Fluid transfer device with integrated flow-based assay and method of using same

Abstract

The system includes a fluid transfer device and a lateral flow assay device. The fluid transfer device has an inlet fluidly connectable to a source of bodily fluid, an outlet fluidly connectable to a sample reservoir, and an isolation chamber configured to receive an initial amount of bodily fluid. The fluid transfer device can be transitioned between (1) a first state in which the isolation chamber is in fluid communication with the inlet to receive the initial amount, (2) a second state in which the outlet is in fluid communication with the inlet to receive a subsequent flow of bodily fluid, and (3) a third state in which the lateral flow assay device is in fluid communication with the isolation chamber to receive a portion of the initial amount of bodily fluid. The lateral flow assay device is configured to provide an indication related to the presence of a target analyte in the bodily fluid.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 62 / 946,680, entitled "Fluid Transfer Devices with Integrated Flow-Based Assay and Methods of Using the Same," filed December 11, 2019, the disclosure of which is incorporated herein by reference in its entirety. [Background technology]

[0002] background

[0002] The embodiments described herein relate generally to bodily fluid sample acquisition and point-of-care diagnostic testing, and more specifically to bodily fluid transfer devices having an integrated flow-based assay system, such as a lateral flow assay, that enables early point-of-care diagnostic testing.

[0003]

[0003] Medical personnel routinely perform a wide variety of microbial and other extensive diagnostic tests on patients using parenterally obtained body fluids. In some cases, effective treatment of some serious patient conditions can be time-dependent, and delays in treatment can increase the risk of morbidity and / or mortality. For example, sepsis is a serious patient condition that typically results from bacterial infection (or less commonly fungal or viral infection). Sepsis is an abnormal systemic response to what would otherwise be a normal infection and appears to represent a pattern of immune system response to injury. The hyperinflammatory response is typically followed by a phase of immunosuppression, during which there is multiple organ dysfunction and patients are susceptible to hospital-acquired infections. Sepsis patients usually present with fatigue, fever, chills, and leukocytosis, which can prompt physicians to assess the presence of bacteria in such patients' bloodstreams, typically by bacterial culture testing.

[0004]

[0004] As bacterial culture testing and / or other advanced diagnostic techniques develop and improve, the speed, accuracy (both sensitivity and specificity), and value of information that can be provided to clinicians continue to improve. Examples of such diagnostic techniques may include, for example, microbial detection, molecular diagnostics, gene sequencing (e.g., deoxyribonucleic acid (DNA), ribonucleic acid (RNA), next generation sequencing (NGS), etc.), biomarker identification, etc. Some well-known culture methods and / or other diagnostic techniques may be prone to high contamination tendencies and may produce results that are inaccurate, distorted, poor, false positive, false negative, and / or otherwise not representative of the patient's actual condition (or in vivo condition). Furthermore, these results may lead to incomplete, inaccurate, confusing, uncertain, unreliable, and / or otherwise undesirable clinical decisions. In some cases, contamination may result from the presence of biological material, including cells and / or other external contaminants, outside the intended sample source that are unintentionally included in the body fluid sample being analyzed. Several known devices and / or systems can be used to reduce the likelihood of contamination and / or adulteration of bodily fluid samples used for testing, thereby reducing the likelihood of inaccurate or erroneous diagnostic test results and leading to better patient outcomes. For example, several known devices can be designed to divert and isolate an initial volume of bodily fluid that is more likely to contain contaminants.

[0005]

[0005] Although such diagnostic techniques can provide sensitive and / or specific information from testing clean or unadulterated bodily fluids, the tests often take from 6 hours to about 5 days or more to obtain results. Furthermore, known diagnostic techniques are often performed using systems that require highly trained personnel and / or often use culture protocols specifically tailored for the identification of various bacterial species. Thus, such culture methods and / or diagnostic techniques are not suitable for rapid diagnosis and / or efficient screening that may be required for the treatment of certain rapidly progressing diseases. For example, sepsis can rapidly progress to multiple organ dysfunction and / or death, which may prompt a physician to prescribe treatment (e.g., antibiotics) before receiving the results of diagnostic tests.

[0006]

[0006] Thus, there is a need for rapid testing of bodily fluids, such as, for example, point-of-care diagnostic tests using lateral flow assays or other rapid diagnostic technologies. Additionally, there is a need to incorporate rapid tests (e.g., lateral flow assays) into devices that can be used to obtain additional bodily fluid samples from a patient, such as, for example, devices configured to obtain bodily fluid samples with reduced contamination. Summary of the Invention [Means for solving the problem]

[0007] overview

[0007] The embodiments and methods described herein relate to a bodily fluid transfer device with an integrated flow-based assay (e.g., a lateral flow assay) that enables early point-of-care diagnostic testing. In some embodiments, a system includes a flow-based assay device and a fluid transfer device. The fluid transfer device has an inlet configured to be fluidly connected to a bodily fluid source and an outlet configured to be fluidly connected to a sample reservoir. The fluid transfer device includes an isolation chamber and a port in selective communication with the isolation chamber. The isolation chamber is configured to be fluidly connected to the inlet to receive a first amount of bodily fluid when the fluid transfer device is in a first state. The outlet is configured to be fluidly connected to the inlet to receive a second amount of bodily fluid when the fluid transfer device is in a second state. The flow-based assay device is configured to be coupled to the port to receive a portion of the first amount of bodily fluid when the fluid transfer device is in a third state. The flow-based assay device is configured to provide an indication related to the presence of a target analyte in the portion of the first amount of bodily fluid. [Brief description of the drawings]

[0008] BRIEF DESCRIPTION OF THE DRAWINGS [Figure 1] 1 is a schematic diagram of a fluid transfer and assay system according to one embodiment. [Diagram 2]

[0009] FIG. 1 is a schematic diagram of a lateral flow assay device according to one embodiment. [Diagram 3]

[0010] FIG. 1 is a schematic diagram of a fluid transfer and assay system according to one embodiment. [Figure 4]

[0011] FIG. 1 is a schematic diagram of a fluid transfer and assay system according to one embodiment. [Figure 5A]

[0012] FIG. 2 is a schematic diagram of a fluid transfer and assay system in a first state according to one embodiment. [Figure 5B]1 is a schematic diagram of a fluid transfer and assay system in a second state according to one embodiment. [Figure 6A]

[0013] 1 is a schematic diagram of at least a portion of a fluid transfer and assay system in a first state according to one embodiment. [Figure 6B] 1 is a schematic diagram of at least a portion of a fluid transfer and assay system in a second state according to one embodiment. [Figure 6C] 1 is a schematic diagram of at least a portion of a fluid transfer and assay system in a third state according to one embodiment. [Figure 6D] 1 is a schematic diagram of at least a portion of a fluid transfer and assay system in a fourth state according to one embodiment. [Figure 7A]

[0014] 1 is a schematic diagram of at least a portion of a fluid transfer and assay system in a first state according to one embodiment. [Figure 7B] 1 is a schematic diagram of at least a portion of a fluid transfer and assay system in a second state according to one embodiment. [Figure 7C] 1 is a schematic diagram of at least a portion of a fluid transfer and assay system in a third state according to one embodiment. [Figure 7D] 1 is a schematic diagram of at least a portion of a fluid transfer and assay system in a fourth state according to one embodiment. [Figure 8]

[0015] FIG. 1 is a perspective view of a fluid transfer and assay device (or system) according to one embodiment. [Figure 9A]

[0016] 13 is a cross-sectional view of the fluid transfer and assay device (or system) of FIG. 12 shown in a first condition. [Figure 9B] 13 is a cross-sectional view of the fluid transfer and assay device (or system) of FIG. 12 shown in a second condition. [Figure 9C] FIG. 13 is a cross-sectional view of the fluid transfer and assay device (or system) of FIG. 12 shown in a third condition. [Figure 9D] FIG. 13 is a cross-sectional view of the fluid transfer and assay device (or system) of FIG. 12 shown in a fourth condition. [Figure 10]

[0017] FIG. 1 is a perspective view of a fluid transfer and assay device (or system) according to one embodiment. [Figure 11]

[0018] FIG. 11 is a side view of the fluid transfer and assay device (or system) of FIG. 10, with the housing of the device partially transparent to show internal features of the device. [Figure 12A]

[0019] FIG. 12 is a side view of the fluid transfer and assay device (or system) of FIG. 11 in a first state. [Figure 12B] FIG. 12 is a side view of the fluid transfer and assay device (or system) of FIG. 11 in a first state. [Figure 12C]

[0020] FIG. 12 is a side view of the fluid transfer and assay device (or system) of FIG. 11 in a second state. [Figure 12D]

[0021] FIG. 12 is a side perspective view of the fluid transfer and assay device (or system) of FIG. 11 in a third condition. [Figure 13]

[0022] FIG. 1 is a diagram of a fluid transfer and assay device (or system) according to one embodiment. [Figure 14] FIG. 1 is a diagram of a fluid transfer and assay device (or system) according to one embodiment. [Figure 15] FIG. 1 is a diagram of a fluid transfer and assay device (or system) according to one embodiment. [Figure 16] FIG. 1 is a diagram of a fluid transfer and assay device (or system) according to one embodiment. [Figure 17]

[0023] 1A-1D are diagrams of fluid transfer and assay devices (or systems) according to different embodiments. [Figure 18] 1 is a diagram of a fluid transfer and assay device (or system) according to different embodiments. [Figure 19] 1 is a diagram of a fluid transfer and assay device (or system) according to different embodiments. [Figure 20] 1 is a diagram of a fluid transfer and assay device (or system) according to different embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] Detailed Description

[0024] Any of the fluid transfer devices described herein may be configured to accept, acquire, and / or transfer a flow, bolus, volume, etc. of bodily fluid. Additionally, any of the fluid transfer devices described herein may include an integrated device for performing one or more rapid diagnostic tests on at least a portion of the bodily fluid acquired by the fluid transfer device. In some embodiments, the fluid transfer device may be a syringe, a transfer adapter, and / or any other device configured to accept a flow of bodily fluid. In some embodiments, the fluid transfer device may be a fluid diversion and / or isolation device configured to accept and isolate an initial amount of bodily fluid from a subsequent sample volume used, for example, in a culture test. In such embodiments, the integrated device for rapid diagnostic testing may be configured to accept at least a portion of the initial amount of bodily fluid or at least a portion of a subsequent sample volume. The integrated device for rapid diagnostic testing may be, for example, a lateral flow assay and / or any other suitable diagnostic testing device. The integrated device for rapid diagnostic testing may be used to test a volume of bodily fluid and provide at least a qualitative result. The qualitative result may further be output at or by a device for visual inspection. In other cases, the test device may communicate data relating to the results to an electronic device (e.g., via a wired or wireless network). The electronic device may then perform any suitable analysis of the data, such as representing at least some of the data (e.g., qualitative or quantitative test results) graphically on a display of the device.

[0010]

[0025] In some implementations, a rapid diagnostic testing device may be included or incorporated into a fluid transfer device (e.g., a sample collection device) and used to provide an initial test result of the acquired bodily fluid. The initial test result may be supplemented by additional testing of the acquired bodily fluid, such as culture testing. For example, an integrated rapid diagnostic testing device (also referred to herein as a "rapid test device" or "initial test device") may provide an approach to perform relatively rapid testing of bodily fluids for the presence of microorganisms (e.g., gram-positive bacteria, gram-negative bacteria, fungi, or viruses) or other types of biological substances (e.g., specific types of cells, biomarkers, proteins, antigens, enzymes, blood components, etc.). This may inform clinicians in making decisions regarding treatment strategies. In some implementations, the initial test device may test for bacteria and / or other infections that may lead to and / or otherwise result in sepsis, thereby allowing clinicians to provide rapid treatment, such as broad-spectrum antibiotics. Additionally, the fluid transfer devices described herein can obtain additional sample volumes that can be used for more sensitive tests, such as culture tests, or other techniques, such as molecular polymerase chain reaction (PCR), magnetic resonance and other magnetic analysis platforms, automated microscopy, spatial clonal isolation, flow cytometry, whole blood ("culture-free") sample analysis (e.g., NGS) and related techniques, morphokinetic cell analysis, and / or other current, advanced, or developing techniques used to characterize patient samples and / or to detect, identify, type, classify, and / or characterize specific organisms, antibiotic sensitivity, and the like.

[0011]

[0026] In some embodiments, the system includes a flow-based assay device and a fluid transfer device. The fluid transfer device has an inlet configured to be fluidly connected to a source of bodily fluid and an outlet configured to be fluidly connected to a sample reservoir. The fluid transfer device includes an isolation chamber and a port in selective communication with the isolation chamber. The isolation chamber is configured to be fluidly connected to the inlet to receive a first amount of bodily fluid when the fluid transfer device is in a first state. The outlet is configured to be fluidly connected to the inlet to receive a second amount of bodily fluid when the fluid transfer device is in a second state. The flow-based assay device is configured to be coupled to the port to receive a portion of the first amount of bodily fluid when the fluid transfer device is in a third state. The flow-based assay device is configured to provide an indication related to the presence of a target analyte in the portion of the first amount of bodily fluid.

[0012]

[0027] In some embodiments, the system includes a fluid transfer device having an inlet configured to receive a flow of bodily fluid from a bodily fluid source, an outlet configured to be in fluid communication with a sample reservoir, an isolation chamber configured to receive a first amount of bodily fluid, and a port in at least temporary fluid communication with the isolation chamber. The fluid transfer device is configured to transition between a first state in which the isolation chamber is in fluid communication with the inlet to receive the first amount of bodily fluid and a second configuration in which the outlet is in fluid communication with the inlet to receive a second amount of bodily fluid. The port of the isolation chamber allows a flow gas to flow through the isolation chamber as the isolation chamber receives the first amount of bodily fluid. The flow-based assay device is configured to be coupled to the fluid transfer device in the second state. A portion of the flow-based assay device engages the port when coupled to the fluid transfer device, allowing a portion of the first amount of bodily fluid to be transferred from the isolation chamber to the flow-based assay device. The flow-based assay device is configured to provide an indication related to the presence of a target analyte in the portion of the initial amount of bodily fluid.

[0013]

[0028] In some embodiments, the method includes fluidly connecting an inlet of the fluid transfer device to a body fluid source and receiving a first amount of body fluid from the inlet into an isolation chamber of the fluid transfer device, where a flow controller of the fluid transfer device passes a flow of gas but not a flow of body fluid through the flow controller to vent the isolation chamber during the receiving. Transitioning the fluid transfer device from a first state to a second state after the first amount of body fluid is received into the isolation chamber. In response to the fluid transfer device being in the second state, establishing fluid communication between the inlet and the outlet of the fluid transfer device and allowing the second amount of body fluid to flow to a sample reservoir in fluid communication with the outlet. Transporting a portion of the first amount of body fluid from the isolation chamber to a sample element of a flow-based assay device at least temporarily fluidly coupled to the isolation chamber, and transporting a buffer solution to the sample element of the flow-based assay device.

[0014]

[0029] In some embodiments, the system includes a fluid transfer device and a lateral flow assay device. The fluid transfer device includes an inlet configured to be in fluid communication with a source of bodily fluid, an outlet configured to be in fluid communication with a sample reservoir, and an isolation chamber configured to receive an initial amount of bodily fluid. The fluid transfer device is configured to be transitioned between (1) a first state in which the isolation chamber is in fluid communication with the inlet to receive the initial amount of bodily fluid, (2) a second state in which the outlet is in fluid communication with the inlet to receive a subsequent flow of bodily fluid, and (3) a third state in which the lateral flow assay device is coupled to a port in fluid communication with the isolation chamber. The lateral flow assay device is configured to receive a portion of the initial amount of bodily fluid and determine the presence of a target analyte in the initial amount of bodily fluid.

[0015]

[0030] As used in this specification and / or any claims contained herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, the term "a member" means a single member or a combination of members, "a material" means one or more materials, and so forth.

[0016]

[0031] As used herein, "body fluid" may include any fluid obtained directly or indirectly from a patient's body. For example, "body fluid" may include, but is not limited to, blood, cerebrospinal fluid, urine, bile, lymphatic fluid, saliva, synovial fluid, serous fluid, pleural fluid, amniotic fluid, mucus, sputum, vitreous humor, air, and the like, or any combination thereof.

[0017]

[0032] As used herein, the terms "proximal" and "distal" refer to directions toward and away from a user who brings the device into contact with a patient, respectively. Thus, for example, the end of the device that first touches the patient's body is the distal end of the device, and the opposite end of the device (e.g., the end of the device that is manipulated by the user) is the proximal end of the device.

[0018]

[0033] As used herein, the terms "about," "approximately," and / or "substantially," when used in connection with a stated value and / or a geometric structure or relationship, convey that the value or characteristic so defined is nominally the stated value or described characteristic. In some cases, the terms "about," "approximately," and / or "substantially" may generally mean and / or generally contemplate the stated value or characteristic within a desired tolerance range (e.g., plus or minus 10% of the stated value or characteristic). For example, a value of about 0.01 may include 0.009 and 0.011, a value of about 0.5 may include 0.45 and 0.55, a value of about 10 may include 9-11, and a value of about 100 may include 90-110. Similarly, a first surface may be described as substantially parallel to a second surface if the first and second surfaces are nominally parallel. It should be understood that while the values, structures, and / or relationships shown may be desirable, some variations may occur, for example, as a result of manufacturing tolerances or other practical considerations (e.g., pressures or forces exerted by portions of a device, conduit, lumen, etc.). Accordingly, the terms "about," "approximately," and / or "substantially" may be used herein to account for such tolerances and / or considerations.

[0019]

[0034] As used herein, the terms "first," "initial," and / or "pre-sample," when used to describe a quantity of bodily fluid, may be used interchangeably to describe a quantity, portion, or volume of bodily fluid that is collected, diverted, isolated, examined, etc., prior to obtaining the "sample" quantity. The "first," "initial," and / or "pre-sample" quantity may be a predetermined, defined, desired, and / or given amount of bodily fluid. For example, the predetermined and / or desired pre-sample volume of a bodily fluid such as blood may be a drop of blood, a few drops of blood, about 0.1 milliliters (mL), about 0.2 mL, about 0.3 mL, about 0.4 mL, about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, about 1.0 mL, about 2.0 mL, about 3.0 mL, about 4.0 mL, about 5.0 mL, about 6.0 mL, about 7.0 mL, about 8.0 mL, about 9.0 mL, about 10.0 mL, about 20.0 mL, about 50.0 mL, and / or any amount or fraction of an amount therebetween. In other cases, the pre-sample volume may be greater than 50 mL or less than 0.1 mL. As a particular example, the predetermined and / or desired pre-sample volume may be between about 0.1 mL and about 5.0 mL. As another example, the pre-sample volume can be, for example, the volume or total volume of any number of lumens (e.g., the lumens of a needle and / or a combination of lumens that form at least a portion of a flow path from a bodily fluid source to an initial collection chamber, portion, reservoir, etc.) As yet another example, the pre-sample volume can be, for example, a volume of bodily fluid sufficient to perform an initial or pre-sample test, such as, for example, a rapid diagnostic test using a lateral flow assay and / or any other rapid test device.

[0020]

[0035] As used herein, the terms "second," "subsequent," and / or "sample," when used to describe a quantity of bodily fluid, may be used interchangeably to describe a quantity, portion, or volume of bodily fluid collected after collecting a first, initial, and / or pre-sample quantity of bodily fluid. The "second," "subsequent," and / or "sample" quantity may be either a random quantity or a predetermined or desired quantity of bodily fluid collected after collecting, diverting, isolating, and / or testing a pre-sample quantity of bodily fluid. In some cases, the desired sample volume of bodily fluid may be from about 10 mL to about 60 mL. In other cases, the desired sample volume of bodily fluid may be less than 10 mL or more than 60 mL. In still other cases, the desired sample volume may be based at least in part on one or more tests, assays, analyses, and / or processes to be performed on the sample volume.

[0021]

[0036] In some implementations, the second, subsequent, and / or sample volume of bodily fluid may be used in one or more sample or diagnostic tests, such as, for example, culture tests, etc. In some cases, collecting a "sample" volume of bodily fluid after collecting, segregating, isolating, and / or testing a "pre-sample" volume of bodily fluid may reduce the likelihood that the sample volume will contain contaminants, such as, for example, skin-resident microorganisms. Thus, the sample volume of bodily fluid may be suitable for sensitive tests that may be prone to inaccurate results due to contamination.

[0022]

[0037] The embodiments and / or portions thereof described herein may be formed or constructed of one or more biocompatible materials. In some embodiments, the biocompatible material may be selected based on one or more properties of the material of construction, such as, for example, stiffness, toughness, durometer, bioreactivity, etc. Examples of suitable biocompatible materials include metals, glasses, ceramics, or polymers. Examples of suitable metals include pharmaceutical grade stainless steel, gold, titanium, nickel, iron, platinum, tin, chromium, copper, and / or alloys thereof. Polymeric materials may be biodegradable or non-biodegradable. Examples of suitable biodegradable polymers include polylactides, polyglycolides, polylactide-co-glycolides (PLGA), polyanhydrides, polyorthoesters, polyetheresters, polycaprolactones, polyesteramides, poly(butyric acid), poly(valeric acid), polyurethanes, and / or blends and copolymers thereof. Examples of non-biodegradable polymers include nylon, polyesters, polycarbonates, polyacrylates, polysiloxanes (silicones), polymers of ethylene vinyl acetate and other acyl substituted cellulose acetates, non-degradable polyurethanes, polystyrene, polyvinyl chloride, polyvinyl fluoride, poly(vinylimidazole), chlorosulfonated polyolefins, polyethylene oxide, and / or blends and copolymers thereof.

[0023]

[0038]

[0023] Referring now to the drawings, Figure 1 is a schematic diagram of a fluid transfer and assay system 100 according to one embodiment. Various components, elements, features and / or functions may be described below, with the understanding that they are presented by way of example only and not limitation. Those skilled in the art will appreciate that changes may be made to the form and / or characteristics of fluid transfer and assay system 100 without altering the ability of fluid transfer and assay system 100 to perform the functions of obtaining bodily fluid samples and providing rapid diagnostic tests as described herein.

[0024]

[0039] The fluid transfer and assay system 100 (also referred to herein as the "system") may include at least a fluid transfer device 105 and a rapid diagnostic test device 170. In some implementations, the system 100 may optionally include at least one electronic device 190 and / or at least one fluid collection device 195.

[0025]

[0040] As described herein with reference to certain embodiments, the fluid transfer device 105 (also referred to herein as a "transfer device") may be of any suitable shape, size, and / or configuration. In some implementations, the transfer device 105 may be configured to draw bodily fluid (e.g., blood) from a patient to the transfer device 105. Further, the transfer device 105 may be configured to transfer at least a portion of the drawn bodily fluid to one or more other devices, reservoirs, containers, vials, machines, tests, assays, etc., such as the rapid diagnostic test device 170 and / or one or more optional fluid collection devices 195.

[0026]

[0041] In some embodiments, the transfer device 105 may be configured to transfer, guide, and / or divert a certain amount or volume of bodily fluid to one or more portions of the transfer device 105 (or through one or more portions of the transfer device 105) and then transfer such amount or volume to one or more devices coupled to or integrated with the transfer device 105, such as one or more sample reservoirs, containers, bottles, etc. For example, the transfer device 105 may be configured to transfer a first portion, amount, or volume of bodily fluid to or through a first or isolated portion of the transfer device 105 and then transfer a second portion, amount, or volume (e.g., a subsequent amount) of bodily fluid to a second or sampling portion of the transfer device 105. In some embodiments, as described in further detail herein with reference to certain embodiments, the transfer device 105 and / or the isolated portion of the transfer device 105 may be configured to isolate the first amount of bodily fluid (e.g., within the isolated portion of the transfer device 105) from the subsequent amount of bodily fluid. In some implementations, the transfer device 105 may be configured to transfer at least a portion of a first quantity of bodily fluid (e.g., contained within an isolated portion of the transfer device 105) to the rapid diagnostic test device 170 and transfer at least a portion of a second quantity of bodily fluid to one or more of the optional fluid collection devices 195.

[0027]

[0042] As described herein with reference to certain embodiments, the rapid diagnostic test device 170 (also referred to herein as a "rapid test device" or simply a "test device") may be of any suitable shape, size, and / or configuration. In some embodiments, the rapid test device 170 may be removably coupled to the transfer device 105 or any suitable portion thereof (e.g., an inlet portion, an outlet portion, an isolation portion, a sampling portion, and / or any other suitable portion). In other embodiments, the rapid test device 170 may be incorporated into the transfer device 105. For example, the transfer device 105 and the rapid test device 170 may be unitarily or monolithically formed and / or otherwise integrated. In still other embodiments, the transfer device 105 may include and / or form a port, adapter, and / or receiving portion to which the rapid test device 170 may be coupled or into which the rapid test device 170 may be inserted to establish fluid communication between the transfer device 105 and the rapid test device 170. In some such embodiments, coupling the rapid test device 170 to the transfer device 105 may function to transition one or more flow controllers, valves, scepters, ports, seals, etc. from a closed or sealed state to an open state to allow fluid communication between the transfer device 105 and the test device 170.

[0028]

[0043] In some implementations, the rapid test device 170 may be configured to receive a first amount of bodily fluid from the transfer device 105 and perform one or more tests, assays, and / or diagnostic procedures using the first amount of bodily fluid. For example, the rapid test device 170 may be a chromatographic lateral flow immunoassay that may test for any suitable analyte, biomarker, protein, molecule, particle, etc. Chromatographic lateral flow immunoassays (referred to herein as "lateral flow assays" or "LFAs") are typically nitrocellulose-based devices configured to detect the presence of a target analyte in a sample (e.g., a biological sample and / or a bodily fluid sample, e.g., blood, urine, etc.). In general, LFAs include a series of capillary beds, such as porous pieces of paper, microstructured or sintered polymers, etc., that may be positioned in desired locations and / or configurations on a substrate to guide the flow of a sample (e.g., at least a portion of the first amount of bodily fluid) along a portion of the LFA.

[0029]

[0044] LFAs may be used in a wide range of applications where it is desirable to have a relatively fast, easy-to-use, low-cost approach for rapid antigen detection. LFAs are typically performed with little sample or reagent preparation and can enable usable test results in as little as a few minutes (or longer if more sensitive test results are desired). Furthermore, in some implementations, LFAs may be configured to test for analytes and / or biomarkers produced by the human body in response to in vivo conditions (e.g., infections such as sepsis). This may further mean that such LFAs have a relatively low sensitivity to contaminants (e.g., skin-resident microorganisms, etc.) that may be included in the first volume of bodily fluid drawn from the patient via the transfer device 105.

[0030]

[0045] Typically, two types of LFAs are used depending on the size and / or number of binding sites of the target analyte. In particular, competitive LFAs are commonly used when testing small analytes, and sandwich LFAs are commonly used when testing large analytes. In this context, home pregnancy tests are well-known sandwich lateral flow assays. In some cases, it may be desirable to use sandwich LFAs to test for antigens, analytes, and / or biomarkers associated with, for example, sepsis and / or other infectious conditions in a sample of a bodily fluid such as blood. It should be understood that, although the embodiments described herein include and / or implement sandwich LFAs, the embodiments are not limited thereto. For example, any of the embodiments described herein may use and / or implement competitive LFAs and / or any other suitable rapid diagnostic test device.

[0031]

[0046] In this regard, a schematic example of a sandwich LFA 170A is shown in FIG. 2. The sandwich LFA 170A (referred to herein as "LFA") includes a substrate 171 on which are a sample element 172, a conjugate element 173, a capture element 174, a control element 175, and a wick 176. The substrate 171 may be of any suitable shape, size, and / or configuration. For example, the substrate 171 may be a rectangular backing card or strip of a certain width and a predetermined length that can provide a sufficient surface area to accommodate the various components of the LFA 170A. The substrate 171 may be made of a semi-rigid polymer designed to provide uniformity and lay-flat characteristics. As described further herein, the substrate 171 may include one or more pressure-sensitive adhesives configured to facilitate attachment of the various components of the LFA 170A.

[0032]

[0047] As shown, the sample element 172 is generally disposed at one end of the substrate and configured to receive a sample volume. The sample element 172 may be a pad that receives a sample of blood and / or other biological fluid for analysis and provides a surface that facilitates smooth, continuous, and homogenous transfer of the sample to other components of the lateral flow test strip. The sample element 172 may be of any suitable shape, size, and / or configuration. The conjugate element 173 is disposed downstream adjacent to the sample element 172. The conjugate element 173 includes a dry matrix (e.g., a salt-sugar matrix) configured to include desired bioactive particles. The bioactive particles included in the matrix include specific antibodies and / or affinity reagents (e.g., DNA aptamers, protein binders, etc.) immobilized on or within the conjugate element 173. The antibodies and / or affinity reagents may be selected based on the target molecule (e.g., antigen or analyte) that the LFA 170A is configured to detect. Additionally, the antibodies and / or affinity reagents are directly or indirectly conjugated to molecules configured to enable detection. For example, the antibodies can be labeled with colored particles (e.g., latex with a blue color, colloidal gold with a red color, and / or any other suitable particles), fluorescent particles, magnetic particles, enzymes for subsequent signal generation, etc. Thus, the labeled antibodies can bind to the desired antigen or analyte, thereby generating a labeled or target analyte 177 that can be detected at other portions or by other elements of the LFA 170A.

