Blood purification for removal of microplastics

Abstract

Provided herein are methods of removing microplastics 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 microplastics from the blood, and otherwise removing microplastics from the tissues or body of a subject, such as a human subject.

Description

[0001] BLOOD PURIFICATION FOR REMOVAL OF MICROPLASTICS

[0002] INVENTORS: Karin Voit-Bak, Richard Straube, Michael Petegorsky, and Carlos Schuster

[0003] CROSS-REFERENCE

[0004]

[0001] Priority is claimed under PCT Art. 8(1) and Rule 4.10 to U.S. Provisional Application No. 63 / 664,651 , filed June 26, 2024, and hereby incorporated by reference in its entirety for all purposes.

[0005] FIELD OF THE INVENTION

[0006]

[0002] The disclosure relates to the removal of microplastics 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 microplastics.

[0007] BACKGROUND OF THE INVENTION

[0008]

[0003] Plastics are synthetic organic polymers typically created by the polymerization of hydrocarbons.

[0009]

[0004] “Microplastics” are small particles of plastics, generally defined by a particle size of less than 5 mm.

[0010]

[0005] Microplastics are manufactured and used commercially in a variety of applications, including pharmaceutical and cosmetic formulations. Microplastics are also formed by the degradation of plastic and plastic-containing goods, such as clothing, water bottles, and packaging materials.

[0011]

[0006] Concern over the health impacts of microplastics has been mounting due to their ubiquitous and increasing presence in the environment and in the food supply (Hale et al. J Geophys Res Oceans. 2020,125: e2018JC014719; Ramsperger et al. NanoImpact. 2023;29: 100441).

[0012]

[0007] Of particular concern, the environmental prevalence of microplastics is mirrored by their prevalence in human blood and tissue. Recent studies have demonstrated that microplastics accumulate in human heart, lung, brain, liver, kidney, spleen, colon, ovarian, prostate, penile, testicular and placental tissues, as well as in blood, arterial plaques, and semen (see, e.g., Prata. Crit Rev Environ Sci Techno\. 2023:53(16); 1489-1511 ; Codrington et al. Int J Impot Res. 2025 May;37(5):377-383; Hu et al. Toxicol Sci. 2024 Aug 1 ;200(2):235-240; Li et al. Sci Total Environ. 2024;937: 173522; Montano et al. MedRxiv. 2024;2024.04.04.24305264; Marfella et al. N Engl J Med. 2024;390(10):900-910; Bleske et al. Nat Med. 2025 Apr;31 (4): 1114-1119).

[0013]

[0008] Primary sources of human exposure to microplastics include inhalation, ingestion, and skin contact (De-la-Torre. J Food Sci Technol. 2020;57(5):1601-1608). Following exposure, microplastics can cause cytotoxicity, inflammation, and the production of reactive oxygen species (id.). Microplastics can translocate to the lymph and circulatory system (Lai et al. Nanomaterials (Basel). 2022; 12(8): 1298), where they may cause or increase the risk of disease and death. For example, one study found an association between the presence of microplastics in arteries and a more than quadrupled risk of heart attack, stroke, and premature death (Marfella 2024). Microplastics also can carry other pathogenic and toxic substances around the body, creating further risk of illness, immune response, and inflammation (Rafa et al. Environ Pollut. 2024;343: 123190).

[0009] Despite such knowledge regarding the increasing accumulation of microplastics in human tissues, and the clear harms to human health, methods to reduce harms have been limited to minimizing exposure to microplastics and to products containing microplastics. To the best of Applicant’s knowledge, before the work of the inventors there were no methods used for the removal of microplastics from the body after exposure, once they are introduced into the body, such as methods to remove microplastics from tissues and blood.

[0014]

[0010] Accordingly, there is an important and growing unmet need for methods to remove microplastics directly from the body, including methods that treat the health issues resulting from the presence of microplastics 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]

[0011] 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]

[0012] 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]

[0013] In some aspects are provided methods for reducing microplastics in the blood, tissue, or both of a subject, the methods comprising: selecting the subject for treatment based on a pre-treatment assessment; and administering a plasmapheresis treatment selected from: double-filtration plasmapheresis (DFPP), therapeutic plasma exchange (TPE), plasma perfusion (PP), plasma adsorption, or coupled plasma filtration adsorption (CPFA), wherein the treatment reduces a concentration of microplastics in the blood, tissue, or both of the subject.

[0020]

[0014] In some embodiments, selecting the subject for treatment comprises determining one or more of: that the subject has a medical condition caused by or associated with microplastics; that the subject is at risk of developing a medical condition caused by or associated with microplastics in the blood, tissue, or both; and that the subject’s athletic performance, fitness, longevity, or wellbeing is likely to be improved by reducing microplastics in the blood, tissue, or both.

[0021]

[0015] In some embodiments, selecting the subject for treatment comprises determining that the subject has a medical condition that is exacerbated by the presence of the microplastics or that can be improved by reducing the microplastics in the blood, tissue, or both.

[0022]

[0016] In some embodiments, the medical condition comprises one or more of a cardiovascular condition, a cardiometabolic condition, a gastrointestinal condition, a hepatic condition, stroke, thrombosis, a respiratory condition, an inflammatory condition, an immunological condition, an autoimmune condition, an immune system condition, a cancer, a neurodegenerative condition, a neurological condition, erectile dysfunction, a hair loss condition, a nutritional or metabolic condition, an endocrine or hormone condition, a reproductive condition, a fertility condition, a mental health condition, a skin condition, a wound, a prostate condition, a fatigue-related condition, a kidney-related condition, a vaccine-associated condition, a pain condition, chronic inflammation, an epigenetic alteration, an allergy condition, a cholesterol-related condition, a complication from cholesterol crystals, a weight-related condition, a pathogenic condition, and an ocular condition.

[0023]

[0017] In some embodiments, the subject is asymptomatic, and the plasmapheresis treatment is prophylactic to reduce future risk of an adverse medical condition or disease. In some embodiments, the plasmapheresis treatment is administered for preventative care.

[0024]

[0018] In some embodiments, the plasmapheresis treatment is administered to improve one or more of longevity, lifespan of the subject, healthspan of the subject, pain management, weight loss, pregnancy preparation, maternal-fetal health, perinatal health, organ transplant preparation, preparing for another medical treatment, inflammation management, detoxification, athletic performance, occupational prophylaxis, blood circulation, blood microcirculation, rheology, slowing of aging, and chemical carrier detox.

[0025]

[0019] In some embodiments, selecting the subject for treatment comprises measuring an amount of microplastics in the blood, tissue, or both of the subject. In some embodiments, measuring the amount of microplastics in the blood, tissue, or both of the subject comprises measuring an amount of microplastics in the blood, tissue, or both of the subject using a fluorescence-assisted detection technique.

[0026]

[0020] In some embodiments, measuring the amount of microplastics in the blood, tissue, or both of the subject comprises fluorescence assistance coupled with flow cytometry, nanoparticle tracking analysis (NTA), or both. In some embodiments, the subject is selected for treatment if the subject has a measurable amount of microplastics in the blood, tissue, or both. In some embodiments, the subject is selected for treatment if the subject has a blood concentration of microplastics of greater than about 0.1 pg / mL to about 10 pg / mL.

[0027]

[0021] In some embodiments, measuring the amount of microplastics in the blood, tissue, or both of the subject comprises one or more of mass spectrometry, spectroscopy, and microscopy.

[0028]

[0022] In some embodiments, the pre-treatment assessment comprises administering or assessing one or more of a medical consultation, one or more blood panels, a gut microbiome test, an environmental toxin test, one or more aging biomarkers, one or more endocrine markers, one or more questionnaires, a medical history evaluation, a medical examination, a health status examination, a physical examination, a cognitive examination, a fitness test, fertility health, and a health scan. In some embodiments, the plasmapheresis treatment is performed before, concurrently, and / or after one or more additional health treatments.

[0029]

[0023] In some embodiments, the at least one additional health treatment comprises one or more of a detox therapy, a supplement, an oral chelation agent, an ozone therapy,, a regenerative treatment, a sauna treatment regimen, hyperbaric oxygen therapy, red light therapy, plused-EMF (PEMF) therapy, hormone therapy, sirtuin-activating therapy, NAD+ therapy, GLP-1 therapy, peptide therapy, stem cell therapy, PRP therapy, exosome therapy, administration of lipid-based carriers, mitochondrial support, a dietary intervention, gut health support, bowel movement support, lymphatic drainage support, liver and kidney detox support, mitochondrial optimization, cellular membrane stabilization, and a blood purification treatment.

[0030]

[0024] In some embodiments, one or more supplements are administered one or more of: orally pre-treatment; intravenously immediately before the plasmapheresis treatment; and subcutaneously for sustained release. In some embodiments, one more more interventions are prescribed to the subject based on one or more metrics associated with the treatment, the one or more interventions comprising one or more of guidance for limiting exposure to microplastics, nervous system regulation interventions, metabolic or endocrine adjunct interventions, and anti-microbial interventions. In some embodiments, one or more additional health treatments are prescribed or administered to the subject, including any of a lifestyle intervention, a supplement, a nervous system regulation intervention, a metabolic or endocrine adjunct intervention, a biologic or regenerative intervention, and an anti-microbial intervention.

[0031]

[0025] In some embodiments, the amount of microplastics in the blood, tissue, or both is measured any of before, during, and after the plasmapheresis treatment is administered. In some embodiments, measuring the amount of microplastics in the blood, tissue, or both of the subject comprises analyzing microplastics filtered from the subject during treatment. In some embodiments, the plasmapheresis treatment is dynamically adjusted based on a microplastics measurement made during the plasmapheresis treatment. In some embodiments, a blood flow rate of the plasmapheresis treatment is selected based on a measurement of an amount of microplastics in the blood, tissue, or both of the subject. In some embodiments, a relatively higher measurement corresponds to a relatively lower blood flow rate to reduce risk of hemolysis and filter clogging.

[0032]

[0026] In some embodiments, the blood flow rate is reduced to about 50-75 mL / min if the measurement exceeds a threshold. In some embodiments, the plasmapheresis treatment reduces microplastics in the subject by about 5% to 99%. In some embodiments, the plasmapheresis treatment reduces system exposure to one or more of PFAS, phthalates, or heavy metals complexed with the removed microplastics.

[0033]

[0027] In some embodiments, the plasmapheresis treatment improves therapeutic outcomes related to one or more of detox treatment, a chelation therapy, an ozone therapy, administering one or more blood panels, a regenerative treatment, a sauna treatment regimen, hyperbaric oxygen therapy, red light therapy, plused-EMF (PEMF) therapy, hormone therapy, sirtuin-activating therapy, NAD+ therapy, GLP-1 therapy, peptide therapy, stem cell therapy, PRP therapy, exosome therapy, administration of lipid-based carriers, mitochondrial support, a dietary intervention, gut health support, bowel movement support, lymphatic drainage support, liver and kidney detox support, mitochondrial optimization, and cellular membrane stabilization.

[0034]

[0028] In some embodiments, the plasmapheresis treatment improves a health metric related to one or more of inflammatory markers, cognitive function, athletic performance, a cardiovascular condition, a cardiometabolic condition, a gastrointestinal condition, a hepatic condition, stroke, thrombosis, a respiratory condition, an inflammatory condition, an immunological condition, an autoimmune condition, an immune system condition, a cancer, a neurodegenerative condition, a neurological condition, erectile dysfunction, a hair loss condition, a nutritional or metabolic condition, an endocrine or hormone condition, a reproductive condition, a fertility condition, a mental health condition, a skin condition, a wound, a prostate condition, a fatigue-related condition, a kidney-related condition, a vaccine-associated condition, a pain condition, chronic inflammation, an epigenetic alteration, an allergy condition, a cholesterol-related condition, a complication from cholesterol crystals, a weight-related condition, a pathogenic condition, an ocular condition, longevity, lifespan of the subject, healthspan of the subject, pain management, weight loss, pregnancy preparation, maternal-fetal health, perinatal health, organ transplant preparation, preparing for another medical treatment, detoxification, occupational prophylaxis, blood circulation, blood microcirculation, rheology, slowing of aging, and chemical carrier detox.

[0035]

[0029] In some embodiments, the plasmapheresis treatment slows aging as evidenced by one or more of increasing telomere length, reducing senescent cell burden, reduction of an epigenetic clock metric, increase in CD4+ / CD8+ naive T cells or stem cell memory T cells, reduction in NK cells or monocytes, normalization of iAge surrogates, reduction in CXCL9 percentile, upregulation of immune resilience proteins, downregulation of senescence-associated proteins, restoration of glycine metabolism, reduction of inflammatory markers, and increase in ATP production.

[0036]

[0030] In some embodiments, the plasmapheresis treatment is repeated one or more of 5 times, 10 times, biweekly, monthly, quarterly, twice per year, and in two sets of treatments per year.

[0037]

[0031] In some embodiments, the plasmapheresis treatment comprises a loading period during which plasmapheresis treatments are administered at a first frequency and a maintenance period during which plasmapheresis treatments are administered at a second frequency that is less than the first frequency.

[0038]

[0032] In some embodiments, the loading period comprises alternating plasmapheresis treatment weeks and rest weeks for 1-2 consecutive months, and the maintenance period comprises quarterly plasmapheresis treatments for a year following the loading period.

[0039]

[0033] In some embodiments, after the plasmapheresis treatment is administered, a period of rest is implemented for one or more days to allow microplastics to diffuse from the blood, tissue, or both of the subject, and one or more additional plasmapheresis treatments are applied after the period of rest.

[0040]

[0034] In some embodiments, the duration of plasmapheresis treatment is between about 0.5 hours and about 4 hours. In some embodiments, a DFPP treatment is administered, comprising: creating a blood circuit via vascular access; separating plasma using a first filter with a pore size of about 200-800 nm; filtering microplastics from the plasma using a second filter with a pore size of about 1-100 nm to create purified plasma; and reinfusing the purified plasma with blood cells. In some embodiments, the first filter has a pore size of about 450 nm and the second filter has a pore size of about 10 nm.

[0035] In some embodiments, the methods comprise measuring microplastics in one or more of DFPP eluate, purified plasma, adsorbate, and blood returned to the subject.

[0041]

[0036] In some embodiments, administering the plasmapheresis treatment comprises: filtering microplastics from whole blood using a third filter with a pore size of about 10-50 pm or more, wherein the third filter is positioned before the first filter and the second filter in the blood circuit.

[0042]

[0037] In some embodiments, a TPE treatment is administered, comprising replacing the plasma of the subject with plasma or albumin solution that is pretreated to remove or reduce microplastics. In some embodiments, a plasma adsorption treatment is administered, further comprising passing the plasma of the subject through an adsorption column comprising binding agents configured to interact with microplastics.

[0043]

[0038] In some embodiments, a CPFA treatment is administered, comprising: creating a blood circuit via vascular access to the subject; separating the blood of the subject into a plasma fraction and a cellular fraction; separating microplastics from the plasma fraction using an adsorption filter; combining the cellular fraction and the filtered plasma fraction; separating ultrafiltrate from the combined cellular fraction and filtered plasma fraction using a membrane; and supplying the combined cellular fraction and filtered plasma fraction to the subject. In some embodiments, the plasmapheresis treatment is PP, comprising removing one or more of pathogenic antibodies, immune complexes, cytokines, or metabolic waste products.

[0044]

[0039] In some aspects are provided methods of treating blood comprising: creating a blood circuit via vascular access to a patient; separating plasma from blood cells of the patient using a first filter; removing microplastics from the plasma using a second filter to create purified plasma; returning the blood cells to the patient; and providing the purified plasma for allogeneic or autologous therapeutic use, storage, or further processing.

[0045]

[0040] In some embodiments, the second filter is configured to remove microplastics having a molecular weight of about 50 kDa - 500 kDa.

[0046]

[0041] In some aspects are provided methods of treating blood comprising: creating a blood circuit via vascular access to a patient; separating plasma from blood cells of the patient using a first filter; removing microplastics from the plasma using a second filter to create purified plasma; combining the purified plasma with the separated blood cells; and providing the combined purified plasma and blood cells for allogeneic or autologous therapeutic use, storage, or further processing.

[0047]

[0042] In further aspects are provided such methods, devices, and systems as described and enabled herein.

[0048]

[0043] 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 appreciated to be also within the scope and spirit of the invention as claimed.

[0049]

[0044] The headings are only for ease of review, and should not be used to limit the invention in any manner.

[0050] BRIEF DESCRIPTION OF THE FIGURES

[0051]

[0045] 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:

[0052]

[0046] FIG. 1 illustrates an exemplary treatment regimen, according to some disclosed embodiments;

[0053]

[0047] FIG. 2 illustrates an exemplary EBP circuit, according to some disclosed embodiments;

[0054]

[0048] FIG. 3 illustrates polystyrene concentration before treatment, after transmission through a plasma separator and plasma fractionator, and after transmission through a plasma fractionator, according to a disclosed embodiment;

[0055]

[0049] FIG. 4A illustrates an eluate sample measured by ATR-FT-IR showing IR spectra and individual spots having a 67.5% match with polyamide 6, confirming the presence of microplastics in the eluate; and

[0056]

[0050] FIG. 4B illustrates an eluate sample measured by ATR-FT-IR showing IR spectra and individual spots having a 35.3% match with polyurethane (PUR-WS), confirming the presence of microplastics in the eluate.

[0057] DETAILED DESCRIPTION OF THE INVENTION

[0058]

[0051] 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.

[0059]

[0052] 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.

[0060]

[0053] 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 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.

[0061]

[0054] 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.

[0062]

[0055] 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.

[0063]

[0056] 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.

[0064] A. General Definitions and Terms

[0065]

[0057] 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.

[0066]

[0058] 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.

[0067]

[0059] 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 some embodiments, “about” refers to plus or minus zero point five percent (±0.5%) of the recited unit of measure. In some embodiments, “about” refers to plus or minus one percent (±1 %) of the recited unit of measure. In some embodiments, “about” refers to plus or minus two point five percent (±2.5%) of the recited unit of measure. In some embodiments, “about” refers to plus or minus five percent (±5%) of the recited unit of measure. In some 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.”

[0068]

[0060] 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%.

[0069]

[0061] In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0070]

[0062] 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.

[0071]

[0063] 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.

[0072]

[0064] 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.

[0073]

[0065] 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.”

[0074]

[0066] Generally, the nomenclature used and procedures performed herein are those 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 are those that 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.

[0075]

[0067] Where definitions are included 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. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0076]

[0068] Further definitions follow, to assist a reader in understanding the embodiments.

