period ranging from about 1 day to several months or more, until, for example, laboratory 2025-09-12 or symptomatic indicators suggest adequate drainage capacity and autonomic readiness for toxin mobilization.

[0382]

[0364] In embodiments, a treatment regimen comprises a “clear” phase, such as to remove pathological and inflammatory burden from the bloodstream and interstitial matrix, for example by administering one or more EBP treatments, such as one or more DFPP (Inuspheresis®) treatments, that provide semi-selective plasma filtration while preserving albumin and endogenous immunoglobulins. In embodiments, the “clear” phase reduces auto-antibodies, immune complexes, viral or toxin debris, pro-inflammatory cytokines, oxidized lipids, coagulation factors, persistent spike protein, mycotoxins, heavy metals, PFAS, and microplastics. In embodiments, adjunctive therapeutics may be administered, including intravenous phosphatidylcholine for membrane repair, glutathione and amino-acid cocktails for phase-ll detoxification support, ultraviolet-blood irradiation or ozone autohemotherapy for immunomodulation, vagus-nerve stimulation for autonomic balance, and gentle oral binders to capture mobilized toxicants in the gastrointestinal tract.

[0383]

[0365] In embodiments, a treatment regimen comprises a “stabilize” phase to restore cellular resilience and immune equilibrium while the subject remains in a post-apheresis state of lowered inflammatory tone. Suitable therapeutics include mitochondrial-rehabilitation infusions (e.g., intravenous B-complex vitamins, magnesium, amino acids, CoQ10, NAD+, ribose, methylene blue, and polyphenolic antioxidants) optionally combined with PEMF, photobiomodulation, or hyperbaric-oxygen therapy; immune-modulating agents such as low-dose naltrexone, thymic peptides, p-glucans, and immune-supportive botanicals (e.g., Reishi, astragalus, Andrographis); membrane- and myelin-repair nutrients (e.g., phosphatidylcholine, omega-3 fatty acids, sphingomyelin, choline, lecithin, vitamin E); antioxidant and anti-inflammatory repletion (e.g., glutathione, N-acetyl-cysteine, alpha-lipoic acid, curcumin, boswellia, sulforaphane); and emotional and / or neurological supports such as neural-retraining protocols, neurofeedback, or somatic-experiencing therapy.

[0384]

[0366] In embodiments, the treatment regimen comprises an “improve” phase. In embodiments, once a subject’s inflammatory load is reduced and metabolic resilience restored, the “improve” phase includes regeneration, performance enhancement, and long-term health optimization. Such means include regenerative biologies (e.g., autologous or allogeneic stem-cell infusions, exosome preparations, platelet-rich plasma, and tissue-healing peptides such as BPC-157, thymosin 04, or LL-37); hormone-balancing interventions (e.g., sex-steroid, thyroid, or adrenal-axis optimization, with optional peptide secretagogues); cognitive or neuro-enhancement agents (e.g., lion’s-mane mushroom, Bacopa monnieri, acetyl-L-carnitine, nootropic peptides such as Dihexa); metabolic-optimization strategies (e.g., berberine, metformin, GLP-1 agonists, intermittent-fasting or fasting-mimicking protocols); and lifestyle interventions (e.g., cold exposure, red-light therapy, sauna, HRV-guided exercise, wearable-tracked activity programs, circadian-rhythm re-balancing, and structured sleep-hygiene interventions). In embodiments, the “improve” phase is maintained indefinitely or cycled periodically, with periodic reassessment of PFAS burden, co-contaminant levels, and functional health metrics to determine the need for repeat “clear” phase or tailored maintenance therapy. 2025-09-12

[0385] G. Treatment of Medical Conditions by Extracorporeal Blood Purification

[0386]

[0367] In some aspects are disclosed methods of treating a subject by administering a DFPP, plasmapheresis, or other extracorporeal blood purification (EBP) treatment. In embodiments, administering a disclosed EBP treatment to a subject treats a condition, such as a disease or disorder.

[0387]

[0368] In embodiments, a subject has a symptom caused by or associated with the presence of PFAS in a biological matrix (“PFAS-related symptom”). In embodiments, the PFAS-related symptom is caused by or associated with a diagnosed or diagnosable condition. In embodiments, the PFAS-related symptom is caused by or associated with a diagnosed or diagnosable condition, where the condition is caused by or associated with the presence of PFAS in the biological matrix of the subject (“PFAS-related condition”). In embodiments, the subject is at risk of a PFAS-related condition, such as a diagnosed or diagnosable disease or disorder. In embodiments, a subject has an increased risk (e.g., increased relative risk) of developing a PFAS-related condition, of being diagnosed with a PFAS-related condition, or of developing a PFAS-related symptom.

[0388]

[0369] In embodiments, administering a disclosed EBP treatment to a subject treats a condition by reducing or improving one or more symptoms of the condition. For any condition treatable by the disclosed methods, the symptoms of the condition will be ascertainable by those of skill, such as by reference to the general knowledge in the art, e.g., using the International Classification of Diseases 11th Revision (ICD-11), or with knowledge otherwise available to a physician or other medical professional in their ordinary practice.

[0389]

[0370] In embodiments, a subject has symptoms caused by or associated with a condition that is not be etiologically linked to PFAS. In such embodiments, the presence of PFAS in the subject’s biological matrix may nevertheless contribute to or exacerbate one or more such symptoms through secondary mechanisms such as chronic inflammation, oxidative stress, endocrine disruption, and immune dysregulation. In embodiments, the symptoms are caused by or associated with a diagnosed or diagnosable condition (e.g., a monogenic disorder, an acute infectious disease, or an autoimmune flare) that is not directly attributed to PFAS but where the clinical burden may be heightened by the presence of PFAS in the body.

[0390]

[0371] In embodiments, a subject is at risk of such a condition, or at risk of worsened outcomes from such a condition, because PFAS impair the subject’s capacity to mount an adequate physiological or immune response. In embodiments, a subject has an increased relative risk of developing symptoms of the condition, of experiencing greater severity of the condition, of responding sub-optimally to conventional therapies typically used to treat the condition, of failing to achieve durable remission after otherwise adequate treatment, or of being (re)diagnosed with the condition due to elevated PFAS load. In embodiments, administering a treatment to a subject may prevent, mitigate, or treat the condition by reducing or improving one or more symptoms of the condition and / or by lowering the inflammatory and immunologic burden imposed by PFAS, thereby enhancing the body’s capacity to resist, respond to, or recover from the condition.

[0391]

[0372] In embodiments, a subject has a cardiovascular condition or a cardiometabolic condition, such as heart disease, atherosclerosis, hypertension, dyslipidemia, hypertension, atherosclerotic plaque, thrombosis, 2025-09-12 arrhythmias, insulin resistance, obesity, diabetes, and metabolic syndrome. In embodiments, a subject is at risk of a cardiovascular condition or a cardiometabolic condition. Diagnosing or determining a risk of cardiovascular condition or a cardiometabolic condition are known to those of skill. In embodiments, a disclosed EBP treatment treats a cardiovascular condition or a cardiometabolic condition in a subject. Measures of improvement of cardiovascular conditions and cardiometabolic conditions are known to those of skill, and include a change in low-density lipoprotein cholesterol (LDL-C), triglycerides, high-sensitivity C-reactive protein (hsCRP), apolipoprotein B (ApoB), lipoprotein(a) [Lp(a)], Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), carotid intima-media thickness, and quality-of-life indices. In embodiments, improvement of cardiovascular or cardiometabolic condition in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0392]

[0373] In embodiments, treatment is for stroke, including for a subject who had a stroke, who has a symptom or condition caused by or associated with having had a stroke, and for a subject at risk of a stroke, including at a high risk of stroke, all of which may be referred to as a “stroke-related condition.” In embodiments, a subject has a stroke-related condition. Diagnosing or determining a risk of a stroke are known to those of skill. In embodiments, an EBP treatment treats a stroke-related condition in a subject. Measures of improvement of a stroke-related condition are known to those of skill, and include a change in NIH Stroke Scale (NIHSS), modified Rankin Scale (mRS), Barthel Index, Fugl-Meyer motor score, gait speed, 6-minute walk distance, Montreal Cognitive Assessment (MoCA), language performance indices, dysphagia assessments including bedside swallow or modified barium swallow findings, neuroimaging markers including infarct volume on diffusion-weighted imaging or fluid-attenuated inversion recovery and perfusion parameters including cerebral blood flow, cerebral blood volume, and mean transit time, transcranial Doppler flow velocities, carotid duplex findings, thromboinflammatory biomarkers including D-dimer, fibrinogen, von Willebrand factor, and platelet activation markers, and validated QOL indices. In embodiments, a stroke-related condition in a subject is improved because of a reduction in the amount of PFAS in the biological matrix of the subject.