[0033]

[0048] The capture element 174 is disposed adjacent to and / or downstream of the conjugate element 173 and includes particles or molecules immobilized within or on the capture element 174. The particles or molecules may be configured to bind to a labeled analyte 177, thereby capturing or immobilizing the labeled analyte 177 within or on the capture element 174. As the concentration of captured and / or immobilized labeled analyte 177 increases (e.g., the number of molecules within the capture element 174 increases), the optical density of the detection molecule (e.g., a colored label) also increases. In this manner, the LFA 170A is configured to exhibit a discrete colorimetric signal line, region, or strip indicative of the presence of the target analyte in the sample volume (e.g., a positive test result).

[0034]

[0049] The control element 175 is disposed adjacent to and / or downstream of the capture element 174. The control element 175 includes particles or molecules immobilized within or on the control element 175. In contrast to the capture element 174, the particles or molecules included within the control element 175 may be configured to bind to a number of different particles, such as, for example, labeled analyte 177, labeled bioactive particles that do not bind to antigens, etc. Thus, the control element 175 may be configured to bind to and / or otherwise immobilize labeled particles that were not immobilized within or on the capture element 174. Thus, the control element 175 may exhibit a colored portion or strip that may be used to indicate that a reaction has occurred and / or a test has been performed. For example, if the target analyte is not present in the sample volume, it may be desirable to confirm that the assay has been performed properly and that a negative result (no colored strip presented on or by the capture element 174) indicates the condition of the sample volume and not a malfunction of the LFA 170A. Wick 176 is positioned adjacent to and / or downstream of control element 175 and is configured to absorb or soak up a portion of the sample that is not immobilized in or on capture element 174 and / or in or on control element 175.

[0035] Assay

[0050] LFA 170A may be used to test for the presence of any suitable target analyte, biomarker, molecule, particle, etc. in a sample volume (e.g., a blood sample or any other suitable sample of a bodily fluid). For example, any of the embodiments described herein may include and / or implement an LFA (e.g., LFA 170A) and / or any other suitable flow-based rapid diagnostic system configured to test for the presence of a particular analyte or biomarker that can provide information used to diagnose a patient condition, such as, for example, sepsis.

[0036]

[0051] For example, blood lactate may be a biomarker used in the clinical diagnosis and management of sepsis. In some cases, many other biomarkers may be used as an alternative or in addition to lactate to guide clinical decisions. A non-exhaustive list of suitable biomarkers may include inflammatory cytokines and / or chemokines associated with the hyperinflammatory phase of sepsis; C-reactive protein and / or procalcitonin (PCT), which are synthesized in response to infection and inflammation; biomarkers associated with neutrophil and / or monocyte activation; anti-inflammatory cytokines associated with the immunosuppressive phase of sepsis; and / or changes in cell surface markers of monocytes and / or lymphocytes. In some cases, a combination of inflammatory and anti-inflammatory biomarkers may be used in a multiplexed LFA, for example, to identify patients developing severe sepsis prior to significant organ dysfunction. In some cases, one or more aptamers may be synthesized to target a particular inflammatory biomarker, anti-inflammatory biomarker, and / or any other suitable biomarker, such as any of those described herein.

[0037] Lactate

[0052] In some implementations, any of the embodiments described herein may be used to detect lactate biomarkers, PCT biomarkers, and / or any other suitable biomarkers described herein associated with and / or otherwise used to identify sepsis. For example, in some implementations, the rapid test device 170 may be configured to test blood lactate levels in a sample of bodily fluid (e.g., blood) using, for example, a portable blood gas analyzer. In other implementations, the rapid test device 170 may be an LFA (e.g., LFA 170A) configured to test blood (e.g., whole blood, serum, etc.) lactate biomarkers (e.g., antigens). For example, the effectiveness of using serum lactate levels to diagnose sepsis is shown in Table 1 below. Table 1 shows the results of a study of acute in-hospital mortality by serum lactate levels in septic patients requiring vasopressors (e.g., agents that cause vasoconstriction).

[0038] [Table 1]

[0039]

[0053] Lactic acid is the end product of the anaerobic breakdown of glucose in tissues and can dissociate into lactate (a hydroxymonocarboxylate anion, which is the conjugate base of lactic acid resulting from deprotonation of the carboxyl group). The generation of lactate in the body occurs when the energy demands of tissues are not met by adequate aerobic respiration. Lactate can be transported in the blood to the liver where it is converted back to glucose via the Cori cycle. However, without adequate clearance of lactate by the liver and kidneys, accumulation of lactate concentrations can lead to lactic acidosis. Clinically, causes of acidosis can be classified into type A disorders, where there is a decrease in tissue oxygenation, such as due to sepsis, and type B disorders, which are caused by certain drugs and / or toxins, among others, along with systemic diseases. Medical evidence suggests that patients with persistently high levels of lactate have increased morbidity and mortality. Excess lactate in the body can also cause bleeding, respiratory failure, trauma, convulsions, ischemia, kidney problems, liver disease, tissue hypoxia, shock, blood loss, and anemia, among others. Therefore, lactate monitoring is of paramount importance to diagnose and evaluate health concerns that arise in conditions of oxygen deficiency (i.e., conditions in which lactate levels in the body increase beyond acceptable limits). Blood lactate concentrations in healthy, non-stressed individuals have been reported to be in the range of 0.1-1.0 millimolar (mM). In contrast, critically ill individuals, such as those with severe sepsis or septic shock, may have concentrations greater than 4 mM.

[0040]

[0054] Lactate can exist as one of two optical isomers, L-lactate and its mirror image, D-lactate. Analytical methods used to detect and quantify lactate include high performance liquid chromatography (HPLC), fluorimetry, colorimetry, chemiluminescence, and magnetic resonance spectroscopy. Although these methods can provide accurate results, they suffer from drawbacks such as time-consuming sample preparation, the use of expensive equipment, and the need for trained personnel. Therefore, the use of these analytical methods to detect and quantify lactate in biological fluids is more suitable for central laboratories, and their implementation as point-of-care diagnostic tools may be limited.

[0041]

[0055] Detection of lactate levels in biological fluids, including blood and / or plasma, may alternatively be accomplished by the use of enzymes. These enzymes may be immobilized on a solid surface or support (e.g., a biosensor) to provide reactive sites and catalyze the lactate chemical reaction by stabilizing the conversion reaction conditions or reducing the activation energy of a particular lactate chemical reaction to produce one or more species. The one or more species may be monitored and their occurrence may be correlated with the concentration of lactate. For example, L-lactate may be detected using enzymes such as L-lactate oxidase (LOD) and L-lactate dehydrogenase (LDH). LOD is a globular flavoprotein that may be obtained from a variety of bacterial sources, such as Pediococcus, Aerococcus, viridans, and Mycobacterium. The source of LOD may affect the range of pH at which the enzyme can exhibit sufficient catalytic activity, with a typical range of 4 to 9. LOD, a member of the flavin mononucleotide (FMN) family, uses FMN as a cofactor to catalyze the oxidation of hydroxyacids in its reaction involving glycolate oxidase, L-lactate monooxygenase, flavocytochrome b2, long-chain alpha hydroxyacid oxidase, and L-mandelate dehydrogenase. LOD can be immobilized on a solid support and exposed to biological fluids such as blood and plasma to detect the presence of L-lactate. LOD can catalyze the oxidation of L-lactate to pyruvate (PA) in the presence of dissolved oxygen, producing reduced LOD and hydrogen peroxide (H2O2) as by-products. The hydrogen peroxide produced by the oxidation of lactate can be accurately quantified by secondary chemical and / or electrochemical reactions. For example, hydrogen peroxide produced during the oxidation of lactate in the presence of LOD enzyme can be electrochemically reduced or oxidized to generate an electrical signal, which can be monitored at an electrode. The reduced LOD enzyme can then be reoxidized in a second reaction step at an electrode, as shown in the following reaction scheme: [ka]

[0042]

[0056] Similar to LOD, the LDH enzyme can be used to detect and quantify the presence of L-lactate in various biological fluids. LDH is a quaternary protein that can be found in animals, plants, and prokaryotes. LDH is present in tissues and is released upon tissue damage. The LDH enzyme contains five different isoenzyme forms that are distinguished by slight structural differences. Depending on the source, the LDH enzyme is known to be stable over a relatively narrow pH range of 5-8, more specifically, a pH range of about 7.2-7.4. LDH also catalyzes the reaction of L-lactate to pyruvate (PA) by oxidizing its cofactor, nicotinic acid adenine dinucleotide (NAD) (NAD + During the reaction, LHD converts L-lactate to pyruvate (PA) and NAD + is converted to NADH. As described above with reference to the detection of L-lactate by LOD enzyme, the detection of lactate by LDH enzyme can then be achieved by a secondary reaction. For example, NADH can be electrochemically oxidized under the influence of an applied potential generated by an electrode, and the generated current is proportional to the concentration of L-lactate, as shown in the following reaction scheme. [ka]

[0043]

[0057] The use of enzymes to detect lactate in biological fluids by lactate enzymatic oxidation relies on the conversion of lactate into one or more by-products, such as NADH and hydrogen peroxide (H2O2), which can be accurately quantified by secondary reactions, as described above. The secondary reactions often involve electrochemical conversion carried out at the surface of an electrode, which generates a transient current proportional to the amount of lactate present in the sample (e.g., electrochemical methods for lactate sensing). Alternatively, as further described herein, the by-products of the enzymatic reaction of lactate can be quantified by phototransfer processes (e.g., electrochemiluminescence and fluorescence techniques for lactate sensing).

[0044]

[0058] Biosensors that rely on electrochemical methods to detect lactate (i.e., electrochemical biosensors) use enzymes immobilized on a support substrate located in close proximity to or near an electrode surface. The performance characteristics of electrochemical biosensors can vary widely depending on the enzyme source, environmental conditions including pH and temperature, the method used to immobilize the enzyme on the biosensor, the chemical nature of the matrix or support used to immobilize the enzyme, and / or the electron transfer mechanism. Enzymes can be immobilized according to different methods, and the reactivity of the enzyme depends on the interaction of the enzyme with the support, the nature of the enzyme, and the presence of adsorbed species, mediators, and additives. Common enzyme immobilization techniques include physical adsorption, encapsulation behind dialysis membranes or polymer films, covalent binding by crosslinkers, and incorporation into the bulk of a carbon composite matrix.

[0045]

[0059] Challenges associated with enzyme immobilization include reproducibility, stability, and deactivation due to the generation and / or accumulation of inhibitors and / or fouling species. For example, an LOD enzyme immobilized by physical adsorption on a biosensor containing an Au electrode may exhibit a 50% loss of stability after only one month of storage, while an LOD enzyme immobilized in mesoporous silica using a polymer matrix of polyvinyl alcohol (PVA) may exhibit 98% of its initial activity after nine months. As a result, the development of a sensor using an LOD enzyme to detect lactate requires the identification of a suitable immobilization technique, a suitable matrix support, and the use and / or storage environmental conditions so that the activity or shell life of the enzyme can be retained over an extended period of time.

[0046]

[0060] Electrochemical biosensors for lactate detection typically include devices that include two or three electrode sensing platforms. Accurate measurement of lactate often involves the use of a reference electrode (typically made of Ag / AgCl2) that is held in close proximity to the working electrode to maintain a stable, known potential. The working electrode acts as a transducer, while the counter electrode establishes a path for passing current due to potential changes at the working electrode. Common techniques for measuring the electrical signal generated during lactate detection include cyclic voltammetry, amperometry, and potentiometry. Electrochemical biosensors can offer high sensitivity, wide linear range, and rapid response. However, their use presents limitations due to complex experimental setups, passivation of the system by fouling factors, and signal reduction and interference due to competing reactions. For example, electrochemical quantification of hydrogen peroxide (H2O2) generated during the enzymatic oxidation of L-lactate by LOD enzymes requires high oxidation potentials, leading to interference due to other electrooxidizable species.

[0047]

[0061] Lateral flow assays (LFAs) configured to test for lactate biomarkers (e.g., antigens) in blood (e.g., whole blood, serum, etc.) provide another tool to facilitate and / or aid in the diagnosis of sepsis. As described above with reference to FIG. 2, LFAs may be performed on a plastic backing laminate or strip that includes one or more components assembled on a substrate 171. The components of the LFA configured to quantify lactate in blood and / or other biological fluids may include at least a sample element 172 and a conjugate element 173.

[0048]

[0062] As described above, the sample element 172 may be a pad that provides a surface that accepts a sample of blood and / or other biological fluid for analysis and promotes smooth, continuous, and homogenous transfer of the sample to other components of the lateral flow test strip. The sample element 172 may be of any suitable shape and / or size. In some embodiments, the shape of the sample element 172 may be a rectangular strip configured to absorb and accept a volume of a sample of blood and / or other biological fluid. In other embodiments, the shape of the sample element 172 may be a rectangular strip, one of whose ends includes a region having a dimension larger than the width of the strip to facilitate pipetting of a volume of a sample of blood and / or other biological fluid. For example, the sample element 172 may be a rectangular strip that includes a circular region attached to one of the ends of the strip. The circular region of the sample element 172 may provide a larger surface area for accepting a sample of blood and / or other biological fluid via a micropipette. Alternatively, in some embodiments, the sample element 172 may include a large diameter circular region with various rectangular strips extending radially from the center of the circular region. Each rectangular strip can facilitate the transfer of a portion of the blood and / or other biological fluid sample to other components of the lateral flow test strip for simultaneous detection of multiple biomarkers (i.e., multiplexing) and / or for replication of the assay for validation purposes.

[0049]

[0063] The sample element 172 may be disposed on a surface of the plastic backing laminate to provide mechanical support to the LFA. In some embodiments, the sample element 172 may include an adhesive coated on one surface of the sample pad to facilitate attachment to the plastic backing laminate. The shape and dimensions of the sample element 172 may be predetermined such that the sample element may be disposed on the plastic backing laminate. The thickness of the sample element 172 may be selected to facilitate attachment of the sample element 172 to the plastic backing laminate while maintaining the mechanical structure of the pad. Additionally, the thickness of the sample element 172 may be selected to accommodate a large amount of blood and / or other biological fluids, preventing oversaturation of the sample on the pad and channeling into the plastic backing laminate. For example, in some embodiments, the thickness of the sample element 172 may be between 0.18 mm and 0.34 mm.

[0050]

[0064] The sample element 172 may be made of cellulose, nitrocellulose, glass fiber, and / or any other suitable material. In some embodiments, the sample element 172 may be made of cellulose membrane and / or chromatography paper configured to facilitate a linear flow rate of about 3-5 mm / min. The sample element 172 may also include one or more chemical reagents configured to pre-treat the sample before it is transferred to other downstream components. In some embodiments, the surface of the sample element 172 may be impregnated with an aqueous buffer solution that provides a pH-controlled environment. In some embodiments, the surface of the sample element 172 may be impregnated with a buffer solution, including, but not limited to, phosphate buffered saline (PBS), 2-ethanesulfonic acid (MES), tris(hydroxymethyl)aminomethane (TRIS), piperazine-N,N'-bis (PIPES), 3-morpholinopropane-1-sulfonic acid (MOPS), 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid (HEPES), [tris(hydroxymethyl)methylamino]propanesulfonic acid (TAPS), N-cyclohexyl-2-aminoethanesulfonic acid (CHES), and / or N-cyclohexyl-3-aminopropanesulfonic acid (CAPS).

[0051]

[0065] In some embodiments, the sample element 172 may include one or more components configured to capture and separate species present in blood and / or other biological fluids that may cause interference with the LFA assay. For example, in some embodiments, the sample element 172 may include one or more regions configured to separate red blood cells present in blood and / or other biological fluid samples. In some cases, the regions configured to separate blood cells may be one or more separate pads that may be disposed on the sample element 172. In other embodiments, the blood separation region may be a pad located adjacent to the sample element 172. In some cases, the blood separation pad may include one or more layers, such as polyester matrices and composite matrices, designed to have an asymmetric morphology with different porosities and pore size distributions that facilitate capture of cellular components of blood (i.e., red blood cells, white blood cells, and platelets) with larger pores while allowing plasma to flow downstream through smaller sized pores.

[0052]

[0066] The conjugate element 173 of the LFA for detecting and quantifying lactate from blood and / or other biological fluid samples can be a pad located adjacent to and downstream of the sample element 172. As described further herein, the conjugate element 173 can include a dry matrix (e.g., a salt-sugar matrix) that includes a bioactive species capable of reacting with lactate to produce a species that can be detected by colorimetry. The conjugate element 173 can be configured to accommodate one or more bioactive species that can be released upon contact with a moving liquid sample deposited on the upstream sample element 172. As described above with reference to the sample element 172, the conjugate element 173 can be a pad of any suitable shape and / or size. In some embodiments, the shape of the conjugate element 173 can be a strip having a size and / or shape substantially similar to the size and / or shape of the sample element 172. In some embodiments, the conjugate element 173 and the sample element 172 can be made in a single pad, can be located on opposite ends of the single pad, and can optionally be attached to the surface of a plastic backing laminate to provide mechanical support to the LFA. In yet another embodiment, the conjugate elements 173 and sample elements 171 can be fabricated in a single pad comprising a rectangular strip, a first end of the strip comprising a region having a dimension greater than the width of the strip to provide an area for accommodating a bioactive species for oxidation and colorimetric detection of lactate, and a second end of the strip opposite the first end having a dimension greater than the width of the strip to provide an area for accommodating a volume of a blood and / or other biological fluid sample. Alternatively, in some embodiments, the conjugate elements 173 can comprise multiple rectangular strips radially joined to a larger diameter circular region, the larger diameter circular region configured to accommodate the sample elements 171. In this configuration, each conjugate element 173 can facilitate detection of multiple biomarkers present in a portion of a blood and / or other biological fluid sample (i.e., multiplexing) and / or replication of the assay for validation purposes.

[0053]

[0067] The conjugate element 173 may include a dry matrix configured to include a desired bioactive species for detecting and quantifying lactate in a sample of blood and / or other biological fluid. For example, in this embodiment, the matrix of the conjugate element 173 may include both a detection enzyme and a quantification enzyme. The detection enzyme may be configured to exhibit high activity and selectivity for catalytic oxidation of lactate, producing one or more by-products. The one or more by-products may be monitored by a secondary chemical reaction to quantify the concentration of lactate present in the sample. For example, in some embodiments, the matrix of the conjugate element 173 may include a detection enzyme, such as L-lactate oxidase (LOD). In other embodiments, the matrix of the conjugate element 173 may include other suitable detection enzymes, such as L-lactate dehydrogenase (LDH). The one or more detection enzymes may be loosely deposited on the surface of the conjugate element 173 pad such that they may be dissolved in a volume of the sample of blood and / or other biological fluid flowing from the sample element 172.

[0054]

[0068] The quantification enzyme can be configured to exhibit high activity and selectivity for the stoichiometric conversion of one or more species produced during the enzymatic oxidation of lactate, generating a signal that can be quantified. In some embodiments, the dry matrix can include one or more heme-containing enzymes, such as catalase and / or peroxidase, that can catalyze an oxidation-reduction reaction with hydroperoxides, such as hydrogen peroxide (H2O2), that are produced during the oxidation of lactate. The heme-containing enzyme can be, for example, horseradish peroxidase. Horseradish peroxidase can catalyze an oxidation-reduction reaction of hydrogen peroxide (H2O2) with 3,3'-diaminobenzidine (DAB), producing a dark brown, insoluble product that can be detected and quantified by colorimetry.

[0055]

[0069] Although LFA 170A is described above as also including capture element 174, control element 175, and wick 176, in this embodiment, detection of lactate may be performed, for example, on or at conjugate element 173. Thus, the LFA need not include separate capture elements, control elements, and / or wicks.

[0056]

[0070] In some embodiments, for example, the LFA may be coupled to an optical device, such as a CMOS or CCD camera, configured to collect images of the dark brown precipitate of 3,3'-diaminobenzidine (DAB) resulting from oxidation with hydrogen peroxide to determine the concentration of lactate originally present in the sample. For example, in some embodiments, the conjugate element 173 of the LFA may be imaged by a camera of a peripheral device, such as a smartphone or a dedicated optical detector, and the intensity of the image may be analyzed by image software to estimate the concentration of the DAB precipitate, the concentration of hydrogen peroxide, and therefore the concentration of lactate originally present in the sample. In some embodiments, the concentration of lactate present in the sample may be determined by (1) recording an image of the DAB brown precipitate, (2) calculating a grayscale mode value using image processing software, and (3) correlating this grayscale mode value with the concentration of lactate present in a sample of known lactate content. The grayscale mode values ​​that the image may take on range from zero to 255, with values ​​closer to zero corresponding to a darker image and values ​​closer to 255 corresponding to a lighter image.

[0057]

[0071] Later Flow Assays (LFAs) configured to detect lactate in blood and / or other biological fluids can overcome certain shortcomings found in lactate detection techniques that rely on electrochemical reactions to quantify the amount of hydrogen peroxide (H2O2) produced upon oxidation of lactate. As described above, the enzymatic reaction of hydrogen peroxide (H2O2) with 3,3'-diaminobenzidine (DAB) produces a brown precipitate. The brown precipitate is insoluble in blood and / or biological fluid samples and can be quantified by optical methods such as colorimetry. Furthermore, the reaction of hydrogen peroxide with DAB proceeds under pH and temperature conditions similar to those required for the oxidation of lactate. Thus, as further described herein, the use of additives in the dry matrix of the LFA can protect both the detection and quantification enzymes from degradation, facilitating storage for periods as long as nine months. In contrast, electrochemical methods for detecting and quantifying lactate typically require the use of high oxidation potentials to convert hydrogen peroxide into an electrical signal. These potentials can often cause interfering reactions with other electrooxidizable species present in the blood and / or biological fluid samples, leading to inaccurate results. Furthermore, immobilization of enzymes to solid surfaces can present several challenges, including (1) the need for complex and / or time-consuming fabrication and characterization methods, as well as reduced stability of the enzymes during storage.

[0058]

[0072] In some embodiments, the detection and quantification enzymes may be included in a dry matrix in the presence of one or more chemical reagents and / or stabilizing additives configured to preserve the activity and stability of the enzymes during storage and oxidation of lactate in blood and / or other biological fluid samples. For example, the dry matrix may include a weak acid or base (e.g., a buffering agent) that can be dissolved in the blood and / or other biological fluid sample, dissociate in the sample, and establish an equilibrium between the acidic species and its conjugate, maintaining the pH of the sample within a range of values ​​at which the enzyme exhibits high catalytic activity. In some embodiments, the dry matrix may include one or more buffering agents, such as phosphate buffered saline (PBS), 2-ethanesulfonic acid (MES), tris(hydroxymethyl)aminomethane (TRIS), piperazine-N,N'-bis (PIPES), 3-morpholinopropane-1-sulfonic acid (MOPS), 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid (HEPES), [tris(hydroxymethyl)methylamino]propanesulfonic acid (TAPS), N-cyclohexyl-2-aminoethanesulfonic acid (CHES), and / or N-cyclohexyl-3-aminopropanesulfonic acid (CAPS).

[0059]

[0073] In some embodiments, the dry matrix may include a polysaccharide such as chitosan, a non-toxic biocompatible biopolymer that can provide antimicrobial and antioxidant activity to preserve the chemical integrity of the enzyme over time. In some embodiments, the chitosan stabilizer may be accompanied by one or more reagents configured to increase the solubility of the chitosan in a sample of blood and / or other biological fluid. For example, in some embodiments, the dry matrix may include chitosan and a weak organic acid, such as formic acid, acetic acid, and / or propionic acid, suitable for increasing the solubility of the chitosan in a volume of blood and / or biological fluid. In some embodiments, the dry matrix may include a combination of additives including chitosan, acetic acid, and / or a buffering agent that are adsorbed onto the surface of the conjugate 173 and configured to dissolve in a volume of blood and / or biological fluid transferred from the sample element 170.

[0060]

[0074] As described above, lateral flow assays (LFAs) configured to test for lactate in blood and / or other biological fluids can detect lactate present in a variety of samples, including buffer solutions, serum, plasma, and / or whole blood. More specifically, in some embodiments, the LFAs can have a dynamic range of detectable lactate of 2-6 (mM) and a sensitivity of 0.5 mM or greater for lactate in buffer and / or serum samples. In some embodiments, the LFAs can have cut-off lactate concentrations of 2 mM and 4 mM in buffer / serum. The total time required to obtain a lactate result using an LFA configured for lactate detection can be about 10 minutes. LFAs configured for lactate detection can remain relatively stable over time, with degradation occurring primarily within the first week of testing, when exposed to accelerated degradation studies at 37°C. More specifically, LFAs configured for lactate detection can remain stable for up to 4 weeks at 37°C, with small changes in signal response, supporting the notion that LFA assays can be performed over long periods of time.

[0061] Procalcitonin

[0075] In some implementations, the rapid test device 170 can be an LFA (e.g., LFA 170A) configured to test for the PCT biomarker. For example, the effectiveness of using serum PCT biomarker concentration in blood in diagnosing sepsis is shown below in Table 2. Table 2 shows the results of a study of the diagnosis of sepsis, severe sepsis, and septic shock by serum PCT measurements.

[0062] [Table 2]

[0063]

[0076] Procalcitonin (PCT) is a peptide of 116 amino acids with an estimated molecular weight MW of 14.5 kDa and belongs to the calcitonin family of peptides. The PCT molecule contains three parts, namely the amino terminus (57 amino acids), immature calcitonin (33 amino acids) and calcitonin carboxy-terminal peptide 1 (CCP-1), also known as katacalcin (21 amino acids). PCT is the precursor hormone of calcitonin and is undetectable in healthy individuals because there is no systematic inflammation and the peptide is not released into the blood. However, in cases of sepsis due to bacterial infection, PCT synthesis is induced in tissues and thus becomes detectable in the blood. PCT production can be triggered by bacterial toxins such as endotoxin and cytokines (e.g., interleukin (IL)-1 beta, interleukin-6 and tumor necrosis factor (TNF)-alpha). PCT levels can increase rapidly within 2 to 6 hours and peak within 6 to 24 hours of bacterial infection. In addition to bacterial infections, some fungal and parasitic infections are also associated with the release of PCT into the bloodstream. Further conditions that can cause high levels of PCT in the body include recent major surgery, severe trauma, severe burns, persistent cardiogenic shock, and chronic kidney disease.

[0064]

[0077] The lack of ability in some non-thyroid tissues to cleave PCT into its mature form, calcitonin, causes PCT to accumulate in blood.Thus, PCT can be used as a biomarker that distinguishes between bacterial and viral inflammation to a relatively high degree, and can be used in patients suffering from sepsis.Furthermore, PCT levels can be related to and / or indicate the severity of bacterial infection.In the case of sepsis, rapid diagnosis of bacterial infection reduces the risk of unnecessary or inappropriate use of antibiotics, which may increase antibiotic resistance or toxic side effects in patients.

[0065]

[0078] Traditional techniques for diagnosing sepsis due to bloodstream infection include cultures of blood, urine, and cerebrospinal fluid samples of bronchial fluid. These testing techniques, which typically take 24-48 hours to obtain results, can often facilitate the identification of the pathogen and provide information about the type of microorganism and its sensitivity to antibiotics. However, clinical symptoms may be evident in the absence of positive cultures, leading to treatment based on false-negative results. The half-life of PCT (25-30 hours), combined with its specificity for bacterial infections and its virtual absence in healthy individuals, make it a suitable biomarker for bacterial infections.

[0066]

[0079] PCT can be quantified by immunoassays based on the sandwich ELISA principle. In these immunoassays, an antibody-procalcitonin-antibody complex is formed and quantified by one or more measurement techniques, including chemiluminescence, enzymatic, fluorescent, and turbidimetric immunoassays. For example, the chemiluminescence assay for PCT uses a two-step sandwich technique. In this method, an anti-PCT monoclonal antibody conjugated with alkaline phosphatase is added to the patient sample in the presence of a reagent buffer. After incubation, paramagnetic particles coated with monoclonal anti-PCT antibodies are added to the test. PCT binds to the paramagnetic particles, and the anti-PCT antibodies in solution react with different antigenic sites on the PCT molecule. The particles are separated from the unconjugated material by a magnet. A chemiluminescent substrate is added to the test, and the light generated by the reaction is measured using a luminometer. The photon generation is proportional to the concentration of PCT in the sample.