[0077]

[0069] “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 microplastics. Blood purification may be performed using one or more filtration, adsorption, or separation modalities, including extracorporeal blood purification (EBP) modalities.

[0078]

[0070] “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).

[0079]

[0071] “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 microplastics and / or for a therapeutic or prophylactic purpose. EBP treatment may involve the reduction or removal of circulating substances or particulates (e.g., microplastics) using any disclosed EBP modality.

[0080]

[0072] 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.

[0081]

[0073] 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 “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.

[0082]

[0074] “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). Other plasmapheresis methods and therapies useful in the disclosed methods will be appreciated by those of skill in view of the disclosure.

[0083]

[0075] “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., American Society for 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 microcirculation. 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.

[0084]

[0076] 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.

[0085]

[0077] “Therapeutic plasma exchange” or “TPE” refers to a method 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 disposal of the plasma fraction, and a subsequent combining of the cellular fraction with a plasma substitution fluid before re-entry into a subject. In some embodiments, TPE refers to a method comprising plasma exchange.

[0086]

[0078] “Plasma perfusion” or “PP” refers to a method 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 a method comprising adsorption, such as plasma adsorption (PA), immunoadsorption (IAS), immunoapheresis (IA), or immunoadsorption plasmapheresis (IAPP).

[0087]

[0079] “Coupled plasma filtration adsorption” or “CPFA” refers to a method 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).

[0088]

[0080] “Hemodialysis” refers to a method comprising the separation of excess water and solutes from a subject’s blood by a dialyzer. The term hemodialysis should not be found limiting on the scope of the disclosure found herein which may be relevant to different types of dialysis based on context.

[0089]

[0081] “Hemofiltration” refers to a method 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. The terms hemofiltration and hemodiafiltration should not be found limiting on the scope of the disclosure found herein which may be relevant to different types of filtration based on context.

[0090]

[0082] “Hemoperfusion” refers to a method comprising the extraction of solutes from a subject’s blood by passing a subject's blood through an adsorbent filter. The term hemoperfusion should not be found limiting on the scope of the disclosure found herein which may be relevant to different types of filtration based on context.

[0091]

[0083] “Ultrafiltration” refers to a method comprising the extraction of water from a subject’s blood across a semipermeable membrane having a molecular weight cutoff of between about 10,000 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). The term ultrafiltration should not be found limiting on the scope of the disclosure found herein which may be relevant to different types of filtration based on context.

[0092]

[0084] 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.

[0093]

[0085] 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 but is not limited to peripheral intravenous lines and central lines.

[0094]

[0086] The terms “return” or “returning” (or any other conjugation of “return”) or “infuse,” or “infusing” (or any 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.

[0095]

[0087] 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.

[0096]

[0088] The terms “purify,” “purified,” or “purifying,” (or any other conjugation of “purify”) means to reduce the amount of a contaminant, such as microplastics, 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.

[0097]

[0089] “Microplastics” refers to small particles of plastic with a particle size of less than about 5 mm. Herein, unless context clearly indicates otherwise, within the definition of microplastics are also “nanoplastics,” a term used in the scientific literature to refer to plastic particles with a particle size of less than 1 pm, or less than 100 nm (see, e.g., Dube et al. Int J Environ Res Public Health. 2023;20(17):6667). Hence, “microplastics” as used herein includes plastic particles with a particle size of less than about 5 mm, less than about 1 pm, and less than about 100 nm, including all intermediate particle sizes and ranges between these sizes. The chemical composition of microplastics can vary depending on their source, and may comprise cellulose acetate (CA), cellophane (CE), ethylene propylene diene monomer rubber (EPDM), extruded polystyrene (EPS), ethylene-vinyl acetate (EVA), polyamide (PA), polyacrylamide (PAAm), polyacrylonitrile (PAN), polybutylene terephthalate (PBT), polyethylene (PE), high-density polyethylene (HDPE), low-density polyethylene (LDPE), polyethylene terephthalate (PET), polyethersulfone (PES), poly(methyl methacrylate) (PMMA), polypropylene (PP), polystyrene (PS), polysulfone (PSU), polytetrafluoroethylene (PTFE), polyurethane (PU), polyvinyl acetate (PVA), polyvinyl chloride (PVC), and other plastics. Although “microplastics,” “nanoplastics,” and like terms may have different definitions in different literature, and different classifications for the particle sizes of microplastics, the methods of the disclosure will be appreciated to work with plastic particles at microparticle, nanoparticle, and other such scales, irrespective of definition, or the choice of terminology herein, which is solely for purposes of explanation and does not impose any limitation. In some embodiments, where context indicates, “microplastics” refers to small particles of plastic with a molecular weight below a defined amount or in a defined range, according to the embodiment.

[0098]

[0090] “Particle size” as used herein (e.g., to describe the size of microplastic particles) refers to any of the diameter, radius, length, width, or any linear dimension of a particle. For a spherical particle, particle size may refer to the diameter of the particle. For a non-spherical particle, particle size can refer to the measurement of any major and minor axes, the particle’s equivalent diameter (e.g., the diameter of a sphere that has the same volume or surface area as the particle), and other definitions known to and used by those of skill to define the size of a particle. In some embodiments, “particle size” refers to mean particle size. Microplastics may have non-uniform sizes and shapes, and may in embodiments be characterized according to the distribution of particle sizes in a sample. In embodiments, “particle size” refers to the mean particle size (e.g., the mathematical average of the distribution of particle sizes). 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, D50, D90, and D99. 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 (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).

[0099]

[0091] “Pore size” refers to the size of the openings (i.e., pores) in a membrane, such as the membranes used in plasmapheresis (e.g., DFPP) devices. 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 are included within the scope of “pore size” as used herein. 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., direct observation of a membrane surface 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). These and other techniques known in the art may be used to determine the molecular weight cutoff (“MWCO”) of a membrane, which in some embodiments can be used to define “pore size.” The MWCO of a membrane is 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. Plasma filters of different mean pore sizes can be selected, according to different embodiments, to allow differentially targeting preferred portions of plasma components, determined by molecular weight and three-dimensional structure.

[0100]

[0092] In some embodiments, administering a DFPP, plasmapheresis, or other EBP treatment reduces the amount of microplastics in a subject’s blood. Techniques of assessing microplastic amounts, such as measuring the amount of microplastics in a subject’s blood, include those known in the art, as well as exemplary techniques disclosed in embodiments herein. “Microplastics” according to disclosed embodiments, including those in the blood of a subject or removed from the blood of a subject using a disclosed method, such as in an eluate from the subject, have in some embodiments a particle size of less than 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, about 100 pm, 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, or about 0.5 pm, as well as other embodiments of particle sizes of less than about each of the above particle sizes.

[0101]

[0093] In some embodiments, microplastics according to disclosed embodiments, including those in the blood of a subject or removed from the blood of a subject using a disclosed method, such as in an eluate from the subject, have a have a particle size of less than about 1 pm, including about 900 nm, about 800 nm, about 700 nm, about 600 nm, about 500 nm, about 400 nm, about 300 nm, about 200 nm, about 100 nm, about 90 nm, about 80 nm, about 70 nm, about 60 nm, about 50 nm, about 40 nm, about 30 nm, about 20 nm, about 10 nm, about 9 nm, about 8 nm, about 7 nm, about 6 nm, about 5 nm, about 4 nm, about 3 nm, about 2 nm, or about 1 nm, as well as other embodiments of particle sizes of less than about each of the above particle sizes.

[0102]

[0094] In some embodiments, microplastics according to disclosed embodiments, including those in the blood of a subject or removed from the blood of a subject using a disclosed method, such as in an eluate from the subject, have a particle size of between about 1 nm and 5 mm, 1 nm and 4 mm, 1 nm and 3 mm, 1 nm and 2 mm, 1 nm and 1 mm, 1 nm and 900 pm, 1 nm and 800 pm, 1 nm and 700 pm, 1 nm and 600 pm, 1 nm and 500 pm, 1 nm and 400 pm, 1 nm and 300 pm, 1 nm and 200 pm, 1 nm and 100 pm, 1 nm and 90 pm, 1 nm and 80 pm, 1 nm and 70 pm, 1 nm and 60 pm, 1 nm and 50 pm, 1 nm and 40 pm, 1 nm and 30 pm, 1 nm and 20 pm, 1 nm and 10 pm, 1 nm and 9 pm, 1 nm and 8 pm, 1 nm and 7 pm, 1 nm and 6 pm, 1 nm and 5 pm, 1 nm and 4 pm, 1 nm and 3 pm, 1 nm and 2 pm, 1 nm and 1 pm, 1 nm and 900 nm, 1 nm and 800 nm, 1 nm and 700 nm, 1 nm and 600 nm, 1 nm and 500 nm, 1 nm and 400 nm, 1 nm and 300 nm, 1 nm and 200 nm, 1 nm and 100 nm, 1 nm and 90 nm, 1 nm and 80 nm, 1 nm and 70 nm, 1 nm and 60 nm, 1 nm and 50 nm, 1 nm and 40 nm, 1 nm and 30 nm, 1 nm and 20 nm, or 1 nm and 10 nm, wherein each range is inclusive, and wherein in some embodiments either of the lower bound or the upper bound of the range is preceded by the term “about” and the other is not, and in other embodiments wherein both the lower and the upper bound of the range is preceded by the term “about,” and in other embodiments wherein neither of the lower or the upper bound of the range is preceded by the term “about,” as well as further embodiments of ranges of particle sizes having any lower bound and any upper bound selected from any of the above embodiments.

[0103]

[0095] In some embodiments, microplastics according to disclosed embodiments, including those in the blood of a subject or removed from the blood of a subject using a disclosed method, such as in an eluate from the subject, have a molecular weight (e.g., a weight-average molecular weight or number-average molecular weight) of between about 1 kDa and about 5 kDa, between about 1 kDa and about 10 kDa, between about 1 kDa and about 20 kDa, between about 1 kDa and about 50 kKa, between about 1 kDa and about 100 kDa, between about 1 kDa and about 1000 kDa, wherein each range is inclusive. In some embodiments, the microplastics have a molecular weight of less than about 1 kDa. In some embodiments, the microplastics have a molecular weight of greater than about 1000 kDa.

[0104]

[0096] In some embodiments, administering a DFPP, plasmapheresis, or other EBP treatment reduces the amount of microplastics in a subject’s blood by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99%, compared to the amount of microplastics in the subject’s blood prior to treatment. In some embodiments, administering a DFPP, plasmapheresis, or other EBP treatment reduces the amount of microplastics in a subject’s blood to an amount less than a detectable amount (e.g., using a measurement technique described herein or otherwise known to one of skill). In some embodiments, wherein the amount of microplastics in a subject’s blood is assessed by measuring blood microplastics concentration (e.g., on a mass / volume basis, such as pig / mL), a disclosed method reduces the amount of microplastics in a subject’s blood by at least 0.1 pg / mL, 0.2 g / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL, compared to the amount of microplastics in the subject’s blood prior to treatment. In embodiments, measuring the amount (e.g., the concentration) of microplastics in a subject’s blood is performed by directly measuring a sample of the subject’s blood. In some embodiments, measuring the amount (e.g., the concentration) of microplastics in a subject’s blood is performed indirectly, i.e., by measuring an amount of microplastics in a fluid other than the subject’s blood, which may in embodiments be derived from the subject’s blood, such as the eluate from a DFPP, plasmapheresis, or other EBP treatment. These and additional measurement techniques are further described in embodiments herein.

[0105]

[0097] In some embodiments, administering a DFPP, plasmapheresis, or other EBP treatment reduces the amount of microplastics in a fluid of a subject by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99%, compared to the amount of microplastics in the fluid of the subject prior to treatment. In some embodiments, administering a DFPP, plasmapheresis, or other EBP treatment reduces the amount of microplastics in a fluid of a subject to an amount less than a detectable amount (e.g., using a measurement technique described herein or otherwise known to one of skill). In some embodiments, wherein the amount of microplastics in a fluid of a subject is assessed by measuring microplastics concentration in the fluid (e.g., on a mass / volume basis, such as pg / mL), a disclosed method reduces the amount of microplastics in the fluid by at least 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL, compared to the amount of microplastics in the fluid prior to treatment. In some embodiments, measuring the amount (e.g., the concentration) of microplastics in a fluid of a subject is performed by directly measuring a sample of the fluid. In some embodiments, measuring the amount (e.g., the concentration) of microplastics in a fluid of a subject is performed by measuring the amount of microplastics in the fluid indirectly. A fluid from a subject 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 such as any of blood, plasma, serum, urine, saliva, sweat, tears, cerebrospinal fluid (CSF), 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, and lavage fluid. Measurement techniques for measuring an amount of microplastics in a fluid from a subject are further described in embodiments herein.

[0106]

[0098] 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 the amount of microplastics, such as a concentration of microplastics in the blood, fluid, and / or tissue of the subject, which may be before or after a treatment, or an amount, such as a concentration, of microplastics in an eluate from the subject.

[0107]

[0099] In some embodiments, administering a DFPP, plasmapheresis, or other EBP treatment to a subject treats a condition, which in some embodiments includes preventing a condition or reducing the risk of a condition, such as a disease or disorder. In some aspects and embodiments, administering a treatment to a subject provides an improvement, such as an improvement to health, to healthspan, or to lifespan.

[0108] B. Selection of Subjects For Treatment

[0109]

[0100] Disclosed devices and methods for EBP to remove microplastics are useful for subjects, such as human subjects. In some aspects, the selection of subjects for treatment using such devices and methods is provided. In some embodiments, disclosed devices and methods are useful for subjects, such as human subjects, having an amount of microplastics in the blood, fluid, and / or tissue.

[0110]

[0101] In some embodiments, disclosed devices and methods are useful for a subject having an amount of microplastics in blood. In embodiments, the blood of a subject has a measurable amount of microplastics. Measurement of the amount of microplastics in the blood of a subject can be performed according to methods disclosed herein or known in the art.

[0111]

[0102] In some embodiments, disclosed devices and methods are useful for a subject having an amount of microplastics in tissue. In embodiments, a tissue of a subject has a measurable amount of microplastics, such as any tissue of the subject, which in some embodiments may be one or more specific tissues, as will be appreciated according to such embodiments. Measurement of the amount of microplastics in a tissue of a subject can be performed according to methods disclosed herein or known in the art.

[0112]

[0103] In some embodiments, disclosed devices and methods are useful for a subject having an amount of microplastics in an eluate from the subject. In embodiments, an eluate from a subject has a measurable amount of microplastics. Measurement of the amount of microplastics in an eluate from a subject can be performed according to methods disclosed herein or known in the art.

[0113]

[0104] In some embodiments, the disclosed devices and methods are useful for a subject having an amount of microplastics in a plasma fraction removed from the subject (e.g., plasma isolated during an EBP treatment). In some embodiments, a plasma fraction from a subject contains a measurable amount of microplastics. Measurement of the amount of microplastics in the removed plasma fraction can be performed according to methods herein or known in the art.

[0114]

[0105] In some embodiments, the disclosed devices and methods are useful for a subject having an amount of microplastics in an adsorbate recovered from an adsorption column or other adsorbent material of an extracorporeal circuit. In embodiments, an adsorbate from a subject, which may comprise one or more materials bound to the adsorbent, contains a measurable amount of microplastics. Measurement of the amount of microplastics in the adsorbate can be performed according to methods herein or known in the art.

[0115]

[0106] 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.

[0116]

[0107] In some embodiments, selecting a subject for treatment comprises measuring an amount of microplastics in a fluid of the subject, such as a sample of a fluid of the subject. Measuring an amount of microplastics “in a fluid of a subject” or “in a subject’s fluid” includes in some embodiments measuring the amount of microplastics in the fluid of the subject when the fluid is in the body of the subject. In some embodiments, it refers to measuring the amount of microplastics in the fluid of the subject when the fluid is obtained from the body of the subject. Fluids may be obtained according to known methods. 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, e.g., blood, plasma, serum, urine, saliva, sweat, tears, CSF, 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.

[0117]

[0108] In some embodiments, selecting a subject for treatment comprises measuring the concentration of microplastics in a fluid of the subject. In some embodiments, a subject may be selected for treatment if the concentration of microplastics in the fluid of the subject is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0118]

[0109] In some embodiments, selecting a subject for treatment comprises measuring an amount of microplastics in the blood of the subject, such as a sample of blood of the subject. Measuring an amount of microplastics “in the blood of a subject” or “in a subject’s blood” includes in some embodiments measuring the amount of microplastics in the subject’s blood when the blood is in the body of the subject. In some embodiments, it refers to measuring the amount of microplastics in the subject’s blood when the blood is withdrawn from the body of the subject. Blood may be withdrawn according to known methods.

[0119]

[0110] In some embodiments, selecting a subject for treatment comprises measuring the concentration of microplastics in the blood of the subject. In some embodiments, a subject may be selected for treatment if the concentration of microplastics in the blood of the subject is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0120]

[0111] In embodiments, “in the blood of a subject” or “from the blood of a subject” include “in a tissue of a subject” or “from a tissue of a subject,” and may be interpreted to mean “in the blood of a subject and / or in the tissue of a subject” (or “in the blood, fluid, and / or tissue of a subject,” and the like) or “from the blood of a subject and / or from the tissue of a subject” (or “from the blood, fluid, and / or tissue of a subject,” and the like), as context permits. Where context permits, the converse is also true, and reference to “tissue” includes blood.

[0121]

[0112] In some embodiments, selecting a subject for treatment comprises measuring an amount of microplastics in an eluate from the subject (e.g., an eluate from a DFPP treatment). Measuring an amount of microplastics “in an eluate from the subject” or “in a subject’s eluate” 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 other embodiments, the eluate of the subject is obtained using a disclosed method or using a disclosed device. In some embodiments, selecting a subject for treatment comprises measuring the concentration of microplastics in an eluate of the subject. In such embodiments, a subject may be selected for treatment if the concentration of microplastics in an eluate of the subject is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0122]

[0113] In some embodiments, selecting a subject for treatment comprises measuring an amount of microplastics in a tissue of the subject. Measuring an amount of microplastics “in a tissue of the subject” or “in a subject’s tissue” includes measuring the amount of microplastics 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 some embodiments, selecting a subject for treatment comprises measuring the concentration of microplastics in the tissue of the subject. In such embodiments, a subject may be selected for treatment if the concentration of microplastics in the tissue of the subject is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0123]

[0114] In some embodiments, selecting a subject for treatment comprises an assessment. Broadly, an “assessment” refers 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. A “computer-assisted” assessment includes any 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.