[0393]

[0374] In embodiments, a subject has thrombosis. In embodiments, a subject is at risk of thrombosis. Diagnosing or determining a risk of thrombosis is known to those of skill. In embodiments, a disclosed EBP treatment treats thrombosis in a subject. Measures of improvement of thrombosis are known to those of skill, and include a change in one or more of D-dimer, fibrinogen, platelet-activation markers, thromboelastography or rotational thromboelastometry parameters, neurologic deficit scales, infarct volume or perfusion imaging metrics, exacerbation or hospitalization rate, and validated QOL indices. In embodiments, improvement of thrombosis in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0394]

[0375] In embodiments, a subject has a respiratory disease. In embodiments, a subject is at risk of a respiratory condition. Diagnosing or determining a risk of a respiratory condition (e.g., that a subject has an increased risk of developing the condition) is known to those of skill. Examples of respiratory conditions that may be treated by EBP include bronchitis and other forms of airway inflammation, asthma and other allergic 2025-09-12 respiratory responses, and fibrosis (e.g., pulmonary fibrosis). In embodiments, a disclosed EBP treatment treats a respiratory condition in a subject. Measures of improvement of a respiratory condition are known to those of skill, and include a change in one or more of forced expiratory volume in one second (FEVi), the FEVi / forced vital capacity ratio (FEVi / FVC), forced vital capacity (FVC), peak expiratory flow (PEF) or diurnal PEF variability, diffusing capacity of the lung for carbon monoxide (DLCO), total lung capacity (TLC) and residual volume (RV), rescue-inhaler use or systemic corticosteroid requirement, blood or sputum eosinophil count, fractional exhaled nitric oxide (FeNO), oxygen saturation or arterial blood gases (PaO2, PaCO2), six-minute walk distance (6MWD), exacerbation frequency, emergency visit or hospitalization rate, and validated disease control or quality-of-life indices including the Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), COPD Assessment Test (CAT), and St. George’s Respiratory Questionnaire (SGRQ). In embodiments, improvement of a respiratory condition in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0395]

[0376] In embodiments, a subject has acute or chronic inflammation, an inflammatory condition such as a chronic inflammatory condition, or an inflammatory disorder (together as shorthand, “inflammation”). In embodiments, a subject is at risk of inflammation. Examples of inflammation that may be treated by EBP include both acute and chronic inflammation, as well as disorders and conditions involving inflammation, wherein the inflammation involves or is any one or more of skin inflammation, muscle inflammation, tendon inflammation, ligament inflammation, bone inflammation, cartilage inflammation, lung inflammation, heart inflammation, liver inflammation, pancreatic inflammation, kidney inflammation, bladder inflammation, gastric inflammation, intestinal inflammation, neuroinflammation, gout, and brain inflammation. Diagnosing or determining a risk of inflammation is known to those of skill. In embodiments, a disclosed EBP treatment treats inflammation in a subject. Measures of improvement of inflammation, such as a reduction in inflammation, including chronic inflammation, are known in the art, e.g., inflammatory biomarkers may be detected from biological specimens, for example, a subject’s blood, such as plasma or serum, or saliva. Inflammation may be detected by measuring high-sensitivity C-reactive protein (CRP) and white blood cell count from a blood test. CRP may also be detected in a saliva sample. Salivary CRP is not synthesized locally in the mouth and may reflect more systemic levels of inflammation compared to other inflammatory biomarkers, such as cytokines (Szabo & Slavish. Psychoneuroendocrinol. 202; 124: 105069). Additionally clinical pathology data, e.g., hematology data on erythrocyte parameters, platelet count, total number of leukocytes, and leukocyte differentials and morphology, coagulation data on clotting times and fibrinogen, and clinical chemistry data on total protein, albumin and globulin, liver enzymes, renal parameters, electrolytes, and bilirubin can provide an initial indication of the presence and potentially the location of inflammation, in the absence of specific data on immune tissues. See, e.g., Germolec et al. Methods Mol Biol. 2018; 1803: 57-79 and Luo et al. Clin Lab. 2019;65(3):10.7754 / Clin.Lab.2018.180715. In embodiments, improvement of inflammation in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject. 2025-09-12

[0396]

[0377] In embodiments, a subject has an immunological condition. In embodiments, a subject is at risk of an immunological condition. Diagnosing or determining a risk of an immunological condition is known to those of skill. In some embodiments, the immunological condition is an autoimmune disorder or an autoimmune disease. Herein, the terms “autoimmune disorder” “autoimmune condition” and “autoimmune disease” are used interchangeably unless the context indicates otherwise, as are the terms “disease” and “disorder.” Autoimmune conditions (e.g., diseases) that may be treated by EBP include arthritis (e.g., rheumatoid arthritis), diabetes, multiple sclerosis, psoriasis, inflammatory bowel disease, Hashimoto’s thyroiditis, increased infection susceptibility, weakened immune response, general systemic inflammation, chronic inflammation, multiple chemical sensitivity syndrome, and lupus. In embodiments, a disclosed EBP treatment treats an autoimmune disease or another immunological disease in a subject. Measures of improvement of an autoimmune disease or another immunological disease are known to those of skill, and include a change in one or more of high-sensitivity C-reactive protein (hsCRP), CRP, erythrocyte sedimentation rate (ESR), serum amyloid A (SAA), ferritin, fibrinogen, interleukin concentrations (e.g., IL-i p, IL-6, IL-8, and IL-10), interferon-gamma (IFN-y), tumor necrosis factor-alpha (TNF-a), chemokines including CXCL9 and CXCL10 with i Age surrogates or CXCL9 percentile, complement factors C3 and C4 and activation fragments C3a and C5a, immunoglobulins including IgG, IgA, IgM, and IgE, autoantibody titers including antinuclear antibodies, anti-double-stranded DNA, anti-cyclic citrullinated peptide, and rheumatoid factor, leukocyte counts and ratios (e.g., absolute lymphocyte count and neutrophil-to-lymphocyte ratio), flow-cytometric immunophenotyping (e.g., CD4 / CD8 ratio, naive and memory T-cell subsets), regulatory T cells, natural killer cell counts or activity, B-cell and monocyte subsets with HLA-DR expression, validated disease activity indices (e.g., DAS28, CDAI, SDAI, BASDAI, SLEDAI, and PASI), and validated quality-of-life indices. In embodiments, improvement of an autoimmune disease or another immunological disease in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0397]

[0378] In embodiments, a subject has cancer. In embodiments, a subject is at risk of cancer. Diagnosing or determining a risk of cancer is known to those of skill. Cancers that may be treated by EBP include breast cancer, lung cancer, testicular cancer, prostate cancer, colorectal cancer, renal cell carcinoma, thyroid cancer, and skin cancer. In embodiments, a disclosed EBP treatment treats cancer in a subject. Measures of improvement of cancer are known to those of skill. In embodiments, improvement of cancer in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0398]