[0067]

[0080] Alternatively, PCT can be measured using a quantitative homogeneous assay (BRAHMS, Hennigsdorf, Germany) based on the Time Resolved Amplified Cryptate Emission technology (TRACE). The test involves directing a 337 nm nitrogen laser beam onto a sample containing PCT and two fluorescently labeled antibodies that recognize different epitopes of the PCT peptide. Exposure to the laser excitation causes a non-radiative transfer of energy between the donor and acceptor molecules, with the donor molecule emitting a long-lived fluorescent signal at 620 nm and the acceptor molecule emitting a short-lived signal at 665 nm. When both donor and acceptor molecules are brought into close proximity by binding to PCT, the combined signal is amplified to 665 nm and lasts for a few microseconds. This is long enough to be detected after decay of the background fluorescence typical in biological samples.

[0068]

[0081] Lateral flow assays (LFAs) configured to test for PCT biomarkers (e.g., antigens) in blood (e.g., whole blood, serum, etc.) provide an alternative tool for the diagnosis of sepsis. As described above with reference to FIG. 2, LFAs may be performed on strips that include one or more components assembled on a substrate 171. The components of the LFA configured to detect and quantify PCT in blood and / or other biological fluids may include a sample element 172, a conjugate element 173, a capture element 174, a control element 175, and a wick 176.

[0069]

[0082] Substrate 171 may be a backing laminate or backing card configured to provide mechanical support to the components of the LFA, as described above. As described above, substrate 171 may be of any suitable shape, size, and / or configuration. For example, substrate 171 may be a rectangular backing card or strip of a certain width and length that can provide sufficient surface area to accommodate the various components of the LFA. Substrate 171 may be made of a semi-rigid polymer designed to provide uniformity and lay-flat characteristics. As described further herein, substrate 171 may include one or more pressure-sensitive adhesives configured to facilitate attachment of the various components of the LFA.

[0070]

[0083] The sample element 172 may be a pad that provides a surface to receive a sample of blood and / or other biological fluid for analysis and facilitates the transfer of the sample in a smooth, continuous, and homogenous manner to other components of the lateral flow test strip. The sample element 172 may be any suitable shape and / or size. In some embodiments, the shape of the sample element 172 may be a rectangular strip configured to absorb and receive a volume of a sample of blood and / or other biological fluid. The sample element 172 may be disposed on a surface of the substrate 171 and provide mechanical support to the LFA. In some embodiments, the sample element 172 may include an adhesive coated on one surface of the sample pad to facilitate attachment to a plastic backing laminate. The shape and dimensions of the sample element 172 may be predetermined such that the sample element may be disposed on the plastic backing laminate. The thickness of the sample element 172 may be selected to facilitate attachment of the sample element 172 to the plastic backing laminate while maintaining the mechanical structure of the pad. Additionally, the thickness of the sample element 172 may be selected to accommodate a large volume of blood and / or other biological fluids while preventing oversaturation of the sample on the pad and channeling into the plastic backing laminate. The sample element 172 may be made of cellulose, nitrocellulose, fiberglass, and / or any other suitable material.

[0071]

[0084] As shown in FIG. 2, the conjugate element 173 of the LFA for detecting and quantifying PCT from blood and / or other biological fluid samples can be a pad located adjacent to and downstream of the sample element 172. The conjugate element 173 can be of any suitable shape and / or size. In some embodiments, the shape of the sample element 172 can be a rectangular strip of a width similar to that of the sample member 171 disposed on the surface of the substrate 171 to provide mechanical support for the LFA. The conjugate element 173 can include a dry matrix (e.g., a salt-sugar matrix) that includes bioactive particles and additives. The bioactive particles included in the matrix include specific antibodies and / or affinity reagents (e.g., DNA aptamers, protein binders, etc.) immobilized on or within the conjugate element 173. For example, in some embodiments, the surface of the sample element 172 can be impregnated with an aqueous buffer solution that provides a pH-controlled environment. In some embodiments, the surface of the sample element 172 may be impregnated with a buffer solution, including, but not limited to, borate buffer solution, phosphate buffered saline (PBS), 2-ethanesulfonic acid (MES), tris(hydroxymethyl)aminomethane (TRIS), piperazine-N,N'-bis (PIPES), 3-morpholinopropane-1-sulfonic acid (MOPS), 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid (HEPES), [tris(hydroxymethyl)methylamino]propanesulfonic acid (TAPS), N-cyclohexyl-2-aminoethanesulfonic acid (CHES), and / or N-cyclohexyl-3-aminopropanesulfonic acid (CAPS).

[0072]

[0085] The dry matrix of the sample element 172 may include one or more surfactants used as wetting agents to solubilize polar species present in the sample. For example, in some embodiments, the dry matrix of the conjugate element 173 may include non-ionic surfactants such as glycidol, tergitol, ethoxylated and alkoxylated fatty acids, ethoxylated amines, alkyl and nonylphenol ethoxylates, ethoxylated sorbitan esters, castor oil ethoxylates, and the like. The dry matrix may include one or more germicide reagents configured to promote extended shelf life of the LFAs by inhibiting a broad range of microorganisms. The germicide reagents may be formulated in low concentrations in the dry matrix of the conjugate element 173 to minimize and / or avoid potential health hazards, toxicity issues, and disposal challenges. For example, in some embodiments, the dry matrix may include 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT), 2-methyl-4-isothiazolin-3-one (MIT), proprietary glycols, modified alkyl carboxylates, and / or other commercially available preservatives such as proclin 300™. In some embodiments, the dry matrix may include one or more detergents or any amphiphilic molecule that can be used for protein solubilization, such as tween 20, Triton X, octylthioglucoside, and others.

[0073]

[0086] The dry matrix of the conjugation element 173 may include one or more antibodies and / or affinity reagents conjugated to a molecule configured to enable detection. In some embodiments, the dry matrix may include one or more detection antibodies capable of binding to PCT and exhibiting high stability. For example, in some embodiments, the detection antibodies may include procalcitonin human antibodies, including monoclonal anti-PCT antibody 14A2cc, monoclonal anti-CT antibody 796, PP3, and the like.

[0074]

[0087] The detection antibody may be immobilized on one or more colored particles (e.g., latex with a blue color, colloidal gold with a red color, and / or any other suitable particles), fluorescent particles, magnetic particles, or any other suitable particles that may be used for the capture and quantification of PCT in blood and / or other biological fluid samples. In some embodiments, the detection antibody may be immobilized on gold nanoparticles. Gold nanoparticles and / or gold nanoshells may be functionalized with antibodies that exhibit specific binding activity for specific regions of PCT molecules (e.g., bioconjugation). During bioconjugation, the surface of the gold nanoparticles may be functionalized with the detection antibody using physical methods that rely on physical interactions between the detection antibody and the surface of the gold nanoparticles, such as ionic interactions, hydrophobic interactions, and / or dative bonds. The physical interaction occurs by spontaneous adsorption of the antibody onto the surface of the gold nanoparticles. In the case of ionic interactions, the positively charged groups of the detection antibody are attracted to the negatively charged surface of the gold nanoparticles. The hydrophobic interactions occur between the hydrophobic portion of the detection antibody and the metal surface.

[0075]

[0088] Advantages of functionalizing gold nanoparticles with detection antibodies by physical methods include ease of preparation, simplicity, low cost, rapid preparation, and minimal use of additives and / or chemicals that may cause adverse toxic effects. However, certain disadvantages of physical methods may include the use of large amounts of detection antibodies in the preparation of functionalized gold nanoparticles, random orientation of the detection antibodies, and the relative ease of replacing the detection antibodies with other molecules with similar properties. These disadvantages are often due to the low specificity of the binding modalities in gold nanoparticles, resulting in high assay variability and poor PCT capture performance. For example, conjugation of antibodies to the surface of gold nanoparticles may proceed through non-specific binding sites, blocking regions of the antibody that are suitable for PCT capture. For example, in some cases, antibodies may be physically adsorbed onto the surface of gold nanoparticles through interactions between constant regions present in the heavy chain and the surface of the nanoparticle. In this configuration, the antigen binding site of the antibody may be partially available for interaction with PCT. In other cases, antibodies may be physically adsorbed onto the surface of gold nanoparticles through interactions with PCT antigen binding sites, eliminating the interaction of the antigen binding sites with PCT.

[0076]

[0089] Alternatively, in some embodiments, antibodies can be conjugated to gold nanoparticles by chemical methods including covalent bonds, such as chemisorption via thiol derivatives, bifunctional linkers and / or adapter molecules. Direct functionalization of gold nanoparticles with thiol derivative groups can be achieved by chemical reactions between gold and sulfur atoms that generate strong bonds on the surface of the particles. For example, thiol-functionalized antibodies can be directly attached to gold nanoparticles. However, this approach presents challenges such as the use of reaction conditions that can compromise the stability of the nanoparticles and can require harsh conditions.

[0077]

[0090] The embodiments, implementations, and / or methods described herein can overcome these limitations by including the use of other groups that can be attached to the gold nanoparticle surface, for example, using bifunctional linkers that provide specific functionalization of the gold nanoparticle surface. For example, carboxylated polyethylene glycol (PEG) molecules functionalized with thiol groups (PEG-SH) can be used to functionalize the surface of the gold nanoparticles. The PEG molecules that functionalize the gold nanoparticles can also include carboxyl end groups. These carboxyl end groups can be modified with coupling agents including water-soluble carbodiimides (EDC) and N-hydroxy-succinimide (NHS) compounds to generate reactive functional groups that bind to primary amine groups of antibody molecules. The water-soluble carbodiimides react with the carboxylic acid moieties of the PEG containing gold nanoparticles to generate intermediate active groups that react with the N-hydroxy-succinimide compounds to form reactive ester groups. When in direct contact with the antibody, the primary amine groups in the antibody react with the ester groups formed on the surface of the gold nanoparticles. This reaction is designed to generate amide bonds for attaching the antibody to the gold nanoparticles without adding a spacer molecule between them.

[0078]

[0091] The capture element 174 of the LFA for detecting and quantifying PCT from blood and / or other biological fluid samples may be a pad disposed adjacent to and / or downstream of the conjugate element 173 and includes particles or molecules immobilized in or on the capture element 174. As described above with reference to FIG. 2, the particles or molecules may be configured to bind to detection antibodies conjugated to stained particles described above with reference to the conjugate element 173 as they flow downstream in a volume of blood and / or other biological fluid sample. In some embodiments, the capture element 174 may include a capture antibody immobilized and / or chemically bound to a surface of the capture element 174. The capture antibody may be configured to interact with the detection antibody to capture PCT bound to the detection antibody, resulting in a localized accumulation of the detection antibody and their conjugated stained particles. In some embodiments, the capture antibody may be adsorbed onto a surface of the capture element 174.

[0079]

[0092] As described above with reference to the detection antibodies, the capture antibodies may include procalcitonin human antibodies, including monoclonal anti-PCT antibody 14A2cc, monoclonal anti-CT antibody 796, PP3, and the like. The immobilized capture antibodies may be configured to bind to PCT molecules previously bound to the detection antibodies (and their conjugated colored particles) in the conjugate element 173. As a result, exposure of the capture element 174 to a sample of blood and / or other biological fluid containing PCT that has previously flowed through the conjugate element 173 may result in the accumulation of colored particles associated with the capture antibodies that bind to the PCT molecules present in the sample. This accumulation of colored particles on the capture element 174 may be registered and quantified by one or more optical methods to determine the concentration of PCT in the sample. For example, in some embodiments, the colored particles accumulated on the capture element 174 may be determined by a standard lateral flow reader, such as the commercially available Leelu reader (LUMOS diagnostics), configured to detect colored particles that provide suitable optical sensitivity and dynamic range sufficient to cover a wide range of concentrations.

[0080]

[0093] The LFA may include a control element 175 for capturing detection antibodies not captured by the capture element 174. In other embodiments, the LFA need not include a control element. The wick 176 of an LFA configured to detect and quantify PCT from blood and / or other biological fluid samples may be a pad disposed adjacent to and / or downstream of the capture element 174 (or control element 175, if included). As described with reference to FIG. 2, the wick 176 may be configured to absorb or soak up a portion of the sample that was not immobilized in or on the capture element 174 (and / or control element 175, if included).

[0081]

[0094] As described above, lateral flow assays (LFAs) configured to test for PCT in blood and / or other biological fluids can detect PCT present in a variety of samples, including buffer solutions, serum, plasma, and / or whole blood. More specifically, in some embodiments, the LFAs can have a dynamic range of detectable PCT of 0.2 ng / mL to 2 ng / mL, with a sensitivity of 0.1 ng / mL or greater in buffer and serum. In some embodiments, the LFAs can have cutoff PCT concentrations of 0.2 ng / mL and 0.5 ng / mL in buffer / serum. The total time required to obtain a result using an LFA configured for PCT detection can be about 10 minutes. An LFA configured for PCT detection can remain relatively stable during accelerated stability testing performed at 37° C., without significant detachment of the conjugate to flow through the lateral flow strip.

[0082]

[0095] Although testing of serum lactate and / or serum PCT concentrations has been described above, it should be understood that testing of blood (e.g., whole blood or other suitable portion of blood) would produce similar or substantially the same results. Although lactate and PCT biomarkers have been described above, it should be understood that they are provided by way of example only and not limitation. In some implementations, the rapid test device (e.g., LFA 170A) may be configured to test for any suitable biomarker associated with and / or otherwise indicative of sepsis and / or any other infection or disease state. Furthermore, it should be understood that the rapid test device 170 and / or LFA 170A (and / or any other suitable flow-based assay) may be used with any of the fluid transfer devices described herein with reference to specific embodiments.

[0083] Aptamers

[0096] In some implementations, the rapid test device 170 can be an LFA (e.g., LFA 170A) configured to use aptamers to test for any suitable biomarkers associated with sepsis and / or any other infectious condition. Aptamers are single-stranded DNA or RNA molecules that can selectively bind to their corresponding targets with high affinity and specificity. These single-stranded molecules consist of a variable region containing a central 20-40 bases, flanked on either side by two constant regions containing binding sites at each end. Aptamers can fold into secondary structures and three-dimensional shapes by intermolecular hybridization. Equilibrium dissociation constants for aptamer-target binding in the 1 picomolar (pM) to 1 nanomolar (nM) range. Aptamers can be generated against desired targets, such as toxic small molecules, non-immunogenic targets, or single molecules that have similar affinities to antibodies for the target molecule and do not bind to antibodies. Furthermore, aptamers can be reversibly denatured by heat or chemicals, which is not possible with antibodies.

[0084]

[0097] Aptamers are similar to antibodies in their range of target recognition and diverse applications. However, the use of aptamers may present advantages over the use of antibodies. Advantages include, for example, their production by in vitro processes that rely on easily controlled and reproducible chemical reactions, as opposed to the complex experiments required to derive antibodies from bacteria, cell cultures, and / or animal cells (including human cells); their ability to bind targets not recognized by antibodies, such as ions, small molecules, complex multi-active site molecules, proteins, bacterial cells, viruses, and / or cancer cells; their ability to be rapidly amplified in large quantities by polymerase chain reaction (PCR); their ease of modification to introduce functional moieties (e.g., fluorescers, quenchers, and nanomaterials); their stability under harsh conditions; and their safe use in in vivo applications due to their non-immunogenic properties. In some cases, aptamers can have improved transport properties, allowing for cell-specific targeting and improved tissue penetration.

[0085]

[0098] Aptamers can be tailored to specific targets obtained by in vitro selection (SELEX: systematic evolution of ligands by exponential enrichment) methods. The process includes three main steps: library generation, selection, and amplification. In the first step, a random library is designed and synthesized by combinatorial chemical synthesis to generate oligonucleotides containing variable regions with 20-40 bases, with upstream and downstream primer binding sites at each end. The resulting library can contain 1012-1015 ssDNA or RNA sequences. In the second step, the target molecule is incubated with the library in the presence of a binding buffer for several minutes. The aptamers bind to the target to form aptamer-target complexes, while non-specific sequences remain in the binding buffer. The aptamer-target complexes can be collected and washed several times with a washing buffer. The aptamers can then be separated from the aptamer-target complexes by treatment with an elution buffer. The selection step may include a counter-selection procedure in which the target is replaced by an analog and nucleic acid sequences that bind to this analog are excluded. In a third step, the sequences that escaped in the second step are amplified by PCR in the case of DNA or by reverse transcriptase (RT)-PCR in the case of RNA to generate a sub-library for use in the second round of the SELEX process. This procedure may be repeated for several rounds until aptamers with high specificity for the target are generated.

[0086]

[0099] Once the affinity of the target-bound sequences is saturated, after identification of aptamer sequences that bind to the target with high sensitivity and specificity, they are sent to clone and sequence. Several techniques can be used to improve the separation of unbound sequences from the aptamer-target complex. For example, in some cases, aptamer selection can include nitrocellulose membrane filtration-based SELEX, affinity chromatography and magnetic bead-based SELEX, capillary electrophoresis and / or microfluidics-based SELEX. Nitrocellulose membrane filtration-based SELEX uses a nitrocellulose membrane to retain the aptamer-target complex and removes unbound oligonucleotide sequences based on size. Multiple micron-sized pores on the surface of the membrane allow DNA or RNA oligonucleotides to pass through the membrane and proteins to be captured on the membrane. The material is then amplified by PCR or RT-PCR for the next round of production. Affinity chromatography and magnetic bead-based SELEX uses agarose beads packed on a column as a stationary phase. Magnetic beads are also used for target immobilization by physical interaction or chemical reaction between a specific tag and its ligand on the bead. Capillary electrophoresis and microfluidic-based SELEX are used to minimize sample dilution and improve separation speed, resolution, and performance. In this method, unbound nucleotides are separated from aptamer-target complexes due to their difference in electrophoretic mobility in an electric field. Aptamers can be obtained due to the migration speed of the target, ligand, or a mixture of target-ligand complexes. Capillary electrophoresis-based SELEX can be used to select aptamers in several rounds compared to other methods. Microfluidic-based SELEX is a technique that uses an automated and miniaturized platform that allows aptamer selection on a chip. To perform the selection process automatically, the system includes several modules with micropumps, microvalves, reservoir manifolds, waste chambers, and PCR chambers.Other methods including atomic force microscopy, high-throughput sequencing, graphene oxide, UV cross-linking, flow cytometry, and surface plasmon resonance (SPR) can be used with the SELEX method to enrich the selection procedure and improve the efficiency of aptamer selection.

[0087]

[0100] Applications of aptamers include in vivo therapy, molecular biosensors, target capture, drug delivery, drug development, hazard detection, environmental monitoring, clinical diagnostics, biomarker discovery, and food testing. Aptamers are used as recognition elements in analytical tools including electrochemical and fluorescent biosensors, colorimetric assays, surface plasmon resonance assays, and amplification methods.

[0088] detection

[0101] In some cases, rapid test device 170 (e.g., LFA 170A and / or any other suitable rapid test device) may be configured to provide a test result that can be detected and / or evaluated by a human (e.g., a doctor, nurse, technician, etc.) by visual inspection. For example, a doctor, nurse, technician, etc. may visually inspect capture element 174 of LFA 170A to determine whether a strip is present along capture element 174. Additionally, control element 175 of LFA 170A may be visually inspected to confirm performance of the test. In some such instances, visual inspection by a human may be relatively simple to perform and may not require the use of additional equipment to provide a qualitative result (e.g., a positive or negative test result).

[0089]

[0102] In other cases, the LFA 170A may be configured to output test results, which may be further received, inspected, analyzed, interpreted, etc., by one or more electronic devices (e.g., electronic device 190 shown in FIG. 1). For example, in some cases, a portable strip reader may be used to read, scan, and / or evaluate the strip along with the capture element 174 and / or control element 175. The strip reader may include a camera, scanner, reader, etc. that may use a complementary metal oxide semiconductor (CMOS) device, a charge-coupled device (CCD), and / or any other suitable detection device or camera to detect the strip. In some implementations, the strip reader may be configured to define a data or digital representation of the test result (strip) that may be qualitative, semi-quantitative, and / or quantitative. For example, the intensity of the capture element may be proportional to the concentration of the analyte, thereby allowing for quantification of the analyte. In some cases, the strip reader may be configured to read, scan, and / or identify the presence of one or more strips as well as the intensity of one or more strips, thereby providing both qualitative and quantitative data. In some implementations, the electronic device 190 may be incorporated into / on the rapid test device 170 or may be a stand-alone device, into which the rapid test device 170 and / or one or more cartridges (e.g., one or more portions of the rapid test device 170) can be inserted for reading and analysis.

[0090]

[0103] In some embodiments, the strip reader may be configured to provide qualitative and / or quantitative data as input to the electronic device 190. The electronic device 190 may analyze, process, and / or otherwise use this data to generate one or more qualitative and / or quantitative test results. The electronic device 190 may be any suitable hardware-based computing device configured to receive, process, define, and / or store data, such as, for example, one or more diagnostic test results, test criteria for measuring result data, predetermined and / or predefined treatment plans, patient profiles, disease profiles, etc. Additionally, the electronic device 190 may be configured to transmit and / or receive data over a wired or wireless connection or network. In some embodiments, the electronic device 190 may be, for example, a mobile electronic device (e.g., a smartphone, tablet, laptop, and / or any other mobile or wearable device), a personal computer (PC), a workstation, a server device or distributed network of server devices, a virtual server or machine, a virtual private server running and / or operated as an instance or guest of a physical server or server group, etc., and / or any other suitable device. In some implementations, the electronic device 190 may be configured to provide a graphical and / or digital representation of the test results generated by the rapid test device 170. Additionally, in some implementations, the electronic device 190 may be configured to determine and graphically or digitally present one or more diagnoses, one or more treatment plans, one or more simulations, and / or any other suitable data related to the bodily fluid sample, the patient, and / or the patient's treatment based on data related to and / or indicative of the test results.

[0091]

[0104] As noted above, in some implementations, the transfer device 105 may be configured to transfer a first amount of bodily fluid to the rapid test device 170 and at least a portion of the second amount of bodily fluid to one or more of the optional fluid collection devices 195. For example, the second or sampling portion of the transfer device 105 may include and / or be in fluid communication with an outlet or port that can allow the second amount of bodily fluid to be transferred from the second or sampling portion of the transfer device 105. In some cases, one or more of the optional fluid collection devices 195 may be physically and / or fluidically coupled to the transfer device 105 (e.g., via an outlet or port) to receive at least a portion of the second amount of bodily fluid.

[0092]

[0105] In some embodiments, the optional fluid collection device 195 may be any suitable device for at least temporarily containing a bodily fluid. For example, the fluid collection device 195 may include, but is not limited to, any suitable vessel, container, reservoir, bottle, adapter, dish, vial, syringe, device, diagnostic and / or testing machine, etc. In some embodiments, the fluid collection device may be substantially similar to or the same as a known sample container, such as, for example, a Vacutainer® (manufactured by Becton Dickinson and Company (BD)), BacT / ALERT® SN or BacT / ALERT® FA (manufactured by Biomerieux, Inc.), and / or any suitable reservoir, vial, microvial, microliter vial, nanoliter vial, container, microcontainer, nanocontainer, etc. In some embodiments, the fluid collection device may be substantially similar to or the same as any of the sample reservoirs described in U.S. Patent No. 8,197,420, entitled "Systems and Methods for Parenterally Procuring Bodily-Fluid Samples with Reduced Contamination," filed December 13, 2007 (the "'420 Patent"), the disclosure of which is incorporated herein by reference in its entirety.

[0093]

[0106] In some embodiments, the fluid collection device 195 may be empty of contents prior to receiving the sample volume of bodily fluid. For example, in some embodiments, the fluid collection device 195 or reservoir may define and / or be configured to define or generate a vacuum, suction, and / or negative pressure condition, such as, for example, a vacuum-based collection tube (e.g., Vacutainer®), syringe, etc. In some implementations, the fluid collection device 195 may be physically and / or fluidly coupled to the transfer device 105 (e.g., an outlet or port) such that a negative pressure condition within the fluid collection device 195 facilitates drawing bodily fluid from the patient into or through one or more portions of the transfer device 105, as described in further detail herein with reference to certain embodiments.

[0094]

[0107] In some embodiments, the fluid collection device 195 may include any suitable additives, media, substances, enzymes, oils, fluids, etc. For example, the fluid collection device 195 may be a sample or culture bottle, for example, including an aerobic or anaerobic medium. The sample or culture bottle may be configured to receive a bodily fluid sample. The bodily fluid sample may then be tested (e.g., after incubation with an in vitro diagnostic (IVD) test and / or any other suitable test) for the presence of, for example, gram-positive bacteria, gram-negative bacteria, yeast, fungi, and / or any other organism. In some cases, if such testing of the medium yields a positive result, the medium may then be tested using a nucleic acid-based system (e.g., a PCR-based system, hybridization probes, nucleic acid amplification tests (NAAT), etc.) to identify the specific organism. In some embodiments, the sample reservoir may include, for example, any suitable additives, etc., in addition to or instead of the medium. Such additives may include, for example, heparin, citrate, ethylenediaminetetraacetic acid (EDTA), oxalate, sodium polyanethol sulfonate (SPS), etc. In some embodiments, the fluid collection device 195 may contain any suitable additive or medium and may be evacuated and / or otherwise freed of air.

[0095]

[0108] Although a "media" has been described above as a substance configured to react with organisms in a bodily fluid (e.g., microorganisms such as bacteria) and an "additive" has been described above as a substance configured to react with a portion of a bodily fluid (e.g., constituent cells of blood, blood, synovial fluid, etc.), it should be understood that the sample reservoir may include any suitable substance, liquid, solid, powder, lyophilized compound, gas, etc. Furthermore, when referring to an "additive" in the sample reservoir, it should be understood that the additive may be a media, such as an aerobic and / or anaerobic medium contained in a culture bottle, an additive contained in a culture bottle and / or any other suitable reservoir such as those described above, and / or any other suitable substance or combination of substances. That is, the embodiments described herein may be used with any suitable fluid reservoir containing any suitable substance or combination of substances, etc.

[0096]

[0109] In some implementations, the second amount of bodily fluid contained in the second or sampling portion of the transfer device 105 and / or contained in any one or more of the fluid collection devices 195 can be used as a biological sample in one or more tests, assays, and / or diagnostic procedures. In some cases, isolating the first amount of bodily fluid from the second amount of bodily fluid can isolate contaminants, etc. in the first amount of bodily fluid and / or in the isolated portion of the transfer device 105. Isolation can further allow the second amount of bodily fluid to remain substantially free of contaminants. Thus, the second portion or amount of bodily fluid can be used in one or more tests, such as blood culture tests, etc., that may be relatively sensitive to contaminants (e.g., the presence of contaminants may result in poor results). In this manner, the system 100 can be configured to obtain a first amount of bodily fluid that can be used in tests that are relatively less sensitive to contaminants and a second amount of bodily fluid that can be used in tests that are relatively more sensitive to contaminants. In some cases, testing of a first volume of bodily fluid may provide a relatively quick initial result that can inform one or more treatment options, while testing of a second volume of bodily fluid may provide a more detailed test result that typically takes longer to produce. Thus, for time-sensitive disease conditions (e.g., sepsis), an initial result from testing the first volume of bodily fluid may enable a physician or doctor to provide rapid initial treatment, while a more detailed test of a second volume of bodily fluid is performed.

[0097]

[0110] 3 is a schematic diagram of a fluid transfer and assay system 200 according to one embodiment. The fluid transfer and assay system 200 (also referred to herein as the "system") may include at least a fluid transfer device 205 and a rapid diagnostic test device 270. Additionally, the system 200 may include at least one fluid collection device 295, which may be physically and / or fluidically coupled to the fluid transfer device 205.

[0098]

[0111] The fluid transfer device 205 (also referred to herein as a "transfer device") may be of any suitable shape, size, and / or configuration. In some implementations, the transfer device 205 may be configured to draw bodily fluid (e.g., blood) from a patient to and / or through the transfer device 205. Additionally, the transfer device 205 may be configured to transfer at least a portion of the drawn bodily fluid to one or more other devices, reservoirs, containers, vials, machines, tests, assays, etc., such as the rapid diagnostic test device 270 and / or one or more fluid collection devices 295.

[0099]

[0112] The transfer device 205 includes a housing 210 and an actuator 250. The housing 210 of the device 205 may be of any suitable shape, size, and / or configuration. For example, in some embodiments, the housing 210 may have a size based at least in part on an initial amount or volume of bodily fluid configured to be transferred to and / or sequestered within a portion of the housing 210. In some embodiments, the housing 210 may have a size and / or shape configured to enhance ergonomics and / or ease of use associated with the device 205. Additionally, in some embodiments, one or more portions of the housing 210 may be formed of a relatively transparent material configured to allow a user to visually inspect and / or confirm the flow of bodily fluid through at least a portion of the housing 210.