[0124]

[0115] 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 some embodiments, a subject may be selected for treatment if an assessment indicates that 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 microplastics in the subject’s blood, fluid, and / or tissue. An 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.

[0125]

[0116] In some embodiments, a subject is selected for treatment (i.e., according to one or more disclosed methods of selection and / or for treatment according to one or more disclosed methods) 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 the disclosed methods are useful to treat.

[0126]

[0117] 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 (i.e., known to those in the art, i.e., known in view of the teachings herein together with 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.

[0127]

[0118] In some embodiments, a subject is selected for treatment if the subject has a reproductive or fertility 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 if the subject is at risk of, a reproductive or fertility condition and the subject has a detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0119] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0128]

[0120] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0129]

[0121] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0130]

[0122] In some embodiments, a subject is selected for treatment if the subject has a gastrointestinal (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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0131]

[0123] In some embodiments, a subject is selected for treatment if the subject has a cardiovascular condition, including a cardiovascular disease 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 cardiovascular disease or a cardiometabolic condition. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a cardiovascular disease or a cardiometabolic condition, and the subject has a detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a cardiovascular disease or a cardiometabolic condition, and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0132]

[0124] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0133]

[0125] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, thrombosis and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0134]

[0126] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0135]

[0127] In some 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 the subject has a detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, inflammation or an inflammatory condition and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0136]

[0128] 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 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0137]

[0129] In some 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 detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, cancer and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0138]

[0130] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0139]

[0131] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0140]

[0132] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0141]

[0133] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0142]

[0134] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, ED and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0143]

[0135] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0144]

[0136] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0145]

[0137] 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 microplastics from their body. In some embodiments, dialysis, such as intermittent or continuous hemodialysis, introduces microplastics 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 microplastics 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 detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, an excretory system disorder and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0146]

[0138] In some 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0147]

[0139] 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 the subject has a detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a metabolic condition and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0148]

[0140] 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 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0149]

[0141] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0150]

[0142] In 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0151]

[0143] In some embodiments, a subject is selected for treatment if the subject has a complication from cholesterol crystals in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject is at risk of a complication from cholesterol crystals in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a complication from cholesterol crystals in their blood, fluid, and / or tissue and the subject has a detectable amount of cholesterol crystals in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, a complication from cholesterol crystals in their blood, fluid, and / or tissue and the subject has a concentration of cholesterol crystals in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0152]

[0144] In some 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 the subject has a detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject is recovering from a wound, injury, or surgery and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0153]

[0145] In some embodiments, a subject is selected for treatment if the subject has a diagnosed or diagnosable condition that is not etiologically linked to microplastics (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 has a detectable amount of micro-plastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject has, or is at risk of, the condition and has a concentration of micro-plastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL. In embodiments, the subject is selected for treatment if an elevated microplastic 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.

[0154]

[0146] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject is undergoing athletic performance training and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0155]

[0147] In some embodiments, a subject is selected for treatment to improve musculoskeletal health, e.g., 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 detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject is undergoing a musculoskeletal health treatment and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0156]

[0148] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject is undergoing a skin rejuvenation procedure and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0149] 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 detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject desires to improve their cognitive functioning and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0157]

[0150] 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 microplastic-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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0158]

[0151] In some embodiments, a subject is selected for treatment to increase the efficacy of a fertility treatment (e.g., 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 detectable amount of microplastics in their blood, fluid, and / or tissue. 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0159]

[0152] In some embodiments, a subject is selected for treatment to reduce the progression of aging in the subject (e.g., slowing the biological processes that drive functional decline, such as 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 detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject is undergoing a treatment to reduce their progression of aging and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0160]

[0153] In some embodiments, a subject is selected for treatment to promote, improve, enhance, or extend longevity in the subject (e.g., 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 detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject is undergoing a treatment to promote, improve, enhance, or extend longevity and has a concentration of microplastics in their blood, fluid, and / or tissue greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0161]

[0154] In some embodiments, a subject is selected for treatment to support weight loss or weight-maintenance objectives (e.g., reducing excess adiposity, maintaining a target body-mass index (BMI), or improving metabolic health markers such as insulin sensitivity or lipid profiles). In embodiments, a subject is selected for treatment if the subject desires to lose weight or maintain weight and the subject has a detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if 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 concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0162]

[0155] In some embodiments, a subject is selected for treatment if the subject has a symptom, condition, or complication caused by or associated with microplastics alone or in combination with co-transported environmental contaminants (e.g., heavy metals, per- and polyfluoroalkyl substances (PFAS), phthalates) present in the subject’s blood, fluid, and / or tissue. 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 microplastics alone or in combination with co-transported environmental contaminants in their blood, fluid, and / or tissue. Other than examples disclosed herein, a symptom, condition, or complication caused by or associated with microplastics alone or in combination with co-transported environmental contaminants in the blood, fluid, and / or tissue 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 microplastics alone or in combination with co-transported environmental contaminants in their blood, fluid, and / or tissue and the subject has a detectable amount of microplastics in their blood, fluid, and / or tissue. 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 microplastics alone or in combination with co-transported environmental contaminants in their blood, fluid, and / or tissue and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0163]

[0156] In some embodiments, a subject is selected for treatment if the subject was exposed to one or more environmental sources of microplastics. In embodiments, an environmental source of microplastics is any feature of a subject’s environment that is made from, contaminated by, or otherwise contains microplastics, or any other source of microplastics exogenous to the subject’s body, and which may introduce microplastics into the subject’s body. Examples of environmental sources of microplastics 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 microplastics 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 microplastics, and the subject has a detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject desires to reduce microplastics from one or more environmental sources in their body. In embodiments, a subject is selected for treatment if the subject desires to reduce microplastics from one or more environmental sources in their body, and the subject has a detectable amount of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject was exposed to one or more environmental sources of microplastics, or if the subject desires to reduce microplastics from one or more environmental sources in their body, and the subject has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0164]

[0157] In some embodiments, a subject is selected for treatment if the subject was exposed to one or more environmental sources of microplastics, and the subject is at risk of having microplastics in their blood, fluid, and / or tissue, 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 microplastics, and the subject is at an increased risk of having microplastics in their blood, fluid, and / or tissue, 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 microplastics, and the subject is at risk, or at an increased risk, of exposure to an environmental source of microplastics.

[0165]

[0158] Exposure to an environmental source of microplastics will be as understood in view of the disclosure, and includes for example living near a water source with elevated microplastics contamination, having an occupation requiring the handling of microplastics-containing materials, and other such risks, including increased risks, as will be known to those in the art. Occupational exposure includes working in, or living 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 some embodiments, exposure arises from indoor microplastic accumulation in offices, gyms, or industrial kitchens, or from residing near waterways, runoff zones, or atmospheric downwind plumes with elevated microplastic contamination. In embodiments, the subject at risk, or at an increased risk, of exposure to an environmental source of microplastics, has a concentration of microplastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0166]

[0159] In some embodiments, a subject is selected for treatment to mitigate microplastic 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 detectable amount of micro-plastics in their blood, fluid, and / or tissue. In embodiments, a subject is selected for treatment if the subject is preparing for or recovering from a closed-habitat deployment and the subject has a concentration of micro-plastics in their blood, fluid, and / or tissue that is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0167]

[0160] In some embodiments, a disclosed method further comprises: (i) determining the difference between the microplastics concentration in the blood, fluid, and / or tissue of the subject before administering a DFPP, plasmapheresis, or other EBP treatment and the microplastics concentration in the blood, fluid, and / or tissue of the subject after administering the DFPP, plasmapheresis, or other EBP treatment; and (ii) repeating the EBP treatment when the difference is greater than or less than an amount.

[0168]

[0161] 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.

[0162] 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 blood, fluid, and / or tissue 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 blood, fluid, and / or tissue 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 blood, fluid, and / or tissue 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 blood, fluid, and / or tissue of the subject before the treatment is less than an amount.

[0169]

[0163] 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 blood, fluid, and / or tissue 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 blood, fluid, and / or tissue 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 blood, fluid, and / or tissue 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 less than an amount, and the concentration in the blood, fluid, and / or tissue of the subject after the treatment is less than an amount.

[0170]

[0164] In some embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the difference is greater than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0171]

[0165] In some embodiments, the method comprises repeating the DFPP, plasmapheresis, or other EBP treatment when the difference is less than about 0.1 pg / mL, 0.2 pg / mL, 0.3 pg / mL, 0.4 pg / mL, 0.5 pg / mL, 0.6 pg / mL, 0.7 pg / mL, 0.8 pg / mL, 0.9 pg / mL, 1 pg / mL, 2 pg / mL, 3 pg / mL, 4 pg / mL, 5 pg / mL, 6 pg / mL, 7 pg / mL, 8 pg / mL, 9 pg / mL, or 10 pg / mL.

[0172]

[0166] In some embodiments, disclosed methods are useful for treating a subject, such as treating a condition in the subject. In embodiments, the subject is a human subject with a condition. In embodiments, the condition is caused by or associated with the presence of microplastics in the blood, fluid, and / or tissue of the subject. In embodiments, the subject has a measurable amount of microplastics in their blood, fluid, and / or tissue, but does not have a condition caused thereby or associated therewith. In embodiments, the subject has a measurable amount of microplastics in their blood, fluid, and / or tissue, but does not have any symptoms caused thereby or associated therewith.

[0167] In some embodiments, disclosed methods are useful for improving the health, healthspan, or lifespan of a subject. In some embodiments, the improvement in the health, healthspan, or lifespan of the subject is caused by a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0173] C. Blood Purification Devices and Systems Configured for Microplastic Removal

[0174]

[0168] In some aspects, extracorporeal blood purification devices and systems are provided that are configured for the removal of microplastics from the blood, fluid, and / or tissue of a subject, such as a human subject, including when used in the disclosed methods. Devices and systems for extracorporeal blood purification include apparatuses and configurations designed to remove microplastics from the blood or plasma of a subject, operating through filtration, adsorption, plasma separation, or combinations thereof. Exemplary EBP devices and systems include those for plasmapheresis, hemodialysis, and hemoperfusion.

[0175]

[0169] As used 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 demands otherwise, the terms “device” and “system” may be used interchangeably to refer to any apparatus, or combination of apparatuses, suitable for performing plasmapheresis, hemodialysis, hemoperfusion, or related blood purification processes. Where exemplary modalities are described, they may be referred to without repeating both terms in each instance.

[0176]

[0170] 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 microplastics 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).

[0177]

[0171] 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 typically 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 also include fluid replacement circuits and may be used in conjunction with hemofiltration or hemodiafiltration modalities. For removal of microplastics 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 particulate contaminants.

[0178]

[0172] 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. These systems may operate as standalone therapies or in conjunction with hemodialysis, hemofiltration, or plasmapheresis. For removal of microplastics according to the disclosed methods, the adsorption 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.

[0179]

[0173] Devices and systems for extracorporeal blood purification 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 these 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. Such systems may be configured or adapted to selectively remove microplastic particles based on size exclusion, charge, hydrophobic interactions, or other engineered binding or capture mechanisms.

[0180]

[0174] In embodiments, a DFPP or plasmapheresis 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 microplastics) from a plasma fraction; (7) a means for rinsing or flushing an eluate from the blood circuit; and (8) a means for collecting waste.

[0181]

[0175] In some embodiments, the plasmapheresis 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.

[0182]

[0176] In some embodiments, the DFPP or other plasmapheresis device comprises a means for removing a subject’s blood. In some embodiments, the DFPP or other plasmapheresis 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.

[0183]

[0177] In some embodiments, the DFPP or other plasmapheresis 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.

[0184]

[0178] In some embodiments, the DFPP or other plasmapheresis device comprises one or more means for supplying 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 plasmapheresis device. Examples of these and other suitable means are known in the art.

[0185]

[0179] In embodiments, the DFPP or other plasmapheresis 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.

[0186]

[0180] In some embodiments, the DFPP or other plasmapheresis 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.

[0187]

[0181] In some embodiments, the DFPP or other plasmapheresis 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.

[0188]

[0182] 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.

[0189]

[0183] In some embodiments, the DFPP or other plasmapheresis device comprises a second filter configured to capture microplastic particles 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 pm, the filter being permeable to dissolved plasma components while retaining particles greater than about 10 pm in diameter.

[0190]

[0184] In some embodiments, microplastics are filtered from the blood of a subject using double-filtration plasmapheresis (DFPP), such as by using a DFPP device. In some embodiments, microplastics are filtered from the blood of a subject using a DFPP device. Examples of DFPP 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 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, Switzerland, fully incorporated by reference herein, as if expressly set forth herein.

[0191]

[0185] 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. 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 microplastics from the plasma (thereby producing a DFPP eluate containing microplastics) 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.

[0192]

[0186] 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 microplastics) 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 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.

[0193]

[0187] 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.

[0194]

[0188] In some embodiments, the DFPP or other plasmapheresis 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.

[0195]

[0189] In some embodiments, the DFPP or other plasmapheresis 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 blood, fluid, and / or tissue 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, amberchrome, 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.

[0196]

[0190] In some embodiments, microplastics are filtered from the blood, fluid, and / or tissue 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.).

[0197]

[0191] 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 are generally known in the art and include, e.g., those disclosed in US4, 954,128 and US2021 / 0128811 , both incorporated by reference as if fully set forth herein.

[0198]

[0192] 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 known in the art.

[0199]

[0193] 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 are known in the art, and examples of rinsing and flushing fluids will be known in the art, suitable for use in disclosed embodiments.

[0200]

[0194] In some embodiments, the TPE device comprises a means for replacing a removed plasma fraction with a physiologically acceptable replacement fluid. Such means include, for example, a replenishment pump and reservoir, albumin solution, or another colloid / crustalloid having a microplastic content below a predefined threshold relative to the subject’s plasma. Examples of these and other suitable replacement-fluid delivery systems will be known in the art, suitable for use in disclosed embodiments.

[0201]

[0195] 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.

[0202]

[0196] In some embodiments, microplastics are filtered from the blood, fluid, and / or tissue 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 disclosed methods, including as taught by and will be appreciated in view of the disclosure, include the HF440 (Infomed SA, Switzerland), those disclosed in US6,960,178 and US4, 215,688, both incorporated by reference as if fully set forth herein.

[0203]

[0197] 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., microplastics) from a plasma fraction; (8) a means for rinsing or flushing waste from the blood circuit; and (9) a means for collecting waste.

[0204]

[0198] 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.

[0205]

[0199] In some embodiments, the PP device comprises a means for separating a target substance (e.g., microplastics) 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, but are not limited to, 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 known in the art.

[0206]

[0200] In some embodiments, microplastics are filtered from the blood, fluid, and / or tissue 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.

[0207]

[0201] 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) a means for separating an ultrafiltrate from a cellular fraction; (7) a means for separating a target substance (e.g., microplastics) from a plasma fraction; (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.

[0208]

[0202] In some embodiments, the CPFA 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 membrane filter. Examples of these and other suitable means are known in the art.

[0209]

[0203] 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 designed to allow water and other low molecular weight molecules (e.g., an ultrafiltrate) to pass while retaining blood cells and large molecules, as will be known to those of skill.

[0210]

[0204] In some embodiments, the CPFA device comprises a means for separating a target substance (e.g., microplastics) 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, but are not limited to, 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.

[0211]

[0205] 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 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.

[0212]

[0206] In some embodiments, the plasmapheresis device comprises a first membrane filter. In some embodiments, the plasmapheresis device comprises a first membrane filter and a second membrane filter.

[0213]

[0207] 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.

[0214]

[0208] 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.

[0215]

[0209] 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.

[0216]

[0210] 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.

[0217]

[0211] 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.

[0218]

[0212] 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.

[0219]

[0213] In some 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.

[0220]

[0214] 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.

[0221]

[0215] In some embodiments, a first membrane filter has a pore size of between about 300 nm and about 1000 nm. 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.

[0222]

[0216] In some embodiments, a first membrane filter has a pore size of between about 300 nm and about

[0223] 400 nm. In embodiments, a first membrane filter has a pore size of between about 400 nm and about 500 nm.

[0224] 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.

[0225]

[0217] In some 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.

[0226]

[0218] In some embodiments, a first membrane filter is structured or selected to be permeable to particles (e.g., microplastics) having a molecular weight (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., microplastics) 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 less than about 5 kDa, 10 kDa, 20 kDa, 30 kDa, 40 kDa, 50 kDa, 60 kDa, 70 kDa, 80 kDa, 90 kDa, 100 kDa, 110 kDa, 120 kDa, 130 kDa, 140 kDa,

[0227] 150 kDa, 160 kDa, 170 kDa, 180 kDa, 190 kDa, 200 kDa, 250 kDa, 300 kDa, 350 kDa, 400 kDa, 450 kDa, 500 kDa, 550 kDa, 600 kDa, 650 kDa, 700 kDa, 750 kDa, 800 kDa, 850 kDa, 900 kDa, 950 kDa, or 1000 kDa. In embodiments, a first membrane filter is structured or selected to be impermeable to particles having a MW greater than about 5 kDa, 10 kDa, 20 kDa, 30 kDa, 40 kDa, 50 kDa, 60 kDa, 70 kDa, 80 kDa, 90 kDa, 100 kDa, 110 kDa, 120 kDa, 130 kDa, 140 kDa, 150 kDa, 160 kDa, 170 kDa, 180 kDa, 190 kDa, 200 kDa, 250 kDa, 300 kDa, 350 kDa, 400 kDa, 450 kDa, 500 kDa, 550 kDa, 600 kDa, 650 kDa, 700 kDa, 750 kDa, 800 kDa, 850 kDa, 900 kDa, 950 kDa, or 1000 kDa.

[0228]

[0219] In some embodiments, a DFPP or other plasmapheresis device comprises a second membrane filter useful for the removal of microplastics from a plasma fraction. In embodiments, a second membrane filter is structured or adapted to be permeable to plasma while rejecting microplastics.

[0220] 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.

[0229]

[0221] In some embodiments, a second membrane filter has a pore size of between about 1 nm and about

[0230] 100 nm. In embodiments, a second membrane filter has a pore size of between about 5 nm and about 100 nm. In embodiments, a second membrane filter has a pore size of between about 10 nm and about 100 nm. In embodiments, a second membrane filter has a pore size of between about 20 nm and about 100 nm. In embodiments, a second membrane filter has a pore size of between about 30 nm and about 100 nm. In embodiments, a second membrane filter has a pore size of between about 40 nm and about 100 nm. In embodiments, a second membrane filter has a pore size of between about 50 nm and about 100 nm. In embodiments, a second membrane filter has a pore size of between about 60 nm and about 100 nm. In embodiments, a second membrane filter has a pore size of between about 70 nm and about 100 nm. In embodiments, a second membrane filter has a pore size of between about 80 nm and about 100 nm. In embodiments, a second membrane filter has a pore size of between about 90 nm and about 100 nm.