[0379] In embodiments, a subject has a mental health condition. In embodiments, a subject is at risk of a mental health condition. Diagnosing or determining a risk of a mental health condition is known to those of skill. Mental health conditions treatable by the disclosure include post-traumatic stress disorder (PTSD), adjustment disorder, affective disorder, a depressive disorder such as major depressive disorder (MDD) and treatment-resistant depression (TRD), atypical depression, postpartum depression, catatonic depression, a depressive disorder due to a medical condition, premenstrual dysphoric disorder, seasonal affective disorder, 2025-09-12 dysthymia, an anxiety disorder such as generalized anxiety disorder (GAD), a phobia disorder, a binge disorder, body dysmorphic disorder, alcohol or drug abuse or dependence disorders, a behavioral addiction, a substance use disorder (SUD), a substance-induced mood disorder, a mood disorder related to another health condition, a disruptive behavior disorder, an eating disorder, an impulse control disorder, obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), a personality disorder, an attachment disorder, and a dissociative disorder. In embodiments, a disclosed EBP treatment treats a mental health disorder in a subject. Measures of improvement of a mental health condition are known in the art and include the Generalized Anxiety Disorder Scale-7 (GAD-7), the Montgomery-Asberg Depression Rating Scale (MADRS), the Global Assessment of Functioning (GAF) Scale, the Clinical Global Impression (CGI), the Substance Abuse Questionnaire (SAQ), the Mini International Neuropsychiatric Interview 5 (MINI 5), the Columbia Suicide Severity Rating Scale (C-SSRS), the Patient Health Questionnaire (PHQ-9), the Pittsburgh Sleep Quality Index (PSQI), the Interpersonal Reactivity Index (IRI), the Short Form (36) Health Survey (SF-36), the Self-Compassion Scale (SCS), the Trauma History Questionnaire (THQ), the Beck Depression Index (BDI), and related subject- or observer-reported measures. In embodiments, improvement of a mental health condition in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0380] In embodiments, a subject has a neurodegenerative condition. In embodiments, a subject is at risk of a neurodegenerative condition. Diagnosing or determining a risk of a neurodegenerative condition is known to those of skill. Neurodegenerative conditions that may be treated by EBP include Alzheimer’s disease, amyotrophic lateral sclerosis or Charcot’s disease, chronic traumatic encephalopathy, corticobasal degeneration, dementias including vascular dementia, Huntington’s disease, Lytico-Bodig disease, mild cognitive impairment, multiple sclerosis, a motor neuron disease, neuromyelitis optica spectrum disorder, Parkinson’s disease or Parkinsonisms, prion diseases, progressive supranuclear palsy, and traumatic brain injury. In embodiments, a disclosed EBP treatment treats a neurodegenerative condition in a subject. Measures of improvement of a neurodegenerative condition are known to those of skill, and include a change in one or more of neurocognitive test performance including Montreal Cognitive Assessment, processing-speed and executive-function scores; functional status indices including activities of daily living and instrumental activities of daily living; validated mental-health scales including depression, anxiety, and post-traumatic stress symptom scores; sleep-quality or sleep-architecture metrics; autonomic markers including heart-rate variability, baroreflex sensitivity, or orthostatic-tolerance testing; gait, balance, and motor-function measures including timed up-and-go, gait speed, posturography, or Unified Parkinson Disease Rating Scale; neuroinflammatory biomarkers; neurodegeneration biomarkers including plasma or cerebrospinal-fluid neurofilament light chain, glial fibrillary acidic protein, total tau, phosphorylated tau, or amyloid-beta 42:40 ratio; imaging-based biomarkers including magnetic-resonance volumetry, cortical thickness, diffusion-tensor metrics, or positron-emission-tomography uptake; and olfactory testing. In embodiments, improvement of a neurodegenerative condition in a subject results from a reduction in the 2025-09-12 amount of PFAS in the biological matrix of the subject.

[0399]

[0381] In embodiments, a subject has pain or a pain condition. In embodiments, a subject is at risk of pain or a pain condition. Diagnosing or determining a risk of thereof is known to those of skill. Examples of pain and pain condition, that may be treated by EBP, include arthritis, allodynia, atypical trigeminal neuralgia, trigeminal neuralgia, somatoform disorder, hypoesthesia, hyperalgesia, neuralgia, neuritis, neurogenic pain, phantom limb pain, analgesia, anesthesia dolorosa, causalgia, sciatic nerve pain disorder, degenerative joint disorder, fibromyalgia, visceral disease, chronic pain disorders, headache disorders, migraine headaches, chronic cluster headaches, concussion headache, short-lasting unilateral neuralgiform headache attacks, chronic fatigue syndrome, complex regional pain syndrome, neurodystrophy, plantar fasciitis, or pain associated with cancer. In embodiments, a disclosed EBP treatment treats pain or a pain condition in a subject. Measures of improvement of pain or a pain condition, such as chronic pain, or pain associated with a pain disorder, are known in the art, e.g., by subject reporting, pain diaries, pain scales, applicable questionnaires (assessments of chronic pain and its impact on physical, emotional and social functions), ecological momentary assessments and computerized versions thereof. See, e.g., Salaffi et al. Best Practice & Research Clinic Rheumatol. 2015; 29(1): 164-186 and Hawker et al. Arthritis Care Res (Hoboken). 2011 ;63 Suppl 11 :S240-52. Exemplary questionnaires include the Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP), Migraine Diagnosis Questionnaire, the Migraine-Screen Questionnaire (MS-Q), the Fibromyalgia Survey Questionnaire (FSQ). In embodiments, improvement of pain or a pain condition in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0400]

[0382] In embodiments, improving a pain condition is evidenced by a change in one or more of fender point count, pressure pain threshold and other quantitative sensory testing metrics, conditioned pain modulation efficiency, temporal summation metrics, range of motion, activity or step count, sleep quality indices, daily analgesic or opioid consumption, medication use, inflammatory biomarkers including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), cytokines including interleukin-6 (IL-6), interleukin-1 p (IL-1 P), and tumor necrosis factor-alpha (TNF-a), neuroinflammation or glial markers including glial fibrillary acidic protein (GFAP) and SWOB, oxidative-stress markers including F2-isoprostanes and 8-hydroxy-2'-deoxyguanosine (8-OHdG), autonomic indices including heart-rate variability (HRV), and validated quality-of-life (QOL) indices.

[0401]

[0383] In embodiments, a subject has a blood condition or disorder. In embodiments, a subject is at risk of a blood condition or disorder. Diagnosing or determining a risk of a blood condition or a blood disorder is known to those of skill. Blood conditions that may be treated by EBP include acute lymphocytic leukemia, acute myelogenous leukemia, amyloidosis, anemia, antiphospholipid syndrome, aplastic anemia, autoimmune hemolytic anemias, autoimmune thrombocytopenia, benign hematologic conditions, bleeding disorders, castleman disease, chronic lymphocytic leukemia, chronic myelomonocytic leukemia, cryoglobulinemia, cutaneous 2025-09-12 T-cell lymphoma, essential thrombocythemia, fanconi anemia, hairy cell leukemia, hemoglobinopathies, hemophilia, hereditary hemolytic anemias, hodgkin lymphoma, hypereosinophilic syndrome, immune thrombocytopenia (ITP), iron deficiency anemia, large granular lymphocyte disorders, macroglobulinemia, monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma, myelodysplastic syndromes, myelofibrosis, myeloproliferative disorders, natural killer cell leukemia, non-hodgkin’s lymphoma, osteosclerotic myeloma, paroxysmal nocturnal hemoglobinuria, pediatric thrombo- cytopenia, pediatric white blood cell disorders, POEMS syndrome, polycythemia vera, sickle cell anemia, systemic capillary leak syndrome, systemic mastocytosis, thalassemia, thrombocytopenia (low platelet count), thrombocytosis, vitamin deficiency anemia, Von Willebrand disease, Waldenstrom macroglobulinemia, and white blood cell disorders. In embodiments, an EBP treatment to remove PFAS treats a blood condition in a subject. Measures of improvement of a blood condition are known to those of skill. In embodiments, improvements of a blood condition in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0402]

[0384] In embodiments, improving a blood condition is evidenced by a change in one or more of hemoglobin, hematocrit, red blood cell indices including mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width, reticulocyte count, peripheral smear morphology, white blood cell count and differential, platelet count and mean platelet volume, iron studies including serum ferritin, serum iron, transferrin, total iron-binding capacity, and transferrin saturation, vitamin B12 and folate, hemolysis markers including lactate dehydrogenase, haptoglobin, indirect bilirubin, plasma free hemoglobin, and serum potassium, coagulation parameters including prothrombin time, international normalized ratio, activated partial thromboplastin time, and fibrinogen, global hemostasis testing including thromboelastography or rotational thromboelastometry parameters, D-dimer, platelet function testing including PFA-100 closure time and light transmission aggregometry, von Willebrand factor activity and antigen, factor assays including factors VIII and IX, ADAMTS13 activity, antiphospholipid antibodies, erythropoietin level, blood viscosity and erythrocyte deformability indices, inflammatory markers including C-reactive protein and erythrocyte sedimentation rate, hemoglobin electrophoresis fractions including HbA, HbF, and variant hemoglobins, and validated quality-of-life indices.