[0100]

[0113] The housing 210 has and / or forms an inlet 212 and an outlet 213, defining at least one fluid flow path 215 between the inlet 212 and the outlet 213. The inlet 212 can be any suitable inlet, opening, port, stopcock, lock (e.g., luer lock), seal, coupler, valve (e.g., one-way, check valve, duckbill valve, umbrella valve, etc.), tubing conduit, etc. The inlet 212 is configured to fluidly couple the housing 210 to a bodily fluid source (e.g., a patient). For example, the inlet 212 can be coupled to a lumen containment device (e.g., a butterfly needle, an intravenous (IV) catheter, a peripherally inserted central catheter (PICC), a midline mid-lumen containment device, etc.) configured to be placed percutaneously within the patient. Thus, fluid can be transferred between the housing 210 and the patient via the inlet 212 and any lumen containment device coupled between the housing 210 and the patient. More specifically, as described in further detail herein, the transfer device 205 may be configured to transfer bodily fluid from a patient and / or any other bodily fluid source through the inlet 212 (and / or any lumen-containing device coupled thereto) and into the housing 210 via the inlet 212.

[0101]

[0114] 3, the housing 210 defines one or more fluid flow paths 215 between an inlet 212 and an outlet 213. As described in further detail herein, the transport device 205 and / or the housing 210 may be configured to transition between any number of states, operational modes, and / or configurations to selectively control the flow of bodily fluid through the one or more fluid flow paths 215. Additionally, the transport device 205 and / or the housing 210 may be configured to transition automatically (e.g., based on pressure differential, time, electronic, membrane saturation, absorbency, and / or barrier material, etc.) or with intervention (e.g., user intervention, mechanical intervention, etc.).

[0102]

[0115] The outlet 213 is in fluid communication with one or more fluid flow paths 215 and is configured to selectively accept a flow of bodily fluid from the inlet 212 (via the fluid flow path 215). The outlet 213 may be any suitable outlet, opening, port, stopcock, lock, seal, coupler, valve, tube, conduit, etc. configured to be physically and / or fluidly coupled to any suitable device coupled to the outlet 213, such as, for example, a fluid collection device 295 (e.g., a fluid or sample reservoir, a syringe, a vacuum container, a culture bottle, etc.). In some embodiments, the outlet 213 may be monolithically formed with the fluid collection device 295. In other embodiments, the outlet 213 may be at least temporarily coupled to the fluid collection device 295 via adhesives, resistance fits, mechanical fasteners, threaded connections, drilling or puncturing configurations, any number of mating recesses, and / or any other suitable connections, or combinations thereof. For example, in some embodiments, the outlet 213 may include and / or be coupled to a fluid transfer adapter, such as those described in U.S. Patent No. 10,123,783, entitled "Apparatus and Methods for Disinfection of a Specimen Container," filed March 2, 2015 (the "'783 Patent") and / or U.S. Provisional Patent Application No. 62 / 986,244, entitled "Universal Transfer Adapters and Methods of Using the Same," filed March 6, 2020 (the "'244 Application"), and / or may be coupled to a fluid transfer device, such as those described in U.S. Patent No. 10,772,548, entitled "Sterile Bodily-Fluid Collection Device and Methods," filed June 2, 2015 (the "'548 Patent"), the disclosures of each of which are incorporated herein by reference in their entirety. In such an embodiment, the fluid transfer adapter may be coupled to and / or may receive a portion of the fluid collection device 295 and may establish fluid communication between the outlet 213 and the fluid collection device 295.In yet other embodiments, the outlet 213 may be operatively coupled to the fluid collection device 295 via an intervening structure (not shown in FIG. 3), such as a sterile tube or the like.

[0103]

[0116] In some embodiments, the configuration of the outlet 213 may be such that the outlet 213 is physically and / or fluidically sealed prior to coupling to the fluid collection device 295. In some embodiments, the outlet 213 may be transitioned from a sealed configuration to a non-sealed configuration in response to being coupled to the fluid collection device 295 and / or in response to a negative pressure differential between the environment within the outlet 213 and / or the housing 210 and the environment within the fluid collection device 295.

[0104]

[0117] The fluid collection device 295 may be any suitable device for at least temporarily containing a bodily fluid (e.g., a vacuum container, a sample reservoir, a syringe, a culture bottle, etc.), such as, for example, any of those described in detail above with reference to the fluid collection device 195. In some embodiments, the fluid collection device 295 may be a sample reservoir that includes a vacuum seal that can maintain a negative pressure (vacuum) condition within the sample reservoir and further facilitate drawing bodily fluid from the patient through the transfer device 205 and into the sample reservoir by vacuum or suction force. As described in more detail herein, in embodiments in which the fluid collection device 295 is a vacuum container or the like, a user can couple the fluid collection device 295 to the outlet 213 and initiate the flow of bodily fluid from the patient to the device 205 such that a first or initial portion of the bodily fluid flow is, for example, transferred to and / or isolated by the rapid diagnostic testing device 270, and a second or subsequent portion of the bodily fluid flow bypasses and / or otherwise diverts from the rapid diagnostic testing device 270 and enters the fluid collection device 295 (e.g., through the outlet 213).

[0105]

[0118] The actuator 250 of the device 205 is at least partially disposed within the housing 210 and is configured to control, guide, and / or otherwise facilitate selective flow of fluid through at least a portion of the housing 210 and / or at least a portion of the one or more fluid flow paths 215. The actuator 250 may be of any suitable shape, size, and / or configuration. In some embodiments, the actuator 250 may be a member or device configured to transition between two or more states (e.g., at least a first state and a second state). For example, the actuator 250 may be a valve, a plunger, a seal, a membrane, a bladder, a flap, a plate, a rod, a switch, etc. The actuator 250 may be actuated and / or transitioned between any number of states (e.g., at least a first state and a second state) in any suitable manner. For example, transitioning the actuator 250 may include activating, pushing, moving, translating, rotating, switching, sliding, opening, closing, and / or otherwise reconfiguring the actuator 250.

[0106]

[0119] In some implementations, the actuator 250 may be configured to transition between at least a first state and a second state in response to manual actuation by a user (e.g., manually applying a force to a button, slider, plunger, switch, valve, rotating member, conduit, etc.). In other implementations, the actuator 250 may be configured to transition automatically between at least a first state and a second state in response to a pressure differential (or lack thereof), a change in electrical potential or kinetic energy, a change in composition or configuration (e.g., a portion of the actuator may at least partially dissolve or deform), etc. In still other implementations, the actuator 250 may be mechanically actuated or transitioned (e.g., by a motor, a spring release mechanism, etc.) and / or electrically based on a predetermined time, an amount of bodily fluid received, a volumetric flow rate of the bodily fluid flow, a flow rate of the bodily fluid flow, etc. While examples of actuators and / or manners in which the actuators may transition are provided, it should be understood that they are presented by way of example only and not limitation.

[0107]

[0120] 3, the actuator 250 may be configured to selectively establish fluid communication between the inlet 212 and the rapid diagnostic testing device 270 when in a first state and to selectively establish fluid communication between the inlet 212 and the outlet 213 when in a second state. When in the first state, the actuator 250 may be configured to allow bodily fluid to flow from the inlet 212 through at least a portion of the fluid flow path 215 to or within the rapid diagnostic testing device 270. In some embodiments, the actuator 250 may be configured to isolate, separate, disconnect, and / or otherwise prevent fluid communication between the outlet 213 and the inlet 212, at least a portion of the fluid flow path 215, and / or the rapid diagnostic testing device 270. As described in more detail herein, when in the second state, actuator 250 may be configured to allow a subsequent amount of bodily fluid (e.g., an amount of bodily fluid after the initial amount of bodily fluid) to be transferred from inlet 212 through at least a portion of fluid flow path 215 to outlet 213 (and / or a fluid collection device 295 fluidly coupled to outlet 213). Additionally, as described in more detail herein, when in the second state, actuator 250 may be configured to isolate, separate, disconnect, and / or otherwise prevent fluid communication between rapid diagnostic test device 270 and at least a portion of inlet 212, outlet 213, and / or fluid flow path 215.

[0108]

[0121] The rapid diagnostic test device 270 (also referred to herein as a "rapid test device" or simply a "test device") may be of any suitable shape, size, and / or configuration. In some embodiments, the rapid test device 270 may be removably coupled to the transfer device 205 or any suitable portion thereof (e.g., an inlet portion, an outlet portion, an isolation portion, a sampling portion, and / or any other suitable portion). In other embodiments, the rapid test device 270 may be incorporated into the transfer device 205. For example, the transfer device 205 and the rapid test device 270 may be unitarily or monolithically formed and / or otherwise integrated. In still other embodiments, the transfer device 205 may include and / or form a port, adapter, and / or receiving portion to which the rapid test device 270 may be coupled or into which the rapid test device 270 may be inserted to establish fluid communication between the transfer device 205 and the rapid test device 270. In some such embodiments, coupling the rapid test device 270 to the transfer device 205 may function to transition one or more flow controllers, valves, scepters, ports, seals, etc. from a closed or sealed state to an open state to allow fluid communication between the transfer device 205 and the test device 270.

[0109]

[0122] In some implementations, the rapid test device 270 may be configured to receive a first amount of bodily fluid from the transfer device 205 and perform one or more tests, assays, and / or diagnostic procedures using the first amount of bodily fluid. The rapid test device 270 may be any suitable test device. For example, the rapid test device 270 may be an LFA, such as those described in detail above with reference to the LFA 170A shown in FIG. 2. In some implementations, the test device 270 may be an LFA configured to test for the presence of a particular analyte or biomarker that may provide information used to diagnose a patient condition, such as sepsis and / or any other disease condition. For example, the LFA may be configured to test for lactate and / or PCT biomarkers, which may be indicative of sepsis. In other embodiments, the test device may be an LFA configured to test for any of the target analytes and / or biomarkers described above with reference to the LFA 170A shown in FIG. 2.

[0110]

[0123] In some cases, the rapid test device 270 may be configured to output a test result associated with testing a quantity of bodily fluid transferred from the transfer device 205 while the transfer device 205 and / or the actuator 250 are in the first state. The test result (indicated by the arrow labeled "OUTPUT" in FIG. 3) may be detected and / or evaluated by human visual inspection and / or may be detected and / or evaluated by one or more electronic devices (e.g., electronic device 290). In some cases, the output of the test result by the rapid test device 270 may be qualitative, semi-quantitative, and / or quantitative. Thus, the rapid test device 270 may be structurally and / or functionally similar or the same as the rapid test device 170 described in detail above. Accordingly, it will not be further detailed herein.

[0111]

[0124] As described above, system 200 may be used to obtain one or more quantities of bodily fluid from a patient that may be used in one or more tests, assays, and / or diagnostic procedures. For example, in some cases, a user, such as a doctor, physician, nurse, phlebotomist, technician, etc., may manipulate device 205 to establish fluid communication between inlet 212 and a bodily fluid source (e.g., a patient's vein, cerebrospinal fluid (CSF) from the spinal cavity, collected urine, etc.). As a particular example, in some cases, inlet 212 may be coupled to and / or include a needle or the like. The needle may be manipulated to pierce the patient's skin and insert at least a portion of the needle into the patient's vein, thereby placing inlet 212 in fluid communication with a bodily fluid source (e.g., a vein, an IV catheter, a PICC, etc.).

[0112]

[0125] In some cases, the actuator 250 may be in a first state when the inlet 212 is in fluid communication with a bodily fluid source (e.g., a portion of a patient) such that at least a portion of the fluid flow path 215 establishes fluid communication between the inlet 212 and the rapid test device 270 (and / or a portion of the device 205 to which the rapid test device 270 is coupled). Thus, the transfer device 205 may be configured to transfer an initial amount of bodily fluid from a bodily fluid source (e.g., a patient) to the rapid test device 270. In some implementations, the initial amount of bodily fluid may flow passively (e.g., without user intervention and / or transition of one or more components) to the rapid test device 270 in response to a positive pressure associated with the patient's vasculature and / or in response to any of the fluid transfer methods described in U.S. Patent Application Publication No. 2018 / 0353117, entitled "Fluid Control Devices and Methods of Using the Same," filed June 11, 2018 (the "'117 Publication"), the disclosure of which is incorporated herein by reference in its entirety.

[0113]

[0126] In other implementations, the transfer device 205 and / or portions thereof may be configured to create a negative pressure differential (e.g., partial vacuum, suction, etc.) within at least a portion of the fluid flow path 215 that can initiate and / or maintain a flow of an initial amount of bodily fluid from a bodily fluid source to the rapid test device 270. For example, in some cases, the actuator 250 may be held in a third state (e.g., a storage state) prior to use and transitioned from the storage state to the first state to initiate a flow of an initial amount of bodily fluid. In such a case, the transition of the actuator 250 may create a negative pressure that can draw bodily fluid from the inlet 212 to the rapid test device 270. In some such implementations, the actuator 250 may be configured to move the actuator 250 in a manner similar to that described in U.S. Pat. No. 8,535,241, entitled “Fluid Diversion Mechanism for Bodily-Fluid Sampling,” filed Oct. 22, 2012 (the “'241 Patent”), U.S. Pat. No. 9,060,724, entitled “Fluid Diversion Mechanism for Bodily-Fluid Sampling,” filed May 29, 2013 (the “'724 Patent”), U.S. Pat. No. 9,155,495, entitled “Syringe-Based Fluid Diversion Mechanism for Bodily-Fluid Sampling,” filed Dec. 2, 2013 (the “'495 Patent”), U.S. Pat. No. 9,155,495, entitled “Devices and Methods for Syringe Based Fluid Transfer for Bodily-Fluid Sampling,” filed Jun. 23, 2016 (the “'495 Patent”), and U.S. Pat. No. 2016 / 0361006, entitled "Devices and Methods for Bodily Fluid Collection and Distribution," filed on Feb. 8, 2019 (the "'524 Publication"), and / or U.S. Patent Application Publication No. 2020 / 0253524, entitled "Devices and Methods for Bodily Fluid Collection and Distribution," filed on Feb. 8, 2019 (the "'524 Publication"), the disclosures of each of which are incorporated herein by reference in their entirety.In yet other implementations, as described in further detail herein with reference to other embodiments, an initial amount of bodily fluid can flow to the rapid test device 270 in response to a negative pressure differential generated by the fluid collection device 295.

[0114]

[0127] The initial amount of bodily fluid may be any suitable amount of bodily fluid, such as any of the volumes or amounts described above. For example, in some cases, the transfer device 205 may remain in the first state or configuration until a predetermined and / or desired amount (e.g., the initial amount) of bodily fluid is transferred to the rapid test device 270. In some embodiments, the initial amount may relate to and / or be based at least in part on a desired amount sufficient for the rapid test device 270 to perform one or more tests or assays. In other embodiments, the initial amount of bodily fluid may relate to and / or be based at least in part on an amount or volume of bodily fluid equal to or greater than an amount associated with a fluid flow path defined between a bodily fluid source and the rapid test device 270. In still other embodiments, the transfer device 205 may be configured to transfer a flow of bodily fluid (e.g., the initial amount) to the rapid test device 270 until a pressure differential between the rapid test device 270 and the inlet 212 or bodily fluid source is substantially balanced and / or otherwise reduced below a desired threshold.

[0115]

[0128] In some implementations, the rapid test device 270 can begin testing and / or assaying the initial amount of bodily fluid or on the initial amount of bodily fluid once the initial amount is transferred, for example, to a sample element (e.g., sample element 171). In some cases, the rapid test device 270 can be configured to provide one or more solutions, buffers, mixtures, additives, etc. that can be mixed or combined with the initial amount. In this manner, the initial amount of bodily fluid (whether alone or mixed with additional components) can flow through the rapid test device 270 (e.g., an LFA as described above with reference to FIG. 2) and one or more tests or assays can be performed on the initial amount. For example, in some cases, the rapid test device 270 can be an LFA configured to test for the presence of lactate and / or PCT, as described in detail above. Furthermore, once the test or assay is completed, the rapid test device 270 can be configured to output a test result. As described in detail above, the test result can be detected and / or evaluated by a person and / or one or more electronic devices.

[0116]

[0129] After the initial amount of bodily fluid has been transferred and / or diverted to the rapid test device 270, the transfer device 205 may be transitioned from a first state or configuration to a second state or configuration. For example, in some embodiments, the actuator 250 may be transitioned from its first state to its first state once the initial amount of bodily fluid has been transferred to the rapid test device 270, which further places the transfer device 205 in its second state. In some embodiments, the configuration of the transfer device 205 may be such that the transfer device 205 cannot transition to the second state prior to collecting the initial amount in the rapid test device 270.

[0117]

[0130] In some embodiments, the configuration of the transfer device 205, the actuator 250, and / or the rapid test device 270 may be such that in response to receiving the initial amount, the flow of bodily fluid into the rapid test device 270 substantially stops or slows. In some cases, a user may visually inspect a portion of the device 205 and / or the housing 210 to determine whether the initial amount of bodily fluid has been disposed in the rapid test device 270 and / or whether the flow of bodily fluid into the rapid test device 270 has slowed or substantially stopped. In some embodiments, a user may apply a force to the actuator 250 and / or may otherwise actuate the actuator 250 to transition the actuator 250 from its first state to its first state. In other embodiments, the actuator 250 may be transitioned automatically (e.g., without user intervention). Additionally, in some implementations, the device 205 and / or the actuator 250 may be transitioned from the first state to the second state while the rapid test device 270 is performing a test or assay on the initial amount of bodily fluid. In other words, the rapid test device 270 can perform an assay on an initial quantity of bodily fluid while the device 205 is being used to transfer one or more subsequent quantities of bodily fluid (e.g., in one or more parallel processes, etc.).

[0118]

[0131] In some embodiments, transitioning the actuator 250 from its first state to its second state (e.g., placing the transfer device 205 in its second state or configuration) may sequester, separate, isolate, and / or retain the initial volume of bodily fluid within the rapid test device 270. In other words, the actuator 250 may isolate and / or isolate the rapid test device 270 from one or more portions of the inlet 212, outlet 213, and fluid flow path 215. As described in more detail herein, in some cases, contaminants may be entrained and / or included in the initial volume of bodily fluid, such as other external sources of contamination, such as, for example, skin-resident microorganisms shed during a venipuncture event, bacterial flora of catheters and PICC lines used to collect the sample, etc. Thus, such contaminants are sequestered in the initial volume. Additionally, the configuration of the rapid test device 270 may be such that the tests and / or assays performed by the rapid test device 270 are not susceptible to such contamination. This means that the accuracy of the test results output by the rapid test device 270, as detailed above, is not affected by such contamination.

[0119]

[0132] In addition to isolating the rapid test device 270 from the inlet 212, the outlet 213, and at least a portion of the fluid flow path 215, placing the actuator 250 in its second state also establishes fluid communication between the inlet 212 and the outlet 213 through at least a portion of the fluid flow path 215. For example, in some embodiments, transitioning the actuator 250 from its first state to its second state may, for example, open or close a port or valve, move one or more seals, move or remove one or more obstructions, define one or more portions of a flow path, etc.

[0120]

[0133] In some implementations, the fluid collection device 295 may be fluidly coupled to the outlet 213 at any time before the actuator 250 transitions from the first state to the second state and / or at the same time as the actuator 250 transitions from the first state to the second state. As described above, the fluid collection device 295 may be any suitable reservoir, container, and / or device configured to receive a quantity of bodily fluid. For example, the fluid collection device 295 may be a vacuum reservoir or container that defines a negative pressure and / or may be a syringe that is operated to generate a negative pressure. In some cases, coupling the outlet 213 to the fluid collection device 295 selectively exposes at least a portion of the fluid flow path 215 to a negative pressure and / or suction force within the fluid collection device 295. Thus, in response to the negative pressure and / or suction force, one or more subsequent quantities of bodily fluid may flow from the inlet 212, through at least a portion of the fluid flow path 215, through the outlet 213, and to the fluid collection device 295. As described above, isolating an initial amount of bodily fluid (e.g., in rapid test device 270) before collecting or obtaining one or more subsequent amounts of bodily fluid reduces and / or substantially eliminates the amount of contaminants in the one or more subsequent amounts. The subsequent amounts of bodily fluid can then be used in one or more tests, such as blood culture tests, that may be relatively sensitive to contaminants (e.g., where the presence of contaminants may result in poor results). In this manner, system 200 may be configured to obtain an initial amount of bodily fluid that may be used in tests that are relatively less sensitive to contaminants and subsequent amounts of bodily fluid that may be used in tests that are relatively more sensitive to contaminants. In some cases, testing of an initial amount of bodily fluid (e.g., with rapid test device 270) may provide relatively quick initial results that may inform one or more treatment options, and testing of subsequent amounts of bodily fluid may provide more detailed test results that typically take longer to produce.

[0121]

[0134] 4 is a schematic diagram of a fluid transfer and assay system 300 according to one embodiment. The fluid transfer and assay system 300 (also referred to herein as a "system") may include at least a fluid transfer device 305 and a rapid diagnostic test device 370. In some implementations, the system 300 may include at least one fluid collection device 395 that may be physically and / or fluidically coupled to the fluid transfer device 305. Portions and / or aspects of the fluid transfer device 305, the rapid diagnostic test device 370 and / or the fluid collection device 395 may be similar and / or substantially the same as the fluid transfer device 105 and / or the fluid transfer device 205, the rapid diagnostic test device 170 (and / or the LFA 170A) and / or the rapid diagnostic test device 270 and / or the fluid collection device 195 and / or the fluid collection device 295, respectively, described in detail above with reference to FIG. 3. Accordingly, such portions and / or aspects will not be described in further detail herein.

[0122]

[0135] The fluid transfer device 305 (also referred to herein as a "transfer device") may be of any suitable shape, size, and / or configuration. In some implementations, the transfer device 305 may be configured to draw bodily fluid (e.g., blood) from a patient to and / or through the transfer device 305. Additionally, the transfer device 305 may be configured to transfer at least a portion of the drawn bodily fluid to one or more other devices, reservoirs, containers, vials, machines, tests, assays, etc., such as a rapid diagnostic test device 370 and / or one or more fluid collection devices 395.

[0123]

[0136] The transfer device 305 includes a housing 310, a flow controller 340, and an actuator 350. The housing 310 of the device 305 may be of any suitable shape, size, and / or configuration. For example, in some embodiments, the housing 310 may be similar and / or substantially the same as the housing 210 described above with reference to FIG. 3. In particular, the housing 310 has and / or forms an inlet 312 and an outlet 313, defining at least one fluid flow path 315 between the inlet 312 and the outlet 313. The inlet 312 may be any suitable inlet or port and may be configured to establish fluid communication between the housing 310 and a body fluid source (e.g., a patient). The outlet 313 may be any suitable outlet or port and may be configured to establish fluid communication between the housing 310 and a fluid collection device 395. Additionally, the fluid collection device 395 may be similar or substantially the same as the fluid collection device 295, and therefore will not be described in further detail herein. As described in further detail herein, one or more fluid flow paths 315 defined by the housing 310 extend between the inlet 312 and the outlet 313, and fluid communication can be selectively established between the inlet 312 and the outlet 313.

[0124]

[0137] However, the housing 310 may differ from the housing 210 by including, forming, and / or being coupled to an isolation chamber 330. As described in further detail herein, the isolation chamber 330 is in selective fluid communication with the fluid flow path 315. Additionally, the isolation chamber 330 may include, be coupled to, and / or otherwise be in fluid communication with a rapid diagnostic testing device 370. As described in further detail herein, the isolation chamber 330 may be configured to (1) receive a flow and / or volume of bodily fluid from the inlet 312, (2) isolate (e.g., separate, block, contain, retain, isolate, etc.) at least a portion of the flow and / or volume of bodily fluid within the isolation chamber 330, and (3) transport at least a portion of the flow and / or volume of bodily fluid to the rapid diagnostic testing device.

[0125]

[0138] The isolation chamber 330 may have any suitable configuration, such as, for example, those described herein with respect to particular embodiments. For example, in some embodiments, the isolation chamber 330 may be at least partially formed by the housing 310. In other embodiments, the isolation chamber 330 may be a reservoir located and / or disposed within a portion of the housing 310. In other embodiments, the isolation chamber 330 may be formed and / or defined by a portion of the fluid flow path 315. That is, the housing 310 may define one or more lumens and / or may include one or more lumen-defining devices configured to receive an initial flow or amount of bodily fluid from the inlet 312, thereby forming and / or functioning as the isolation chamber 330. Although examples of isolation chambers are described herein, it should be understood that the transfer device 305 and / or the housing 310 may have the isolation chamber disposed in any suitable manner, and thus, the isolation chamber 330 is not limited to what has been shown and described herein.

[0126]

[0139] The isolation chamber 330 may have any suitable volume and / or fluid capacity. For example, in some embodiments, the isolation chamber 330 may have a volume and / or fluid capacity of about 0.1 mL to about 5.0 mL. In some embodiments, the isolation chamber 330 may have a volume measured in terms of an amount of bodily fluid (e.g., an initial or first amount of bodily fluid) configured to be transferred into the isolation chamber 330. For example, in some embodiments, the isolation chamber 330 may have a volume sufficient to accommodate an initial amount of bodily fluid that is less than or equal to a microliter of bodily fluid (e.g., 20 drops of bodily fluid, 10 drops of bodily fluid, 5 drops of bodily fluid, 1 drop of bodily fluid, or any suitable amount therebetween). In other embodiments, the isolation chamber 330 may have a volume sufficient to accommodate an initial amount of bodily fluid of up to, for example, about 5.0 mL, 10.0 mL, 15.0 mL, 20.0 mL, 30.0 mL, 40.0 mL, 50.0 mL, or more. In some embodiments, the isolated chamber 330 can have a volume equal to at least some of the volume of one or more lumens that fluidly connect the isolated chamber 330 to a source of bodily fluid (e.g., the combined volume of the lumens of the needle, the inlet 312, and at least a portion of the fluid flow path 315). In still other embodiments, the isolated chamber 330 can have a volume based at least in part on a desired amount of bodily fluid to be used in or by the rapid diagnostic test device 370.

[0127]

[0140] 4, device 305 includes a flow controller 340. Flow controller 340 is at least partially disposed within housing 310 and configured to control, direct, and / or otherwise facilitate selective flow of fluid through at least a portion of housing 310, at least a portion of fluid flow path 315, and / or at least a portion of isolation chamber 330. In this context, the fluid flow may be a liquid, such as, for example, water, oil, dampening fluid, body fluid, and / or any other suitable liquid, and / or a gas, such as air, oxygen, carbon dioxide, helium, nitrogen, ethylene oxide, and / or any other suitable gas.

[0128]

[0141] The flow controller 340 can be of any suitable shape, size, and / or configuration. In some embodiments, the flow controller 340 can be, for example, a valve, a membrane, a diaphragm, a bladder, a plunger, a piston, a bag, a pouch, and / or any other suitable member having a desired stiffness, flexibility, and / or durometer, or any suitable combination thereof. In some embodiments, the flow controller 340 can be, for example, a restrictor, a vent, an absorbent member, a selectively permeable member (e.g., a fluid-impermeable barrier or seal that at least selectively allows the passage of air or gas), a port, a junction, an actuator, or the like, or any suitable combination thereof. In some embodiments, the flow controller 340 may be similar to or substantially the same as any of those described in the '117 Publication, U.S. Patent Application Publication No. 2019 / 0076074, entitled "Fluid Control Devices and Methods of Using the Same," filed on September 12, 2018 (the "'074 Publication"), U.S. Patent Application Publication No. 2019 / 0365303, entitled "Fluid Control Devices and Methods of Using the Same," filed on May 30, 2019 (the "'303 Publication"), and / or U.S. Patent Application Publication No. 2020 / 0289039, entitled "Fluid Control Devices and Methods of Using the Same," filed on March 11, 2019 (the "'039 Publication"), the disclosures of each of which are incorporated herein by reference in their entirety.

[0129]

[0142] In some embodiments, the transfer device 305 may be configured to selectively transfer a quantity of bodily fluid to the isolation chamber 330 or the outlet 313 based at least in part on a pressure differential between two or more portions of the transfer device 305. For example, the pressure differential may result from fluidly coupling the outlet 313 to the fluid collection device 395. The fluid collection device 395 may define and / or be configured to generate a negative pressure (e.g., a vacuum reservoir, a syringe, a pressurized canister, and / or other source or potential energy for creating a vacuum or pressure differential). In other embodiments, the pressure differential may result from a change in volume and / or temperature. In still other embodiments, the pressure differential may result from at least a portion of the transfer device 305, the housing 310, the actuator 350, and / or a portion of the fluid flow path 315 being evacuated and / or filled (e.g., the isolation chamber 330 and / or any other suitable portion). In some embodiments, the pressure differential may be established automatically or by direct or indirect intervention (e.g., by a user).