[0231]

[0222] In some embodiments, a second membrane filter has a pore size of less than 100 nm. In embodiments, a second membrane filter has a pore size of less than 90 nm. In embodiments, a second membrane filter has a pore size of less than 80 nm. In embodiments, a second membrane filter has a pore size of less than 70 nm. In embodiments, a second membrane filter has a pore size of less than 60 nm. 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.

[0232]

[0223] In some embodiments, a second membrane filter is structured or selected to be permeable to particles (e.g., microplastics) 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., microplastics) 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,

[0233] 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,

[0234] 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.

[0235]

[0224] 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.

[0236]

[0225] 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 microplastics 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 microplastics 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.

[0237]

[0226] 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 microplastics (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.

[0238]

[0227] In some embodiments, a DFPP, plasmapheresis, or other EBP treatment is conducted at a specified

[0239] 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. In embodiments, an EBP treatment is conducted at a TMP between about 30 and about 150 mmHg.

[0240] 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 600 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 embodiments, an EBP treatment is conducted at a TMP between about 300 and about 400 mmHg. In embodiments, an EBP treatment is conducted at a TMP between about 400 and about 500 mmHg. In embodiments, an EBP treatment is conducted at a TMP greater than about 500 mmHg.

[0241]

[0228] In some 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 between above about 450 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a first membrane filter above about 500 mmHg. In embodiments, an EBP treatment is conducted at a TMP of a first membrane filter above about 550 mmHg.

[0242]

[0229] 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.

[0243]

[0230] 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.

[0244]

[0231] In embodiments, microplastics are filtered from the blood, fluid, and / or tissue of a subject with an EBP device, or using an EBP treatment, such as by using an EBP device.

[0245]

[0232] In embodiments, an EBP device is a hemodialysis device, a hemofiltration device, a hemodiafiltration device, a hemoperfusion device, or an ultrafiltration device.

[0246]

[0233] In some embodiments, the EBP device is used together with an additional EBP treatment. In some embodiments, the additional EBP treatment is a plasmapheresis treatment, such as using a plasmapheresis device. In some embodiments, the additional EBP treatment is a DFPP treatment, such as using a DFPP device. In some embodiments, the additional EBP treatment is a TPE treatment, such as using a TPE device. In some embodiments, the additional EBP treatment is a PP treatment, such as using a PP device. In some embodiments, the additional EBP treatment is a PA treatment, such as using a PA device. In some embodiments, the additional EBP treatment is a CPFA treatment, such as using a CPFA device.

[0247]

[0234] In embodiments, the EBP device is used together with a plasmapheresis treatment, such as using a plasmapheresis device. In embodiments, the EBP device is used together with a DFPP treatment, such as using a DFPP device. In embodiments, the EBP device is used together with a TPE treatment, such as using a TPE device. In embodiments, the EBP device is used together with a PP treatment, such as using a PP device. In embodiments, the EBP device is used together with a PA treatment, such as using a PA device. In embodiments, the EBP device is used together with a CPFA treatment, such as using a CPFA device.

[0248]

[0235] 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 some 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, about 24 hours, about 48 hours, about 72 hours, and about 1 week, including periods in between. In some 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 some 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 some 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 some embodiments, “at the same time as” means the two treatments are provided on the same day. In some 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 some embodiments, “at the same time as” means the two treatments are provided concurrently.

[0249]

[0236] In some embodiments, microplastics 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 some embodiments, microplastics are filtered from the blood of a subject using a hemodialysis device together with an additional EBP treatment.

[0250]

[0237] In some embodiments, microplastics 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.,

[0251] US2005 / 0082210. In some embodiments, microplastics are filtered from the blood of a subject using a hemofiltration device together with an additional EBP treatment.

[0252]

[0238] In some embodiments, microplastics 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.,

[0253] US10,322,220 and EP2280748B1 (Wallenborg et al.). In some embodiments, microplastics are filtered from the blood of a subject using a hemodiafiltration device together with an additional EBP treatment.

[0254]

[0239] In some embodiments, microplastics 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 some embodiments, microplastics are filtered from the blood of a subject using a hemoperfusion device together with an additional EBP treatment.

[0255]

[0240] In some embodiments, microplastics 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 some embodiments, microplastics are filtered from the blood of a subject using an ultrafiltration device together with an additional EBP treatment.

[0256]

[0241] 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 microplastics) from whole blood.

[0257]

[0242] 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).

[0258]

[0243] 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 some embodiments, an EBP device comprises one device configuration, or performs one blood filtration method. In some embodiments, an EBP device comprises more than one device configuration, or performs more than one blood filtration method.

[0259]

[0244] 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 some 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).

[0260] D. Measuring Microplastics In or From the Tissue, Blood, or Other Fluid of Subjects

[0261]

[0245] In some aspects are provided methods which comprise measuring an amount of microplastics. In some embodiments, a method comprises measuring an amount of microplastics in the blood, fluid, and / or tissue of a subject, such as a subject administered a treatment using a disclosed device, system, or method.

[0262]

[0246] In embodiments, a method comprises measuring an amount of microplastics in a fluid of a subject. In embodiments, a method comprises measuring an amount of microplastics in the blood of a subject. In embodiments, a method comprises measuring an amount of microplastics in a fluid other than the blood of a subject, i.e., in a non-blood fluid of the subject, including a non-blood biological fluid of the subject. In embodiments, the non-blood biological fluid of a subject is an interstitial fluid of the subject. In embodiments, the non-blood fluid of a subject is an eluate derived from the subject, such as a DFPP eluate obtained during a DFPP treatment administered to the subject.

[0263]

[0247] In some embodiments, measuring an amount of microplastics comprises measuring the amount of microplastics in the blood, fluid, and / or tissue of a subject prior to administering a DFPP, plasmapheresis, or other EBP treatment. In some embodiments, measuring the amount of microplastics comprises measuring the amount of microplastics in the blood, fluid, and / or tissue of a subject after administering a DFPP, plasmapheresis, or other EBP treatment. In some embodiments, measuring the amount of microplastics comprises measuring the amount of microplastics in the blood, fluid, and / or tissue of a subject both prior to and after administering a DFPP, plasmapheresis, or other EBP treatment. In some embodiments, measuring the amount of microplastics comprises measuring the amount of microplastics in the blood, fluid, and / or tissue of a subject during administration of a DFPP, plasmapheresis, or other EBP treatment. In some embodiments, measuring an amount of microplastics comprises measuring the amount of microplastics in the eluate from a subject after administering a DFPP, plasmapheresis, or other EBP treatment. In some embodiments, measuring the amount of microplastics comprises measuring the amount of microplastics in the eluate from a subject during administration of a DFPP, plasmapheresis, or other EBP treatment. In some embodiments, measuring the amount of microplastics comprises measuring the amount of microplastics in the eluate from a subject both during and after administering a DFPP, plasmapheresis, or other EBP treatment.

[0264]

[0248] In some embodiments, measuring an amount of microplastics comprises measuring a concentration of microplastics. A “concentration” of microplastics refers to an amount, e.g., a number of pieces, a volume, a mass, of microplastics per unit volume of fluid, such as per unit volume of blood, or per unit volume of eluate.

[0265]

[0249] In some embodiments, measuring an amount of microplastics comprises measuring a composition of microplastics. A “composition” of microplastics refers to one or more characteristics of the microplastics present in a sample, such as their chemical makeup (e.g., polymer type), physical properties (e.g., size distribution, shape, surface morphology), or associated substances (e.g., adsorbed toxins, metals, or biofilms).

[0266]

[0250] Numerous analytical techniques are suitable for measuring microplastic composition and / or concentration in fluids, as described herein and as otherwise known to those of skill in the art. In some embodiments, measuring a composition and / or concentration of microplastics comprises a spectroscopy method, such as Fourier-transform infrared (FTIR) spectroscopy, micro Fourier-transform infrared (pFTIR) spectroscopy, nano Fourier-transform infrared (nFTIR) spectroscopy, Raman spectroscopy, Raman micro-spectroscopy (pRaman), near-infrared (NIR) spectroscopy, or laser direct infrared (LDIR) spectroscopy.

[0267]

[0251] In some embodiments, measuring a composition and / or concentration of microplastics comprises a microscopy technique, such as optical microscopy or electron microscopy, optionally in combination with a digital imaging means (e.g., a digital camera) and artificial intelligence (Al)-based image analysis. In some embodiments, measuring a composition and / or concentration of microplastics comprises a mass spectrometry technique, including tandem MS / MS methods, optionally combined with chromatography (e.g., gas chromatography-mass spectrometry (GC-MS), pyrolysis-GC-MS (Py-GC-MS), thermal extraction desorption-GC-MS (TED-GC-MS), liquid chromatography-mass spectrometry (LC-MS), or high-performance liquid chromatography-mass spectrometry (HPLC-MS)). In some embodiments, measuring a composition and / or concentration of microplastics comprises a light scattering technique (e.g., static light scattering, dynamic light scattering (DLS), or nanoparticle tracking analysis (NTA)), a laser diffraction analysis, or an optofluidic force induction (0F2i) technique. In some embodiments, measuring a composition and / or concentration of microplastics comprises a flow cytometry method or an electrical sensing zone technique (e.g., Coulter counter). In some embodiments, acoustic spectroscopy, analytical ultracentrifugation, atomic force microscopy (AFM), small-angle X-ray scattering (SAXS), or resistive pulse sensing (RPS) is used. Other suitable analytical techniques for measuring microplastic composition and / or concentration, including by chemical, mechanical, or optical analysis, will be appreciated by those of skill. These techniques may be used alone or in combination, and may be used together with additional steps such as sample pre-processing, calibration with standards, or coupling with imaging, particle counting, or Al-based classification techniques.

[0268]

[0252] In some embodiments, measuring a composition and / or concentration of microplastics in a sample (wherein “sample” includes any of blood, biological fluid, tissue, eluate, and the like from a subject) comprises analyzing the sample using FTIR spectroscopy. In some embodiments, measuring a concentration of microplastics in a sample comprises analyzing the sample using Raman spectroscopy (see, e.g., Xu et al. Trends Anal Chem. 2019;119:115629). In some embodiments, measuring a composition and / or concentration of microplastics in a sample comprises analyzing the sample using FTIR spectroscopy, which may be further coupled to a microscopy technique (e.g., FTIR microscopy) (see, e.g., Leonard et al. Environ Int. 2024; 118:108751 ). In some embodiments, measuring a composition and / or concentration of microplastics in a sample comprises analyzing the sample using Raman spectroscopy, which may be further coupled to a microscopy technique (e.g., Raman microscopy) (see, e.g., Araujo et al. Water Res. 2018;142:426-440).

[0269]

[0253] In some embodiments, measuring a composition and / or concentration of microplastics in a sample comprises analyzing the sample using LDIR spectroscopy (see, e.g., Ourgaud et al. Environ Sci Technol. 2022;56(14): 9999-10009). In some embodiments, measuring a composition and / or concentration of microplastics in a sample comprises analyzing the sample using flow cytometry (see, e.g., Tse et al. Water. 2022; 14(9): 1436 and Bianco et al. Environ Chem Lett. 2022;21 :647-653). In some embodiments, measuring a composition and / or concentration of microplastics in a sample comprises analyzing the sample using NIR spectroscopy (see, e.g., Scholkmann & Tsenkova. Molecules. 2022;27(12):3947). In some embodiments, measuring a composition and / or concentration of microplastics in a sample comprises analyzing the sample using mass spectrometry (MS), including gas chromatography-MS (e.g., GC-MS, Py-GC-MS, TED-GC-MS), liquid chromatography-MS (e.g., LC-MS, HPLC-MS), and tandem MS (i.e., MS / MS; such as LC-MS / MS and the like.) (see, e.g., Peng et al. Anal. Chem. 2020;(92)20: 13930-13935; Zhang et al. Anal Chem. 2020;92(6):4656— 4662). In some embodiments, measuring a composition and / or concentration of microplastics in a sample comprises analyzing the sample using more than one measuring technique (see, e.g., Nueper et al. Anal Chem. 2024;96(21):8291 -8299).

[0270]

[0254] In some embodiments, measuring a composition and / or concentration of microplastics in a sample comprises the use of one or more fluorescent dyes in combination with microscopy. Fluorescent dyes may be selected to preferentially bind to or adsorb onto microplastic particles, enhancing optical visibility and enabling discrimination from background biological or non-plastic 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 microplastics in the sample. Further embodiments may include compositional analysis based on dye affinity profiles or quantitative assessment based on particle counts or relative fluorescence intensity.

[0271] E. Administering Extracorporeal Blood Purification (EBP) Treatments to Subjects

[0272]

[0255] In some aspects are provided methods of administering extracorporeal blood purification (EBP) treatments to subjects, such as human subjects, using an extracorporeal blood purification (EBP) device.

[0273]

[0256] Exemplary methods comprise administering EBP treatments to subjects using a plasmapheresis device, a DFPP device, a TPE device, a PP device, a PA device, or a CPFA device. In some embodiments, the method comprises administering an EBP treatment to a subject using a plasmapheresis device. In some embodiments, the method comprises administering an EBP treatment to a subject using a DFPP device. In some embodiments, the method comprises administering an EBP treatment to a subject using a TPE device. In some embodiments, the method comprises administering an EBP treatment to a subject using a PP device. In some embodiments, the method comprises administering an EBP treatment to a subject using a PA device. In embodiments, the method comprises administering an EBP treatment to a subject using a CPFA device.

[0274]

[0257] Further exemplary methods comprise administering EBP treatments to subjects using a hemodialysis device, a hemofiltration device, a hemodiafiltration device, a hemoperfusion device, or an ultrafiltration device. In some embodiments, the method comprises administering an EBP treatment to a subject using a hemodialysis device. In some embodiments, a method comprises administering an EBP treatment to a subject using a hemofiltration device. In some embodiments, a method comprises administering an EBP treatment to a subject using a hemoperfusion device. In some embodiments, a method comprises administering an EBP treatment to a subject using an ultrafiltration device.

[0275]

[0258] FIG. 2 illustrates an exemplary EBP circuit 200. In some implementations, the EBP circuit 200 could be used as part of a EBP treatment such as DFPP. Whole blood is received from a subject 202. The whole blood passes through a first filter 204. The first filter 204 separates the whole blood into a cellular fraction and a plasma fraction. The plasma fraction passes through a second filter 206. The second filter 206 removes microplastics from the plasma fraction to provide a filtered plasma fraction. The filtered plasma fraction is combined with the cellular fraction, and the combin

[0276]

[0259] A “treatment,” such as a DFPP, plasmapheresis, or other EBP treatment, refers to a single session of the DFPP, plasmapheresis, or other EBP treatment administered to a subject using a DFPP, plasmapheresis, or other EBP device, such as a single session in which the subject is connected to the DFPP, plasmapheresis, or other EBP device, the blood of the subject is filtered using the DFPP, plasmapheresis, or other EBP device, and the subject is disconnected from the DFPP, plasmapheresis, or other EBP device.

[0277]

[0260] In some embodiments, microplastics are filtered from the blood, fluid, and / or tissue 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. In some embodiments, microplastics are filtered from the blood, fluid, and / or tissue 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.

[0278]

[0261] An exemplary administration of a DFPP treatment using a DFPP device is described in the Examples.

[0279]

[0262] In some embodiments, the amount of microplastics in one or more of a subject’s tissues is reduced by administering to the subject an EBP treatment, such as using an EBP device, according to a disclosed method. A “tissue” may be any tissue in the subject. In some embodiments, the amount of microplastics in one or more of a subject’s organs is reduced by administering to the subject an EBP treatment, using an EBP device, according to a disclosed method. An “organ” may be any organ in the subject. In some embodiments, the amount of microplastics in a subject’s body is reduced by administering to the subject an EBP treatment, using an EBP device, according to a disclosed method.

[0280]

[0263] In some embodiments, the amount of microplastics in one or more of a subject’s tissues is reduced by administering to the subject a plasmapheresis treatment, such as using a plasmapheresis device, according to a disclosed method. In some embodiments, the amount of microplastics in one or more of a subject’s organs is reduced by administering to the subject a plasmapheresis treatment, using a plasmapheresis device, according to a disclosed method. In some embodiments, the amount of microplastics in a subject’s body is reduced by administering to the subject a plasmapheresis treatment, using a plasmapheresis device, according to a disclosed method.

[0281]

[0264] In some embodiments, the amount of microplastics in one or more of a subject’s tissues is reduced by administering to the subject a DFPP treatment, using a DFPP device, according to a disclosed method. In some embodiments, the amount of microplastics in one or more of a subject’s organs is reduced by administering to the subject a DFPP treatment, using a DFPP device, according to a disclosed method. In some embodiments, the amount of microplastics in a subject’s body is reduced by administering to the subject a DFPP treatment, using a DFPP device, according to a disclosed method.

[0282]

[0265] In some embodiments, the amount of microplastics in one or more of a subject’s tissues is reduced by administering to the subject a TPE treatment, such as using a TPE device, according to a disclosed method. In some embodiments, the amount of microplastics in one or more of a subject’s organs is reduced by administering to the subject a TPE treatment, such as using a TPE device, according to a disclosed method. In some embodiments, the amount of microplastics in a subject’s body is reduced by administering to the subject a TPE treatment, such as using a TPE device, according to a disclosed method.

[0266] In some embodiments, the amount of microplastics in one or more of a subject’s tissues is reduced by administering to the subject a PP treatment, such as using a PP device, according to a disclosed method. In some embodiments, the amount of microplastics in one or more of a subject’s organs is reduced by administering to the subject a PP treatment, such as using a PP device, according to a disclosed method. In some embodiments, the amount of microplastics in a subject’s body is reduced by administering to the subject a PP treatment, such as using a PP device, according to a disclosed method.

[0283]

[0267] In some embodiments, the PP treatment is a PA treatment. In some embodiments, the amount of microplastics in one or more of a subject’s tissues is reduced by administering to the subject a PA treatment, such as using a PA device, according to a disclosed method. In some embodiments, the amount of microplastics in one or more of a subject’s organs is reduced by administering to the subject a PA treatment, such as using a PA device, according to a disclosed method. In some embodiments, the amount of microplastics in a subject’s body is reduced by administering to the subject a PA treatment, such as using a PA device, according to a disclosed method.