[0403]

[0385] In embodiments, a subject has a fertility condition. In embodiments, a subject is at risk of a pregnancy condition. Diagnosing or determining a risk of a fertility or pregnancy condition is known to those of skill. Examples of fertility conditions that may be treated by EBP include cystic fibrosis, Tay-Sachs disease, spinal muscular atrophy, Canavan disease, sickle cell disease, thalassemias, Turner syndrome, Klinefelter syndrome, polycystic ovary syndrome (PCOS), overactive thyroid gland, underactive thyroid gland, premature ovarian failure, fibroids, endometriosis, pelvic inflammatory disease (PID), primary ovarian insufficiency disorder, testicular infection, ejaculation disorder, chlamydia, gonorrhea, and hypogonadism. In embodiments, the fertility condition is a male fertility disorder, including any impairment of male reproductive function, such as abnormalities in sperm count, motility, or morphology, semen volume, or semen composition. In embodiments, 2025-09-12 the male fertility condition comprises oligospermia, azoospermia, asthenozoospermia, teratozoospermia, hypospermia, or abnormal semen composition. In embodiments, improvements of a fertility or pregnancy condition in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0404]

[0386] In embodiments, improving a fertility condition is evidenced by a change in one or more of semen analysis parameters including semen volume, pH, sperm concentration, total motile sperm count, progressive motility, morphology by strict criteria, computer-assisted sperm analysis kinematics, sperm DNA fragmentation index, high DNA stainability, oxidative-reduction potential, and leukocytospermia, male endocrine markers including FSH, luteinizing hormone (LH), total or free testosterone, estradiol, inhibin B, sex hormone-binding globulin (SHBG), prolactin, thyroid-stimulating hormone (TSH), free thyroxine (free T4), female ovarian-reserve and ovulatory metrics including anti-Mullerian hormone (AMH), antral follicle count, day-3 FSH, LH, estradiol, mid-luteal progesterone, luteal-phase length, basal-body-temperature pattern, ovulation-predictor results, and follicular and endometrial ultrasound measures including dominant-follicle growth and endometrial thickness, assisted-reproduction outcomes including number of oocytes retrieved, mature oocyte rate, fertilization rate, cleavage rate, blastocyst formation rate, euploidy rate, embryo-quality scores, implantation rate, clinical pregnancy rate, ongoing pregnancy rate, live birth rate, and miscarriage rate, time-to-pregnancy, cycle regularity, dysmenorrhea or menorrhagia scores, uterine-receptivity markers, cervical-mucus quality, reproductive inflammatory and metabolic markers including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a), homocysteine, fasting insulin, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and validated fertility-specific quality-of-life indices including FertiQoL.

[0405]

[0387] In embodiments, a subject has an epigenetic alteration. Diagnosing or determining a risk of an epigenetic alteration is known to those of skill. Examples of epigenetic alterations that may be treated by EBP include aberrant DNA-methylation patterns, histone modifications, and changes in non-coding-RNA expression. In embodiments, the epigenetic alterations are transgenerational, i.e., transmissible through the germ line and conferring increased risk of subfertility, metabolic dysfunction, or reduced health span in offspring. In embodiments, PFAS present in the parental biological matrix contributes to epigenetic alterations (see Liu et al. Front Cell Dev Biol. 2025 Feb 28;13:1562331 ). In embodiments, normalization of germline epigenetic marks results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0406]

[0388] In embodiments, a subject has erectile dysfunction (ED). In embodiments, a subject is at risk of ED. Diagnosing or determining a risk of ED is known to those of skill. In embodiments, a disclosed EBP treatment treats erectile dysfunction in a subject. Measures of improvement of erectile dysfunction are known to those of skill, and include a change in one or more of International Index of Erectile Function— Erectile Function domain (IIEF-EF) score, Sexual Health Inventory for Men (SHIM) score, Erection Hardness Score (EHS), Sexual Encounter Profile (SEP) diary Q2 and Q3 success rates, nocturnal penile tumescence and rigidity metrics by RigiScan including event count and duration and base / tip rigidity, penile duplex Doppler ultrasound parameters including peak systolic velocity, end-diastolic velocity, and resistive index at rest and after 2025-09-12 pharmacostimulation, penile-brachial index, endothelial function measures including flow-mediated dilation, serum hormones including total testosterone, free testosterone, sex-hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone, estradiol, prolactin, and thyroid-stimulating hormone, cardiometabolic markers relevant to vasculogenic erectile dysfunction including fasting glucose, hemoglobin A1c, lipid profile, and high-sensitivity C-reactive protein, validated quality-of-life and sexual-satisfaction indices including Sexual Quality of Life-Male and partner-reported outcomes. In embodiments, improvements of erectile dysfunction in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0407]

[0389] In embodiments, a subject has a hair loss condition. In embodiments, a subject is at risk of a hair loss condition. Diagnosing or determining a risk of a hair loss condition is known to those of skill. Examples of hair loss conditions that may be treated by EBP include male pattern hair loss, female pattern hair loss, telogen effluvium, anagen effluvium, alopecia areata, tinea capitis, cicatricial alopecia, lichen planopilaris, discoid lupus erythematosus, folliculitis decalvans, dissecting cellulitis of the scalp, frontal fibrosing alopecia, central centrifugal cicatricial alopecia, loose anagen syndrome, trichotillomania, traction alopecia, and hypotrichosis. In embodiments, a disclosed EBP treatment treats a hair loss condition in a subject. Measures of improvement of a hair loss condition are known to those of skill. In embodiments, improvements of a hair loss condition in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0408]

[0390] In embodiments, a subject has a skin condition. In embodiments, a subject is at risk of a skin condition. Diagnosing or determining a risk of a skin condition is known to those of skill. Skin conditions that may be treated by EBP include acanthosis nigricans, acne, actinic keratosis, athlete’s foot, atopic dermatitis, basal cell carcinoma, boils and styes, botulinum toxin, bullous pemphigoid, cellulitis, contact dermatitis, cradle cap, cutaneous T-cell lymphoma, dermato-fibrosarcoma protuberans (DFSP), dyshidrotic eczema, eczema, epidermolysis bullosa, granuloma annulare, hand-foot-and-mouth disease, hives, hyperhidrosis, ichthyosis vulgaris, imiquimod, impetigo, isotretinoin, keratosis pilaris, leprosy, lichen planus, lupus, lyme disease, melanoma, melasma, Merkel cell carcinoma, molluscum contagiosum, nail fungus, neurodermatitis, nummular dermatitis, pemphigus, perioral dermatitis, pityriasis rosea, prurigo nodularis, psoriasis, psoriatic arthritis, rashes, rosacea, sarcoidosis, scabies, scarring, scleroderma, sebaceous carcinoma, seborrheic dermatitis, seborrheic keratoses, shingles, skin cancer, squamous cell carcinoma, stasis dermatitis, syphilis, tinea versicolor, vitiligo, warts, and xeroderma pigmentosum. In embodiments, the EBP treatment treats a skin condition in a subject. In embodiments, improvements of a skin condition in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject. In embodiments, a subject is recovering from a wound. Wound refers to an injury to living tissue caused by various physical, chemical, thermal, or biological means, typically one in which the skin is cut or broken. In embodiments, administering a disclosed DFPP treatment according to a disclosed method promotes wound recovery in a subject. In embodiments, administering a disclosed DFPP treatment, as part of a disclosed treatment regimen, promotes wound recovery in a subject. In embodiments, administering a disclosed DFPP treatment according to a disclosed 2025-09-12 method, including as part of a disclosed treatment regimen, promotes wound recovery in a subject because of a reduction in the amount of PFAS in the biological matrix of the subject. Measures of improvement of skin conditions and wound recovery are known to those of skill, and include a change in lesion counts, Eczema Area and Severity Index (EASI) score, Psoriasis Area and Severity Index (PASI) score, wound-closure time, body surface area involvement, Dermatology Life Quality Index, and local inflammatory markers.

[0409]

[0391] In embodiments, a subject has a prostate condition. In embodiments, a subject is at risk of a prostate condition. Diagnosing or determining a risk of a prostate condition is known to those of skill. Examples of prostate condition that may be treated by EBP include prostatitis, chronic prostatitis, acute bacterial prostatitis, chronic bacterial prostatitis, asymptomatic prostatitis, benign prostatic hyperplasia, prostatism, prostatalgia, and prostate cancer. In embodiments, a disclosed EBP treatment treats a thyroid disorder in a subject. Measures of improvement of a prostate condition are known to those of skill, and include a change in one or more of an International Prostate Symptom Score (IPSS), nocturia episode frequency, maximum urinary flow rate (Qmax), post-void residual (PVR) volume, prostate volume on ultrasound or MRI, prostate-specific antigen (PSA) (e.g., if elevated due to benign prostatic hyperplasia), NIH Chronic Prostatitis Symptom Index (NIH-CPSI), leukocyte count or inflammatory markers in expressed prostatic secretions, semen, or urine, pelvic or perineal pain scores, erectile- or ejaculatory-function indices, urinary-tract infection frequency, and validated quality-of-life indices. In embodiments, improvement of a prostate condition in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0410]

[0392] In embodiments, a subject has a nutritional or metabolic condition. In embodiments, a subject is at risk of a nutritional or metabolic condition. Diagnosing or determining a risk of a nutritional or metabolic disorder is known to those of skill. Examples of metabolic conditions that may be treated by EBP include obesity, adrenoleukodystrophy, diabetes type 1 , Gaucher disease, glucose galactose malabsorption, hereditary hemochromatosis, Hunter syndrome, Lesch- Nyhan syndrome, Menkes syndrome, Niemann-Pick disease, phenylketonuria, Prader-Willi syndrome, porphyria, Refsum disease, Tangier disease, Tay-Sachs disease, Wilson’s disease, Krabbe disease, maple syrup urine disease, metachromatic leukodystrophy, and Zellweger syndrome. In embodiments, a disclosed EBP treatment treats a metabolic condition in a subject. Measures of improvement of a metabolic disorder are known to those of skill, and include a change in one or more of body weight, body mass index (BMI), waist circumference, body-fat percentage, fasting glucose, fasting insulin, Homeostatic Model Assessment of insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (ApoB), lipoprotein(a) (Lp(a)), non-HDL cholesterol, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), high-sensitivity C-reactive protein (hsCRP), leptin, adiponectin, omega-3 index, 25-hydroxyvitamin D, vitamin B12, ferritin, transferrin saturation, homocysteine, prealbumin, albumin, essential amino-acid profile, and validated quality-of-life or symptom indices. In embodiments, improvement of a metabolic condition in a subject results from a reduction in the 2025-09-12 amount of PFAS in the biological matrix of the subject.