[0130]

[0143] In some embodiments, the flow controller 340 may be configured to facilitate the displacement of air (or other fluid) through one or more portions of the transfer device 305. This may allow or result in a pressure differential and / or pressure equalization in one or more portions of the housing 310, as the case may be. Additionally, the flow of fluid (e.g., gas and / or liquid) resulting from the pressure differential may be selectively controlled by the flow controller 340. For example, the flow controller 340 may be configured to transition between one or more operating states or conditions to control the flow of fluid. In some embodiments, the flow controller 340 may be a member or device formed of an absorbent or semi-permeable material configured to selectively permit the flow of fluid. For example, as detailed in the '117 publication and / or the '380 application, such absorbent materials may be transitioned from a first state in which the material permits the flow of gas (e.g., air) but not the flow of liquid (e.g., body fluids) to a second state in which the material is substantially impermeable to the flow of gas and liquid (e.g., the flow controller 340 may be a selectively permeable blood barrier).

[0131]

[0144] In some embodiments, the flow controller 340 may be configured to transition from a first state to a second state in response to a negative pressure differential and / or suction applied to at least a portion of the flow controller 340. For example, the flow controller 340 may include one or more valves, membranes, diaphragms, etc. For example, the flow controller 340 may be in a first state (e.g., a storage or non-use state) prior to using the device 305, and the flow controller 340 may be transitioned to a second state in response to the outlet 313 being fluidly coupled to a fluid collection device 395 (e.g., a collection device that defines or is configured to define a negative pressure and / or suction). In some embodiments, as detailed in the '380 and / or '477 applications, the flow controller 340 may be a bladder configured to transition or "convert" from a first state to a second state in response to a negative pressure differential and / or suction applied to a surface of the bladder.

[0132]

[0145] In some embodiments, the size, shape, configuration, and / or materials of construction of the flow controller 340 may be configured and / or otherwise selected to transition the flow controller 340 from a first state to a second state in a predetermined manner and / or at a predetermined or desired rate. In some cases, controlling the rate at which the flow controller 340 transitions from the first state to the second state may further control and / or adjust the rate at which bodily fluid flows into the isolation chamber 330 and / or the magnitude of the suction force generated within the isolation chamber 330 that serves to draw an initial amount of bodily fluid into the isolation chamber 330. Although not shown in FIG. 4, in some embodiments, the housing 310 and / or the flow controller 340 may include any suitable members, features, openings, etc. configured to adjust the suction force acting on or within the flow controller 340 and further adjust the rate at which the flow controller 340 transitions from the first state to the second state. In some cases, controlling the rate at which the flow controller 340 transitions and / or the magnitude of the pressure differential and / or suction force generated within the isolation chamber 330 can, for example, reduce the likelihood of hemolysis of the blood sample and / or venous rupture (e.g., this is particularly important when drawing bodily fluid samples from fragile patients). In some cases, adjusting the transition of the flow controller 340 and / or the pressure differential generated within the isolation chamber 330 can at least partially control the amount or volume of bodily fluid transferred to the isolation chamber 330 (i.e., the volume of the initial amount of bodily fluid can be controlled).

[0133]

[0146] In some embodiments, the flow controller 340 may include any suitable combination of devices, components, and / or features. It should be understood that the flow controllers included in the embodiments described herein are shown by way of example and not limitation. Thus, although specific flow controllers are described herein, it should be understood that the flow of fluid may be controlled by the transfer device 305 in any suitable manner.

[0134]

[0147] The actuator 350 of the device 305 is at least partially disposed within the housing 310 and is configured to control, guide, and / or otherwise facilitate selective flow of fluid through at least a portion of the housing 310 and / or at least a portion of one or more fluid flow paths 315. The actuator 350 may be of any suitable shape, size, and / or configuration. In some embodiments, the actuator 350 may be a member or device configured to transition between any number of states and in any suitable manner. Furthermore, the actuator 350 may be actuated in any suitable manner (e.g., actuated by a user, automatically actuated, mechanically actuated, electronically actuated, chemically actuated, etc.). For example, the actuator 350 may be similar and / or substantially the same as any of those described above with reference to the actuator 250.

[0135]

[0148] 4, the actuator 350 may be configured to selectively establish fluid communication between the inlet 312 and the isolation chamber 330 when in a first state and to selectively establish fluid communication between the inlet 312 and the outlet 313 when in a second state. When in the first state, the actuator 350 may be configured to allow bodily fluid to flow from the inlet 312 through at least a portion of the fluid flow path 315 to or within the isolation chamber 330. In some embodiments, the actuator 350 may be configured to isolate, separate, disconnect, and / or otherwise prevent fluid communication between the outlet 313 and the inlet 312, at least a portion of the fluid flow path 315, and / or the isolation chamber 330. As described in further detail herein, when in the second state, the actuator 350 may be configured to allow a subsequent amount of body fluid (e.g., an amount of body fluid after the initial amount of body fluid) to be transferred from the inlet 312 through at least a portion of the fluid flow path 315 to the outlet 313 (and / or a fluid collection device 395 fluidly coupled to the outlet 313). Furthermore, when in the second state, the actuator 350 may be configured to isolate, separate, disconnect, and / or otherwise prevent fluid communication between the isolation chamber 330 and at least a portion of the inlet 312, the outlet 313, and / or the fluid flow path 315. In the embodiment shown in FIG. 4, as described in further detail herein, the transfer device 305 is such that the actuator 350 and the flow controller 340 collectively control the flow of fluid (e.g., gas and / or liquid) through the device.

[0136]

[0149] The rapid diagnostic test device 370 (also referred to herein as a "rapid test device" or simply a "test device") may be of any suitable shape, size, and / or configuration. In some embodiments, the rapid test device 370 may be removably coupled to the transfer device 305 or any suitable portion thereof. For example, in the embodiment shown in FIG. 4, the rapid test device 370 may be at least fluidly coupled to the isolation chamber of the transfer device 305. In other embodiments, the rapid test device 370 may be incorporated into the transfer device 305 such that the rapid test device 370 is in fluid communication with the isolation chamber 330. For example, the transfer device 305 and the rapid test device 370 may be unitarily or monolithically formed and / or otherwise integrated. In still other embodiments, the housing 310 may include and / or form a port, adapter, and / or receiving portion to which the rapid test device 370 may be coupled or into which the rapid test device 370 may be inserted to establish fluid communication between the rapid test device 370 and the isolation chamber 330.

[0137]

[0150] In some such embodiments, coupling the rapid test device 370 to the transfer device 305 may function to transition one or more flow controllers, valves, scepters, ports, seals, etc. from a closed or sealed state to an open state to allow fluid communication between the transfer device 305 and the test device 370. Although not shown in FIG. 4, in some embodiments the transfer device 305 may include a second actuator, etc. that may be operated to establish fluid communication between the isolation chamber 330 and the rapid test device 370. In other embodiments, the actuator 350 may be transitioned to establish fluid communication between the isolation chamber 330 and the rapid test device 370.

[0138]

[0151] In some implementations, the rapid test device 370 may be configured to receive a first amount of bodily fluid from the transfer device 305 and perform one or more tests, assays, and / or diagnostic procedures using the first amount of bodily fluid. The rapid test device 370 may be any suitable test device. For example, the rapid test device 370 may be an LFA, such as described in detail above with reference to the LFA 170A shown in FIG. 2. In some implementations, the test device 370 and / or aspects or portions thereof may be substantially similar to the rapid test device 170 and / or the rapid test device 270 described in detail above. Thus, the rapid test device 370 and / or aspects or portions thereof will not be described in further detail herein.

[0139]

[0152] As described above, system 300 may be used to obtain one or more quantities of bodily fluid from a patient that may be used in one or more tests, assays, and / or diagnostic procedures. For example, in some cases, as described above, a user, such as a doctor, physician, nurse, phlebotomist, technician, etc., may manipulate device 305 to establish fluid communication between inlet 312 and a source of bodily fluid (e.g., a patient's vein, cerebrospinal fluid (CSF) from the spinal cavity, collected urine, etc.). In some cases, actuator 350 may be in a first state when inlet 312 is in fluid communication with a source of bodily fluid (e.g., a portion of a patient) such that at least a portion of fluid flow path 315 establishes fluid communication between inlet 312 and isolation chamber 330.

[0140]

[0153] Thus, the transfer device 305 may be configured to transfer an initial amount of bodily fluid from a bodily fluid source (e.g., a patient) to the rapid test device 370. More specifically, in the embodiment shown in FIG. 4, when the inlet 312 is fluidly connected to a bodily fluid source (e.g., a portion of a patient), the outlet 313 may be fluidly coupled to the fluid collection device 395. As described above, in some embodiments, the fluid collection device 395 may be any suitable reservoir, container, and / or device configured to receive a quantity of bodily fluid. For example, the fluid collection device 395 may be a vacuum reservoir or container that defines a negative pressure and / or may be a syringe that is operated to generate a negative pressure. In some cases, coupling the outlet 313 to the fluid collection device 395 selectively exposes at least a portion of the fluid flow path 315 to a negative pressure and / or suction force within the fluid collection device 395. In some implementations, the actuator 350 may be in a first state such that the outlet 313 is isolated from the inlet 312. Additionally, when the actuator 350 is in the first state, the outlet 313 may be in fluid communication with the flow controller 340 (e.g., via a portion of the fluid flow path 315). The flow controller 340 may likewise be in its first state when the fluid collection device 395 is coupled to the outlet 313.

[0141]

[0154] In embodiments in which flow controller 340 is a selectively permeable member or membrane, the configuration of flow controller 340 and actuator 350 may be such that it allows the flow of air or gas to pass through flow controller 340 between outlet 313 and isolation chamber 330. In such embodiments, as detailed in the '117 publication and / or the '380 application, this configuration transfers at least a portion of the negative pressure differential or suction force generated by fluid collection device 395 into and / or through isolation chamber 330, which in turn serves to draw an initial amount of bodily fluid from a bodily fluid source through inlet 312 and at least a portion of fluid flow path 315 into isolation chamber 330.

[0142]

[0155] Alternatively, in embodiments in which the flow controller 340 is a diaphragm, flap, valve, sleeve, or the like, the configuration of the flow controller 340 and actuator 350 may be such that a portion and / or surface of the flow controller 340 is in fluid communication with the outlet 313 (e.g., via a portion of the fluid flow path 315). Thus, negative pressure and / or suction may act on a portion and / or surface of the flow controller 340, which may further act to transition the flow controller 340 from its first state in which the isolation chamber 330 has a first volume to its second state in which the isolation chamber 330 has a second volume that is greater than the first volume. The isolation chamber 330 may be such that an increase in volume causes a decrease in pressure within the isolation chamber 330, creating a negative pressure differential that acts to draw body fluid into the isolation chamber 330. Thus, as detailed in the '380 application and / or the '477 application, in such embodiments, an initial amount of bodily fluid may be drawn into the isolation chamber 330 in response to a transition of the flow controller 340 (e.g., an increase in the volume of the isolation chamber 330 as a result of the flow controller 340 transitioning from a first state to a second state).

[0143]

[0156] The initial amount of bodily fluid may be any suitable amount of bodily fluid, such as any of the volumes or amounts described above. For example, in some cases, the transfer device 305 may remain in the first state or configuration until a predetermined and / or desired amount (e.g., an initial amount) of bodily fluid is transferred to the isolation chamber 330. In some embodiments, the initial amount may be related to and / or at least partially based on a volume of the isolation chamber 330 or a portion thereof (e.g., an amount sufficient to fill the isolation chamber 330 or a desired portion of the isolation chamber 330). In some embodiments, the initial amount may be related to and / or at least partially based on a desired amount sufficient for the rapid test device 370 to perform one or more tests or assays. In other embodiments, the initial amount of bodily fluid may be related to and / or at least partially based on an amount or volume of bodily fluid equal to or greater than an amount associated with a fluid flow path defined between a bodily fluid source and the isolation chamber 330. In yet other embodiments, the transfer device 305 may be configured to transfer a flow (e.g., an initial amount) of bodily fluid to the isolation chamber 330 until the pressure differential between the isolation chamber 330 and the inlet 312 or bodily fluid source is substantially balanced and / or otherwise reduced below a desired threshold.

[0144]

[0157] In some embodiments, the transfer device 305 may be configured to transfer a flow of bodily fluid (e.g., an initial amount) to the isolation chamber 330 until the flow controller 340 transitions to its second configuration. In other words, in some embodiments, transferring the initial amount of bodily fluid to the isolation chamber 330 may function to place the flow controller 340 in its second state or configuration. For example, as detailed in the '117 and / or '380 applications, in embodiments in which the flow controller 340 is a selectively permeable member, transferring the initial amount of bodily fluid to the isolation chamber 330 may be such that at least a portion of the initial amount wets and / or saturates the flow controller 340, thereby further placing the flow controller 340 in its second state. In embodiments in which flow controller 340 is a diaphragm or the like, as detailed in the '380 and / or '477 applications, the transfer of the initial volume to isolation chamber 330 may occur substantially simultaneously with flow controller 340 being placed in its second state and / or configuration (e.g., in response to negative pressure being created by fluid collection device 395). Further, in the embodiment shown in FIG. 4, the configuration of flow controller 340 is such that when in its second state and / or configuration, flow controller 340 isolates and / or fluidly isolates isolation chamber 330 from outlet 313 such that the negative pressure and / or suction force generated by fluid collection device 395 no longer acts on or within isolation chamber 330.

[0145]

[0158] In some implementations, at least a portion of the initial amount of bodily fluid may be transferred from the isolation chamber 330 to the rapid test device 370 when the flow controller 340 is in its second state and before the actuator transitions from its first state to its second state. In some embodiments, the actuator 350 is configured to isolate the isolation chamber 330 from the inlet 313, the outlet 315, and at least a portion of the fluid flow path 315. In such embodiments, a portion of the initial amount of bodily fluid may be transferred from the isolation chamber 330 before, during, and / or after the actuator 350 transitions from its first state to its second state. In some implementations, the transfer of a portion of the initial amount may be automatic. In other implementations, the transfer of a portion of the initial amount may be in response to one or more user inputs, or the like.

[0146]

[0159] In some embodiments, as described in detail above with reference to rapid test device 270, transferring a portion of the initial amount of bodily fluid to rapid test device 370 can initiate a test and / or assay on or for a portion of the initial amount of bodily fluid. Furthermore, rapid test device 370 can be configured to perform any suitable test and / or assay. For example, as described in detail above, rapid test device 370 can be an LFA configured to test for the presence of lactate and / or PCT. Furthermore, as described in detail above, once a test or assay is completed, rapid test device 370 can be configured to output a test result. The test result can be detected and / or evaluated by a human and / or one or more electronic devices.

[0147]

[0160] In some embodiments, transitioning the actuator 350 from its first state to its second state (e.g., causing the transfer device 305 to its second state or configuration) can isolate, separate, isolate, and / or retain an initial amount of bodily fluid within the isolation chamber 330 and / or the rapid test device 370. In other words, the actuator 350 can isolate and / or isolate the isolation chamber 330 from one or more portions of the inlet 312, the outlet 313, and the fluid flow path 315. In some cases, isolating the initial amount of bodily fluid within the isolation chamber 330 can also isolate contaminants within the initial amount. Furthermore, as described in detail above, the configuration of the rapid test device 370 can be such that the tests and / or assays performed by the rapid test device 370 are not susceptible to such contamination. This means that the accuracy of the test result output by the rapid test device 370 is not affected by such contamination.

[0148]

[0161] In addition to isolating the isolation chamber 330 from the inlet 312, the outlet 313, and at least a portion of the fluid flow path 315, placing the actuator 350 in its second state (and placing the flow controller 340 in its second state) also establishes fluid communication between the inlet 312 and the outlet 313 through at least a portion of the fluid flow path 315. For example, in some embodiments, transitioning the actuator 350 from its first state to its second state may, for example, open or close a port or valve, move one or more seals, move or remove one or more obstructions, define one or more portions of a flow path, etc. Thus, in response to the negative pressure and / or suction force generated by the fluid collection device 395, one or more subsequent amounts of bodily fluid may flow from the inlet 312, through at least a portion of the fluid flow path 315, through the outlet 313, and to the fluid collection device 395. As discussed above, isolating an initial amount of bodily fluid (e.g., in rapid test device 370) before collecting or obtaining one or more subsequent amounts of bodily fluid reduces and / or substantially eliminates the amount of contaminants in the one or more subsequent amounts. Thus, as discussed above with reference to system 100 and / or system 200, system 300 may be configured to obtain an initial amount of bodily fluid that may be used in rapid tests that are relatively less sensitive to contamination and subsequent amounts of bodily fluid that may be used in tests that are relatively more sensitive to contamination.

[0149]

[0162] 5A and 5B are schematic diagrams of a fluid transfer and assay system 400 according to one embodiment, shown in a first state and a second state, respectively. The fluid transfer and assay system 400 (also referred to herein as a "system") may include at least a fluid transfer device 405 and a rapid diagnostic test device 470. Portions and / or aspects of the fluid transfer device 405 and / or rapid diagnostic test device 470 may be similar and / or substantially the same as the fluid transfer devices 105, 205 and / or 305 and / or rapid diagnostic test devices 170 (and / or LFA 170A), 270 and / or 370, respectively, described in detail above. Accordingly, such portions and / or aspects will not be described in further detail herein.

[0150]

[0163] The fluid transfer device 405 (also referred to herein as a "transfer device") may be of any suitable shape, size, and / or configuration. In some implementations, the transfer device 405 may be configured to draw bodily fluid (e.g., blood) from a patient to and / or through the transfer device 405. Additionally, the transfer device 405 may be configured to transfer at least a portion of the drawn bodily fluid to one or more other devices, reservoirs, containers, vials, machines, tests, assays, etc., such as a rapid diagnostic test device 470 and / or one or more fluid collection devices (not shown in FIGS. 5A and 5B ).

[0151]

[0164] The transfer device 405 includes at least a housing 410 and an actuator 450. The housing 410 of the device 405 may be of any suitable shape, size, and / or configuration. For example, in some embodiments, the housing 410 may be similar and / or substantially the same as the housing 210 and / or the housing 310 described above. In particular, the housing 410 may have and / or form an inlet 412 and an outlet 413, defining at least one fluid flow path (not shown in FIGS. 5A and 5B ) between the inlet 412 and the outlet 413. The inlet 412 may be any suitable inlet or port and may be configured to establish fluid communication between the housing 410 and a bodily fluid source (e.g., a patient). The outlet 413 may be any suitable outlet or port and may be configured to establish fluid communication between the housing 410 and a fluid collection device (not shown in FIGS. 5A and 5B ), such as any of those described in detail above. As described in further detail herein, one or more fluid flow paths defined by the housing 410 extend between the inlet 412 and the outlet 413, and fluid communication can be selectively established between the inlet 412 and the outlet 413.

[0152]

[0165] As discussed above with reference to the housing 310, the housing 410 shown in FIGS. 5A and 5B includes, forms, and / or couples to the isolation chamber 430 configured to be selectively in fluid communication with the fluid flow path and / or at least the inlet 412. Additionally, the isolation chamber 430 includes, couples to, and / or is otherwise configured to be in fluid communication with the rapid diagnostic testing device 470. The isolation chamber 430 may have any suitable shape, size, and / or configuration. For example, in some embodiments, the isolation chamber 430 may have a volume and / or fluid capacity of about 0.1 mL to about 5.0 mL. In some embodiments, the isolation chamber 430 may have a volume measured in terms of an amount of bodily fluid (e.g., an initial or first amount of bodily fluid) configured to be transferred into the isolation chamber 430 and / or tested by the rapid diagnostic testing device 470. In some embodiments, isolation chamber 430 and / or at least a portion thereof may be substantially similar in form and / or function to isolation chamber 330 described above with reference to Figure 4. Accordingly, portions and / or aspects of isolation chamber 430 will not be described in further detail herein.

[0153]

[0166] 5A and 5B, at least a portion of the isolation chamber 430 can include an absorbent and / or hydrophilic material 431. Additionally, the isolation chamber 430 includes a sampling portion 435 and a vent 424. The absorbent material 431 can be disposed within a portion of the isolation chamber 430. For example, one or more inner surfaces of the isolation chamber 431 can be covered and / or formed with the absorbent material 431. As shown in FIGS. 5A and 5B , the isolation chamber 430 may be positioned such that the sampling portion 435 of the isolation chamber 430 is downstream of the absorbent material 431 (e.g., for a portion of the isolation chamber 430, temporarily fluidly coupled to the inlet 412). In this manner, the absorbent material 431 may be configured to receive and / or absorb a first portion or part of an initial amount of bodily fluid transferred to the isolation chamber 430. In some implementations, the absorbent material 431 may be saturated after absorbing a predetermined amount or volume of bodily fluid, and any additional amount or volume of bodily fluid transferred to the isolation chamber 430 may flow to the sampling portion 435. As described in more detail herein, the sampling portion 435 of the isolation chamber 430 may be in fluid communication with a rapid diagnostic testing device 470 to transfer a portion of the initial amount of bodily fluid disposed in the sampling portion 435 to the rapid diagnostic testing device 470.

[0154]

[0167] The vent 424 is coupled to the housing 410 and / or the isolation chamber 430 and is in fluid communication with the interior volume of the isolation chamber 430. The vent 424 may be configured to vent and / or otherwise allow a flow of air or gas to exit the isolation chamber 430 as an initial amount of bodily fluid is transferred to the isolation chamber 430. In some implementations, venting air or gas from the isolation chamber 430 (e.g., through the vent 424) can reduce the amount of pressure in the isolation chamber 430 that may restrict and / or prevent the flow of bodily fluid into the isolation chamber 430. In some implementations, venting air or gas through the vent 424 can enable a negative pressure differential that may facilitate the transfer of the initial amount of bodily fluid into the isolation chamber 430. 5A and 5B as separate components, in other embodiments, absorbent material 431 may form one or more vents configured to absorb a first portion or portion of the initial amount as well as to vent isolation chamber 430. For example, absorbent material 431 may form one or more walls or one or more portions of a wall of isolation chamber 430.

[0155]

[0168] The actuator 450 of the device 405 may be of any suitable shape, size, and / or configuration. In some embodiments, the actuator 450 and / or aspects or portions thereof may be similar to and / or substantially the same as the actuators 150, 250, and / or 350 described in detail above. In some embodiments, the actuator 450 may be at least partially disposed within and / or partially formed by the housing 410. As described above, the actuator 450 may be configured to control, direct, and / or otherwise facilitate selective flow of fluid through at least a portion of the housing 410 and / or at least a portion of one or more fluid flow paths. In some embodiments, the actuator 450 may be a member or device configured to transition between any number of states (e.g., two, three, four, or more) and in any suitable manner (e.g., user actuation, automatic actuation, mechanical actuation, electronic actuation, chemical actuation, etc.).

[0156]

[0169] More specifically, in the embodiment shown in Figures 5A and 5B, the actuator 450 may be configured to transition between a first state (Figure 5A) in which the inlet 412 is in fluid communication with the isolation chamber 430 and a second state (Figure 5B) in which the inlet 412 is in fluid communication with the outlet 413. In some embodiments, when in the first state, the actuator 450 may be configured to isolate, separate, disconnect, and / or otherwise prevent fluid communication between the outlet 413 and the inlet 412 and / or the outlet 413 and the isolation chamber 430. In contrast, in the second state, the actuator 450 may be configured to allow a subsequent amount of body fluid (e.g., an amount of body fluid after the initial amount of body fluid) to be transferred from the inlet 412 through one or more fluid flow paths (not shown in Figures 5A and 5B) to the outlet 413 (and / or a fluid collection device fluidly coupled to the outlet 413). Moreover, when in the second state, the actuator 450 may be configured to isolate, separate, disconnect, and / or otherwise prevent fluid communication between the isolation chamber 430 and the inlet 412, the isolation chamber 430 and the outlet 413, and / or at least a portion of the fluid flow path extending between the isolation chamber 430 and the inlet 412 and the outlet 413. As such, the actuator 450 may be structurally and / or functionally similar to the actuators 150, 250 and / or 350 described in detail above.

[0157]

[0170] The rapid diagnostic test device 470 (also referred to herein as a "rapid test device" or simply a "test device") may be of any suitable shape, size, and / or configuration. In some embodiments, the rapid test device 470 may be removably coupled to the transfer device 405 or any suitable portion thereof. For example, in the embodiment shown in FIGS. 5A and 5B, the rapid test device 470 may be configured to engage or couple with the housing 410 and / or the isolation chamber 4350 such that the rapid test device 470 is in fluid communication with the sampling portion 435 of the isolation chamber 430. In some embodiments, the housing 410 may include and / or form a port, adapter, and / or receiving portion into which the rapid test device 470 may be coupled or into which the rapid test device 470 may be inserted to establish fluid communication between the rapid test device 470 and the sampling portion 435 of the isolation chamber 430. 5A and 5B, transitioning the actuator 450 from its first state to its second state can establish fluid communication (e.g., via one or more flow controllers, valves, septa, ports, seals, aligned channels, and / or other suitable members or devices for establishing fluid communication) between the isolation chamber 430 and the rapid test device 470. In some embodiments, transitioning the actuator 450 from its first state to its second state can establish fluid communication between the isolation chamber 430 and the rapid test device 470.

[0158]

[0171] In some implementations, the rapid test device 470 may be configured to receive a first amount of bodily fluid from the sampling portion 435 of the isolation chamber 430 and perform one or more tests, assays, and / or diagnostic procedures using the first amount of bodily fluid. The rapid test device 470 may be any suitable test device. For example, the rapid test device 470 may be an LFA, such as described in detail above with reference to the LFA 170A shown in FIG. 2. In some implementations, the test device 470 and / or aspects or portions thereof may be substantially similar to the rapid test devices 170, 270, and / or 370 described in detail above. Thus, the rapid test device 470 and / or aspects or portions thereof will not be described in further detail herein.

[0159]

[0172] The system 400 may be used to obtain one or more amounts of bodily fluid from a patient that may be used in one or more tests, assays, and / or diagnostic procedures. As described above, for example, the inlet 412 may be in fluid communication with a bodily fluid source. In some cases, as shown in FIG. 5A, when the inlet 412 is in fluid communication with a bodily fluid source (e.g., a portion of a patient), the actuator 450 may be in a first state, thereby establishing fluid communication between the inlet 412 and the isolation chamber 430 and isolating the outlet 413 from the inlet 412. Thus, the transfer device 405 may be configured to transfer an initial amount of bodily fluid from a bodily fluid source (e.g., a patient) to the rapid test device 470. In some implementations, the initial amount of bodily fluid may flow to and / or into the isolation chamber 430 depending on a pressure differential between the isolation chamber 430 and the inlet 412 and / or the bodily fluid source. In some embodiments, vent 424 may be configured to allow a flow of air or gas to exit isolated chamber 430, which may facilitate the flow of an initial amount of bodily fluid into isolated chamber 430. In some embodiments, vent 424 may be configured to vent isolated chamber 430 in a manner similar to the vents described in the '117 publication, for example.

[0160]

[0173] The initial amount of bodily fluid may be any suitable amount of bodily fluid, such as any of the volumes or amounts described above. More specifically, in the embodiment shown in Figures 5A and 5B, the initial amount of bodily fluid may be sufficient to saturate and / or wet (or substantially saturate and / or wet) the absorbent material 431 disposed within the isolation chamber 430 and fill (or substantially fill) the sampling portion 435 of the isolation chamber 430. In some embodiments, filling the isolation chamber 430 may be sequential in that the flow of the initial amount of bodily fluid is first absorbed by the absorbent material 431 until the absorbent material 431 is saturated, and then a remaining portion of the initial amount of bodily fluid may flow to and / or fill the sampling portion 435 of the isolation chamber 430. In some implementations, the continuous filling of the isolation chamber 430 may be such that a portion (e.g., a first portion) of the initial amount of bodily fluid may include contaminants (e.g., associated with and / or resulting from a venipuncture event, fluidly coupling to one or more components, etc.) and a portion (e.g., a second portion) of the initial amount of bodily fluid may include a reduced amount of contaminants and / or may be substantially free of contaminants. In some cases, once the initial amount of bodily fluid is transferred to the isolation chamber 430, the flow of bodily fluid may stop and / or the pressure differential may be substantially equalized, slowing or stopping the flow of bodily fluid.

[0161]

[0174] In some embodiments, after transferring an initial amount of bodily fluid to the isolation chamber 430, the actuator 450 may be transitioned from its first state ( FIG. 5A ) to its second state ( FIG. 5B ). For example, in some embodiments, the actuator 450 may be moved, slid, switched, rotated, and / or otherwise transitioned relative to the inlet 412 and the outlet 413. In some embodiments, transitioning and / or moving the actuator 450 may include transitioning and / or moving at least a portion of the housing 410. In other embodiments, the actuator 450 may be moved relative to the housing 410 (e.g., the housing 410 need not be transitioned and / or moved).