[0284]

[0268] In some embodiments, the amount of microplastics in one or more of a subject’s tissues is reduced by administering to the subject a CPFA treatment, such as using a CPFA device, according to a disclosed method. In some embodiments, the amount of microplastics in one or more of a subject’s organs is reduced by administering to the subject a CPFA treatment, such as using a CPFA device, according to a disclosed method. In some embodiments, the amount of microplastics in a subject’s body is reduced by administering to the subject a CPFA treatment, such as using a CPFA device, according to a disclosed method.

[0285]

[0269] In some embodiments, the amount of microplastics in one or more of a subject’s tissues is reduced by administering to the subject a hemodialysis treatment, such as using a hemodialysis device, according to a disclosed method. In some embodiments, the amount of microplastics in one or more of a subject’s organs is reduced by administering to the subject a hemodialysis treatment, such as using a hemodialysis device, according to a disclosed method. In some embodiments, the amount of microplastics in a subject’s body is reduced by administering to the subject a hemodialysis treatment, such as using a hemodialysis device, according to a disclosed method.

[0286]

[0270] In some embodiments, the amount of microplastics in one or more of a subject’s tissues is reduced by administering to the subject a hemofiltration treatment, such as using a hemofiltration device, according to a disclosed method. In some embodiments, the amount of microplastics in one or more of a subject’s organs is reduced by administering to the subject a hemofiltration treatment, such as using a hemofiltration device, according to a disclosed method. In some embodiments, the amount of microplastics in a subject’s body is reduced by administering to the subject a hemofiltration treatment, such as using a hemofiltration device, according to a disclosed method.

[0287]

[0271] In some embodiments, the amount of microplastics in one or more of a subject’s tissues is reduced by administering to the subject a hemodiafiltration treatment, such as using a hemodiafiltration device, according to a disclosed method. In some embodiments, the amount of microplastics in one or more of a subject’s organs is reduced by administering to the subject a hemodiafiltration treatment, such as using a hemodiafiltration device, according to a disclosed method. In some embodiments, the amount of microplastics in a subject’s body is reduced by administering to the subject a hemodiafiltration treatment, such as using a hemodiafiltration device, according to a disclosed method.

[0288]

[0272] In some embodiments, the amount of microplastics in one or more of a subject’s tissues is reduced by administering to the subject a hemoperfusion treatment, such as using a hemoperfusion device, according to a disclosed method. In some embodiments, the amount of microplastics in one or more of a subject’s organs is reduced by administering to the subject a hemoperfusion treatment, such as using a hemoperfusion device, according to a disclosed method. In some embodiments, the amount of microplastics in a subject’s body is reduced by administering to the subject a hemoperfusion treatment, such as using a hemoperfusion device, according to a disclosed method.

[0289]

[0273] In some embodiments, the amount of microplastics in one or more of a subject’s tissues is reduced by administering to the subject an ultrafiltration treatment, such as using an ultrafiltration device, according to a disclosed method. In some embodiments, the amount of microplastics in one or more of a subject’s organs is reduced by administering to the subject an ultrafiltration treatment, such as using an ultrafiltration device, according to a disclosed method. In some embodiments, the amount of microplastics in a subject’s body is reduced by administering to the subject an ultrafiltration treatment, such as using an ultrafiltration device, according to a disclosed method.

[0290]

[0274] In a subject, according to disclosed embodiments, and without being bound by theory, an equilibrium or stasis exists between microplastics accumulated in one or more tissues and microplastics circulating in the blood. In some embodiments, the removal of circulating microplastics by a DFPP, plasmapheresis, or other EBP treatment creates a diffusion gradient between the tissue(s) and the blood in the subject, whereby microplastics are pulled from the former to the latter, and in some embodiments, filtered from the latter according to disclosed methods. In some embodiments, DFPP, plasmapheresis, and other EBP treatments, such as second and subsequent EBP treatments administered to a subject according to a disclosed treatment regimen, will filter microplastics that have diffused from tissue to blood in the subject, with the net effect that the amount of microplastics in the subject, including that in blood and tissues, is reduced, and in some embodiments continues to be further reduced in the body of the subject, including in the blood and tissues of the subject, by subsequent EBP treatments administered by disclosed methods.

[0291]

[0275] In some embodiments, a disclosed method comprises administering a DFPP, plasmapheresis, or other EBP treatment for a specified treatment duration. In some embodiments, the treatment duration refers to the time at which a subject administered a DFPP, plasmapheresis, or other EBP treatment is connected to a DFPP, plasmapheresis, or other EBP device, until the time at which the subject is disconnected from the device. In some embodiments, the treatment duration refers to the time during which the subject’s blood is filtered using the device, the time the device is run during administration, or a time interval set by the device as the treatment duration.

[0292]

[0276] In some 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.

[0293]

[0277] In some embodiments, a disclosed method comprises administering a DFPP, plasmapheresis, or other EBP treatment at a specified temperature. In some embodiments, the temperature of a treatment refers to a temperature set by the a DFPP, plasmapheresis, or other EBP device as the treatment temperature. In some embodiments, the temperature of a treatment refers to the temperature set by the a DFPP, plasmapheresis, or other 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. For example, in some embodiments, a DFPP, plasmapheresis, or other EBP device comprises a heater that can be set to a temperature of between about 35 °C and about 38 °C. In some embodiments, the temperature of a treatment refers to the temperature of the subject. In some 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, 38.0 °C. In embodiments, the temperature is less than about 35.0 °C. In embodiments, the temperature is greater than about 38.0 °C.

[0294] F. Treatment Regimens for Extracorporeal Blood Purification

[0295]

[0278] In some aspects are provided treatment regimens for administering extracorporeal blood purification (EBP) procedures to a subject, such as a human subject, including to reduce an amount of microplastics in the blood, fluid, and / or tissue of the subject (i.e., an “EBP treatment regimen” or simply a “treatment regimen”).

[0296]

[0279] In some embodiments, a treatment regimen includes administering an additional health treatment, including one or more of lifestyle interventions, adjuvant therapeutic interventions, supportive health modalities, integrative detoxification therapies, and systemic bioenhancement therapies in conjunction with the EBP treatment. Additional health treatments also include the administration of one or more supplements.

[0297]

[0280] FIG. 1 illustrates an exemplary treatment regimen. At block 102, a subject is selected for therapy on the basis of a pre-treatment assessment (e.g., toxin panel, clinical history, physical exam). At block 104, 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 106, the plasmapheresis treatment is administered to reduce the subject’s microplastic burden. The dashed blocks represent optional feedback operations: block 108 comprises measuring one or more treatment-associated metrics (e.g., post-session micro-plastic load, inflammatory markers, hemodynamic parameters); block 110 comprises dynamically adjusting one or more treatment variables (e.g., filter pore size, flow rate, session length, replacement-fluid composition) in view of those measurements, after which the method may loop back to block 106 for a modified session. At block 112, 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.

[0298]

[0281] In some embodiments, a treatment regimen comprises administering two or more EBP treatments to a subject, such as two or more plasmapheresis treatments, such as two or more DFPP treatments.

[0299]

[0282] In some embodiments, a treatment regimen comprises administering two or more DFPP, plasmapheresis, or other EBP treatments to the subject, including three EBP treatments, four EBP treatments, five EBP treatments, six EBP treatments, seven EBP treatments, eight EBP treatments, nine EBP treatments, 10 EBP treatments, and more than 10 EBP treatments. In some embodiments, a treatment regimen comprises administering at least two DFPP, plasmapheresis, or other EBP treatments, including at least three EBP treatments, at least four EBP treatments, at least five EBP treatments, at least six EBP treatments, at least seven EBP treatments, at least eight EBP treatments, at least nine EBP treatments, and at least 10 EBP treatments. In some embodiments, a treatment regimen comprises administering more than two DFPP, plasmapheresis, or other EBP treatments, including more than three EBP treatments, more than four EBP treatments, more than five EBP treatments, more than six EBP treatments, more than seven EBP treatments, more than eight EBP treatments, more than nine EBP treatments, and more than 10 EBP treatments. In embodiments, a treatment regimen comprises administering to a subject two plasmapheresis treatments, three plasmapheresis treatments, four plasmapheresis treatments, five plasmapheresis treatments, six plasmapheresis treatments, seven plasmapheresis treatments, eight plasmapheresis treatments, nine plasmapheresis treatments, 10 plasmapheresis treatments, or more than 10 plasmapheresis treatments. In embodiments, a treatment regimen comprises administering to a subject two DFPP treatments, three DFPP treatments, four DFPP treatments, five DFPP treatments, six DFPP treatments, seven DFPP treatments, eight DFPP treatments, nine DFPP treatments, 10 DFPP treatments, or more than 10 DFPP treatments.

[0300]

[0283] In some embodiments, a treatment regimen comprises administering a combination of EBP treatments to the subject. In embodiments, a treatment regimen comprises one or more DFPP treatments and one or more other EBP treatments. In embodiments, a treatment regimen comprises one or more DFPP treatments and one or more other plasmapheresis treatments. In embodiments, a treatment regimen comprises administering one or more DFPP treatments and one or more TPE treatments. In embodiments, a treatment regimen comprises administering one or more DFPP treatments and one or more PP treatments. In embodiments, a treatment regimen comprises administering one or more DFPP treatments and one or more PA treatments. In embodiments, a treatment regimen comprises administering one or more DFPP treatments and one or more CPFA treatments. In embodiments, a treatment regimen comprises administering one or more DFPP treatments and one or more hemodialysis treatments. In embodiments, a treatment regimen comprises administering one or more DFPP treatments and one or more hemofiltration treatments. In embodiments, a treatment regimen comprises administering one or more DFPP treatments and one or more hemodiafiltration treatments. In embodiments, a treatment regimen comprises administering one or more DFPP treatments and one or more hemoperfusion treatments. In embodiments, a treatment regimen comprises administering one or more DFPP treatments and one or more ultrafiltration treatments.

[0301]

[0284] Where a treatment regimen comprises administering two or more EBP treatments to the subject, 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 multiple days, at least one week, at least multiple weeks, at least one month, at least multiple weeks, at least one year, and at least multiple years. A “multiple” may be any number greater than 1 , including a non-integer number.

[0302]

[0285] Where a treatment regimen comprises administering two different EBP treatments to the subject, such as a DFPP treatment and a TPE treatment, the DFPP treatment may be administered before or after the other EBP treatment in the regimen. In embodiments, the DFPP treatment is before the other EBP treatment in the regimen. In embodiments, the DFPP treatment is after the other EBP treatment in the regimen. In embodiments, the DFPP treatment is between two other EBP treatments in the regimen.

[0303]

[0286] In some embodiments, each treatment in a series of treatments greater than two is administered after the same period of time. In other embodiments, each treatment in a series of treatments greater than two is administered after a different period of time. In embodiments, the period of time between treatments is preselected in advance of the first treatment, such as according to a disclosed protocol or a protocol known in the art. In other embodiments, the period of time between treatments is determined after the first treatment, such as based on a measurement of an amount of microplastics in the blood, fluid, and / or tissue of the subject. In embodiments, the period of time between treatments is determined after each treatment, and before the following treatment, such as based on a measurement of an amount of microplastics in the blood, fluid, and / or tissue of the subject, which in some embodiments is compared to one or more previous measurement(s), or a number calculated based on one or more previous measurement(s).

[0304]

[0287] In embodiments, one or more EBP treatments are 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. In some embodiments, one or more EBP treatments are 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, using a compact cart-mounted device operated by trained clinical staff during a same-day visit. In some embodiments, one or more EBP treatments are administered in a home-based setting, wherein 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, for example, the subject, a caregiver, or a visiting healthcare professional under tele-medical supervision. In embodiments, ancillary equipment (e.g., pumps, filters, adsorbent columns, replacement-fluid reservoirs) and procedural protocols are selected and scaled to match the clinical environment, ensuring safety, efficacy, and regulatory compliance across inpatient, outpatient, and at-home use cases.

[0305]

[0288] In some embodiments, a treatment regimen comprises bi-weekly treatments, such as by administering one EBP treatment approximately every two weeks.

[0306]

[0289] In some embodiments, a treatment regimen comprises semi-annual treatments, such as by administering two EBP treatments per year.

[0307]

[0290] In some 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.

[0308]

[0291] In some 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.

[0309]

[0292] In some 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.

[0310]

[0293] In some embodiments, a treatment regimen comprises a “loading + maintenance” regimen, such as comprising a loading phase followed by a maintenance phase. In embodiments, the loading phase comprises two bi-weekly EBP treatments, followed by a maintenance 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 (treatment-rest-treatment), followed by quarterly EBP treatments.

[0311]

[0294] In some embodiments, a treatment regimen comprises measuring an amount of microplastics in the blood, fluid, and / or tissue of a subject. In embodiments, a treatment regimen comprises measuring an amount of microplastics in the eluate of a subject. In embodiments, a treatment regimen comprises measuring the amount of microplastics in the blood, fluid, and / or tissue of a subject prior to a DFPP, plasmapheresis, or other EBP treatment. In embodiments, a disclosed method comprises assessing the amount of microplastics in a blood purification waste eluate, such as from a DFPP or other plasmapheresis eluate from a subject. In embodiments, a disclosed method comprises measuring the amount of microplastics in the blood, fluid, and / or tissue of a subject after a DFPP, plasmapheresis, or other EBP treatment.

[0312]

[0295] In some embodiments, a disclosed method comprises (i) measuring the amount of microplastics in the blood, fluid, and / or tissue of a subject; and (ii) administering to the subject an EBP treatment. In embodiments, the method further comprises (iii) measuring the amount of microplastics in the blood purification eluate from the subject. In embodiments, the method further comprises (iv) measuring the amount of microplastics in the blood, fluid, and / or tissue of the subject post-treatment, such as after an EBP treatment, such as after a first EBP treatment, or after another EBP treatment.

[0313]

[0296] In some embodiments, a disclosed method comprises (i) measuring the amount of microplastics in the blood, fluid, and / or tissue of a subject; and (ii) administering to the subject a DFPP treatment. In embodiments, the method further comprises (iii) measuring the amount of microplastics in the DFPP eluate from the subject. In embodiments, the method further comprises (iv) measuring the amount of microplastics in the blood, fluid, and / or tissue of the subject post-treatment, such as after a DFPP treatment, such as after a first DFPP treatment, or after another DFPP treatment.

[0314]

[0297] In some 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 the microplastic concentration in the 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 the microplastic concentration in a blood sample from a subject taken after a DFPP, plasmapheresis, or other EBP treatment.

[0315]

[0298] In some embodiments, a treatment regimen comprises a diagnostic step (e.g., a clinical assessment of the subject). In embodiments, a treatment regimen comprises measuring microplastic concentrations in a pre-treatment blood sample, an eluate, and a post-treatment blood sample.

[0316]

[0299] In embodiments, a treatment regimen is determined by a subject’s progress towards a target level of microplastic amounts (e.g., a maximum concentration in the subject’s blood, or measured in their eluate).

[0317]

[0300] In some embodiments, a treatment regimen is updated after a subject’s DFPP, plasmapheresis, or other EBP treatment, such as after the subject’s first DFPP treatment, or after a subsequent DFPP treatment.

[0318]

[0301] In some embodiments, a disclosed method comprises administering to a subject an anticoagulant during the subject’s DFPP, plasmapheresis, or other EBP treatment. Examples of suitable anticoagulants are known in the art, and include, e.g., citrate, heparin, argatroban, bivalirudin, fondaparinux, and danaparoid.

[0319]

[0302] In some embodiments, a disclosed method comprises providing a subject with one or more agents, such as therapeutic agents, including supplements. “Providing” a supplement to a subject will broadly refer to 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.

[0320]

[0303] As used herein, a “supplement” refers to any composition, formulation, or ingredient administered to a subject to support, enhance, or modulate one or more benefits of a disclosed method, to reduce one or more adverse effects thereof, or to provide one or more adjunct therapeutic, physiological, or symptomatic benefits.

[0321]

[0304] In embodiments, the supplement helps to reduce the amount of microplastics in a subject’s blood.

[0322]

[0305] In embodiments, a treatment regimen comprises administering to a subject a supplement to reduce the amount of microplastics in the subject’s blood. In embodiments, a treatment regimen comprises instructing a subject to self-administer a supplement to reduce the amount of microplastics in the subject’s blood.

[0323]

[0306] In some embodiments, the supplement comprises a detoxification enzyme or an inducer, precursor, or cofactor thereof. 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, a glutathione precursor, or a detoxification enzyme inducer such as sulforaphane.

[0324]

[0307] In some embodiments, the supplement is an oral chelation agent. In embodiments, an oral chelation agent is a substance that can be orally administered to a subject (or self-administered by a subject), which can bind to microplastics, thereby forming a complex that can be excreted. In embodiments, the supplement is activated charcoal (i.e., activated carbon). In embodiments, the supplement is humic acid. In embodiments, the supplement is algae. In embodiments, the supplement is coriander. In embodiments, the supplement is selected to reduce the amount of microplastics absorbed from the gastrointestinal tract (e.g., reducing the transport of microplastics across the gut lining). In embodiments, the supplement is a probiotic supplement. In embodiments, the supplement is a Lactobacillus supplement. In embodiments, the supplement is a Bifidobacterium supplement. In embodiments, the supplement is L-glutamine. In embodiments, the supplement is pectin. In embodiments, the supplement is selected to improve the functioning of a subject’s immune system, which may in embodiments improve the subject’s ability to excrete microplastics (e.g., through the kidney and / or liver). In embodiments, the supplement is selected to improve the functioning of a subject’s kidney and / or liver, thereby improving the subject’s ability to excrete microplastics. In embodiments, the supplement is a prokinetic. In embodiments, the supplement is a nootropic. In embodiments, the supplement is a neurotrophic peptide. In embodiments, the supplement is an amino acid. In embodiments, the supplement is an amino acid with glutathione. In some embodiments, the supplement is nicotinamide adenine dinucleotide hydride (NADH). In embodiments, the supplement is nicotinamide adenine dinucleotide (NAD+). In embodiments, the supplement is coenzyme Q10 (CoQ10). In embodiments, the supplement is carnitine. In embodiments, the supplement is magnesium. In embodiments, the supplement is zeolite. In embodiments, the supplement is chlorella. In embodiments, the supplement is ginger. In embodiments, the supplement is tauroursodeoxycholic acid (TUDCA). In embodiments, the supplement is bitters. In embodiments, the supplement is ox bile. In embodiments, the supplement is lion’s mane. In embodiments, the supplement is bacopa. In embodiments, the supplement is acetyl-L-carnitine.