[0411]

[0393] In embodiments, a subject has an endocrine or hormone condition. In embodiments, a subject is at risk of an endocrine or hormone condition. In embodiments, a subject at risk of an endocrine or hormone condition is being exposed, or has been exposed, to endocrine disruptors (e.g., PFAS in the subject’s biological matrix). Diagnosing or determining a risk of an endocrine or hormone condition is known to those of skill. Examples of endocrine conditions that may be treated by EBP include diabetes, hypoglycemia (e.g., idiopathic hypoglycemia, insulinoma), glucagonoma, goiter, hyperthyroidism, Graves-Basedow disease, toxic multinodular goiter, thyrotoxic myopathy, Kocher-Debre-Semelaigne syndrome, Hoffman syndrome, myasthenic syndrome, thyroiditis (e.g., Hashimoto’s thyroiditis), thyroid cancer, thyroid hormone resistance, a parathyroid gland disorder, hyperparathyroidism (e.g., primary, secondary, tertiary, and hyperparathyroid myopathy), osteoporosis, osteitis deformans, rickets, osteomalacia, hypopituitarism, pituitary tumors (e.g., pituitary adenomas, prolactinoma, acromegaly, Cushing’s disease), Addison’s disease, adrenal crisis, adrenal insufficiency, adrenal tumor, hypoaldosteronism, hyperaldosteronism, disorders of puberty, multiple endocrine neoplasia (e.g., MEN type 1 , MEN type 2a, MEN type 2b), and carcinoid syndrome. In embodiments, a disclosed EBP treatment treats an endocrine condition in a subject. Measures of improvement of an endocrine condition are known to those of skill, and include a change in one or more of thyroid-stimulating hormone (TSH), free thyroxine (free T4), anti-Mullerian hormone (AMH), ovulatory metrics (e.g., luteinizing hormone surge, mid-luteal progesterone, basal body temperature pattern, and follicular ultrasound findings), validated erectile-function scores, and quality-of-life indices. In embodiments, improvement of an endocrine condition in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0412]

[0394] In embodiments, a subject has a complication from a vaccine (equivalently herein, a “vaccine-associated condition”). In some embodiments, a subject with PFAS exposure has an altered response to a vaccine. In some embodiments, a subject with PFAS exposure has a reduced antibody response to a vaccine. In embodiments, a subject is at risk of a vaccine-associated condition. The diagnosis of such a condition, and a subject’s risk for such a condition, is known to those of skill. Polymers, such as PEGylated lipids, are frequently used as excipients in vaccines, including as components of the liposome-encapsulated mRNA vaccines widely used for the treatment of SARS-CoV-2 (Gregoriadis G. Med Drug Discov. 2021 ; 12: 100104). In embodiments, a disclosed EBP treatment treats a vaccine-associated condition in a subject. Measures of improvement of such conditions are known to those of skill, and include a change in one or more of antibody avidity index, seroconversion or seroprotection status, antigen-specific memory B-cell frequency, T-cell responses, intracellular cytokine staining (e.g., CD4+ and CD8+ T cells), T-cell receptor repertoire breadth, innate-immune activation markers and cytokine panels, high-sensitivity C-reactive protein, reactogenicity diary scores and adverse-event grades, autonomic measures (e.g., heart-rate variability), cardiac biomarkers (e.g., troponin and B-type natriuretic peptide), electrocardiographic or echocardiographic parameters, coagulation markers including D-dimer and fibrinogen, validated fatigue or 2025-09-12 quality-of-life indices, and clinician global assessment. In embodiments, improvement of a vaccine-associated condition in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0413]

[0395] In embodiments, a subject has a cholesterol-related condition. In embodiments, a subject is at risk of a cholesterol-related condition. Diagnosing or determining a risk of a cholesterol-related condition is known to those of skill. Examples of cholesterol-related conditions that may be treated by EBP include hyperlipidemia, familial hyperlipidemia, sitosterolemia, type III dysbetalipoproteinemia, ABCAI deficiency (Tangier disease), family combined dyslipidemia, atherosclerosis, coronary artery disease, carotid artery disease, peripheral artery disease, stroke, and peripheral vascular disease In embodiments, a disclosed EBP treatment treats a cholesterol-related condition in a subject. Measures of improvement of a cholesterol-related condition are known to those of skill. In embodiments, improvement of a cholesterol-related condition in a subject results from a reduction in the amount of PFAS in the biological matrix of the subject.

[0414]

[0396] In embodiments, a subject has a complication from cholesterol crystals in a biological matrix. In embodiments, a subject is at risk of a complication from cholesterol crystals in a biological matrix. Microscopic cholesterol crystals (with a size of, e.g., between about 10 and 50 pm) may be introduced into a subject’s blood from cholesterol present in liposomes for drug delivery, or in liposome-based vaccines. Like PFAS, cholesterol crystals in a subject’s blood may cause or contribute to a variety of deleterious health effects, such as those described in embodiments herein pertaining to PFAS. Diagnosing or determining a risk of a complication from cholesterol crystals is known to those of skill. Certain disclosed techniques for measuring PFAS amounts in a sample (e.g., blood, biological fluid, tissue, eluate), among others known to skill in the art, are also useful for measuring amounts of cholesterol crystals. In embodiments, a disclosed EBP treatment treats a condition associated with or caused by cholesterol crystals in a subject. Measures of improvement of such conditions are known in the art, and include a change in one or more of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), lipoprotein(a) [Lp(a)], high-density lipoprotein cholesterol (HDL-C), triglycerides, total cholesterol, LDL particle number (LDL-P), LDL particle size pattern, remnant lipoprotein cholesterol (RLP-C), oxidized LDL, total-cholesterol / HDL-C ratio, triglyceride / HDL-C ratio, ApoB / ApoA1 ratio, high-sensitivity C-reactive protein (hsCRP), lipoprotein-associated phospholipase A2 (Lp-PLA2), coronary artery calcium (CAC) score, carotid intima-media thickness (cIMT), carotid plaque burden, ankle-brachial index (ABI), endothelial function by flow-mediated dilation (FMD), and validated quality-of-life or symptom indices. In embodiments, improvement of a condition associated with or caused by cholesterol crystals in a subject results from a reduction in the amount of cholesterol crystals in the biological matrix of the subject.

[0415]

[0397] In embodiments, a subject has a gastrointestinal or hepatic condition, including a gastrointestinal or hepatic disease or disorder. In embodiments, a subject is at risk of a gastrointestinal or hepatic condition. Diagnosing or determining a risk of a gastrointestinal or hepatic condition are known to those of skill. Examples of gastrointestinal or hepatic conditions that may be treated by EBP include liver fibrosis, 2025-09-12 non-alcoholic fatty liver disease (NAFLD), gut-microbiome disruption, intestinal inflammation, digestive dysfunction, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). In embodiments, a disclosed EBP treatment treats a gastrointestinal or hepatic condition in a subject. Measures of improvement of gastrointestinal or hepatic conditions are known to those of skill, and include a change in one or more of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total and / or direct bilirubin, serum albumin, international normalized ratio (INR), platelet count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), symptom score, fecal calprotectin, fecal lactoferrin, FIB-4, NAFLD Fibrosis Score (NFS), aspartate aminotransferase-to-platelet ratio index (APRI), Enhanced Liver Fibrosis (ELF) score, FibroScan® liver stiffness measurement and / or controlled attenuation parameter (CAP), magnetic resonance proton density fat fraction (MRI-PDFF), magnetic resonance elastography (MRE), endoscopic disease-activity indices including Mayo endoscopic subscore, Ulcerative Colitis Endoscopic Index of Severity (UCEIS), Simple Endoscopic Score for Crohn’s Disease (SES-CD), Crohn’s Disease Activity Index (CDAI), Harvey-Bradshaw Index (HBI), small-intestinal bacterial overgrowth (SIBO) breath-test hydrogen / methane levels, and validated gastrointestinal or liver-specific quality-of-life indices. In embodiments, improvement of the condition is attributable to a reduction in the amount of PFAS in the biological matrix of the subject.