[0162]

[0175] 5B, transitioning the actuator 450 from a first state to a second state can establish fluid communication between the sampling portion 435 of the isolation chamber 430 and the rapid test device 470 and can isolate the isolation chamber 430 from one or more portions of the inlet 412, the outlet 413, and / or the fluid flow path between the inlet 412 and the outlet 413. In some embodiments, the arrangement of the actuator 450 can be such that transitioning the actuator 450 to the second state creates and / or increases an air gap between a portion of the isolation chamber 430 that includes the absorbent material 431 and a portion of the isolation chamber 430 that includes, forms, and / or defines the sampling portion 435. The air gap can facilitate transfer of bodily fluid from the sampling portion 435 to the rapid test device 470 (e.g., by allowing a desired relative pressure or pressure differential). Further, in instances where contaminants are contained within a portion of the initial volume absorbed by the absorbent material 431, such an arrangement can ensure that only a portion of the initial volume placed within the sampling portion 435 of the isolation chamber 430 is transferred to the rapid test device 470.

[0163]

[0176] At least a portion of the initial amount of bodily fluid may be transferred from the sampling portion 435 of the isolation chamber 430 to the rapid test device 470 when the actuator 450 transitions from its first state to its second state. In some implementations, the transfer of the portion of the initial amount may be automatic. In other implementations, the transfer of the portion of the initial amount may be in response to one or more user inputs, or the like. In some implementations, placing the actuator 450 in the second state may fluidly couple the rapid test device 470 to the sampling portion 435 of the isolation chamber 430, thereby enabling fluid transfer between the rapid test device 470 and the sampling portion 435 of the isolation chamber 430.

[0164]

[0177] In some embodiments, as described in detail above with reference to the rapid test device 270, upon transfer of the portion of the initial amount of bodily fluid to the rapid test device 470, tests and / or assays can be initiated on or with respect to the portion of the initial amount of bodily fluid. In some cases, as shown in FIG. 5B, the system 400, transfer device 405, and / or rapid test device 470 can be configured to provide a buffer 481 (or any other suitable solution) that can be mixed with the portion of the initial amount of bodily fluid. The rapid test device 470 can be configured to perform any suitable tests and / or assays. For example, as described in detail above with reference to the rapid test device 170, 270, and / or 370, the rapid test device 470 can be configured to output test results once the tests or assays are completed. The test results can be detected and / or evaluated by a person and / or one or more electronic devices.

[0165]

[0178] Transitioning the actuator 450 from its first state to its second state can isolate, separate, isolate, and / or retain an initial amount of bodily fluid within the isolation chamber 430 and / or the rapid test device 470. In other words, the actuator 450 can isolate and / or isolate the isolation chamber 430 from the inlet 412, the outlet 413, and one or more portions of the fluid flow path. In some cases, isolating the initial amount of bodily fluid within the isolation chamber 430 can also isolate contaminants within the initial amount (e.g., at least a portion of the initial amount absorbed by the absorbent material 431). Furthermore, the configuration of the rapid test device 470 can be such that the tests and / or assays performed by the rapid test device 470 are not susceptible to such contamination. This means that the accuracy of the test result output by the rapid test device 470 is not affected by such contamination, as described in detail above. In other cases, having a first portion or portions of the initial amount of bodily fluid received and / or absorbed by the absorbent material 431 may enable the rapid test device 470 to perform one or more tests that may be at least partially sensitive to contaminants.

[0166]

[0179] Additionally, transitioning the actuator 450 to its second state establishes fluid communication between the inlet 412 and the outlet 413 via at least a portion of a fluid flow path disposed between the inlet 412 and the outlet 413. For example, transitioning the actuator 450 from its first state to its second state may open or close a port or valve, move one or more seals, move or remove one or more obstructions, define one or more portions of a flow path, etc. In some implementations, the outlet 413 may be in fluid communication with a fluid collection device before or after the actuator is placed in its second state. As discussed in detail above, the fluid collection device may be configured to define and / or generate a negative pressure and / or suction force that may function to draw bodily fluid into the fluid collection device. Thus, in response to the negative pressure and / or suction force, one or more subsequent amounts of bodily fluid may flow from the inlet 412 through any suitable fluid flow path or portion thereof, through the outlet 413, and into the fluid collection device. As described above, isolating an initial amount of bodily fluid in isolation chamber 430 prior to collecting or obtaining one or more subsequent amounts of bodily fluid reduces and / or substantially eliminates the amount of contaminants in the one or more subsequent amounts. Thus, as described above with reference to systems 100, 200 and / or 300, system 400 may be configured to obtain an initial amount of bodily fluid that may be used in one or more rapid testing processes and a subsequent amount of bodily fluid that may be used in tests that are relatively sensitive to contamination (e.g., blood culture tests).

[0167]

[0180] 6A-6D are schematic diagrams of at least a portion of a fluid transfer and assay system 500 according to one embodiment. The fluid transfer and assay system 500 (also referred to herein as a "system") may include at least a fluid transfer device 505 and a rapid diagnostic test device 570. Portions and / or aspects of the fluid transfer device 505 and / or rapid diagnostic test device 570 may be similar and / or substantially the same as the fluid transfer devices 105, 205, 305 and / or 405 and / or rapid diagnostic test devices 170 (and / or LFA 170A), 270, 370 and / or 470, respectively, described in detail above. Accordingly, such portions and / or aspects will not be described in further detail herein.

[0168]

[0181] The fluid transfer device 505 (also referred to herein as a "transfer device") may be of any suitable shape, size, and / or configuration. In some implementations, the transfer device 505 may be configured to draw bodily fluid (e.g., blood) from a patient to and / or through the transfer device 505. Additionally, the transfer device 505 may be configured to transfer at least a portion of the drawn bodily fluid to one or more other devices, reservoirs, containers, vials, machines, tests, assays, etc., such as a rapid diagnostic test device 570 and / or one or more fluid collection devices (not shown in FIGS. 6A-6D). The transfer device 505 and / or aspects or portions thereof may be substantially similar to any of the transfer devices 105, 205, 305 and / or 405 described in detail above. Accordingly, the transfer device 505 will not be described in further detail herein.

[0169]

[0182] The rapid diagnostic test device 570 (also referred to herein as a "rapid test device" or simply a "test device") may be any suitable test device. In some implementations, the test device 570 and / or aspects or portions thereof may be substantially similar to the rapid test devices 170 (and / or LFA 170A), 270, 370 and / or 470 described in detail above. Accordingly, the rapid test device 570 and / or aspects or portions thereof will not be described in further detail herein.

[0170]

[0183] In the embodiment shown in FIGS. 6A-6D, the rapid test device 570 may be an LFA or the like, as described in detail above with reference to the LFA 170A shown in FIG. 2. The rapid test device 570 includes a substrate 571 having a capillary bed or the like of any suitable configuration, as described in detail above. Additionally, the rapid test device 570 includes a coupling member 578 that may be coupled to the substrate 571 via an attachment mechanism 579. The coupling member 578 may be any suitable coupling member configured to establish fluid communication with an interior volume of the transfer device 505 in response to the rapid test device 570 being coupled to the transfer device 505. For example, as shown in FIGS. 6A and 6B, the rapid test device 570 and / or its coupling member 578 may be configured to couple to the transfer device 505 via a port 525 (e.g., any suitable port, vent, coupler, opening, valve, joint, etc.). In some embodiments, the coupling member 578 may be, for example, a piercing member, needle, tube, etc. that may be pierced and / or otherwise advanced within the port 525. In some embodiments, coupling member 578 may be a capillary member or the like configured to transport fluid by capillary action. In some embodiments, port 525 may be self-repairing, allowing port 525 to seal when coupling portion 578 of rapid test device 570 is removed from port 525. In some embodiments, port 525 and / or at least a portion thereof may include and / or form a vent similar to vent 424.

[0171]

[0184] Attachment mechanism 579 may be any suitable member, mechanism, device, etc. configured to attach coupling member 578 to substrate 571. In some embodiments, attachment mechanism 579 may be configured to transition between two or more states or configurations to selectively place coupling member 578 in fluid communication with a portion of substrate 571 (e.g., a sample portion, element, and / or capillary bed). More specifically, attachment mechanism 579 may be configured to transition between a first state and / or configuration (FIGS. 6A-6C) and a second state and / or configuration (FIG. 6D).

[0172]

[0185] When in the first state, the rapid test device 570 can be coupled to the transfer device 505, and the coupling portion 578 can establish fluid communication with an interior volume of the transfer device 505 (e.g., via port 525). As shown in FIG. 6B, the coupling member 578 can receive at least a portion of an amount of bodily fluid disposed within the transfer device 505 (e.g., by capillary action, pressure differential, and / or any other fluid transfer modality). As shown in FIGS. 6C and 6D, once the coupling member 578 has received a desired amount of bodily fluid, the rapid test device 570 can be decoupled from the transfer device 505, and the attachment mechanism 579 can be transitioned from its first state to its second state.

[0173]

[0186] For example, in some embodiments, the attachment mechanism 579 may be a living hinge or the like that may bend, fold, deform, and / or otherwise reconfigure. As shown in FIG. 6D, when the attachment mechanism 579 is in the second state, the coupling member 578 may be in fluid communication with a portion of the substrate 571 (e.g., a sample portion, an element, and / or a capillary bed). Thus, a volume of bodily fluid contained in the coupling member 578 may be transferred to the portion of the substrate 571. Furthermore, in some implementations, when the attachment mechanism 579 is in the second state, a buffer 581 and / or any other suitable solution may be transferred to the substrate 571. The buffer 581 may be transferred to the substrate 571 via the coupling member 578, any suitable portion of the attachment mechanism 579, and / or any other suitable portion of the rapid test device 570. Thus, as described in detail above, the buffer 581 may be mixed with a volume of bodily fluid, and the mixture may flow along the substrate 571 for testing. In some implementations, the rapid test device 570 may be configured to test for the presence of lactate and / or PCT, which may be indicative of a patient condition, such as sepsis. Additionally, once a test or assay is completed, the rapid test device 570 may be configured to output a test result, as described in detail above with reference to the rapid test devices 170, 270, 370 and / or 470. The test result may be detected and / or evaluated by a human and / or one or more electronic devices.

[0174]

[0187] 7A-7D are schematic diagrams of a fluid transfer and assay system 600 according to one embodiment. The fluid transfer and assay system 600 (also referred to herein as a "system") may include at least a fluid transfer device 605 and a rapid diagnostic test device 670. Portions and / or aspects of the fluid transfer device 605 and / or rapid diagnostic test device 670 may be similar and / or substantially the same as the fluid transfer devices 105, 205, 305, 405 and / or 505 and / or rapid diagnostic test devices 170 (and / or LFA 170A), 270, 370, 470 and / or 570, respectively, described in detail above. Accordingly, such portions and / or aspects will not be described in further detail herein.

[0175]

[0188] The fluid transfer device 605 (also referred to herein as a "transfer device") may be of any suitable shape, size, and / or configuration. In some implementations, the transfer device 605 may be configured to draw bodily fluid (e.g., blood) from a patient to and / or through the transfer device 605. Additionally, the transfer device 605 may be configured to transfer at least a portion of the drawn bodily fluid to one or more other devices, reservoirs, containers, vials, machines, tests, assays, etc., such as a rapid diagnostic test device 670 and / or one or more fluid collection devices (not shown in FIGS. 7A-7D ).

[0176]

[0189] The transfer device 605 includes at least a housing 610 and an actuator 650. The housing 610 of the device 605 may be of any suitable shape, size, and / or configuration. For example, in some embodiments, the housing 610 may be similar and / or substantially the same as the housings 210, 310, and / or 410 described above. In particular, the housing 610 may have and / or form an inlet 612 and an outlet 613, defining a fluid flow path 615 between the inlet 612 and the outlet 613. The inlet 612 may be any suitable inlet or port and may be configured to establish fluid communication between the housing 610 and a body fluid source (e.g., a patient). The outlet 613 may be any suitable outlet or port and may be configured to establish fluid communication between the housing 610 and a fluid collection device (not shown in FIGS. 7A-7D), such as any of those described in detail above. As described in further detail herein, a fluid flow path 615 defined by the housing 610 extends between the inlet 612 and the outlet 613, and fluid communication can be selectively established between the inlet 612 and the outlet 613.

[0177]

[0190] As described above with reference to housing 410, housing 610 as shown in FIGS. 7A-7D includes, forms, and / or couples to isolation chamber 630 configured to be selectively in fluid communication with fluid flow path and / or at least inlet 612. Additionally, isolation chamber 630 includes, forms, and / or defines sampling portion 635 and port 625. Isolation chamber 630 may have any suitable shape, size, and / or configuration. For example, in some embodiments, isolation chamber 630 and / or at least a portion thereof may be substantially similar in form and / or function to isolation chamber 330 and / or isolation chamber 430, described in detail above. Accordingly, portions and / or aspects of isolation chamber 630 will not be described in further detail herein.

[0178]

[0191] The port 625 is coupled to the housing 610 and / or the isolation chamber 630 and is in fluid communication with an interior volume of the isolation chamber 630. More specifically, as shown in FIGS. 7A-7D , the port 625 is included in and / or coupled to the housing 610 and is in fluid communication with a sampling portion 635 of the isolation chamber 630. In some embodiments, as described in detail above with reference to the vent 424, the port 625 and / or at least a portion thereof may be configured to vent and / or otherwise allow a flow of air or gas to exit the isolation chamber 630 as the initial amount of bodily fluid is transferred to the isolation chamber 630. The sampling portion 635 of the isolation chamber 630 may be in fluid communication with the rapid diagnostic test device 670 to transfer a portion of the initial amount of bodily fluid disposed in the sampling portion 635 to the rapid diagnostic test device 670. In the embodiment shown in Figures 7A-7D, for example, the rapid diagnostic test device 670 may be fluidly connected to the sampling portion 635 via port 625 as described above with reference to port 525 shown in Figures 6A and 6B and / or any other suitable port.

[0179]

[0192] The actuator 650 of the device 605 may be of any suitable shape, size, and / or configuration. In some embodiments, the actuator 650 and / or aspects or portions thereof may be similar to and / or substantially the same as the actuators 150, 250, 350, and / or 450 described in detail above. In some embodiments, the actuator 650 may be at least partially disposed within and / or formed in part by the housing 610. As described above, the actuator 650 may be configured to control, direct, and / or otherwise facilitate selective flow of fluid through at least a portion of the housing 610 and / or at least a portion of one or more fluid flow paths. The actuator 650 may be any suitable member or device configured to transition between any number of states (e.g., two, three, four, or more) and in any suitable manner (e.g., user actuation, automatic actuation, mechanical actuation, electronic actuation, chemical actuation, etc.).

[0180]

[0193] More specifically, in the embodiment shown in FIGS. 7A-7D, the actuator 650 includes a first member 651 and a second member 660. The first member 651 of the actuator 650 can be of any suitable shape, size, and / or configuration. The first member 651 can be a plunger having at least one seal 652 (e.g., disposed at an end portion of the first member 651), or the like. In some embodiments, the end portion of the first member 651 can separate and / or at least partially define, for example, a sampling portion 635 of the isolation chamber 630. For example, the sampling portion 635 of the isolation chamber 630 can be disposed on one side of the end portion of the first member 651, with the remainder of the isolation chamber 630 disposed on the opposite side of the end portion of the first member 651. Additionally, the configuration of seal 652 may be such that seal 652 engages and / or contacts an inner surface of housing 610 to form and / or define a substantially fluid-tight seal between seal 652 and the inner surface of housing 610. First member 651 also includes one or more valves, ports, openings, channels, selectively permeable members, etc. (referred to herein as "valve 653") configured to establish selective fluid communication between sampling portion 635 of isolation chamber 635 and the remainder of isolation chamber 630, as described in further detail herein.

[0181]

[0194] The second member 660 of the actuator 650 may be of any suitable shape, size, and / or configuration. For example, in the embodiment shown in FIGS. 7A-7D, the second member 660 may be disposed around and / or on at least a portion of the first member 651. The second member 660 includes a set of seals 661. More specifically, the second member 660 may include a set of three seals. As shown, the second member 660 may have a first end portion and a second end portion opposite the first end portion. The first end portion of the second member 660 includes an outer seal 661 configured to engage and / or contact an inner surface of the housing 610 to define a substantially fluid-tight seal between the outer seal 661 and the inner surface of the housing 610. Additionally, the first end portion of the second member 660 includes an internal seal 661 configured to engage and / or contact a portion of the first member 651 to define a substantially fluid-tight seal between the internal seal 661 and a portion of the first member 651. The second end portion of the second member 660 includes an external seal 661 configured to engage and / or contact an inner surface of the housing to define a substantially fluid-tight seal between the external seal 661 and the inner surface of the housing.

[0182]

[0195] 7A-7D, the arrangement of the first member 651 and the second member 660 of the actuator is such that a portion of the isolation chamber 630 (e.g., a portion other than the sampling portion 635) is disposed and / or defined, for example, between an end portion of the first member 651 and a first end portion of the second member 660. Further, the second member 660 is configured to at least partially define a fluid flow path 615 between the first end portion and the second end portion of the second member 660. Thus, the seal 661 included in the first end portion and the first end portion of the second member 660 isolates and / or fluidly isolates the isolation chamber 630 from the fluid flow path 615.

[0183]

[0196] The actuator 650 is configured to transition between at least a first state, a second state, and a third state. As shown in FIGS. 7A to 7D, regardless of the state of the actuator 650, an end portion of the first member 651 and a seal 652 included in the end portion of the first member 651 are disposed and maintained on a first side of the inlet 612 and a first side of the outlet 613. Similarly, regardless of the state of the actuator 650, a second end portion of the second member 660 and a seal member 661 included in the second end portion of the second member 660 are disposed and maintained on a second side (opposite the first side) of the inlet 612 and a second side (opposite the first side) of the outlet 613. However, the first end portion of the second member 660 and the seal member 661 disposed on the first end portion of the second member 660 are configured to (i) be disposed on a second side of the inlet 612 and a first side of the outlet 613 when the actuator 650 is in the first and second states (FIGS. 7A and 7B), and (ii) be disposed on a first side of the inlet 612 and a first side of the outlet 613 when the actuator 650 is in the third state (FIGS. 7C and 7D). Thus, as described in further detail herein, the configuration of the actuator 650 is such that transitioning the actuator 650 can selectively direct and / or divert fluid flow (i) between the inlet 612 and the isolation chamber 630, and (ii) between the inlet 612 and the outlet 613 via the fluid flow passage 615.

[0184]

[0197] The rapid diagnostic test device 670 (also referred to herein as a "rapid test device" or simply a "test device") may be any suitable test device. For example, the rapid test device 670 may be an LFA, such as described in detail above with reference to the LFA 170A shown in FIG. 2. In some implementations, the test device 670 and / or aspects or portions thereof may be substantially similar to the rapid test devices 170, 270, 370 and / or 470 described in detail above. Accordingly, the rapid test device 670 and / or aspects or portions thereof will not be described in further detail herein.

[0185]

[0198] As shown in FIG. 7D, the rapid test device 670 may be configured to engage or couple to the housing 610 via the port 625. In some embodiments, for example, the port 625 may be a valve, coupler, and / or any suitable reconfigurable member or device configured to (i) vent air or gas from the isolation chamber 630 as described above with reference to the vent 424, and (ii) receive a portion of the rapid test device 670 to fluidly communicate the rapid test device 670 with the sampling portion 635 of the isolation chamber 630. For example, the rapid test device 670 may include a coupling member 678 that can establish fluid communication with the sampling portion 635 of the isolation chamber 630 when the rapid test device 670 is coupled to the sampling portion 635 of the isolation chamber 630. In some embodiments, the coupling member 678 may be, for example, a piercing member, needle, tube, capillary, etc. that can pierce and / or otherwise advance within the port 625. In some embodiments, the coupling member 678 may be substantially similar to the coupling member 578 described above with reference to FIGS. 6A-6D. In some embodiments, the port 625 may be self-repairing, allowing the port 625 to be sealed when the coupling portion 678 of the test device 670 is removed from the port 625. As shown in FIG. 7D , the coupling portion 678 of the test device 670 may be coupled to a substrate 671 of the test device 670 (e.g., coupled directly to the substrate 671 and / or coupled via an attachment mechanism such as attachment mechanism 579). In this manner, the coupling portion 678 may transfer a volume of bodily fluid from the sampling portion 635 of the isolation chamber 630 to the test device 670. In response, the test device 670 may perform one or more tests, assays, and / or diagnostic procedures using the volume of bodily fluid.

[0186]

[0199] The system 600 may be used to obtain one or more quantities of bodily fluid from a patient, which may be used in one or more tests, assays, and / or diagnostic procedures. As described above, for example, the inlet 612 may be in fluid communication with a bodily fluid source. As shown in FIG. 7A, when the inlet 612 is in fluid communication with a bodily fluid source (e.g., a portion of a patient), the actuator 650 may be in a first state, thereby establishing fluid communication between the inlet 612 and the isolation chamber 630 and isolating the outlet 613 from the inlet 612. Furthermore, when the actuator 650 is in the first state, an end portion of the first member 651 may be close to or adjacent to a first side of the inlet 612, and a first end portion of the second member 660 may be close to or adjacent to a second side of the inlet 612. In this manner, a portion of the isolation chamber 630 defined between the first member 651 and the second member 660 may have a first volume.

[0187]

[0200] In some cases, when the inlet 612 is placed in fluid communication with a body fluid source, the actuator 650 may be transitioned from its first state to its second state. For example, as shown in FIG. 7B, the first member 651 may be transitioned or moved relative to the inlet 612 and the second member 660, which in turn increases the volume of the portion of the isolation chamber 630 disposed between the first member 651 and the second member 660. Additionally, the transition and / or movement of the first member 651 may reduce the volume of the sampling portion 635 of the isolation chamber 630, and the location of the port 625 may be such that air or gas contained within the sampling portion 635 may be allowed to exit and / or flow out of the sampling portion 635. As shown in FIG. 7B, the end portion of the first member 651 can be configured to restrict and / or substantially prevent the flow of air from the sampling portion 635 of the isolation chamber 630 to the remainder of the isolation chamber 630 such that an increase in volume within the remainder of the isolation chamber 630 creates a negative pressure differential that acts to draw an initial amount of body fluid from the body fluid source into the isolation chamber 630 through the inlet 612.

[0188]

[0201] The initial amount of bodily fluid may be any suitable amount of bodily fluid, such as any of the volumes or amounts described above. In some implementations, once the initial amount of bodily fluid is transferred to the isolation chamber 630, the flow of bodily fluid may stop and / or the pressure differential may be substantially equalized, slowing or stopping the flow of bodily fluid. In such implementations, the actuator 650 may then be transitioned from its second state to its third state. In other implementations, the transition of the actuator 650 through the three states may be a substantially continuous transition. In such implementations, the initial amount of bodily fluid may be the amount of bodily fluid transferred to the isolation chamber 630 as the actuator 650 transitions from its first state to its second state, and continuing to transition the actuator 650 from its second state to its third state may function to stop the flow to the isolation chamber 630.

[0189]

[0202] The actuator 650 may be transitioned from its second state to its third state once an initial amount of bodily fluid is contained within the isolation chamber 630. As shown in FIG. 7C, transitioning the actuator 650 to the third state may include transitioning and / or moving a second member 660 relative to the inlet 612 and a first member 651 of the actuator 650. The transitioning and / or moving of the second member 660 transitions and / or moves a first end portion of the second member from a second side of the inlet 612 to a first side of the inlet 612, thereby isolating and / or fluidly isolating the isolation chamber 630 from the inlet 612. Additionally, the transitioning and / or moving of the second member 660 relative to the first member 651 may reduce a volume of a portion of the isolation chamber 630 disposed between the first member 651 and the second member 660. In some implementations, as shown in FIG. 7C, the reduction in volume of a portion of the isolation chamber 630 results in an increase in pressure that may act to transition the valve 653 from a closed state to an open state, thereby allowing at least a portion of the initial amount of bodily fluid to be transferred to the sampling portion 635 of the isolation chamber 630.

[0190]

[0203] As shown in FIG. 7D , the rapid test device 670 may be coupled to the housing 610 (e.g., via a coupling member 678) and / or otherwise in fluid communication with the sampling portion 635 of the isolation chamber 630. Thus, at least a portion of the bodily fluid may be transferred from the sampling portion 635 of the isolation chamber 630 to the rapid test device 670. In some implementations, the transfer of the portion of the initial amount of bodily fluid may be automatic. In other implementations, the transfer of the portion of the initial amount of bodily fluid may be in response to one or more user inputs, or the like (e.g., via the actuator 650 and / or any other suitable actuation mechanism not shown in FIGS. 7A-7D ). In some embodiments, as described in detail above with reference to the rapid test device 270, the transfer of the portion of the initial amount of bodily fluid to the rapid test device 670 may initiate testing and / or assaying of or on the portion of the initial amount of bodily fluid. Although not shown in FIGS. 7A-7D, in some cases, system 600, transfer device 605, and / or rapid test device 670 may be configured to provide a buffer (or any other suitable solution) that may be mixed with a portion of the initial amount of bodily fluid. Rapid test device 670 may be configured to perform any suitable test and / or assay. For example, as described in detail above, rapid test device 670 may be an LFA configured to test for the presence of lactate and / or PCT. Furthermore, as described in detail above with reference to rapid test devices 170, 270, 370 and / or 470, once a test or assay is completed, rapid test device 670 may be configured to output a test result. The test result may be detected and / or evaluated by a person and / or one or more electronic devices.

[0191]

[0204] As discussed above, transitioning the actuator 650 from its second state to its third state may isolate, separate, isolate, and / or retain an initial volume of bodily fluid within the isolation chamber 630 and / or the rapid test device 670, which may also isolate contaminants within the initial volume. Furthermore, the configuration of the rapid test device 670 may be such that the tests and / or assays performed by the rapid test device 670 are not susceptible to such contamination. This means that the accuracy of the test results output by the rapid test device 670 is not affected by such contamination, as discussed in detail above.

[0192]

[0205] As shown in FIGS. 7C and 7D, transitioning the actuator 650 from its second state to its third state establishes fluid communication between the inlet 612 and the outlet 613 via a fluid flow path 615 disposed between a first end portion and a second end portion of a second member 660 of the actuator 650. More specifically, when the actuator 650 is in its third state, the first end portion of the second member 660 is disposed on a first side of the inlet 612, and the second end portion of the second member 660 is disposed on a second side of the outlet 613. In other words, both the inlet 612 and the outlet 613 are disposed between the first end portion and the second end portion of the second member 660. Thus, when the actuator 650 is in the third state, the fluid flow path 615 can establish fluid communication between the inlet 612 and the outlet 613.

[0193]

[0206] In some implementations, the outlet 613 may be in fluid communication with a fluid collection device (not shown in FIGS. 7A-7D ) before or after the actuator 650 is placed in its third state. As described in detail above, the fluid collection device may be configured to define and / or generate a negative pressure and / or suction force that may function to draw bodily fluid into the fluid collection device. Thus, in response to the negative pressure and / or suction force, one or more subsequent quantities of bodily fluid may flow from the inlet 612, through the fluid flow path 615, through the outlet 613, and into the fluid collection device. As described above, isolating an initial quantity of bodily fluid in the isolation chamber 630 prior to collecting or obtaining one or more subsequent quantities of bodily fluid reduces and / or substantially eliminates the amount of contaminants in the one or more subsequent quantities. Thus, as described above with reference to systems 100, 200, 300 and / or 400, system 600 may be configured to obtain an initial amount of bodily fluid that may be used for rapid testing that is relatively less sensitive to contamination and a subsequent amount of bodily fluid that may be used for testing that is relatively more sensitive to contamination.

[0194]

[0207] 8 and 9A-9D show a fluid transfer and assay system 700 according to one embodiment. The fluid transfer and assay system 700 (also referred to herein as a "system") may include at least a fluid transfer device 705 and a rapid diagnostic test device 770. Portions and / or aspects of the fluid transfer device 705 and / or rapid diagnostic test device 770 may be similar and / or substantially the same as the fluid transfer devices 105, 205, 305, 405, 505 and / or 605 and / or rapid diagnostic test devices 170 (and / or LFA 170A), 270, 370, 470, 570 and / or 670, respectively, described in detail above. Accordingly, such portions and / or aspects will not be described in further detail herein.

[0195]

[0208] The fluid transfer device 705 (also referred to herein as a "transfer device") may be of any suitable shape, size, and / or configuration. In some implementations, the transfer device 705 may be configured to draw bodily fluid (e.g., blood) from a patient to and / or through the transfer device 705. Additionally, the transfer device 705 may be configured to transfer at least a portion of the drawn bodily fluid to one or more other devices, reservoirs, containers, vials, machines, tests, assays, etc., such as a rapid diagnostic test device 770 and / or one or more fluid collection devices (not shown in FIGS. 8 and 9A-9D).

[0196]

[0209] The transfer device 705 includes at least a housing 710 and an actuator 750. The housing 710 of the device 705 may be of any suitable shape, size, and / or configuration. For example, in some embodiments, the housing 710 may be similar and / or substantially the same as at least the housing 610 described above. In particular, the housing 710 may have and / or form an inlet 712 and an outlet 713, defining a fluid flow path 715 between the inlet 712 and the outlet 713. The inlet 712 may be any suitable inlet or port and may be configured to establish fluid communication between the housing 710 and a bodily fluid source (e.g., a patient). The outlet 713 may be any suitable outlet or port and may be configured to establish fluid communication between the housing 710 and a fluid collection device (not shown in FIGS. 8-9D), such as any of those described in detail above. As described in further detail herein, a fluid flow path 715 defined at least in part by the housing 710 extends between the inlet 712 and the outlet 713, and fluid communication can be selectively established between the inlet 712 and the outlet 713.