[0325]

[0308] In some embodiments, a treatment regimen comprises providing a subject with a lifestyle intervention. A lifestyle intervention may be provided a DFPP, plasmapheresis, or other EBP treatment; after a DFPP, plasmapheresis, or other EBP treatment; or in between DFPP, plasmapheresis, or other EBP treatments (e.g., in a treatment regimen comprising more than one DFPP, plasmapheresis, or other EBP treatment). Lifestyle interventions useful in disclosed embodiments can include for a subject any one or more of lifestyle changes, dietary changes, product choice changes, and the like, for example to reduce or limit the exposure to microplastics in the environment or by 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 microplastics), 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 also include methods and procedures recognized as promoting bodily detoxification, examples of which include sauna use, infrared sauna use, ozone therapy, hyperbaric oxygen therapy, red-light photobiomodulation, pulsed-electromagnetic-field (PEMF) therapy, dry brushing, lymphatic drainage massage, vagal stimulation, intermittent hypoxia therapy, and intravenous (IV) infusion therapy.

[0326]

[0309] In some embodiments, a treatment regimen comprises providing a subject with one or more nervous system regulation interventions that may, for example, optimize autonomic balance and stress resilience. A nervous system regulation intervention may be provided before a DFPP, plasmapheresis, or other EBP treatment; after a DFPP, plasmapheresis, or other EBP treatment; or in between DFPP, plasmapheresis, or other EBP treatments (e.g., in a treatment regimen comprising more than one DFPP, plasmapheresis, or other EBP treatment). Examples include structured breath-work protocols (e.g., paced diaphragmatic breathing at about 4-6 breaths per minute for a certain timeframe), vagus-nerve stimulation, heart-rate-variability (HRV) biofeedback sessions, and craniosacral therapy.

[0327]

[0310] In some embodiments, a treatment regimen comprises providing a subject with one or more metabolic or endocrine adjunct interventions. A metabolic or endocrine adjunct intervention may be provided before, after, or between DFPP, plasmapheresis, or other EBP sessions (e.g., in a treatment regimen comprising more than one DFPP, plasmapheresis, or other EBP treatment). Examples include 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, and peptide therapeutics (e.g., BPC-157, thymosin 04, LL-37) delivered according to protocols known in the art.

[0328]

[0311] In some embodiments, a treatment regimen comprises one or more biologic or regenerative interventions. A biologic or regenerative intervention may be provided before, after, or between DFPP, plasmapheresis, or other EBP sessions (e.g., in a treatment regimen comprising more than one DFPP, plasmapheresis, or other EBP treatment). Examples include autologous or allogeneic stem-cell therapy (e.g., mesenchymal stromal cells), platelet-rich plasma (PRP) therapy, and exosome-based therapy derived from conditioned media or purified extracellular vesicles. In some embodiments, the biologic or regenerative interventions may enhance bodily repair efficacy.

[0329]

[0312] In some embodiments, a treatment regimen comprises providing a subject with one or more anti-microbial interventions that may, for example, reduce systemic bioburden that may synergize with, or exacerbate, micro-plastic-related toxicities. An anti-microbial intervention may be provided before, after, or between DFPP, plasmapheresis, or other EBP sessions (e.g., in a treatment regimen comprising more than one DFPP, plasmapheresis, or other EBP treatment). Examples include botanical or 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). In embodiments, a treatment regimen comprises dental and gastrointestinal “cleanup” measures, such as surgical or laser debridement of jaw-bone cavitations, revision or removal of problematic root-canal-treated teeth, and eradication protocols for small-intestinal bacterial overgrowth (SIBO) or dysbiosis (e.g., combined herbal and low-FODMAP approaches).

[0330]

[0313] In embodiments, metrics associated with a treatment regimen for a subject, such as functional health metrics, are assessed before and / or after, as well as, where applicable, between one or more lifestyle interventions, nervous system regulation interventions, metabolic or endocrine adjunct interventions, biologic or regenerative 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 according to methods appreciated in view of the disclosure to quantify treatment efficacy.

[0331]

[0314] In embodiments, a treatment regimen comprises administering to a subject a detoxification therapy. Herein, “detoxification therapy” or “detox therapy” broadly refers to any therapeutic intervention or combination of 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 microplastics and their adsorbed contaminants, heavy metals, persistent organic pollutants (e.g., PFAS, phthalates), pathogenic metabolites, pro-inflammatory cytokines, oxidized lipids, metabolic waste products, and pharmacologic or environmental chemicals. In embodiments, a treatment regimen comprises administering to a subject a detoxification therapy to reduce the level of one or more endogenous toxicants. In embodiments, a treatment regimen comprises administering to a subject a detoxification therapy to reduce the level of one or more exogenous toxicants. In embodiments, a treatment regimen comprises administering to a subject a detoxification therapy to reduce the level of one or more exogenous toxicants other than microplastics.

[0332]

[0315] In some embodiments, a treatment regimen comprises a health status examination. A health status examination may be provided before a DFPP, plasmapheresis, or other EBP treatment, after a DFPP, plasmapheresis, or other EBP treatment, or in between DFPP, plasmapheresis, or other EBP treatments (e.g., in a regimen comprising more than one DFPP, plasmapheresis, or other EBP treatment). 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). In embodiments, a health status examination comprises an assessment.

[0333]

[0316] In some embodiments, a health status examination comprises an exogenous toxin assessment. An exogenous toxin assessment may be provided before a DFPP, plasmapheresis, or other EBP treatment, after a DFPP, plasmapheresis, or other EBP treatment, or in between DFPP, plasmapheresis, or other EBP treatments (e.g., in a treatment regimen comprising more than one DFPP, plasmapheresis, or other EBP treatment). In embodiments, an exogenous-toxin assessment may include measuring a concentration of microplastics and / or co-transported toxicants that adsorb to or are carried by microplastics, including, for example, heavy metals (e.g., lead, mercury, cadmium, arsenic), per- and polyfluoroalkyl substances (PFAS), phthalate metabolites, and other persistent organic pollutants.

[0334]

[0317] In some embodiments, a health status examination comprises a blood panel. In embodiments, a blood panel useful in disclosed embodiments comprises any one or more of a complete blood count, basic metabolic panel, comprehensive metabolic panel, lipid panel, thyroid function test, hemoglobin A1C, C-reactive protein panel, and erythrocyte sedimentation rate test. In embodiments, a blood panel comprises a small blood count. In embodiments, a small blood count useful in disclosed embodiments comprises measuring the levels of any one or more of haematocrit, coagulation, fibrinogen, and electrolytes. In embodiments, a small blood count useful in disclosed embodiments comprises either a PT / INR (prothrombin time / international normalized ratio) test or a PTT (partial thromboplastin time) test.

[0335]

[0318] In some embodiments, a health status examination comprises a cardiovascular health panel. In some embodiments, a cardiovascular health panel comprises any one or more 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.

[0336]

[0319] In some embodiments, a health status examination comprises a renal health panel. In embodiments, a renal health panel comprises an analysis of any one or more of serum creatine, blood urea nitrogen, glomerular filtration rate, blood electrolyte concentration, blood calcium and phosphorus concentration, and blood albumin. In embodiments, a renal health panel comprises a urinalysis, a proteinuria analysis, a urine albumin-to-creatinine ratio analysis. In embodiments, a renal health panel comprises an analysis of urine collected over a 24-hour period. In embodiments, a renal health panel comprises a renal scan.

[0337]

[0320] In some embodiments, a health status examination comprises an aging biomarker panel. Biological aging progresses in cell-, tissue-, organ-, and / or system-specific manners, reflecting distinct environments, stresses, and genetic and regulatory architectures of individuals. An aging biomarker refers to a measurable indicator of an aging state or condition, which may be specific to an organ or system. In embodiments, a biological age assessment is made with one aging biomarker or a plurality of aging biomarkers. The accuracy of a biological age assessment may increase as more aging biomarkers are utilized for analysis. In embodiments, an aging biomarker panel comprises any one or more 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.

[0338]

[0321] In some embodiments, a health status examination comprises a fertility health panel. In embodiments, a fertility health panel is a male fertility health panel. In embodiments, a male fertility health panel comprises any one or more of an erectile dysfunction analysis, a semen analysis, sperm function analysis, a scrotal ultrasound, and a male fertility blood hormone test. In embodiments, a semen analysis comprises any one or more of an assessment of sperm count, sperm motility, sperm morphology, semen composition, and volume. In embodiments, a sperm function analysis comprises any one or more of a sperm penetration assay, an acrosome reaction test, and a DNA fragmentation test. In embodiments, a male fertility hormone test comprises any one or more of assessing circulating levels of testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, and estradiol.

[0339]

[0322] In embodiments, a fertility health panel is a female fertility health panel. In embodiments, a female fertility health panel comprises any one or more of an ovarian reserve test, a female fertility blood hormone test, and a pelvic ultrasound. In embodiments, an ovarian reserve test comprises any one or more of an antral follicle count and a clomiphene citrate challenge test. In embodiments, a female fertility blood hormone test comprises any one or more of assessing the circulating levels of follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, prolactin, thyroid-stimulating hormone, and anti-Mullerian hormone.

[0340]

[0323] In some embodiments, a health status examination comprises an assessment of erectile dysfunction (ED). In embodiments, an erectile dysfunction assessment useful in disclosed embodiments comprises any one or more of ED-related blood tests, erectile function tests, and an ED-related psychological assessment. In embodiments, an ED-related blood test comprises any one or more of testosterone level, lipid profile, blood glucose levels, thyroid hormone levels, and prolactin levels. In embodiments, an erectile function test comprises 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. In embodiments, an ED-related psychological assessment comprises the International Index of Erectile Function (IIEF).

[0341]

[0324] In some embodiments, a health status examination comprises an endocrine health panel. In embodiments, an endocrine health assessment comprises 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. In embodiments, a thyroid function test comprises 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). In embodiments, an adrenal function test comprises any one or more of assessing circulating levels of cortisol, adrenocorticotropic hormone, and aldosterone. In embodiments, a pituitary function test comprises any one or more of assessing circulating levels of prolactin, growth hormone, and insulin-like growth factor 1. In embodiments, a reproductive hormone test comprises 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. In embodiments, a pancreatic function test comprises any one or more of assessing circulating levels of insulin, c-peptide, and hemoglobin A1c. In embodiments, a bone metabolism test comprises any one or more of assessing circulating levels of parathyroid hormone, calcium, and vitamin D.

[0342]

[0325] In some embodiments, a health status examination comprises a mental health assessment. In embodiments, a mental health assessment comprises 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.

[0343]

[0326] Exemplary treatment regimens are provided below and herein; further treatment regimens according to the disclosure will be readily appreciated according to the teachings herein and ordinary skill in the art, such as by combining individual aspects and features of the exemplary treatment regimens to provide further such treatment regimens, with such combinations made according to ordinary skill and the teachings herein.

[0344]

[0327] 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.

[0345]

[0328] 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.

[0346]

[0329] For further example, for each of the exemplary treatment regimens, in some alternative treatment regimens, the post-treatment measurement of microplastic concentration after the first treatment, such as in a subject’s blood sample and / or in DFPP eluate, is not provided. In some such alternative embodiments, only the post-treatment measurement of microplastic concentration after the last treatment is provided, such as after the second treatment where there are two treatments, after the third treatment where there are three treatments, and the like. In some alternative embodiments, where three or more treatments are provided, only the post-treatment measurement of microplastic concentration after the first treatment is not provided. In other alternative embodiments, where three or more treatments are provided, the post-treatment measurement of microplastic concentration after the first treatment is provided, but no post-treatment measurement of microplastic concentration is provided again until after the last treatment.

[0347]

[0330] For each of the exemplary treatment regimens where “and / or” is used, in some embodiments “and / or” should be understood to mean “and.” In other such embodiments, “and / or” should be understood to mean “or.”

[0348]

[0331] 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 such 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).

[0349]

[0332] In some embodiments, including for each of the exemplary treatment regimens, a treatment regimen may be dynamically adjusted for a subject in response to real-time or periodic assessments of one or more parameters, for example, blood, fluid, and / or tissue concentrations of microplastics 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); and validated symptom or performance scores. 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.

[0350]

[0333] In some embodiments, including for each of the exemplary treatment regimens, a treatment regimen may be structured in sequential categories. In embodiments, the sequential categories are (1) prepare, (2) clear, (3) stabilize, and (4) improve, each category comprising one or more interventions that may be administered before, after, or between EBP treatments.

[0351]

[0334] In some embodiments, the treatment regimen first comprises a “prepare” phase designed to optimize detoxification and immune readiness prior to systemic mobilization of toxicants. In such embodiments, the “prepare” phase addresses 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, intravenous ozone, or hyperbaric-oxygen sessions); and nervous-system-regulation techniques (e.g., structured breath-work, transcutaneous vagus-nerve stimulation, HRV biofeedback, or craniosacral therapy). In embodiments, the “prepare” phase may be performed over a period ranging from about one day to several months or more, until, for example, laboratory or symptomatic indicators suggest adequate drainage capacity and autonomic readiness for toxin mobilization.

[0352]

[0335] In some embodiments, the treatment regimen comprises a “clear” phase to remove pathological and inflammatory burden from the bloodstream and interstitial matrix. Such means include 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 micro-plastics. In embodiments, adjunctive therapeutics may be administered, including, for example, 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.

[0353]

[0336] In embodiments, the 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.

[0354]

[0337] 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 micro-plastic burden, co-contaminant levels, and functional health metrics to determine the need for repeat “clear” phase or tailored maintenance therapy.

[0355] G. Treatment of Medical Conditions by Extracorporeal Blood Purification

[0356]

[0338] In some aspects are disclosed methods of treating a subject by administering a DFPP, plasmapheresis, or other extracorporeal blood purification (EBP) treatment. In some embodiments, administering a DFPP, plasmapheresis, or other extracorporeal blood purification (EBP) treatment to a subject treats a condition, such as a disease or disorder.

[0339] In some embodiments, the subject has symptoms caused by or associated with the presence of microplastics in their blood, fluid, and / or tissue. In embodiments, the symptoms are caused by or associated with a diagnosed or diagnosable condition. In embodiments, the symptoms are caused by or associated with a diagnosed or diagnosable condition, where the condition is caused by or associated with the presence of microplastics in the blood, fluid, and / or tissue of the subject. In embodiments, the subject is at risk of a condition, such as a diagnosed or diagnosable disease or disorder, caused by or associated with the presence of microplastics in their blood, fluid, and / or tissue. In embodiments, a subject has an increased risk (e.g., increased relative risk) of developing a condition, of developing symptoms of a condition, or of being diagnosed with a condition. For any condition treatable by the disclosed methods, the symptoms of the condition will be known to 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 by the knowledge otherwise available to a physician or other medical professional, in their ordinary practice. In embodiments, administering a treatment to a subject treats a condition by reducing or improving one or more symptoms of the condition.

[0357]

[0340] In some embodiments, the subject has symptoms caused by or associated with a condition that may not be etiologically linked to microplastics. In such embodiments, the presence of microplastics in the subject’s blood, fluid, and / or tissue contributes to, or exacerbates, the 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 microplastics but whose clinical burden may be heightened by the presence of microplastics in the body. In embodiments, the subject is at risk of such a condition, or at risk of worsened outcomes from such a condition, because micro-plastics may impair the subject’s capacity to mount an adequate physiological or immune response. In embodiments, a subject may have 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 microplastic 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 micro-plastics, thereby enhancing the body’s capacity to resist, respond to, or recover from the condition.

[0358]

[0341] In some embodiments, a subject has a cardiovascular condition or a cardiometabolic condition, such as heart disease, atherosclerosis, hypertension, dyslipidemia, hypertension, atherosclerotic plaque, thrombosis, arrhythmias, insulin resistance, obesity, diabetes, and metabolic syndrome. In embodiments, a subject is at risk of a cardiovascular condition or a cardiometabolic condition. The diagnosis of cardiovascular condition and cardiometabolic condition and determining that a subject is at risk of cardiovascular condition or a cardiometabolic condition are known to those of skill. In embodiments, use of an EBP device to remove microplastics, such as according to a disclosed method, treats cardiovascular condition or a cardiometabolic condition in a subject. Measures of improvement of cardiovascular condition and cardiometabolic condition are known to those of skill. In embodiments, improvement of cardiovascular or cardiometabolic condition in a subject results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0359]

[0342] In some 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” herein. In embodiments, a subject has a stroke-related condition. The diagnosis of a stroke-related condition, such as a stroke or the risk of a stroke, is known to those of skill. In embodiments, use of an EBP device to remove microplastics, such as according to a disclosed method, treats a stroke-related condition in a subject. Measures of improvement of a stroke-related condition are known to those of skill. In embodiments, a stroke-related condition in a subject is improved because of a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0360]

[0343] In some embodiments, a subject has thrombosis. In embodiments, a subject is at risk of thrombosis. The diagnosis of thrombosis and determining that a subject is at risk of thrombosis is known to those of skill. In embodiments, use of an EBP device to remove microplastics, such as according to a disclosed method, treats thrombosis in a subject. Measures of improvement of thrombosis are known to those of skill. In embodiments, improvement of thrombosis in a subject results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0361]

[0344] In some embodiments, a subject has a respiratory disease. In embodiments, a subject is at risk of a respiratory condition. The diagnosis of a respiratory condition and determining that a subject is at risk of a respiratory condition is known to those of skill. Examples of respiratory condition treatable by the disclosed devices and methods include bronchitis and other forms of airway inflammation, asthma and other allergic respiratory responses, and fibrosis (e.g., pulmonary fibrosis). In embodiments, use of an EBP device to remove microplastics, such as according to a disclosed method, treats a respiratory condition in a subject. Measures of improvement of a respiratory condition are known to those of skill. In embodiments, improvement of a respiratory condition in a subject results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0362]

[0345] In some 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 treatable by the disclosed devices and methods 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, and brain inflammation. The diagnosis of an inflammation and determining that a subject is at risk of inflammation is known to those of skill. In embodiments, use of an EBP device to remove microplastics, such as according to a disclosed method, 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. In one example, and in some disclosed embodiments, inflammation is detected by measuring high-sensitivity

[0363] 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.

[0364] 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 microplastics in the blood, fluid, and / or tissue of the subject.