[0416]

[0398] In embodiments, a subject has an ulcerative condition, including an ulcerative disease or disorder. In embodiments, a subject is at risk of an ulcerative condition. Diagnosing or determining a risk of an ulcerative are known to those of skill. Examples of an ulcerative condition that may be treated by EBP include peptic ulcer disease, gastric ulcers, duodenal ulcers, stress-induced ulcers, ischemic ulcers, pressure ulcers (decubitus ulcers, bedsores), diabetic foot ulcers, venous stasis ulcers, arterial insufficiency ulcers, mixed etiology ulcers, traumatic ulcers, infectious ulcers (e.g., those caused by Helicobacter pylori, cytomegalovirus, syphilis, or mycobacterial infection), oral ulcers (e.g., aphthous ulcers, herpetic ulcers), inflammatory bowel disease-associated ulcers (e.g., Crohn’s disease-related ulcers, ulcerative colitis-related ulcers), drug- induced ulcers (e.g., NSAID-associated ulcers), and radiation-induced ulcers, as well as other ulcerative lesions of the gastrointestinal tract, skin, or mucosal surfaces. In embodiments, a disclosed EBP treatment treats an ulcerative condition in a subject. Measures of improvement of ulcerative conditions are known to those of skill, and include a change in one or more of stool frequency, rectal bleeding score, fecal calprotectin, C-reactive protein, erythr...

Claims

2025-09-12CLAIMSThe invention claimed is:1 . A method for removing per- and polyfluoroalkyl substances (PFAS) from a subject, comprising: a. selecting the subject for treatment; and b. administering an extracorporeal blood purification (EBP) treatment; wherein the EBP treatment is effective to remove an amount of PFAS from the body of the subject.2 The method of claim 1 , wherein the PFAS comprise one or more compounds selected from the group consisting of perfluoroalkyl perfluoroalkyl carboxylic acids (PFCAs), perfluoroalkyl sulfonic acids (PFSAs), perfluoroalkyl sulfonamides, and fluorotelomer sulfonates.3 The method of claim 2, wherein the PFAS is selected from the group consisting of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), and perfluoroheptanoic acid (PFHpA).4 The method of claim 1 , wherein selecting the subject for treatment comprises measuring a concentration of PFAS in a biological matrix of the subject.5 The method of claim 4, wherein the biological matrix of the subject comprises blood and blood derivatives, body fluids, tissues and organs, cellular and extracellular components, and processed fractions derived therefrom.6 The method of claim 5, wherein the biological matrix of the subject comprises blood, plasma, serum, an eluate, a retentate, an adsorbate, an ultrafiltrate, and a dialysate.7 The method of claim 4, wherein the concentration of PFAS in the biological matrix of the subject is at least about 0.005 ng / mL to about 100 ng / mL.8 The method of claim 5, wherein measuring the concentration of PFAS in the biological matrix of the subject comprises using liquid chromatography-mass spectrometry (LC-MS), liquid chromatography tandem mass spectrometry (LC-MS / MS), high-performance liquid chromatography-mass spectrometry (HPLC-MS), high-performance liquid chromatography tandem mass spectrometry (HPLC-MS / MS), ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS), ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS / MS), gas chromatography-mass spectrometry (GC-MS), or gas chromatography tandem mass spectrometry (GC-MS / MS).9 The method of claim 1 , wherein selecting the subject for treatment comprises determining that the subject has one or more symptoms of a PFAS-related condition.2025-09-1210. The method of claim 1 , wherein selecting the subject for treatment comprises determining that the subject has a PFAS-related condition or is at risk of developing a PFAS-related condition.11 . The method of claim 9 or 10, wherein the PFAS-related condition comprises a cardiometabolic condition, a vascular condition, a hepatic condition, a gastrointestinal condition, a respiratory condition, an inflammatory condition, an immunological condition, an endocrine condition, a reproductive condition, a urologic condition, a neurodegenerative condition, a mental health condition, a skin condition, a hair condition, a wound condition, a renal condition, a kidney condition, a pathogenic condition, an infectious condition, an ocular condition, a weight condition, an obesity condition, a thrombotic condition, a stroke condition, cancer, a thyroid condition, a pregnancy condition, a fertility condition, a condition related to pregnancy preparation, an ulcerative condition, a nutritional condition, a metabolic condition, a prostate condition, a cholesterol-related condition, a complication from cholesterol crystals, a fatigue-related condition, a pain condition, a blood condition, or a vaccine-associated condition.

12. The method of claim 9 or 10, wherein the PFAS-related condition comprises inflammation, immune dysregulation, endocrine disruption, metabolic dysfunction, oxidative stress, or impairment of cellular function.

13. The method of claim 9 or 10, wherein the PFAS-related condition is exacerbated by the presence of PFAS in the biological matrix of the subject and / or is improved by reducing the concentration of PFAS in the biological matrix of the subject.

14. The method of claim 1 , wherein selecting the subject for treatment comprises a pre-treatment assessment.

15. The method of claim 14, wherein the pre-treatment assessment comprises a medical consultation, a medical history evaluation, a physical examination, a cognitive examination, a fitness examination, a blood panel, an aging biomarker test, a gut microbiome test, an environmental toxin test, a fertility test, a reproductive health test, a questionnaire, or a health scan.

16. The method of claim 14 or 15, wherein selecting the subject for treatment comprises determining that the subject does not have symptoms of a PFAS-related condition.

17. The method of claim 14 or 15, wherein selecting the subject for treatment comprises determining that the subject is at risk of developing a PFAS-related condition, and wherein the EBP treatment is administered prophylactically to reduce the subject’s risk of developing the PFAS-related condition.

18. The method of claim 17, wherein the subject does not have symptoms of the PFAS-related condition.

19. The method of claim 14 or 15, wherein the pre-treatment assessment comprises a determination that2025-09-12 the subject would benefit from removing PFAS from the body of the subject.

20. The method of claim 19, wherein the benefit from removing PFAS from the body of the subject comprises an improvement in athletic performance, fitness, pain management, musculoskeletal health, blood circulation, blood microcirculation, rheology, mitochondrial function, cognitive function, wellbeing, body detoxification, chemical carrier detox, longevity, lifespan, healthspan, inflammation management, aging, weight management, obesity management, pregnancy preparation, maternal-fetal health, perinatal health, fertility treatment, organ transplant preparation, preparation for another medical treatment, or occupational prophylaxis.21 . The method of claim 20, wherein the EBP treatment is effective to provide the improvement.

22. The method of claim 21 , wherein the improvement is determined by a post-treatment assessment.

23. The method of claim 22, wherein the post-treatment assessment comprises a physical examination, a health status examination, a cognitive examination, a fitness examination, a blood panel, an aging biomarker test, a reproductive test, a fertility test, a gut microbiome test, an environmental toxin test, a questionnaire, a health scan, and / or comprises measuring a PFAS concentration, a co-contaminant concentration, inflammatory markers, immunologic markers, endocrine markers, metabolic markers, cardiovascular or vascular function, respiratory function, hepatic or gastrointestinal function, renal function, exposure burden metrics, neurologic metrics, cognitive metrics, dermatologic metrics, musculoskeletal metrics, performance metrics, aging metrics, longevity metrics, or condition-specific disease-activity indices.

24. The method of claim 1 , wherein the method further comprises an additional health treatment.

25. The method of claim 24, wherein the additional health treatment comprises a lifestyle intervention, a nervous system regulation intervention, a metabolic or endocrine adjunct intervention, an antimicrobial intervention, an adjunct oral therapy intervention, a detox-pathway support intervention, a bioenergetic intervention, a carrier modulating intervention, or an albumin modulating intervention.

26. The method of claim 24 or 25, wherein the additional health treatment is provided before administering the EBP treatment, concurrently with administering the EBP treatment, after administering the EBP treatment, or any combination thereof.