[0197]

[0210] As described above with reference to at least the housing 610, the housing 710 shown in FIGS. 8-9D includes, forms and / or couples to, the isolation chamber 730 configured to be selectively in fluid communication with the fluid flow path and / or at least the inlet 712. Additionally, as described in more detail herein, the housing defines an opening 721 and / or a port configured to receive a portion of the rapid diagnostic test device 770. The isolation chamber 730 may have any suitable shape, size, and / or configuration. For example, in some embodiments, the isolation chamber 730 and / or at least a portion thereof may be substantially similar in form and / or function to the isolation chambers 330, 430 and / or 630 described in more detail above. Accordingly, portions and / or aspects of the isolation chamber 730 will not be described in further detail herein.

[0198]

[0211] The actuator 750 of the device 705 may be of any suitable shape, size, and / or configuration. In some embodiments, the actuator 750 and / or aspects or portions thereof may be similar to and / or substantially the same as the actuators 150, 250, 350, 450, and / or 650, described in detail above. In some embodiments, the actuator 750 may be at least partially disposed within and / or partially formed by the housing 710. As described above, the actuator 750 may be configured to control, direct, and / or otherwise facilitate selective flow of fluid through at least a portion of the housing 710 and / or at least a portion of one or more fluid flow paths. The actuator 750 may be any suitable member or device configured to transition between any number of states (e.g., two, three, four, or more) and in any suitable manner (e.g., user actuation, automatic actuation, mechanical actuation, electronic actuation, chemical actuation, etc.).

[0199]

[0212] More specifically, as shown in FIGS. 9A-9D , the actuator 750 includes a first member 751, a second member 760, and a third member 765. The first member 751 of the actuator 750 may be of any suitable shape, size, and / or configuration. For example, the first member 751 may be similar in form and / or function at least to the first member 651 of the actuator 650, described in detail above. The first member 751 includes at least one seal 752 disposed at a first end portion of the first member 751. The configuration of the seal 752 may be such that the seal 752 engages and / or contacts an inner surface of the housing 710 to form and / or define a substantially fluid-tight seal between the seal 752 and the inner surface of the housing 710.

[0200]

[0213] The first end portion of the first member 751 also includes a port 725 in fluid communication with the sampling channel 735. In some embodiments, e.g., as described above with reference to port 625, the port 725 may be a valve, coupler, and / or any suitable reconfigurable member or device configured to (i) vent and / or allow an air or gas flow from the sampling channel 735 and (ii) receive a portion of the rapid test device 770 to place the rapid test device 770 in fluid communication with the sampling channel 735. The sampling channel 735 is disposed within and / or defined by the first member 751. For example, in some embodiments, the first member 751 may have a hollow elongated portion that defines the sampling channel 735. Additionally, such portion of the first member 751 may define and / or have an opening, port, valve, selectively permeable member, etc. configured to selectively place the sampling channel 735 in fluid communication with the isolation chamber 730. In some embodiments, the sampling channel 735 is included in and / or defined by the first member 751 of the actuator 750, although the sampling channel 735 may be at least similar in form and / or function to the sampling portion 635 of the isolation chamber 630 described above with reference to Figures 7A-7D.

[0201]

[0214] As shown in FIGS. 9A-9D , the first member 751 also includes an engagement member 755 disposed at or on a second end portion of the first member 751 opposite the first end portion. The engagement member 755 may be of any suitable shape, size, and / or configuration. For example, in some embodiments, the engagement member 755 may be a protrusion, a tab, a button, a knob, and / or any other suitable engagement member. As described in more detail herein, the engagement member 755 is configured to selectively engage a portion of the third member 765 of the actuator 750 to guide and / or at least partially control relative motion between the first member 751, the second member 760, and / or the third member 765.

[0202]

[0215] The second member 760 of the actuator 750 may be of any suitable shape, size, and / or configuration. As shown in FIGS. 9A-9D, the second member 760 may be disposed around and / or over at least a portion of the first member 751. The second member 760 includes a set of seals 761. As shown, the second member 760 may include a first end portion having an inner seal 761 and an outer seal 761, and a second end portion opposite the first end portion having the outer seal 761. As such, the second member 760 may be similar and / or substantially the same as the second member 660 of the actuator 650. Accordingly, the second member 760 and / or aspects or portions thereof will not be described in further detail herein.

[0203]

[0216] The third member 765 may be of any suitable shape, size, and / or configuration. In some embodiments, the third member 765 may be included in and / or form a portion of the housing 710 and / or an external portion of the transport device 705. For example, as shown in FIGS. 9A-9D, at least a portion of the housing 710, the first member 751, and the second member 760 may be disposed within a portion of the third member 765. More specifically, the third member 765 may be a substantially hollow cylinder having an open end and a substantially closed end, or the like. The substantially closed end includes and / or defines a detent, recess, opening, and / or engagement structure (referred to herein as "engagement structure 766"). The engagement structure 766 may contact and / or otherwise selectively engage the engagement member 755 of the first member 751. For example, as described in more detail herein, the engagement member 755 may be configured to engage and / or contact the engagement structure 766, which may further result in the first member 751 and the third member 765 moving collectively and / or simultaneously as the actuator 750 transitions between two or more states or configurations. Additionally, as described in more detail herein, a portion of the transition of the actuator 750 may result in the engagement member 755 disengaging and / or moving relative to the engagement structure 766, which may further result in the first member 751 moving relative to the third member 765 (or vice versa).

[0204]

[0217] 9A-9D, the configuration of the actuator's first member 751 and second member 760 is such that the isolation chamber 730 is disposed and / or defined, for example, between a first end portion of the first member 751 and a first end portion of the second member 760. Further, the second member 760 is configured to at least partially define a fluid flow path 715 between the first end portion and the second end portion of the second member 760. Thus, a seal 761 included in the first end portion and the first end portion of the second member 760 isolates and / or fluidly isolates the isolation chamber 730 from the fluid flow path 715.

[0205]

[0218] The actuator 750 is configured to transition between at least a first state, a second state, a third state, and a fourth state. As shown in FIGS. 9A-9D, regardless of the state of the actuator 750, a first end portion of the first member 751 and a seal 752 included in the first end portion of the first member 751 are disposed and maintained on a first side of the inlet 712 and a first side of the outlet 713. Similarly, regardless of the state of the actuator 750, a second end portion of the second member 760 and a seal member 761 included in the second end portion of the second member 760 are disposed and maintained on a second side (opposite the first side) of the inlet 712 and a second side (opposite the first side) of the outlet 713. However, the first end portion of the second member 760 and the seal member 761 disposed on the first end portion of the second member 760 are configured to (i) be disposed on a second side of the inlet 712 and a first side of the outlet 713 when the actuator 750 is in the first state ( FIG. 9A ), the second state ( FIG. 9B ), and the third state ( FIG. 9C ), and (ii) be disposed on a first side of the inlet 712 and a first side of the outlet 713 when the actuator 750 is in the fourth state ( FIG. 9D ). Thus, as described in further detail herein, the configuration of the actuator 750 is such that transitions of the actuator 750 can selectively direct and / or divert fluid flow (i) between the inlet 712 and the isolation chamber 730, and (ii) between the inlet 712 and the outlet 713 via the fluid flow passage 715.

[0206]

[0219] The rapid diagnostic test device 770 (also referred to herein as a "rapid test device" or simply a "test device") may be any suitable test device. For example, the rapid test device 770 may be an LFA, such as those described in detail above with reference to the LFA 170A shown in FIG. 2. In some implementations, the test device 770 and / or aspects or portions thereof may be substantially similar to the rapid test devices 170, 270, 370, 470, 570 and / or 670 described in detail above. Accordingly, the rapid test device 770 and / or aspects or portions thereof will not be described in further detail herein.

[0207]

[0220] 9D, the rapid test device 770 includes a coupling member 778 coupled to and / or in at least fluid communication with (e.g., coupled directly to the substrate 771 and / or coupled via an attachment mechanism such as attachment mechanism 579) a substrate 771 of the test device 770. When the rapid test device 770 is coupled to the transfer device 705, the coupling member 778 can be at least partially inserted through the opening 721 of the housing 710 to establish fluid communication with the sampling channel 735. For example, the coupling member 778 can be a piercing member, needle, tube, capillary, etc. that can pierce and / or otherwise advance within the port 725. In some embodiments, the substrate 771 and the coupling member 778 can be substantially similar to the substrate 571 and / or substrate 671 and the coupling member 578 and / or the coupling member 678 described in detail above. Accordingly, the substrate 771 and the coupling member 778 (and / or aspects or portions thereof) will not be described in further detail herein.

[0208]

[0221] The system 700 may be used to obtain one or more quantities of bodily fluid from a patient, which may be used in one or more tests, assays, and / or diagnostic procedures. As described above, for example, the inlet 712 may be in fluid communication with a bodily fluid source. As shown in FIG. 9A, when the inlet 712 is in fluid communication with a bodily fluid source (e.g., a portion of a patient), the actuator 750 may be in a first state, thereby establishing fluid communication between the inlet 712 and the isolation chamber 730 and isolating the outlet 713 from the inlet 712. Furthermore, when the actuator 750 is in the first state, a first end portion of the first member 751 may be close to or adjacent to a first side of the inlet 712, and a first end portion of the second member 760 may be close to or adjacent to a second side of the inlet 712. In this manner, the isolation chamber 730 defined between the first member 751 and the second member 760 may have a first volume.

[0209]

[0222] In some cases, the actuator 750 may be transitioned from its first state to its second state when the inlet 712 is placed in fluid communication with a source of bodily fluid. For example, as shown in FIG. 9B, a user may exert a force on the third member 765 that may function to move the third member 765 relative to the housing 710. As described above, the configuration of the engagement member 755 of the first member 751 and the engagement structure 766 of the third member 765 are such that movement of the third member 765 relative to the housing 710 causes a similar movement of the first member 751. The movement of the first member 751 also relative to the second member 760 (e.g., the second member 760 has not yet moved), which in turn increases the volume of the isolation chamber 730 disposed between the first member 751 and the second member 760. Further, the transition and / or movement of the first member 751 may reduce a volume within the housing 710 on a side of the first member 751 opposite the isolation chamber 730, and the opening 721 may be such that air or gas contained within the housing 710 may be allowed to exit and / or flow out of the sampling channel 735. Thus, as described in detail above with reference to the isolation chamber 630, the transition of the actuator 750 from its first state ( FIG. 9A ) to its second state ( FIG. 9B ) may result in the creation of a negative pressure differential within the isolation chamber that acts to draw an initial amount of body fluid from the body fluid source through the inlet 712 and into the isolation chamber 730. Further, the initial amount of body fluid may be any suitable amount of body fluid, such as any of the volumes or amounts described above.

[0210]

[0223] The actuator 750 may be transitioned from its second state (FIG. 9B) to its third state (FIG. 9C) once an initial amount of bodily fluid is contained within the isolation chamber 730. As described above with reference to the transfer device 605, the transition of the actuator 750 from the second state to the third state may be in response to an initial amount of bodily fluid being disposed within the isolation chamber 730, in response to the equalization of one or more pressure differentials, in response to a given point in a continuous process of transitioning the actuator 750 from the first state to the fourth state, etc. In some cases, the transition may be automatic or in response to an applied force.

[0211]

[0224] As shown in FIG. 9C, transitioning the actuator 750 to the third state may include transitioning and / or moving the first member 751 and the third member 765 a further amount relative to the housing 710 and the second member 760. More specifically, as shown in FIG. 9C, when in the third state, the first member 751 may be disposed at a predetermined position relative to the second member 760 such that an opening, port, valve, or the like (referred to herein as "opening 754") is in fluid communication with the isolation chamber 730 and / or the inlet 712. In this manner, a quantity of bodily fluid may be transferred to the sampling channel 735 defined by the first member 751. As noted above, in some embodiments, the port 725 may be configured to vent the sampling channel 735 to facilitate the flow of bodily fluid into the sampling channel 735.

[0212]

[0225] With a quantity of bodily fluid contained within the sampling channel 735, the actuator 750 may be transitioned from its third state (FIG. 9C) to its fourth state (FIG. 9D). More specifically, in some implementations, the third member 765 and the second member 760 may move relative to the housing 710, while the first member 751 is maintained in a substantially fixed position relative to the housing 710. In other words, the third member 765 and the second member 760 move together and relative to the first member 751.

[0213]

[0226] 9D, when the actuator 750 transitions to the fourth state, the engagement member 755 disengages from and / or moves relative to the engagement surface 766. In some embodiments, the engagement member 755 and / or engagement surface 766 may be sized and / or configured to maintain contact and / or engagement until a desired and / or predetermined force is applied sufficient to overcome the force maintaining the engagement (e.g., a frictional force, a force sufficient to elastically and / or plastically deform the engagement member 755 and / or engagement surface 766, and / or any other suitable force). In other words, the third member 765 may move relative to the first member 751 if the force meets a criterion and / or is greater than a threshold force amount.

[0214]

[0227] When the actuator 750 transitions to the fourth state, the second member 760 of the actuator 750 moves with the third member 765 in the same direction as the third member 765. As shown in FIG. 9D , the transition and / or movement of the second member 760 transitions and / or moves a first end portion of the second member 760 from the second side of the inlet 712 to the first side of the inlet 712, thereby isolating and / or fluidly isolating the isolation chamber 730 from the inlet 712. Additionally, as described in more detail herein, the transition and / or movement of the second member 760 relative to the first member 751 can position the opening 754 of the first member 751 opposite an internal seal 561 included at or on the first end portion of the second member 760, which can in some cases allow for venting of the sampling channel 735.

[0215]

[0228] 9D, the rapid test device 770 may be coupled to the housing 710 and / or otherwise inserted at least partially into and / or at the opening 721 of the housing 710 to allow the coupling member 778 to establish fluid communication with the sampling channel 735 (e.g., via the port 725). Thus, at least a portion of the bodily fluid may be transferred from the sampling channel 735 to the rapid test device 770, as described in detail above with reference to the rapid test devices 470, 570 and / or 670. In some embodiments, transferring a quantity of bodily fluid from the sampling channel 735 to the rapid test device 770 may initiate testing and / or assaying of or on a portion of the initial quantity of bodily fluid, as described in detail above with reference to the rapid test device 270. Additionally, in some cases, venting the sampling channel 735 via the opening 754 may enable a desired pressure differential in the sampling channel 735 that may facilitate the transfer of bodily fluid from the sampling channel 735 to the rapid test device 770. The rapid test device 770 may be configured to perform any suitable test and / or assay, such as any of those described in detail above (e.g., testing for the presence of lactate and / or PCT). Furthermore, upon completion of a test or assay, the rapid test device 770 may be configured to output a test result, as described in detail above with reference to rapid test devices 170, 270, 370, 470, 570 and / or 670. The test result may be detected and / or evaluated by a human and / or one or more electronic devices.

[0216]

[0229] As discussed above, transitioning the actuator 750 from its third state to its fourth state may isolate, separate, isolate, and / or retain an initial volume of bodily fluid within the isolation chamber 730 and / or the rapid test device 770, which may also isolate contaminants within the initial volume. Furthermore, the configuration of the rapid test device 770 may be such that the tests and / or assays performed by the rapid test device 770 are not susceptible to such contamination. This means that the accuracy of the test results output by the rapid test device 770 is not affected by such contamination, as discussed in detail above.

[0217]

[0230] 9D, transitioning the actuator 750 from its third state to its fourth state establishes fluid communication between the inlet 712 and the outlet 713 via a fluid flow path 715 disposed between a first end portion and a second end portion of a second member 760 of the actuator 750. As described in detail above with reference to the actuator 650, when the actuator 750 is in its fourth state, the first end portion of the second member 760 is disposed on a first side of the inlet 712 and the second end portion of the second member 760 is disposed on a second side of the outlet 713.

[0218]

[0231] In some implementations, the outlet 713 may be in fluid communication with a fluid collection device (not shown in FIGS. 8-9D ) before or after the actuator 750 is placed in its fourth state. As described in detail above, the fluid collection device may be configured to define and / or generate a negative pressure and / or suction force that may function to draw bodily fluid into the fluid collection device. Thus, in response to the negative pressure and / or suction force, one or more subsequent quantities of bodily fluid may flow from the inlet 712, through the fluid flow path 715, through the outlet 713, and into the fluid collection device. As described above, isolating an initial quantity of bodily fluid in the isolation chamber 730 prior to collecting or obtaining one or more subsequent quantities of bodily fluid reduces and / or substantially eliminates the amount of contaminants in the one or more subsequent quantities. Thus, as described above with reference to systems 100, 200, 300, 400 and / or 600, system 700 may be configured to obtain an initial amount of bodily fluid that may be used for rapid testing that is relatively less sensitive to contamination and a subsequent amount of bodily fluid that may be used for testing that is relatively more sensitive to contamination.

[0219]

[0232] 10, 11 and 12A-12D show a fluid transfer and assay system 800 according to one embodiment. The fluid transfer and assay system 800 (also referred to herein as a "system") may include at least a fluid transfer device 805 and a rapid diagnostic test device 870. Portions and / or aspects of the fluid transfer device 805 and / or rapid diagnostic test device 870 may be similar and / or substantially the same as the fluid transfer devices 105, 205, 305, 405, 505, 605 and / or 705 and / or rapid diagnostic test devices 170 (and / or LFA 170A), 270, 370, 470, 570, 670 and / or 770, respectively, described in detail above. Accordingly, such portions and / or aspects will not be described in further detail herein.

[0220]

[0233] The fluid transfer device 805 (also referred to herein as a "transfer device") may be of any suitable shape, size, and / or configuration. In some implementations, the transfer device 805 may be configured to draw bodily fluid (e.g., blood) from a patient to and / or through the transfer device 805. Additionally, the transfer device 805 may be configured to transfer at least a portion of the drawn bodily fluid to one or more other devices, reservoirs, containers, vials, machines, tests, assays, etc., such as a rapid diagnostic test device 870 and / or one or more fluid collection devices (not shown in FIGS. 10, 11, and 12A-12D).

[0221]

[0234] The transfer device 805 includes at least a housing 810 and an actuator 850. The housing 810 of the device 805 may be of any suitable shape, size, and / or configuration. For example, in some embodiments, the housing 810 may be similar to and / or substantially the same as any of the housings 210, 310, 410, 510, 610, and / or 710 described above. In particular, the housing 810 has and / or forms an inlet 812 and an outlet 813. The housing 810 may form and / or define an actuator chamber 814, a fluid flow path 815, and an isolation chamber 830. The inlet 812 may be any suitable inlet or port and may be configured to establish fluid communication between the housing 810 and a body fluid source (e.g., a patient). As shown in FIG. 11, the inlet 812 is in fluid communication with the actuator chamber 814, which in turn is in fluid communication with the fluid flow path 815 and the isolation chamber 830. Outlet 813 may be any suitable outlet or port and may be configured to establish fluid communication between housing 810 and a fluid collection device (not shown in FIGS. 10-12D ), such as any of those described in detail above. Outlet 813 is in fluid communication with fluid flow path 815. Additionally, outlet 813 is configured in selective fluid communication with isolation chamber 830 via flow controller 840, as described in more detail herein.

[0222]

[0235] As described in further detail herein, isolation chamber 830 may be configured to receive a flow and / or amount of bodily fluid from inlet 812 and isolate (e.g., separate, block, contain, hold, isolate, etc.) at least a portion of the flow and / or amount of bodily fluid within isolation chamber 830. Isolation chamber 830 may have any suitable shape, size, and / or configuration. For example, in some embodiments, isolation chamber 830 and / or at least a portion thereof may be substantially similar in form and / or function to isolation chambers 330, 430, 630, and / or 730, described in detail above. Accordingly, portions and / or aspects of isolation chamber 830 will not be described in further detail herein.

[0223]

[0236] Flow controller 840 is at least partially disposed within housing 810 and configured to control, direct, and / or otherwise facilitate selective flow of fluid through at least a portion of housing 810, at least a portion of fluid flow path 815, and / or at least a portion of isolation chamber 830. Flow controller 840 may be configured to facilitate displacement of fluid within one or more portions of housing 810, which may in some cases enable or create a pressure differential and / or pressure equalization across one or more portions of housing 810. In this context, the fluid flow may be a liquid, such as, for example, water, oil, dampening fluid, body fluid, and / or any other suitable liquid, and / or a gas, such as air, oxygen, carbon dioxide, helium, nitrogen, ethylene oxide, and / or any other suitable gas.

[0224]

[0237] The flow controller 840 may be of any suitable shape, size, and / or configuration. In some embodiments, the flow controller 840 may be similar to and / or substantially the same as the flow controller 340 described in detail above with reference to FIG. 4. For example, the flow controller 840 may be configured to transition from a first state to a second state in response to a pressure differential, suction, contact, and / or bodily fluid flow, etc. More specifically, in the embodiment shown in FIGS. 10-12D, the flow controller 840 may be a member or device formed of an absorbent or semi-permeable material configured to be permeable to the flow of gas or air and impermeable to the flow of liquid (e.g., blood or other bodily fluid) when in the first state, and impermeable to both gas and liquid when in the second state. Accordingly, the flow controller 840 and / or aspects or portions thereof will not be described in further detail herein.

[0225]

[0238] The actuator 850 of the device 805 may be of any suitable shape, size, and / or configuration. For example, the actuator 850 may be any suitable member or device configured to transition between any number of states (e.g., two, three, four, or more) and in any suitable manner (e.g., user actuation, automatic actuation, mechanical actuation, electronic actuation, chemical actuation, etc.). In some embodiments, the actuator 850 and / or aspects or portions thereof may be similar to and / or substantially the same as the actuators 150, 250, 350, 450, 650, and / or 750, described in detail above. As shown in FIG. 11 , the actuator 850 forms and / or includes a rod that is at least partially movably disposed within a portion of the actuator chamber 814 of the housing 810. Additionally, the actuator 850 includes a set of seals 852 disposed at predetermined locations along the length of the actuator 850 (or rod) that may enable the actuator 850 to control, guide, and / or otherwise facilitate selective flow of fluid through at least a portion of the housing 810. As described in further detail herein, the actuator 850 includes a set of four seals 852 positioned at desired locations along the length of the actuator 850 (or rod) to selectively control the flow of fluid from the inlet 812 to at least one of the isolation chamber 830, the rapid diagnostic test device 870, and / or the fluid flow path 815. Furthermore, the placement of the seals 852 can also enable the actuator 850 to isolate the isolation chamber 830, the rapid diagnostic test device 870, and / or the fluid flow path 815 when the actuator 850 is transitioned between two or more states.

[0226]

[0239] While the rapid test devices included in the embodiments discussed above are shown and / or described as being coupled to a housing 810, in the embodiment shown in FIGS. 10-12D, the rapid test device 870 is disposed within and / or incorporated into the housing 810. The rapid diagnostic test device 870 (also referred to herein as a "rapid test device" or simply a "test device") may be any suitable test device. For example, the rapid test device 870 and / or aspects or portions thereof may be substantially similar to the rapid test devices 170, 270, 370, 470, 570, 670 and / or 770 described in detail above. In some implementations, the rapid test device 870 may be an LFA, or the like, as described in detail above with reference to the LFA 170A shown in FIG. 2.

[0227]

[0240] 11, the rapid test device 870 includes at least a sample element 872 disposed on an end portion of a substrate 871, a conjugate element 873 disposed on the substrate 871 downstream of the sample element 872, a capture element 874 disposed on the substrate 871 downstream of the conjugate element 873, and a control element 875 disposed on the substrate 871 downstream of the capture element 874. The rapid test device 870 may be disposed within a housing 810 such that the capture element 874 and the control element 875 can be observed from outside the housing 810, such as through an observation opening 819. Additionally, the housing 810 and / or the rapid test device 870 include and / or are coupled to a buffer actuator 880 that contains a quantity of a buffer solution 881. In some embodiments, the buffer actuator 880 may be a blister pack, a frangible or pierceable container, a reservoir including one or more reconfigurable portions (e.g., one or more valves or flow controllers), or the like. As described in further detail herein, the buffer actuator 880 can be actuated to provide a flow of buffer solution 881 to the sample element 872 of the rapid test device 870, which flow of buffer solution 881 can further mix with a quantity of bodily fluid transferred to the sample element 872.

[0228]

[0241] The system 800 may be used to obtain one or more quantities of bodily fluid from a patient, which may be used in one or more tests, assays, and / or diagnostic procedures. As described above, for example, the inlet 812 may be in fluid communication with a bodily fluid source. As shown in FIG. 11 , when the inlet 812 is in fluid communication with a bodily fluid source (e.g., a portion of a patient), the actuator 850 may be in a first state, thereby establishing fluid communication between the inlet 812 and the isolation chamber 830. More specifically, when the actuator 850 is in the first state, the inlet 812 and the isolation chamber 830 may be in fluid communication with a portion of the actuator chamber 814 defined between two of the seals 852 of the actuator 850. For example, a first seal 852 (e.g., an end seal) disposed at or near an end portion of the actuator 850 may be disposed in the actuator chamber 814 at a position between the rapid test device 870 and the isolation chamber 830, and a second seal 852 adjacent (or closest to) the first or end seal 852 may be disposed in the actuator chamber 814 between the inlet 812 and the fluid flow path 815. Thus, as shown in FIG. 11 , when the actuator 850 is in the first state, the inlet 812 is in fluid communication with the isolation chamber 830.

[0229]

[0242] In the embodiment shown in FIGS. 10-12D, when the inlet 812 is fluidly connected to a source of bodily fluid (e.g., a portion of a patient), the outlet 813 can be fluidly coupled to a fluid collection device, such as any of those described herein. For example, the fluid collection device can be any suitable reservoir, container, and / or device configured to receive a quantity of bodily fluid. In some embodiments, the fluid collection device can be a vacuum reservoir or container that defines a negative pressure and / or can be a syringe that is operated to generate a negative pressure. Thus, coupling the fluid collection device to the outlet 813 selectively exposes at least a portion of the fluid flow path 815 to a negative pressure and / or suction force within the fluid collection device.

[0230]

[0243] The actuator 850 is configured to be in a first state when a fluid collection device is fluidly coupled to the outlet 813. As shown in FIG. 12A, the fluid flow path 815 is in fluid communication with a portion of the actuator chamber 814 defined between a seal 852 (e.g., second from the bottom) disposed between the inlet 812 and the fluid flow path 815 and an adjacent seal 852 (e.g., third from the bottom) disposed on the opposite side of the fluid flow path 815. In this manner, the fluid flow path 815 fluidly communicates the outlet 813 with a portion of the actuator chamber 814 that is isolated and / or fluidically separated by the seals 852 disposed on either side of the fluid flow path 815. As described above, the outlet 813 and / or the fluid flow path 815 are also in fluid communication with the flow controller 840, which may be in its first state when a fluid collection device is coupled to the outlet 813.

[0231]

[0244] The configuration of the flow controller 840 (e.g., the selectively permeable member) may be such that air or gas flow is permitted to pass through the flow controller 840 between the outlet 813 (and / or fluid flow path 815) and the isolation chamber 830, but liquid (e.g., body fluid) flow is not permitted to pass through the flow controller 840. As a result, as described in detail above with reference to the transfer device 305, at least a portion of the negative pressure differential or suction force generated by the fluid collection device may be transferred to and / or through the isolation chamber 830, and further serves to draw an initial amount of body fluid from the body fluid source through the inlet 812, a portion of the actuator chamber 814 defined between the two corresponding seals 852, and into the isolation chamber 830.

[0232]

[0245] The initial amount of bodily fluid may be any suitable amount of bodily fluid, such as any of the volumes or amounts described above. For example, in some cases, the actuator 850 and / or the transfer device 805 may remain in a first state or configuration until a predetermined and / or desired amount (e.g., an initial amount) of bodily fluid is transferred to the isolation chamber 830. In some embodiments, the initial amount may be related to and / or based at least in part on a volume of the isolation chamber 830 or a portion thereof (e.g., an amount sufficient to fill the isolation chamber 830 or a desired portion of the isolation chamber 830). In some embodiments, the transfer device 805 may be configured to transfer a flow of bodily fluid (e.g., an initial amount) to the isolation chamber 830 until the flow controller 840 transitions to its second configuration. In other words, in some embodiments, transferring the initial amount of bodily fluid to the isolation chamber 830 may function to place the flow controller 840 in its second state or configuration. For example, as described in detail above with reference to flow controller 340, transferring an initial amount of bodily fluid to isolation chamber 830 may be such that at least a portion of the initial amount wets and / or saturates flow controller 840, thereby further placing flow controller 840 in its second state. As shown in Figures 12A and 12B, the initial amount of bodily fluid may be sufficient to substantially fill isolation chamber 830 such that at least a portion of the initial amount is disposed within actuator chamber 814 between two seals 852 (e.g., two bottom seals 852).