[0365]

[0346] In some embodiments, a subject has an immunological condition. In embodiments, a subject is at risk of an immunological condition. The diagnosis of an immunological condition and determining that a subject is at 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 generally the terms “disease” and “disorder.” Autoimmune conditions (e.g., diseases) treatable by the disclosed devices and methods 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, use of an EBP device to remove microplastics, such as according to a disclosed method, 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. In embodiments, improvement of an autoimmune disease or another immunological disease in a subject results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0366]

[0347] In some embodiments, a subject has cancer. In embodiments, a subject is at risk of cancer. The diagnosis of cancer and determining that a subject is at risk of cancer is known to those of skill. Cancers treatable by the disclosed devices and methods include breast cancer, lung cancer, testicular cancer, prostate cancer, colorectal cancer, renal cell carcinoma, thyroid cancer, and skin cancer. In embodiments, use of an EBP device to remove microplastics, such as according to a disclosed method, 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 microplastics in the blood, fluid, and / or tissue of the subject.

[0367]

[0348] In some embodiments, a subject has a mental health condition. In embodiments, a subject is at risk of a mental health condition. The diagnosis of a mental health condition and determining that a subject is at risk of a mental health condition is known to those of skill. Mental health conditions treatable by the disclosed devices and methods 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, 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, use of an EBP device to remove microplastics, such as according to a disclosed method, 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 microplastics in the blood, fluid, and / or tissue of the subject.

[0368]

[0349] In some embodiments, a subject has a neurodegenerative condition. In embodiments, a subject is at risk of a neurodegenerative condition. The diagnosis of a neurodegenerative condition and determining that a subject is at risk of a neurodegenerative condition is known to those of skill. Neurodegenerative conditions treatable by the disclosed devices and methods 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, use of an EBP device to remove microplastics, such as according to a disclosed method, treats a neurodegenerative condition in a subject. Measures of improvement of a neurodegenerative condition are known to those of skill. In embodiments, improvement of a neurodegenerative condition in a subject results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0369]

[0350] In some embodiments, a subject has pain or a pain condition. In embodiments, a subject is at risk of pain or a pain condition. The diagnosis of pain or a pain condition and determining that a subject is at risk thereof is known to those of skill. Examples of pain and pain condition, treatable by the disclosed devices and methods, 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, use of an EBP device to remove microplastics, such as according to a disclosed method, 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 microplastics in the blood, fluid, and / or tissue of the subject.

[0370]

[0351] In some embodiments, a subject has a blood condition. In embodiments, a subject is at risk of a blood condition. The diagnosis of a blood condition and determining that a subject is at risk of a blood disorder is known to those of skill. Examples of blood condition treatable by the disclosed devices and methods 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 T-cell lymphoma, essential thrombocythemia, fanconi anemia, hairy cell leukemia, hemoglobinopathies, hemophilia, hereditary hemolytic anemias, hodgkin lymphoma, hypereo- sinophilic 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 thrombocytopenia, 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, use of an EBP device to remove microplastics, such as according to a disclosed method, 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 microplastics in the blood, fluid, and / or tissue of the subject.

[0371]

[0352] In some embodiments, a subject has a fertility condition. In embodiments, a subject is at risk of a fertility condition. The diagnosis of a fertility condition and determining that a subject is at risk of a fertility disorder is known to those of skill. Examples of fertility conditions treatable by the disclosed devices and methods 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, sperm motility, sperm morphology, semen volume, or semen composition. In embodiments, the male fertility condition comprises any of oligospermia, azoospermia, asthenozoospermia, teratozoospermia, hypospermia, or abnormal semen composition. In embodiments, improvements of a fertility condition in a subject results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0372]

[0353] In some embodiments, a subject has an epigenetic alteration. The diagnosis of an epigenetic alteration and determining that a subject is at risk of an epigenetic alteration is known to those of skill. Examples of epigenetic alterations treatable by the disclosed devices and methods include aberrant DNA- methylation patterns, histone modifications, and changes in non-coding-RNA expression. In embodiments, the epigenetic alterations are transgenerational, such as being transmissible through the germ line and conferring increased risk of subfertility, metabolic dysfunction, or reduced health span in offspring. In embodiments, microplastics present in parental blood, fluid, and / or tissue contribute 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 microplastics in the blood, fluid, and / or tissue of the subject.

[0373]

[0354] In some embodiments, a subject has erectile dysfunction (ED). In embodiments, a subject is at risk of ED. The diagnosis of ED and determining that a subject is at risk of ED is known to those of skill. In embodiments, use of an EBP device to remove microplastics, such as according to a disclosed method, treats erectile dysfunction in a subject. Measures of improvement of erectile dysfunction are known to those of skill. In embodiments, improvements of erectile dysfunction in a subject results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0374]

[0355] In some embodiments, a subject has a hair loss condition. In embodiments, a subject is at risk of a hair loss condition. The diagnosis of a hair loss condition and determining that a subject is at risk of a hair loss condition is known to those of skill. Examples of hair loss conditions treatable by the disclosed devices and methods 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, use of an EBP device to remove microplastics, such as according to a disclosed method, 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 microplastics in the blood, fluid, and / or tissue of the subject.

[0375]

[0356] In some embodiments, a subject has a skin condition. In embodiments, a subject is at risk of a skin condition. The diagnosis of a skin condition and determining that a subject is at risk of a skin condition is known to those of skill. Skin conditions treatable by the disclosed devices and methods 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-fi brosarcoma 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, use of an EBP device to remove microplastics, such as according to a disclosed method, treats a skin condition in a subject. Measures of improvement of a skin condition are known to those of skill. In embodiments, improvements of a skin condition in a subject results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0376]

[0357] In some 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. Measures of wound recovery are known to those of skill. 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 method, including as part of a disclosed treatment regimen, promotes wound recovery in a subject because of a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0377]

[0358] In some embodiments, a subject has a prostate condition. In embodiments, a subject is at risk of a prostate condition. The diagnosis of a prostate condition and determining that a subject is at risk of a prostate condition is known to those of skill. Examples of prostate condition treatable by the disclosed devices and methods include prostatitis, chronic prostatitis, acute bacterial prostatitis, chronic bacterial prostatitis, asymptomatic prostatitis, benign prostatic hyperplasia, prostatism, prostatalgia, and prostate cancer. In embodiments, use of an EBP device to remove microplastics, such as according to a disclosed method, treats a thyroid disorder in a subject. Measures of improvement of a prostate condition are known to those of skill. In embodiments, improvement of a prostate condition in a subject results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0378]

[0359] In some embodiments, a subject has a nutritional or metabolic condition. In embodiments, a subject is at risk of a nutritional or metabolic condition. The diagnosis of a nutritional or metabolic condition and determining that a subject is at risk of a nutritional or metabolic disorder is known to those of skill. Examples of metabolic condition treatable by the disclosed devices and methods 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, use of an EBP device to remove microplastics, such as according to a disclosed method, treats a metabolic condition in a subject. Measures of improvement of a metabolic disorder are known to those of skill. In embodiments, improvement of a metabolic condition in a subject results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0379]

[0360] In some 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., microplastics in the subject’s blood, fluid, and / or tissue). The diagnosis of an endocrine or hormone condition and determining that a subject is at risk of an endocrine or hormone condition is known to those of skill. Examples of endocrine condition treatable by the disclosed devices and methods 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, use of an EBP device to remove microplastics, such as according to a disclosed method, treats an endocrine condition in a subject. Measures of improvement of an endocrine condition are known to those of skill. In embodiments, improvement of an endocrine condition in a subject results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0380]

[0361] In some embodiments, a subject has a complication from microplastics from a vaccine (equivalently herein, a “vaccine-associated condition”). 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, use of an EBP device to remove microplastics, such as according to a disclosed method, treats a vaccine-associated condition in a subject. Measures of improvement of such conditions are known to those of skill. In embodiments, improvement of a vaccine-associated condition in a subject results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0381]

[0362] In some embodiments, a subject has a cholesterol-related condition. In embodiments, a subject is at risk of a cholesterol-related condition. The diagnosis of a cholesterol-related condition and determining that a subject is at risk of a cholesterol-related condition is known to those of skill. Examples of cholesterol-related condition treatable by the disclosed devices and methods 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, use of an EBP device to remove microplastics, such as according to a disclosed method, 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 microplastics in the blood, fluid, and / or tissue of the subject.

[0382]

[0363] In another aspect, disclosed methods are useful for treating a subject who has a complication from cholesterol crystals in their blood, fluid, and / or tissue. In embodiments, a subject is at risk of a complication from cholesterol crystals in their blood, fluid, and / or tissue. 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 microplastics, 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 microplastics. The diagnosis of a complication from cholesterol crystals and determining that a subject is at risk of a complication from cholesterol crystals is known to those of skill. Certain disclosed techniques for measuring microplastic 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, use of an EBP device to remove microplastics, such as according to a disclosed method, treats a condition associated with or caused by cholesterol crystals in a subject. Measures of improvement of such conditions are known in the art. 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 blood, fluid, and / or tissue of the subject.

[0383]

[0364] In some 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. The diagnosis of a gastrointestinal or hepatic condition and determining that a subject is at risk of a gastrointestinal or hepatic condition are known to those of skill. Examples of gastrointestinal or hepatic conditions treatable by the disclosed devices and methods include liver fibrosis, non-alcoholic fatty liver disease (NAFLD), gut-microbiome disruption, intestinal inflammation, digestive dysfunction, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). In embodiments, use of an EBP device to remove microplastics according to a disclosed method treats a gastrointestinal or hepatic condition in a subject. Measures of improvement of gastrointestinal or hepatic conditions are known to those of skill. In embodiments, improvement of the condition is attributable to a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0384]

[0365] In some embodiments, a subject has a fatigue-related condition, including a fatigue-related disease or disorder. In embodiments, a subject is at risk of a fatigue-related condition. The diagnosis of fatigue-related conditions and determining that a subject is at risk are known to those of skill in the art. Examples of fatigue-related conditions treatable by the disclosed devices and methods include chronic fatigue syndrome (myalgic encephalomyelitis), post-viral fatigue (including post-COVID or “long COVID” fatigue), fibromyalgia with predominant fatigue, adrenal insufficiency-associated fatigue, overtraining syndrome, and idiopathic chronic fatigue. In embodiments, use of an EBP device to remove microplastics according to a disclosed method treats a fatigue-related condition in a subject. Measures of improvement of fatigue-related conditions (e.g., validated fatigue-severity scales, functional capacity testing, mitochondrial function assays) are known to those of skill. In embodiments, improvement of the condition is attributable to a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0385]

[0366] In some embodiments, a subject has a weight-related condition, including a weight-related disease or disorder. In embodiments, a subject is at risk of a weight-related condition. The diagnosis of weight-related conditions and determining that a subject is at risk are known to those of skill in the art. Examples of weight-related conditions treatable by the disclosed devices and methods include being overweight, class l / ll / lll obesity, central (visceral) obesity, metabolic syndrome, insulin-resistant obesity, obesity associated with polycystic ovary syndrome (PCOS), and obesity-related cardiometabolic dysfunction. In embodiments, use of an EBP device to remove microplastics according to a disclosed method treats a weight-related condition in a subject. Measures of improvement of weight-related conditions (e.g., BMI, waist-to-hip ratio, body-fat percentage, HOMA-IR, lipid panels) are known to those of skill. In embodiments, improvement of the condition results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0386]

[0367] In some embodiments, a subject has a kidney-related condition, including a kidney-related disease or disorder. In embodiments, a subject is at risk of a kidney-related condition. The diagnosis of kidney-related conditions and determining that a subject is at risk thereof are known to those of skill in the art. Examples of kidney-related conditions treatable by the disclosed devices and methods include chronic kidney disease (CKD stages 1-5), acute kidney injury, diabetic nephropathy, hypertensive nephrosclerosis, glomerulonephritis, polycystic kidney disease, dialysis-related microplastic overload, and dialysis-associated nephropathy. In embodiments, use of an EBP device to remove microplastics according to a disclosed method treats a kidney-related condition in a subject. Measures of improvement of kidney-related conditions (e.g., estimated glomerular filtration rate, serum creatinine, blood urea nitrogen, albumin-to-creatinine ratio) are known to those of skill. In embodiments, improvement of the condition results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0387]

[0368] In some embodiments, a subject has a pathogenic condition, including a pathogenic disease or disorder. In embodiments, a subject is at risk of a pathogenic condition. Pathogenic conditions may be characterized by, for example, ongoing or post-infectious pathogenic burden.The diagnosis of pathogenic conditions and determining that a subject is at risk are known to those of skill in the art. Examples of pathogenic conditions treatable by the disclosed devices and methods include post-acute sequelae of SARS-CoV-2 infection (“long COVID”), chronic Epstein-Barr virus or cytomegalovirus reactivation, post-treatment Lyme condition syndrome, chronic bacterial endocarditis, chronic Q-fever, and persistent mycotoxin-associated illness. In embodiments, use of an EBP device to remove microplastics according to a disclosed method treats a pathogenic condition in a subject. Measures of improvement of pathogenic conditions (e.g., pathogen load by PCR or serology, validated symptom-burden scales, fatigue-severity scores, six-minute-walk distance, cytokine panels, and quality-of-life indices) are known to those of skill. In embodiments, improvement of the pathogenic disorder results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0388]

[0369] In another aspect, disclosed methods are useful for treating a subject that has a symptom, condition, or complication caused by or associated with microplastics in their blood, fluid, and / or tissue. In another aspect, disclosed methods are useful for treating a subject that is at risk of a symptom, condition, or complication caused by or associated with microplastics in their blood, fluid, and / or tissue. In embodiments, use of an EBP device to remove microplastics, such as according to a disclosed method, treats a symptom, condition, or complication caused by or associated with microplastics in the blood, fluid, and / or tissue of a subject. Measures of improvement are known in the art, in reference to the symptom, condition, or complication sought to be treated. In embodiments, improvement of a symptom, condition, or complication caused by or associated with microplastics in the blood, fluid, and / or tissue of a subject results from a reduction in the amount of microplastics in the blood, fluid, and / or tissue of the subject.

[0389]

[0370] In some embodiments, treatment of a condition, such as a disease or disorder, will be durable. The durability of a treatment can be shown using a measurement of an improvement in the condition, such as in a symptom of the condition, at a time following treatment by a period of time, such as a period of time of at least one month, at least three months, at least six months, at least nine months, at least one year, or greater than one year, including measurements at times in between. In embodiments, treatment by a disclosed device, system, or method will produce a durable improvement of a condition treated of at least one month. In embodiments, treatment will result in a durable improvement of the condition of at least three months. In embodiments, treatment will result in a durable improvement of the condition of at least six months. In embodiments, treatment will result in a durable improvement of the condition of at least nine months. In embodiments, treatment will result in a durable improvement of the condition of at least one year. In embodiments, treatment will result in a durable improvement of the condition of greater than one year. A measurement of an improvement in a condition “following treatment” may be based on a measurement taken at a time point following treatment compared to an earlier time point, wherein the earlier time point may be a baseline measurement or another measurement prior to initiating treatment (such as an intake or pre-treatment measurement), a measurement at the time of the last treatment, a measurement after the last treatment, and the like. Exemplary such measurements are described in the numbered Exemplary Treatment Regimens, in the section on treatment regimens, and generally herein, and will be otherwise appreciated.

[0390] H. Methods of Improving Health, Healthspan, Lifespan, and Longevity

[0391]

[0371] In some aspects are disclosed methods of improving the health, healthspan, lifespan, or longevity of a subject by administering a DFPP, plasmapheresis, or other EBP treatment.

[0392]

[0372] In some embodiments, administering a disclosed plasmapheresis treatment, such as a DFPP, plasmapheresis, or other EBP treatment according to a disclosed method improves a subject’s health. In some embodiments, administering a DFPP, plasmapheresis, or other EBP treatment according to a disclosed method improves the health of a subject that does not have a diagnosed or diagnosable medical condition. In some embodiments, improving a subject’s health comprises increasing a measure of physical health, physical appearance, mental health, and general well-being.

[0393]

[0373] In some embodiments, administering a disclosed plasmapheresis treatment, such as a DFPP, plasmapheresis, or other EBP treatment according to a disclosed method provides preventative care. In some embodiments, administering a disclosed plasmapheresis treatment, such as a DFPP, plasmapheresis, or other EBP treatment provides preventative care to an asymptomatic subject. In embodiments, administering a DFPP, plasmapheresis, or other EBP treatment improves the health of a subject who exhibits no current symptoms and has no diagnosed or diagnosable medical condition. In embodiments, improving a subject’s health in a preventative context comprises lowering baseline toxin burden, enhancing physiologic resilience, decreasing future disease risk, and maintaining or optimizing measurable indicators of physical health, mental health, and general well-being.

[0394]

[0374] In some embodiments, administering a DFPP, plasmapheresis, or other EBP treatment to a subject improves the athletic performance of a subject. Athletic performance refers to a subject’s ability to execute physical activities or sports with effectiveness, efficiency, and proficiency, and includes, for example, physical capabilities, technical skills, tactical understanding, and mental fortitude. Athletic performance can be assessed by how well a subject can achieve the demands of a specific sport or activity, and can be measured as known in the art. In embodiments, administering a DFPP, plasmapheresis, or other EBP treatment according to a disclosed method improves the athletic performance of a subject. In embodiments, administering a disclosed DFPP treatment including as part of a disclosed treatment regimen, improves the athletic performance of a subject because of a reduction in the amount of microplastics in the subject’s blood.

[0395]

[0375] In some embodiments, administering a DFPP, plasmapheresis, or other EBP treatment to a subject improves the musculoskeletal health of a subject. Musculoskeletal health refers to the overall wellbeing and functional capacity of the muscles, bones, joints, tendons, ligaments, and connective tissues of the body. Measurements of musculoskeletal health are known in the art. In embodiments, administering a disclosed DFPP treatment according to a disclosed method improves the musculoskeletal health of a subject. In embodiments, administering a disclosed DFPP treatment, including as part of a disclosed treatment regimen, improves the musculoskeletal health of a subject because of a reduction in the amount of microplastics in the subject’s blood.

[0396]

[0376] In some embodiments, administering a DFPP, plasmapheresis, or other EBP treatment to a subject promotes the skin rejuvenation of a subject. Skin rejuvenation refers to the process of improving the overall appearance, texture, and quality of skin, including reducing visible signs of aging. Measurements of skin rejuvenation are known in the art. In embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment according to a disclosed method improves the skin rejuvenation of a subject. In embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment, including as part of a disclosed treatment regimen, improves the skin rejuvenation of a subject because of a reduction in the amount of microplastics in the subject’s blood.

[0397]

[0377] In some embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment treatment according to a disclosed method improves a subject’s cognitive function. Examples of improvements in cognitive function include a subject’s ability to process information, store memories, handle cognitive tasks, and includes such concepts as cognitive capacity, working memory capacity, long term memory capacity, brain volume, and neural efficiency, all of which are encompassed within the definition of “cognitive function,” and which may also be referred to as “brain capacity.” Measurements of cognitive functioning are known in the art. In embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment according to a disclosed method improves the cognitive function of a subject. In embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment, including as part of a disclosed treatment regimen, improves the cognitive function of the subject because of a reduction in the amount of microplastics in the subject’s blood.