27. The method of claim 19, wherein the additional health treatment improves a therapeutic outcome of the EBP treatment.

28. The method of claim 9, further comprising reducing the one or more symptoms of the PFAS-related condition.2025-09-1229. The method of claim 28, further comprising performing a post-treatment assessment on the subject to measure a reduction in the one or more symptoms.

30. The method of claim 29, wherein the post-treatment assessment comprises one or more of measuring PFAS concentrations, measuring co-contaminant concentrations, a physical examination, a health status examination, a cognitive examination, a fitness examination, a blood panel, an aging biomarker test, a gut microbiome test, an environmental toxin test, a questionnaire, a health scan, exposure burden metrics, inflammatory or immunologic markers, endocrine or metabolic markers, cardiovascular or vascular function metrics, respiratory function metrics, hepatic or gastrointestinal function metrics, renal function metrics, neurologic metrics, cognitive metrics, dermatologic metrics, musculoskeletal metrics, performance metrics, a reproductive test, a fertility test, aging metrics, longevity metrics, and condition-specific disease-activity indices.31 . The method of claim 25, wherein the albumin modulating intervention comprises one or more of selecting a treatment schedule with a rest interval between two EBP treatments, administering an adjunct oral therapy, administering a reversible albumin-binding competitor or lipid emulsion, adjusting ionic strength or pH within physiologic limits, and administering exogenous human serum albumin.

32. The method of claim 25 or 31 , wherein the adjunct oral therapy comprises one or more of dietary fiber, gel-forming fiber, oat B-glucan, pectin, acacia fiber, psyllium, bile-acid sequestrant, holestyramine, colesevelam, colestipol, activated carbon, zeolite, bentonite, chitosan, calcium alginate, sodium alginate, inulin, fructo-oligosaccharide, galacto-oligosaccharide, resistant starch, phosphatidylcholine, and tauroursodeoxycholic acid.

33. The method of claim 32, wherein the adjunct oral therapy is selected based on a a pre-treatment assessment.

34. The method of claim 7, wherein the concentration of PFAS in the biological matrix of the subject is measured: a. at one or more times before the EBP treatment; b. at one or more times during the EBP treatment; c. at one or more times after the EBP treatment; or d. any combination thereof.

35. The method of claim 34, wherein measuring the concentration of PFAS in the biological matrix of the subject comprises analyzing PFAS filtered from the subject during the EBP treatment.

36. The method of claim 34, wherein the EBP treatment is dynamically adjusted based on a PFAS measurement made during the EBP treatment or during a previous EBP treatment.2025-09-1237. The method of claim 34, wherein a plasma flow rate of the EBP treatment is selected based on one or both of the concentration of PFAS in the biological matrix of the subject and a detection of PFAS breakthrough downstream of an adsorption module.

38. The method of claim 37, wherein a relatively higher PFAS measurement or detected breakthrough corresponds to one or both of a lower plasma flow rate and an increased number of recirculation passes.

39. The method of claim 37 wherein the plasma flow rate is reduced to about 10—40 mL / min when the concentration of PFAS exceeds a threshold or PFAS breakthrough is detected.

40. The method of claim 1 , wherein the EBP treatment reduces PFAS in the subject by about 5% to about 100%.41 . The method of claim 40, wherein the EBP treatment reduces PFAS in the subject by about 40% to about 99%.

42. The method of claim 1 , wherein the EBP treatment reduces PFAS in the biological matrix of the subject by removing one or more of free, albumin-bound, globulin-bound, lipoprotein-bound, and other protein-bound PFAS.

43. The method of any one of claims 40-42, wherein removal of PFAS from the the subject reduces one or more protein-bound or hydrophobic small molecule co-contaminant toxicants, selected from the group consisting of phthalates, phthalate metabolites, bisphenols, alkylphenols, parabens, brominated flame retardants, polychlorinated biphenyls, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, pyrethroids, organophosphates, oxybenzone, octocrylene, galaxolide, cyanotoxins, methylmercury, ethylmercury, dioxins, furans, organochlorine pesticides, mycotoxins, bile acids, bilirubin, and oxidized lipids.

44. The method of claim 43, wherein the one or more protein-bound or hydrophobic small molecule co-contaminant toxicants are removed by an adsorption module configured for PFAS capture, the adsorption module comprising one or more of a strong base anion exchange resin, a fluorophilic polymer, activated carbon, and a molecularly imprinted polymer.

45. The method of claim 44, wherein a concentration of the one or more protein-bound or hydrophobic small molecule co-contaminant toxicants is measured pre- and post-treatment using one or more of liquid chromatography-tandem mass spectrometry (LC-MS / MS), high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS / MS), ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS / MS), capillary electrophoresis-mass2025-09-12 spectrometry (CE-MS), and capillary electrophoresis-tandem mass spectrometry (CE-MS / MS).

46. The method of any of claims 37-39, wherein the EBP treatment reduces a concentration of the one or more protein bound or hydrophobic small molecule co-contaminant toxicants by about 5% to about 99%.

47. The method of any of claims 37-39, wherein PFAS and the one or more protein-bound or hydrophobic small molecule co-contaminant toxicants are removed while preserving serum albumin concentration at greater than about 3.0 g / dL.

48. The method of claim 1 , wherein the EBP treatment causes a change in one or more aging associated biomarkers, the aging associated biomarkers comprising telomere metrics, cellular senescence indices, epigenetic age measures; immune cell composition metrics, inflammatory and immune proteomic signatures, metabolic and mitochondrial markers, and immunoglobulin G N-linked oligosaccharide (IgG N-glycan) profile.

49. The method of claim 48, wherein the change in one or more aging associated biomarkers comprise an increase in mean leukocyte telomere length, a reduction in senescent cell burden, a reduction in a DNA-methylation clock value, an increase in CD4-positive naive T cells, an increase in CD8-positive naive T cells, an increase in stem-cell-memory T cells, a reduction in natural killer cells, a reduction in monocytes, normalization of iAge surrogates, a reduction in C-X-C motif chemokine ligand 9 (CXCL9) percentile, upregulation of immune resilience proteins, downregulation of senescence associated proteins, restoration of glycine metabolism, an increase in ATP production, and an increase in galactosylation and sialylation.

50. The method of claim 42 or 43, wherein the change in the one or more aging associated biomarkers comprises one or more of reducing an epigenetic age metric of the subject by at least 0.25, 0.5, 1 , 2, or 3 years, reducing CXCL9 percentile to below about the 75th, 50th, or 25th percentile, and increasing ATP production by at least about 5%, about 10%, about 20%, or about 30% relative to a baseline measurement.51 . The method of claim 50, wherein the change in the one or more aging associated biomarkers is measured by one or more of quantitative polymerase chain reaction (qPCR), flow-FISH, validated de DNA-methylation clocks, flow cytometry, proteomics or cytokine panels, targeted metabolomics, luminescence-based assays or respirometry, and glycomics.

52. The method of claim 1 , wherein the EBP treatment is repeated according to a schedule comprising one or more of: two treatments, three treatments, four treatments, five treatments, six treatments, seven treatments, eight treatments, nine treatments, ten treatments, biweekly treatments, monthly treatments, bi-monthly treatments, quarterly treatments, annual treatments, bi-annual treatments, and two or more2025-09-12 clusters of treatments per year, wherein EBP treatment repetition is for one or both of: (a) to achieve a reduction in PFAS or a PFAS concentration at or below a threshold amount; and (b) to maintain PFAS or the PFAS concentration at or below the threshold amount.

53. The method of claim 46, wherein the threshold amount is greater than about a 20%, 30%, 40%, 50%, or 60% reduction in PFAS concentration relative to a baseline concentration of the subject.

54. The method of claim 46, wherein a subsequent EBP treatment in the schedule is selected to be the same as or different from a previous EBP treatment with respect to one or more of extracorporeal modality, presence or type of an adsorption module, membrane pore size or molecular weight cut-off, processed plasma volume, plasma-flow rate, residence time, session duration, order relative to adjunct therapy, and albumin modulating intervention, the selection being based on one or more treatment-associated metrics, the one or more treatment-associated metrics comprising PFAS concentration, co-contaminant concentration, detection of PFAS breakthrough downstream of an adsorption module, inflammatory markers, endocrine markers, validated symptom scores, disease or condition specific metrics, and safety parameters.

55. The method of claim 46, wherein the schedule comprises a loading period during which EBP treatments are administered at a first frequency and a maintenance period during which EBP treatments are administered at a second frequency that is less than the first frequency.

56. The method of claim 49, wherein the loading period comprises alternating one or more EBP treatment weeks and one or more rest weeks for 4-12 weeks, and the maintenance period comprises an EBP treatment about every 90 days for about 12 months following the loading period.

57. The method of claim 49 or 50, wherein the loading period comprises relatively lower per-session processed plasma volumes (PV) and relatively higher treatment frequency, and the maintenance period comprises relatively higher per-session processed PV and relatively lower treatment frequency.

58. The method of claim 57, wherein the relatively lower per-session processed PV comprises about 0.75 PV, about 1 PV or about 1.5 PV, and the relatively higher per-session processed PV comprises about 1.5 PV, about 2 PV, about 2.5 PV, or about 3 PV.

59. The method of claim 52, wherein an EBP treatment having a higher per-session processed PV is performed with a PFAS adsorption module with albumin-preserving DFPP settings, the albumin-preserving settings comprising a second membrane filter selected to be albumin permissive.

60. The method of claim 51 , wherein a transmembrane pressure and plasma flow rate that preserve albumin above a predefined safety limit are selected.2025-09-1261 . The method of claim 51 , wherein replacement human serum albumin (HSA) is administered.

62. The method of claim 1 , wherein the EBP treatment comprises: a. a first phase to optimize detoxification and immune readiness prior to systemic mobilization of toxicants; b. a second phase to remove pathological and inflammatory burden from the bloodstream and interstitial matrix; c. a third phase to restore cellular resilience and immune equilibrium while the subject remains in a post-apheresis state of lowered inflammatory tone; and d. a fourth phase to promote regeneration, performance enhancement, and long-term health optimization.

63. The method of claim 1 , wherein after the EBP treatment, a rest interval of one or more days is prescribed to allow dissociation of PFAS from tissues and organs, interrupt enterohepatic recirculation, and promote redistribution of PFAS into plasma to enhance PFAS and co-contaminant removal during a subsequent EBP treatment.

64. The method of claim 57, comprising administering one or both of an oral bile-acid sequestrant and a probiotic during the rest interval to increase fecal elimination of PFAS, wherein the bile-acid sequestrant or probiotic is one or more of cholestyramine, colesevelam, colestipol, holestyramine, Bacteroides caccae, B. clams, B. dorei, B. stercoris, B. thetaiotaomicron, B. uniforms, Odoribacter splanchnicus, Parabacteroides distasonis, and P. merdae.

65. The method of claim 1 , wherein the duration of the EBP treatment is between about 0.5 hours and about 4 hours.

66. The method of claim 59, wherein the duration of the EBP treatment is between about 2 hours and 3 hours.

67. The method of claim 1 , wherein a DFPP treatment is administered, comprising: a. creating a blood circuit via vascular access; b. separating plasma from whole blood using a first filter with a pore size of about 200-800 nm; c. filtering PFAS from the plasma using a second filter with a pore size of about 1 nm-20 nm to create purified plasma; and d. reinfusing the purified plasma with blood cells.

68. The method of claim 1 , wherein a DFPP treatment is administered, comprising: a. creating a blood circuit via vascular access; b. separating plasma from whole blood using a first filter with a pore size of about 200-800 nm;2025-09-12 c. fractionating the plasma using a second filter having a molecular weight cut-off that passes albumin and immunoglobulins and retains macromolecular species, thereby yielding a permeate comprising the albumin and the immunoglobulins and a retentate comprising the macromolecular species; d. passing the permeate through an adsorption media configured to bind PFAS to yield purified plasma; and e. reinfusing the purified plasma with blood cells.

69. The method of claim 1 , wherein the EBP treatment comprises a first treatment session in which DFPP is administered, and a subsequent treatment session in which plasma adsorption configured to bind PFAS is administered, wherein the first treatment session and the subsequent treatment session are separated by a rest interval of about 24-72 hours.

70. The method of claim 61 or 62, wherein the first filter has a pore size of about 450 nm and the second filter has a pore size of about 10 nm.

71. The method of claim 61 or 62, wherein the first filter has a pore size of about 450 nm and the second filter has a pore size of about 5 nm to about 10 nm.

72. The method of claim 62, wherein the first filter has a pore size of about 450 nanometers, and the adsorption media comprises a strong-base anion-exchange resin, a fluorophilic polymer, activated carbon, or a molecularly imprinted polymer.

73. The method of claim 62, comprising measuring PFAS in one or more of a sample upstream of the adsorption media, a sample downstream of the adsorption media, the purified plasma, and the biological matrix of the subject.

74. The method of claim 61 or 62, wherein administering the DFPP treatment comprises filtering PFAS from whole blood using a third filter with a pore size of greater than about 10 pm, 20 pm, 30 pm, 40 pm, or 50 pm, wherein the third filter is positioned upstream from the first filter and the second filter in the blood circuit.

75. The method of claim 1 , wherein a therapeutic plasma exchange (TPE) treatment is administered, comprising removing a portion of plasma from whole blood of the subject and replacing the portion of removed plasma with a plasma or albumin solution.

76. The method of claim 75, wherein the plasma or albumin solution has been pretreated to remove or reduce PFAS, the plasma or albumin solution having a PFAS concentration below a threshold amount.

77. The method of claim 1 , wherein a plasma adsorption treatment is administered, further comprising2025-09-12 passing a plasma fraction of whole blood of the subject through an adsorption column comprising one or more binding agents configured to interact with PFAS to produce processed plasma.

78. The method of claim 1 , wherein a coupled plasma filtration adsorption (CPFA) treatment is administered, comprising:

79. creating a blood circuit via vascular access to the subject;80. separating whole blood of the subject into a plasma fraction and a cellular fraction;81 . removing PFAS from the plasma fraction by passing the plasma fraction through an adsorption filter or cartridge configured to bind PFAS to yield a processed plasma fraction;82. combining the cellular fraction and the processed plasma fraction;83. separating ultrafiltrate from the combined cellular fraction and processed plasma fraction using a membrane; and84. supplying the combined cellular fraction and processed plasma fraction to the subject.

85. The method of claim 1 , wherein a plasma perfusion (PP) treatment is administered, comprising removing one or more pathogenic antibodies, immune complexes, cytokines, metabolized waste products, and oxidized lipids.

86. The method of claim 62, wherein one or more of plasma flow rate, residence time, recirculation passes, and cartridge configuration is adjusted based on detection of PFAS breakthrough downstream from the adsorption media in the blood circuit.

87. The method of claim 1 , comprising administering an albumin modulating intervention prior to the EBP treatment, wherein the albumin modulating intervention comprises administering exogenous human serum albumin, a reversible albumin-binding competitor, a lipid emulsion, or adjustment of ionic strength within physiologic limits.

88. The method of claim 1 , further comprising administering human serum albumin (HSA) during or immediately after the EBP treatment, the HSA comprising 5%-25% albumin, wherein: a. albumin is administered when a baseline serum albumin concentration of the subject is less than about 3.4g / dL or when an albumin concentration of the subject following the EBP treatment decreases by about 40% or more; and b. the human albumin replacement fluid is delivered from a glass or non-plastic container and is selected to have a PFAS and free floating molecule content below a threshold amount.2025-09-1289. A method of treating blood of a subject comprising: a. creating a blood circuit via vascular access to the subject; b. separating whole blood of the subject into a plasma portion and a blood cell portion using a first filter; c. removing one or both of albumin-bound PFAS and microplastics from the plasma portion using a second filter to yield purified plasma; d. returning the blood cell portion to the subject; and e. providing the purified plasma for allogeneic or autologous therapeutic use, storage, or further processing f. The method of claim 76 comprising: g. further reducing PFAS in the purified plasma by passing the purified plasma through an adsorption media to create PFAS-reduced purified plasma; h. returning the blood cell portion to the subject; and i. providing the PFAS-reduced purified plasma for allogeneic or autologous therapeutic use, storage, or further processing.

90. The method of claim 76, wherein the second filter is configured to remove PFAS having a molecular weight of about 0.1 kDa-500 kDa.91 . The method of claim 76 or 78, wherein the second filter reduces a concentration of PFAS from the purified plasma by greater than about 10%, about 20%, about 30%, about 40%, or about 50% in a single pass through the blood circuit or a single EBP treatment.

92. A method of treating blood of a subject comprising: a. creating a blood circuit via vascular access to the subject; b. separating whole blood of the subject into a plasma portion and a blood cell portion using a first filter; c. removing PFAS from the plasma portion using a second filter to yield purified plasma; d. combining the purified plasma with the blood cell portion; and e. providing the combined purified plasma and blood cell portion for allogeneic or autologous therapeutic use, storage, or further processing.

93. Any method, device, or system for EBP to reduce PFAS and optionally microplastics in one or more of blood, tissue, and fluid of a human subject, as described and enabled herein.

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