[0398]

[0378] In embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment according to a disclosed method increases the efficacy of another therapeutic intervention. In embodiments, the subject is administered a disclosed DFPP, plasmapheresis, or other EBP treatment as an adjunctive to another therapeutic intervention. Examples of therapeutic interventions include hormone therapy, nutritional therapy, exercise therapy, pharmacotherapy, physical therapy, occupational therapy, behavioral therapy, immunotherapy, pulmonary rehabilitation therapy, breathwork therapy, probiotic therapy, enzyme replacement therapy, stem cell therapy, peptide therapy, and the like. Measurements of the efficacy of a therapeutic intervention are known in the art. In embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment, including as part of a disclosed treatment regimen, improves the efficacy of another therapeutic intervention in a subject because of a reduction in the amount of microplastics in the subject’s blood.

[0399]

[0379] In some embodiments, a therapeutic intervention that can be improved in conjunction with a disclosed DFPP, plasmapheresis, or other EBP treatment is stem cell therapy. Microplastics induce chronic inflammation and oxidative stress, which disrupt cellular signaling pathways and impair the regenerative microenvironment. In the context of stem cell therapy, microplastics compromise niche viability, hindering engraftment, differentiation, and paracrine signaling. Microplastics can adsorb proteins and biomolecules, potentially trapping therapeutic peptides or altering stem cell exosome profiles. By removing microplastics, DFPP, plasmapheresis, or another EBP treatment can optimize stem cell efficiency via reduced inflammatory cytokines (e.g., TNF-a, IL-6) and improved mitochondrial function in recipient cells. Microplastic removal could enhance outcomes in therapies like BPC-157 for tissue repair or mesenchymal stem cell therapy (MSC) treatments for degenerative diseases.

[0400]

[0380] In some embodiments, a therapeutic intervention that can be improved in conjunction with a disclosed DFPP, plasmapheresis, or other EBP treatment is peptide therapy. The tendency of microplastics to induce chronic inflammation and oxidative stress can disrupt cellular signaling pathways and impair the regenerative microenvironment. This interference, in turn, can reduce receptor sensitivity and downstream effects (e.g., growth hormone secretagogues failing to trigger release of one or more hormones). By reducing microplastics, a disclosed DFPP, plasmapheresis, or other EBP treatment can restore peptide bioavailability by preventing plastic-particle binding and improving target tissue responsiveness.

[0401]

[0381] In some embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment according to a disclosed method, prepares a subject for a procedure (e.g., a surgery) for example by increasing the likelihood of success of the procedure (e.g., for surgery, by increasing operative success and / or accelerating postoperative recovery). Measurements of improved procedural outcomes (e.g., reduced infection rates, faster wound closure, lower transfusion requirements, or improved functional scores) are known to those of skill. In some embodiments, administering an EBP treatment prior to a procedure may reduce circulating toxins (including microplastics, heavy metals, PFAS, phthalates, and pro-inflammatory mediators) that are known to impair wound healing, promote postoperative inflammation, or increase the risk of surgical complications. In some embodiments, a subject receives one or more EBP treatments in the post-operative period to remove, for example, debris, inflammatory cytokines, and residual anesthetic or pharmaceutical metabolites, and to further reduce the systemic toxicant burden mobilized during surgical stress. In embodiments, administering an EBP treatment, including as part of a disclosed treatment regimen, improves a procedure outcome and / or recovery time in a subject because of a reduction in the amount of microplastics in the subject’s blood.

[0402]

[0382] In some embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment according to a disclosed method improves a subject’s mitochondrial function. Examples of improvements in mitochondrial function include a subject’s capacity for oxidative phosphorylation, ATP production rate, mitochondrial membrane potential, reactive-oxygen-species (ROS) balance, mitochondrial biogenesis markers (e.g., PGC-1a expression), mitophagy efficiency, and overall cellular energy availability. Measurements of mitochondrial function (e.g., high-resolution respirometry, ATP / ADP ratios, serum or cellular lactate-to-pyruvate ratios, mitochondrial membrane-potential assays, and circulating cell-free mitochondrial DNA) are known in the art. In embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment according to a disclosed method improves the mitochondrial function of a subject. In embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment, including as part of a disclosed treatment regimen, improves the mitochondrial function of the subject because of a reduction in the amount of microplastics in the subject’s blood, fluid, and / or tissue.

[0403]

[0383] In some embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment according to a disclosed method increases the efficacy of a fertility treatment. Examples of fertility treatments include in vitro fertilization (IVF), intrauterine insemination (IUI), intracervical insemination (ICI), intracytoplasmic sperm injection (ICSI), ovulation induction, oocyte cryopreservation (OC), sperm cryopreservation, embryo cryopreservation, assisted hatching, sperm donation, egg donation, embryo donation, and the like. In embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment according to a disclosed method improves the efficacy of a fertility treatment in a subject. In embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment, including as part of a disclosed treatment regimen, improves the efficacy of a fertility treatment in a subject because of a reduction in the amount of microplastics in the subject’s blood.

[0404]

[0384] In some embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment according to a disclosed method slows aging in a subject. Aging refers to the process of accumulation of the consequences of life, such as molecular and cellular damage, that leads to functional decline, chronic diseases, and ultimately mortality (Moqri et al. Cell. 2023;186:3758-3775). Aging progression in a subject may be influenced by a variety of genetic and environmental factors, and may be influenced by various genetic, pharmacological, dietary, and lifestyle interventions. Aging can be assessed by quantifying one or more aging biomarkers, and can be measured as known in the art. In embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment according to a disclosed method slows aging in a subject. In embodiments, administering a disclosed DFPP, plasmapheresis, or other EBP treatment including as part of a disclosed treatment regimen, slows aging in a subject because of a reduction in the amount of microplastics in the subject’s blood.

[0405]

[0385] In some embodiments, reducing the progression of aging of a subject increases the subject’s healthspan...

Claims

CLAIMSThe invention claimed is:1 . A method for reducing microplastics in the blood, tissue, or both of a subject, comprising: selecting the subject for treatment based on a pre-treatment assessment; and administering a plasmapheresis treatment selected from: double-filtration plasmapheresis (DFPP), therapeutic plasma exchange (TPE), plasma perfusion (PP), plasma adsorption, or coupled plasma filtration adsorption (CPFA), wherein the treatment reduces a concentration of microplastics in the blood, tissue, or both of the subject.2 The method of claim 1 , wherein selecting the subject for treatment comprises determining one or more of: that the subject has a medical condition caused by or associated with microplastics; that the subject is at risk of developing a medical condition caused by or associated with microplastics in the blood, tissue, or both; and that the subject’s athletic performance, fitness, longevity, or wellbeing is likely to be improved by reducing microplastics in the blood, tissue, or both.3 The method of claim 1 , wherein selecting the subject for treatment comprises determining that the subject has a medical condition that is exacerbated by the presence of the microplastics or that can be improved by reducing the microplastics in the blood, tissue, or both.4 The method of claim 2 or 3, wherein the medical condition comprises one or more of a cardiovascular condition, a cardiometabolic condition, a gastrointestinal condition, a hepatic condition, stroke, thrombosis, a respiratory condition, an inflammatory condition, an immunological condition, an autoimmune condition, an immune system condition, a cancer, a neurodegenerative condition, a neurological condition, erectile dysfunction, a hair loss condition, a nutritional or metabolic condition, an endocrine or hormone condition, a reproductive condition, a fertility condition, a mental health condition, a skin condition, a wound, a prostate condition, a fatigue-related condition, a kidney-related condition, a vaccine-associated condition, a pain condition, chronic inflammation, an epigenetic alteration, an allergy condition, a cholesterol-related condition, a complication from cholesterol crystals, a weight-related condition, a pathogenic condition, and an ocular condition.5 The method of claim 1 , wherein the subject is asymptomatic, and the plasmapheresis treatment is prophylactic to reduce future risk of an adverse medical condition or disease.

6. The method of claim 1 , wherein the plasmapheresis treatment is administered for preventative care.

7. The method of claim 1 , wherein the plasmapheresis treatment is administered to improve one or more of longevity, lifespan of the subject, healthspan of the subject, pain management, weight loss, pregnancy preparation, maternal-fetal health, perinatal health, organ transplant preparation, preparing for another medical treatment, inflammation management, detoxification, athletic performance, occupational prophylaxis, blood circulation, blood microcirculation, rheology, slowing of aging, and chemical carrier detox.8 The method of claim 1 , wherein selecting the subject for treatment comprises measuring an amount of microplastics in the blood, tissue, or both of the subject.9 The method of claim 8, wherein measuring the amount of microplastics in the blood, tissue, or both of the subject comprises measuring an amount of microplastics in the blood, tissue, or both of the subject using a fluorescence-assisted detection technique.10 The method of claim 9, wherein measuring the amount of microplastics in the blood, tissue, or both of the subject comprises fluorescence assistance coupled with flow cytometry, nanoparticle tracking analysis (NTA), or both.11 The method of claim 8, wherein the subject is selected for treatment if the subject has a measurable amount of microplastics in the blood, tissue, or both.12 The method of claim 11 , wherein the subject is selected for treatment if the subject has a blood concentration of microplastics of greater than about 0.1 pg / mL to about 10 pg / mL.13 The method of claim 8, wherein measuring the amount of microplastics in the blood, tissue, or both of the subject comprises one or more of mass spectrometry, spectroscopy, and microscopy.14 The method of claim 1 , wherein the pre-treatment assessment comprises administering or assessing one or more of a medical consultation, one or more blood panels, a gut microbiome test, an environmental toxin test one or more aging biomarkers, one or more endocrine markers, one or more questionnaires, a medical history evaluation, a medical examination, a health status examination, a physical examination, a cognitive examination, a fitness test, fertility health, and a health scan.

15. The method of claim 1 , wherein the plasmapheresis treatment is performed before, concurrently, and / or after one or more additional health treatments.

16. The method of claim 15, wherein the at least one additional health treatment comprises one or more of a detox therapy, a supplement, an oral chelation agent, an ozone therapy,, a regenerative treatment, a sauna treatment regimen, hyperbaric oxygen therapy, red light therapy, plused-EMF (PEMF) therapy, hormone therapy, sirtuin-activating therapy, NAD+ therapy, GLP-1 therapy, peptide therapy, stem cell therapy, PRP therapy, exosome therapy, administration of lipid-based carriers, mitochondrial support, a dietary intervention, gut health support, bowel movement support, lymphatic drainage support, liver and kidney detox support, mitochondrial optimization, cellular membrane stabilization, and a blood purification treatment.

17. The method of claim 16, wherein one or more supplements are administered one or more of: orally pre-treatment; intravenously immediately before the plasmapheresis treatment; and subcutaneously for sustained release.

18. The method of claim 1 , wherein one more more interventions are prescribed to the subject based on one or more metrics associated with the treatment, the one or more interventions comprising one or more of guidance for limiting exposure to microplastics, nervous system regulation interventions, metabolic or endocrine adjunct interventions, and anti-microbial interventions.

19. The method of claim 15, wherein one or more additional health treatments are prescribed or administered to the subject including any of a lifestyle intervention, a supplement, a nervous system regulation intervention, a metabolic or endocrine adjunct intervention, a biologic or regenerative intervention, and an anti-microbial intervention.

20. The method of claim 8, wherein the amount of microplastics in the blood, tissue, or both is measured any of before, during, and after the plasmapheresis treatment is administered.21 . The method of claim 20, wherein measuring the amount of microplastics in the blood, tissue, or both of the subject comprises analyzing microplastics filtered from the subject during treatment.

22. The method of claim 20, wherein the plasmapheresis treatment is dynamically adjusted based on a microplastics measurement made during the plasmapheresis treatment.

23. The method of claim 22, wherein a blood flow rate of the plasmapheresis treatment is selected based on a measurement of an amount of microplastics in the blood, tissue, or both of the subject.

24. The method of claim 23, wherein a relatively higher measurement corresponds to a relatively lower blood flow rate to reduce risk of hemolysis and filter clogging.

25. The method of claim 22, wherein the blood flow rate is reduced to about 50-75 mL / min if the measurement exceeds a threshold.

26. The method of claim 1 , wherein the plasmapheresis treatment reduces microplastics in the subject by about 5% to 99%.

27. The method of claim 1 , wherein the plasmapheresis treatment reduces system exposure to one or more of PFAS, phthalates, or heavy metals complexed with the removed microplastics.

28. The method of claim 1 , wherein the plasmapheresis treatment improves therapeutic outcomes related to one or more of detox treatment, a chelation therapy, an ozone therapy, administering one or more blood panels, a regenerative treatment, a sauna treatment regimen, hyperbaric oxygen therapy, red light therapy, plused-EMF (PEMF) therapy, hormone therapy, sirtuin-activating therapy, NAD+ therapy, GLP-1 therapy, peptide therapy, stem cell therapy, PRP therapy, exosome therapy, administration of lipid-based carriers, mitochondrial support, a dietary intervention, gut health support, bowel movement support, lymphatic drainage support, liver and kidney detox support, mitochondrial optimization, and cellular membrane stabilization.

29. The method of claim 1 , wherein the plasmapheresis treatment improves a health metric related to one or more of inflammatory markers, cognitive function, athletic performance, a cardiovascular condition, a cardiometabolic condition, a gastrointestinal condition, a hepatic condition, stroke, thrombosis, a respiratory condition, an inflammatory condition, an immunological condition, an autoimmune condition, an immune system condition, a cancer, a neurodegenerative condition, a neurological condition, erectile dysfunction, a hair loss condition, a nutritional or metabolic condition, an endocrine or hormone condition, a reproductive condition, a fertility condition, a mental health condition, a skin condition, a wound, a prostate condition, a fatigue-related condition, a kidney-related condition, a vaccine-associated condition, a pain condition, chronic inflammation, an epigenetic alteration, an allergy condition, a cholesterol-related condition, a complication from cholesterol crystals, a weight-related condition, a pathogenic condition, an ocular condition, longevity, lifespan of the subject, healthspan of the subject, pain management, weight loss, pregnancy preparation, maternal-fetal health, perinatal health, organ transplant preparation, preparing for another medical treatment,detoxification, occupational prophylaxis, blood circulation, blood microcirculation, rheology, slowing of aging, and chemical carrier detox.

30. The method of claim 1 , wherein the plasmapheresis treatment slows aging as evidenced by one or more of increasing telomere length, reducing senescent cell burden, reduction of an epigenetic clock metric, increase in CD4+ / CD8+ naive T cells or stem cell memory T cells, reduction in NK cells or monocytes, normalization of iAge surrogates, reduction in CXCL9 percentile, upregulation of immune resilience proteins, downregulation of senescence-associated proteins, restoration of glycine metabolism, reduction of inflammatory markers, and increase in ATP production.

31. The method of claim 1 , wherein the plasmapheresis treatment is repeated one or more of 5 times, 10 times, biweekly, monthly, quarterly, twice per year, and in two sets of treatments per year.

32. The method of claim 31 , wherein the plasmapheresis treatment comprises a loading period during which plasmapheresis treatments are administered at a first frequency and a maintenance period during which plasmapheresis treatments are administered at a second frequency that is less than the first frequency.

33. The method of claim 32, wherein the loading period comprises alternating plasmapheresis treatment weeks and rest weeks for 1-2 consecutive months, and the maintenance period comprises quarterly plasmapheresis treatments for a year following the loading period.

34. The method of claim 1 , wherein after the plasmapheresis treatment is administered, a period of rest is implemented for one or more days to allow microplastics to diffuse from the blood, tissue, or both of the subject, and one or more additional plasmapheresis treatments are applied after the period of rest.

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

36. The method of claim 1 , wherein a DFPP treatment is administered, comprising: creating a blood circuit via vascular access; separating plasma using a first filter with a pore size of about 200-800 nm; filtering microplastics from the plasma using a second filter with a pore size of about 1-100 nm to create purified plasma; and reinfusing the purified plasma with blood cells.

37. The method of claim 36, wherein the first filter has a pore size of about 450 nm and the second filter has a pore size of about 10 nm.

38. The method of claim 36, comprising measuring microplastics in one or more of DFPP eluate, purified plasma, adsorbate, and blood returned to the subject.

39. The method of claim 36, wherein administering the plasmapheresis treatment comprises: filtering microplastics from whole blood using a third filter with a pore size of about 10-50 pm or more, wherein the third filter is positioned before the first filter and the second filter in the blood circuit.

40. The method of claim 1 , wherein a TPE treatment is administered, comprising replacing the plasma of the subject with plasma or albumin solution that is pretreated to remove or reduce microplastics.41 . The method of claim 1 , wherein a plasma adsorption treatment is administered, further comprising passing the plasma of the subject through an adsorption column comprising binding agents configured to interact with microplastics.

42. The method of claim 1 , wherein a CPFA treatment is administered, comprising: creating a blood circuit via vascular access to the subject; separating the blood of the subject into a plasma fraction and a cellular fraction; separating microplastics from the plasma fraction using an adsorption filter; combining the cellular fraction and the filtered plasma fraction; separating ultrafiltrate from the combined cellular fraction and filtered plasma fraction using a membrane; and supplying the combined cellular fraction and filtered plasma fraction to the subject.

43. The method of claim 1 , wherein the plasmapheresis treatment is PP, comprising removing one or more of pathogenic antibodies, immune complexes, cytokines, or metabolic waste products.

44. A method of treating blood comprising: creating a blood circuit via vascular access to a patient; separating plasma from blood cells of the patient using a first filter; removing microplastics from the plasma using a second filter to create purified plasma; returning the blood cells to the patient; andproviding the purified plasma for allogeneic or autologous therapeutic use, storage, or further processing.

45. The method of claim 44, wherein the second filter is configured to remove microplastics having a molecular weight of about 50 kDa - 500 kDa.

46. A method of treating blood comprising: creating a blood circuit via vascular access to a patient; separating plasma from blood cells of the patient using a first filter; removing microplastics from the plasma using a second filter to create purified plasma; combining the purified plasma with the separated blood cells; and providing the combined purified plasma and blood cells for allogeneic or autologous therapeutic use, storage, or further processing.

47. Any method, device, or system for extracorporeal blood purification, preferably to reduce microplastics in the blood and / or tissue of a human subject, as described and enabled herein.

Images