[0233]

[0246] When the flow controller 840 transitions to its second state and / or configuration, the flow controller 840 isolates and / or fluidly isolates the isolation chamber 830 from the outlet 813. Thus, the negative pressure and / or suction force generated by the fluid collection device no longer acts on or within the isolation chamber 830. In some cases, this may allow the pressure differential between the isolation chamber 830 and the inlet 812 to substantially equalize and / or decrease below a desired threshold. In some cases, the pressure equalization may be such that the flow of bodily fluid into the isolation chamber 830 stops.

[0234]

[0247] Actuator 850 may be transitioned from its first state (FIGS. 11 and 12A) to its second state (FIGS. 12B and 12C) after an initial amount of bodily fluid is contained within isolation 830, thereby transitioning transfer device 805 from its first state to its second state. As discussed above with reference to transfer device 605, transition of actuator 850 from the first state to the second state may be in response to an initial amount of bodily fluid being disposed within isolation chamber 830, in response to the equalization of one or more pressure differentials, etc. In some cases, the transition may be automatic or in response to an applied force (e.g., as indicated by the arrow in FIG. 12B).

[0235]

[0248] 12B, when in the second state or configuration, the actuator 850 can be positioned within the actuator chamber 814 such that the seal 852 is in a desired position relative to the rapid test device 870, the isolation chamber 830, the inlet 812, and the fluid flow path 815. For example, the isolation chamber 830 is in fluid communication with a portion of the actuator chamber 814 that is disposed between the seal 852 disposed between the rapid test device 870 and the isolation chamber 830 and the seal 852 disposed between the isolation chamber 830 and the inlet 812. Thus, when the flow controller 840 is in its second state and the actuator 850 is transitioned to its second state, the isolation chamber 830 is isolated and / or fluidically decoupled from other portions of the transfer device 805 (see, e.g., FIGS. 12B-12D). In other words, the actuator 850 (and flow controller 840) can isolate and / or decouple the isolation chamber 830 from the inlet 812, the outlet 813, the fluid flow path 815, and the rapid test device 870. In some cases, isolating an initial volume of bodily fluid within the isolation chamber 830 can also isolate contaminants in the initial volume.

[0236]

[0249] 12C, when in the second state or configuration, the actuator 850 also establishes fluid communication between the inlet 812 and the outlet 813 via the fluid flow path 815 and a portion of the actuator chamber 814. For example, in some embodiments, the inlet 812 and the fluid flow path 815 are each in fluid communication with a portion of the actuator chamber 814 disposed between a corresponding pair of seals 852 (e.g., the upper pair of seals 852). Thus, in response to negative pressure and / or suction forces generated by the fluid collection device, one or more subsequent quantities of bodily fluid can flow from the inlet 812, through a portion of the actuator chamber 814 and the fluid flow path 815, through the outlet 813, and to a fluid collection device (not shown). As described above, isolating an initial quantity of bodily fluid within the isolation chamber 830 reduces and / or substantially eliminates the amount of contaminants in the one or more subsequent quantities prior to collecting or obtaining the one or more subsequent quantities of bodily fluid.

[0237]

[0250] 12C, when the actuator 850 is in a second state or configuration, the rapid test device 870 can be in fluid communication with a portion of the actuator chamber 814 disposed between a corresponding pair (e.g., a pair of ends) of the seals 852 to allow a portion of the initial amount of bodily fluid disposed in the actuator chamber 814 between the pair of seals 852 to be transferred into or onto the sample element 872 of the rapid test device 870. As shown in FIG. 12D, the transfer device 805 can be transitioned from its second state to its third state by manipulating and / or engaging the buffer actuator 880 to transition the buffer actuator 880 from its first state to its second state to transfer at least a portion of the buffer solution 881 contained within the buffer actuator 880 into or onto the sample element 872. For example, the buffer actuator 880 can include a frangible portion that can be broken and / or punctured in response to a force applied to the buffer actuator 880 by a user. 12D, the rapid test device 870 and / or the housing 810 may include a piercing member 882 or the like that may be configured to rupture, puncture, and / or otherwise open a buffer solution. In such an embodiment, the piercing member 882 may define an internal cavity that may be in fluid communication with the sample element 872. Thus, a force applied to the buffer actuator 880 may function to transfer at least a portion of the buffer solution 881 into and / or onto the sample element 872. Additionally, an amount of bodily fluid may also be transferred to the sample element 872 such that the bodily fluid and the buffer solution 881 may begin to mix.

[0238]

[0251] In some embodiments, a test and / or assay of or on the bodily fluid may be initiated by mixing the bodily fluid with buffer solution 881 in or on sample element 872, as described in detail above with reference to rapid test device 270. Furthermore, rapid test device 870 may be configured to perform any suitable test and / or assay. In some embodiments, buffer solution 881 may be based at least in part on the test to be performed. For example, in some cases, rapid test device 870 may be configured to test for the presence of lactate and / or PCT, as described in detail above. Furthermore, upon completion of a test or assay, rapid test device 870 may be configured to output a test result, which may be detected and / or evaluated. For example, in some cases, a person may view capture element 874 and / or control element 875 through a viewing opening 819 defined by housing 810. In other embodiments, an electronic device may perform one or more scans of capture element 874 and / or control element 875 through viewing opening 819. In other embodiments, one or more electronic devices may be incorporated and / or positioned within housing 810 without the need for human observation of capture element 874 and / or control element 875.

[0239]

[0252] As described in detail above, in some implementations, the configuration of the rapid test device 870 may be such that the tests and / or assays performed by the rapid test device 870 are not susceptible to such contamination. This means that the accuracy of the test result output by the rapid test device 870 is not affected by contamination that may be present in the initial amount of bodily fluid, as described in detail above. Thus, as described above with reference to systems 100, 200, 300, 400, 600 and / or 700, system 800 may be configured to obtain an initial amount of bodily fluid that may be used in rapid tests that are relatively less sensitive to contamination and subsequent amounts of bodily fluid that may be used in tests that are relatively more sensitive to contamination.

[0240]

[0253] 13-16 show at least a portion of a fluid transfer and assay system 900 according to one embodiment. The fluid transfer and assay system 900 (also referred to herein as a "system") may include at least a fluid transfer device 905 and a rapid diagnostic test device 970. Portions and / or aspects of the system 900 may be similar and / or substantially the same as systems (or devices) 100, 200, 300, 400, 500, 600, 700 and / or 800, described in detail above. Accordingly, such portions and / or aspects will not be described in further detail herein.

[0241]

[0254] The fluid transfer device 905 (also referred to herein as a "transfer device") may be of any suitable shape, size, and / or configuration. In some implementations, the transfer device 905 may be configured to draw bodily fluid (e.g., blood) from a patient to and / or through the transfer device 905. Additionally, the transfer device 905 may be configured to transfer at least a portion of the drawn bodily fluid to one or more other devices, reservoirs, containers, vials, machines, tests, assays, etc., such as a rapid diagnostic test device 970 and / or one or more fluid collection devices (not shown in FIGS. 13-16). In some implementations, the transfer device 905 and / or aspects or portions thereof may be substantially similar to any of the transfer devices 105, 205, 305, 405, 505, 605, 705, and / or 805 described in detail above.

[0242]

[0255] For example, the transfer device 905 includes at least a housing 910 and an actuator 950. The housing 910 has and / or forms an inlet 912 and an outlet 913. The inlet 912 may be any suitable inlet or port and may be configured to establish fluid communication between the housing 910 and a bodily fluid source (e.g., a patient). The outlet 913 may be any suitable outlet or port and may be configured to establish fluid communication between the housing 910 and a fluid collection device (not shown in FIGS. 13-16 ), such as any of those described in detail above. Additionally, the housing 910 includes and / or defines a port 925 that may be configured to establish fluid communication between at least a portion of the housing 910 and / or one or more reservoirs or chambers disposed within the housing 910 and, for example, a rapid diagnostic test device 970. In some embodiments, the port 925 may be substantially similar in form and / or function to the port 525 described above with reference to FIGS. 6A-6D . As such, the housing 910 and / or portions or aspects thereof may be similar and / or substantially the same as any of the housings 210, 310, 410, 510, 610, 710 and / or 810 described above and will not be described in further detail herein.

[0243]

[0256] The actuator 950 is at least partially disposed within the housing 910. The actuator 950 of the device 905 may be of any suitable shape, size, and / or configuration. For example, the actuator 950 may be a member or device configured to transition between two or more states to control, guide, and / or otherwise facilitate the selective flow of fluid through at least a portion of the housing 910. Furthermore, the actuator 950 may be actuated and / or transitioned between any number of states in any suitable manner. In the embodiment shown in FIGS. 13-16, the actuator 950 may be transitioned between at least a first state and a second state. When in the first state, the actuator 950 may be configured to allow an initial amount of bodily fluid to flow from the inlet 912 to an initial or first portion of the housing 910, such as an isolation chamber, such as those described in detail above with reference to the isolation chambers 330, 430, 630, 730, and / or 830. In some embodiments, when the actuator 950 is in a first state, it can be configured to isolate, separate, disconnect, and / or otherwise prevent fluid communication between the outlet 913 and the inlet 912 and / or the outlet 913 and the initial or first portion of the housing 910. When the actuator 950 is in a second state, it can be configured to allow a subsequent amount of body fluid (e.g., an amount of body fluid after the initial amount of body fluid) to be transferred from the inlet 912 through at least a portion (e.g., a second portion) of the housing 910 to the outlet 913 (and / or a fluid collection device fluidly coupled to the outlet 913). Further, when actuator 950 is in the second state, it may be configured to isolate, separate, disconnect, and / or otherwise prevent fluid communication between the initial or first portion of housing 910 and inlet 912, outlet 913, and / or one or more other portions of housing 910.As such, actuator 950 and / or portions or aspects thereof may be substantially similar to any of actuators 250, 350, 450, 650, 750 and / or 850 described in detail above and will not be described in further detail herein.

[0244]

[0257] The rapid diagnostic test device 970 (also referred to herein as a "rapid test device" or simply a "test device") may be any suitable test device. For example, the test device 970 and / or aspects or portions thereof may be substantially similar to the rapid test devices 170, 270, 370, 470, 570, 670, 770 and / or 870 described in detail above. In some implementations, the rapid test device 970 may be an LFA, or the like, as described in detail above with reference to the LFA 170A shown in FIG. 2. For example, the rapid test device 970 includes at least a sample element 972 disposed on an end portion of a substrate 971, a conjugate element 973 disposed on the substrate 971 downstream of the sample element 972, a capture element 974 disposed on the substrate 971 downstream of the conjugate element 973, and a control element 975 disposed on the substrate 971 downstream of the capture element 974.

[0245]

[0258] The rapid test device 970 also includes a housing 983 configured to contain and / or accommodate at least a portion of the rapid test device 970 and a test device actuator 986 configured to selectively establish fluid communication between the rapid test device 970 and the housing 910. In some embodiments, the rapid test device 970 may be configured as a substantially modular device that may be coupled and / or attached to any suitable fluid transfer device, tube, reservoir, mechanism, transfer adapter, or the like. In some implementations, the modular configuration of the test device 970 may allow the transfer device 905 and the test device 970 to be manufactured and / or shipped separately and coupled and / or assembled at the time of use. In some implementations, the modular configuration of the test device 970 may allow various types of test devices 970 to fit into the transfer device 905, with each type of test device 970 configured to perform a different test or assay. In other words, the modular configuration of the test device 970 may allow different styles of test device 970 to test for different biomarkers while maintaining substantially the same form factor and / or compatibility.

[0246]

[0259] As shown in FIGS. 14-16, the housing 983 may be of any suitable shape, size, and / or configuration. In some embodiments, the housing 983 of the inspection device 970 may be configured to be coupled to a portion of the housing 910 of the transfer device 905. The housing 983 includes, contains, and / or defines a vent 985 configured to allow air or gas flow to exit the housing 983. As described in detail above with reference to the transfer device, in some implementations, venting the housing 983 of the inspection device 970 may facilitate fluid flow through the inspection device 970 (e.g., along the substrate 971). Additionally, the housing 983 includes and / or defines an observation opening 984. As shown in FIGS. 14 and 15, the inspection device 970 may be positioned within the housing 983 such that at least the capture element 974 and / or the control element 975 are visible and / or detectable through the observation opening 984.

[0247]

[0260] The testing device actuator 986 is movably coupled to the housing 983 of the testing device 970 and is configured to transition between a first state and a second state to establish fluid communication between the transfer device 905 and the testing device 905. For example, in some embodiments, the testing device actuator 986 may be a spring-loaded button, which may include a piercing member 987, or the like. The testing device 970 and / or the housing 983 of the testing device 970 may include and / or form a septum 988. Further, the testing device actuator 986 may be aligned with the septum 988. In some implementations, the testing device actuator 986 may be configured such that the puncture member 987 is positioned on a first side of the septum 988 and within the housing 983 of the testing device 970 when the testing device actuator 986 is in a first state (see, for example, FIG. 15 ), and such that the puncture member 987 extends through the septum 988 and out of the housing 983 of the testing device 970 when the testing device actuator 986 is in a second state (not shown in FIGS. 13-16 ).

[0248]

[0261] The testing device 970 and / or its housing 983 are configured to couple to the housing 910 of the transfer device 905 such that the testing device actuator 986 is substantially aligned with the port 925 contained within and / or formed by the housing 910. Thus, when the testing device actuator 986 transitions to its second state, the piercing member 987 can extend into the septum 988 of the testing device 970 and the port 925 of the transfer device 905 to establish fluid communication between the testing device 970 and the transfer device 905. In this manner, the piercing member 987 can receive at least a portion of an initial amount of bodily fluid disposed within the transfer device 905 (e.g., by capillary action, pressure differential, and / or any other fluid transfer modality). As shown in FIG. 15, the piercing member 987 is in fluid communication with a portion of the substrate 971, such as the sample element 972. Thus, a flow of bodily fluid may be transferred from a portion of the transfer device 905 (eg, a portion of the housing, isolation chamber, etc.) to the sample element 972.

[0249]

[0262] Although not shown in FIGS. 13-16 , in some implementations, the test device 970 may be configured to transport a buffer solution or the like along with a volume of bodily fluid to the sample element 972 (e.g., as described above with reference to the test device 870). In such implementations, the buffer solution may be mixed with a volume of bodily fluid, and the mixture may flow along the substrate 971 for testing, as described in detail above. In some implementations, the rapid test device 970 may be configured to test for the presence of lactate and / or PCT, which may be indicative of a patient condition, such as sepsis. Furthermore, upon completion of the test or assay, the rapid test device 970 may be configured to output a test result. The test result may be detected and / or evaluated. For example, in some cases, a person may view the capture element 974 and / or the control element 975 through a viewing opening 984 defined by a housing 983 of the test device 970. In other embodiments, an electronic device may perform one or more scans of the capture element 974 and / or the control element 975 through the viewing opening 984. In other embodiments, one or more electronic devices may be incorporated and / or positioned within the housing 910 without the need for human observation of the capture element 974 and / or the control element 975.

[0250]

[0263] In addition to transferring a quantity of bodily fluid to the rapid test device 970, in some cases, transfer device 905 may be configured to transfer one or more subsequent quantities of bodily fluid to any suitable device, reservoir, test, etc. coupled to outlet 913. Thus, as described above with reference to systems 100, 200, 300, 400, 600, 700 and / or 800, system 900 may be configured to obtain an initial quantity of bodily fluid that may be used in a rapid test (e.g., relatively less sensitive to contamination) and a subsequent quantity of bodily fluid that may be used in a subsequent test (e.g., relatively more sensitive to contamination).

[0251]

[0264] 17-20 show various examples of fluid transfer and assay systems and / or devices according to various embodiments. For example, FIG. 17 shows a fluid transfer and assay system 1000 (also referred to herein as a "system"). System 1000 may be substantially similar in form and / or function to system 900 described above with reference to FIGS. 13-16. Although port 925 of transfer device 905 is shown in FIG. 14 as being located at or near an end portion of housing 910, in the embodiment shown in FIG. 17, the transfer device included in system 1000 may include and / or form a port located proximate or adjacent to its inlet. In this manner, the flow of bodily fluid through a rapid test device coupled to a transfer device of system 1000 may be substantially counter-directional relative to the flow of bodily fluid through rapid test device 970 described above with reference to FIGS. 13-17, for example.

[0252]

[0265] FIG. 18 illustrates a fluid transfer and assay system 1100 (also referred to herein as a "system"). In this embodiment, the system 1100 includes an "in-line" rapid diagnostic test device. For example, in some embodiments, the system 1100 may include an in-line rapid diagnostic test device included and / or coupled to an inlet tube, an outlet tube, and / or any other suitable portion of the system 1100. In some implementations, the in-line rapid test device included in the system may receive a flow of bodily fluid and may perform a test or assay as described in detail above. Additionally, in some cases, the in-line rapid test device may include one or more flow-through or bypass mechanisms, etc. (e.g., automatic or manually actuated mechanisms) that may allow the flow of bodily fluid to pass through the in-line rapid test device after receiving an initial amount of bodily fluid. Thus, the in-line rapid test device may perform one or more tests or assays on the initial amount of bodily fluid while a subsequent amount of bodily fluid continues to flow through the system 1100.

[0253]

[0266] FIG. 19 illustrates a fluid transfer and assay system 1200 (also referred to herein as a "system"). In this embodiment, the system 1200 includes a fluid transfer device configured as a syringe. In some embodiments, the syringe can be, for example, a standard syringe configured to withdraw a volume of bodily fluid. In other embodiments, the syringe can be, for example, a syringe configured to withdraw and isolate an initial volume of bodily fluid before withdrawing a "sample volume" of bodily fluid. For example, such a syringe can be similar and / or substantially the same as any of those described in the '495 patent and / or the '006 publication incorporated by reference above. As shown in FIG. 19, the system 1200 can include a rapid diagnostic test device that can be coupled to any suitable portion of the syringe and in fluid communication with its internal volume. In embodiments in which the syringe is configured to withdraw and isolate an initial volume of bodily fluid, the rapid test device can be coupled to the syringe such that fluid communication is established between the isolated portion of the syringe and the rapid test device. As such, system 1200 may be similar to at least systems 300, 400, 600, 700 and / or 800, described in detail above.

[0254]

[0267] FIG. 20 illustrates a fluid transfer and assay system 1300 (also referred to herein as a "system"). In this embodiment, the system 1300 includes a fluid transfer device fluidly coupled to, for example, a syringe. As described above with reference to at least systems 200, 300, and 800, the system 1300 may include a fluid transfer device configured to draw an initial amount of bodily fluid to an isolation chamber, and to draw a subsequent amount of bodily fluid in response to, for example, a negative pressure differential generated by a fluid collection device or the like. While some of the embodiments are described herein as being coupled to a vacuum container (e.g., a Vacutainer®, etc.), the embodiment illustrated in FIG. 20 is configured to be coupled to a syringe that can be operated to generate a negative pressure differential. Additionally, the fluid transfer device illustrated in FIG. 20 is configured to be coupled to a rapid test device, such as any of those described herein. In this manner, the system 1300 may be similar in form and / or function to any of the systems detailed herein.

[0255]

[0268] Although various embodiments have been described above, it should be understood that they are presented by way of example only and not limitation. For example, while some of the embodiments are described herein as being used to obtain bodily fluids for one or more assays, tests, etc., it should be understood that the embodiments are not limited to such uses. Any of the embodiments and / or methods described herein may be used to transfer a flow of bodily fluid to any suitable device in fluid communication therewith. Thus, although specific examples are described herein, it is not intended that the devices, methods, and / or concepts be limited to such specific examples.

[0256]

[0269] While embodiments have been particularly shown and described, it will be understood that various changes in form and detail may be made. Where the drawings and / or embodiments show particular components disposed in particular orientations or locations, the arrangement of the components may be modified. Although various embodiments have been described as having particular features, concepts, and / or combinations of components, other embodiments are possible having any combination or subcombination of any of the features, concepts, and / or components of any of the embodiments described herein.

[0257]

[0270] The specific configuration of the various components may also be modified. For example, the size and specific shape of the various components may differ from the illustrated embodiment while still providing the functionality described herein. In some embodiments, modifying the size and / or shape of such components may reduce the overall size of the device and / or enhance the ergonomics of the device without changing the functionality of the device. In some embodiments, the size and / or shape of the various components may be specifically selected for a desired or intended use. For example, in some implementations, a device configured for use in or with a supposedly healthy adult patient may be configured to obtain a first amount of bodily fluid, while a device configured for use in or with, for example, a seriously ill and / or pediatric patient may be configured to obtain a second amount of bodily fluid that is less than the first amount. Thus, unless the context dictates otherwise, it should be understood that the size, shape and / or configuration of the embodiments and / or their components may be adapted for a given application.

[0258]

[0271] The embodiments and / or portions thereof described herein may include components formed of one or more parts, features, structures, etc. When referring to such components, it should be understood that the components may be formed by a single part having any number of sections, regions, portions, and / or properties, or may be formed by multiple parts or features. When referring to a structure such as, for example, a wall or a chamber, the structure may be considered as a single structure having multiple parts, or multiple sub-structures that are joined to form the structure, etc. Thus, a monolithically constructed structure may include, for example, a series of sub-structures. Such a series of sub-structures may include multiple parts that are either continuous or discontinuous with each other. A series of sub-structures may also be fabricated from multiple articles or components that are made separately and later joined together (e.g., via welds, adhesives, or any suitable method).

[0259]

[0272] Any of the embodiments described herein may be used with any suitable diagnostic testing device or machine, rapid diagnostic testing device, assay device (e.g., lateral flow assay device), etc. Any of the embodiments described herein may include and / or be used with any suitable fluid transfer device, fluid collection device, and / or fluid storage device, such as, for example, sample reservoirs, vessels, containers, bottles, adapters, dishes, vials, syringes, and / or devices (e.g., including micro- and / or nano-configurations thereof). Additionally, any of the embodiments described herein may incorporate, include, and / or be used in conjunction with any suitable fluid transfer devices, transfer adapters, and / or components thereof, such as any of the devices and / or components described in the '420 patent, the '783 patent, the '244 application, the '510 publication, the '117 publication, the '241 patent, the '724 patent, the '495 patent, the '006 publication, the '999 application, the '074 publication, the '380 application, and / or the '477 application, the disclosures of which are incorporated herein by reference in their entireties.

[0260]

[0273] While some of the above-described embodiments include a flow controller and / or actuator that physically and / or mechanically isolates one or more portions of the fluid transfer device, in other embodiments, the fluid transfer device does not need to physically and / or mechanically isolate one or more portions of the fluid transfer device. For example, in some embodiments, an actuator such as any of those described herein can be transitioned from a first state in which an initial amount of bodily fluid can flow from an inlet to an isolated chamber or portion to a second state in which (1) the isolated chamber or portion is physically and / or mechanically isolated and (2) the inlet is in fluid communication with an outlet of the fluid transfer device. However, in other embodiments, the actuator and / or any other suitable portion of the fluid transfer device can be transitioned from a first state in which an initial amount of bodily fluid can flow from an inlet to an isolated chamber or portion to a second state in which the inlet is in fluid communication with the outlet without physically and / or mechanically isolating (or decoupling) the isolated chamber or portion. When such a transport device is in a second state, one or more features and / or geometric shapes of the transport device can provide preferential flow of bodily fluid from the inlet to the outlet, and an initial amount of bodily fluid can be retained in the isolation chamber or portion without being physically and / or mechanically isolated or separated.

[0261]

[0274] Although not shown, any of the devices described herein may include an opening, port, coupler, septum, luer lock, gasket, valve, threaded connector, standard fluid interface, etc. (referred to as a "port" for simplicity) in fluid communication with the isolation chamber; in some such embodiments, the port may be configured to couple to and / or receive any suitable device, reservoir, pressure source, testing device, etc. For example, in some embodiments, the port may be configured to couple to any of the rapid diagnostic testing devices described herein. In some embodiments, the port may be coupled to a negative pressure source, such as a vacuum container, pump, syringe, etc., to collect a portion or the entire amount of bodily fluid into the isolation chamber, channel, reservoir, etc., such that the amount of bodily fluid (e.g., a pre-sample volume) can be used for additional clinical and / or in vitro diagnostic testing purposes. In some embodiments, the isolation chamber may be configured with the addition of a rapid diagnostic testing component (e.g., any of the rapid diagnostic testing devices described herein) incorporated into the chamber, allowing at least a portion of the initial amount of bodily fluid to be used for that test. In still other embodiments, the isolation chamber and / or rapid test device coupled to or forming a portion of the isolation chamber is removable and may be designed, sized, and configured to fit testing equipment and / or be specifically accessible for other types of bodily fluid testing commonly performed on patients with suspected conditions (e.g., rapid diagnostic test devices described herein configured to test for sepsis, etc.). In some embodiments, the port (or the like) may be coupled to any suitable pressure source or infusion device configured to infuse at least a portion of the initial amount of bodily fluid sequestered within the isolation chamber back into the patient and / or bodily fluid source (e.g., in the case of pediatric patients, critically ill patients, patients with low blood volume, etc.).

[0262]

[0275] While some embodiments described herein include a rapid diagnostic test device coupled to or inserted into a portion of a fluid transfer device to receive a volume of bodily fluid for testing, in other embodiments, the rapid diagnostic test device may be incorporated into one or more portions of the transfer device. For example, any of the embodiments described herein may include an integrated transfer and assay device, such as the devices described above with reference to system 800. Although the rapid test device 870 is shown as being disposed or contained within the housing 810, in other embodiments, the rapid test device may form an external portion of the fluid transfer device and / or may be at least temporarily coupled to an external portion of the fluid transfer device.

[0263]

[0276] Although not shown, in some embodiments, the fluid transfer device may include one or more lumens, channels, flow paths, etc., configured to selectively allow a "bypass" flow of bodily fluid. An initial amount or volume of bodily fluid may flow from an inlet through a lumen, canal, flow path, etc., to a collection device to bypass the isolation chamber (or rapid test device). In some embodiments, the fluid transfer device may include an actuator having, for example, at least three states: a first state in which bodily fluid may flow from the inlet to the isolation chamber (or rapid test device), a second state in which bodily fluid may flow from the inlet to the outlet after the initial amount is isolated in the isolation chamber, and a third state in which bodily fluid may flow from the inlet through the bypass flow path to the outlet. In other embodiments, the transfer device may include a first actuator configured to transition the device between the first and second states, as described in detail above with reference to certain embodiments, and may include a second actuator configured to transition the device to a bypass configuration, etc. In still other embodiments, the transfer device may include any suitable device, feature, component, mechanism, actuator, control, etc., configured to selectively place the fluid transfer device in a bypass configuration or state.

[0264]

[0277] Although some methods are described herein as including steps recited in a particular order, in other embodiments, the order of certain events and / or steps in any of the methods or processes described herein can be modified, and such modifications are amenable to variations of the invention. Additionally, certain events and / or steps may be performed sequentially as described above, as well as simultaneously in parallel processes where possible. Certain steps may be partially completed or omitted before proceeding to the next step.

[0265]

[0278] For example, although some devices are described herein as transitioning from a first state to a second state in a separate operation or the like, it should be understood that the devices described herein can be configured to transition from the first state to the second state automatically and / or passively, and such transition can occur over a period of time. In other words, the transition from the first state to the second state can be relatively gradual in some cases. For example, in some cases, the device can begin to transition from the first state to the second state when the last portion of the initial amount of bodily fluid (e.g., the initial or isolated portion thereof) is transferred to the device. In some cases, the rate of change when transitioning from the first state to the second state can be selectively controlled to achieve one or more desired characteristics associated with the transition. Furthermore, in some such examples, the inflow of the last portion of the initial amount can limit and / or substantially prevent bodily fluid already disposed in the initial or isolated portion from exiting the initial or isolated portion. Thus, while the transition from the first state to the second state can occur over a given amount of time, the initial or isolated portion of the device can still sequester the initial amount of bodily fluid disposed in the initial or isolated portion of the device.

[0266]

[0279] Some embodiments and / or methods described herein include one or more electronic devices configured to perform one or more processes included and / or associated with the fluid transfer and / or rapid diagnostic testing systems and methods described herein. An electronic device described herein (e.g., electronic device 190) may be any suitable hardware-based computing device configured to receive, process, define, and / or store data, such as, for example, one or more diagnostic test results, test criteria for measuring result data, predetermined and / or predefined treatment regimens, patient profiles, disease profiles, etc. In some cases, an electronic device may receive data related to a diagnostic test, assay, etc. (e.g., rapid test device 170) and may be configured to analyze, process, and / or otherwise use the data to generate one or more qualitative and / or quantitative test results associated with the test. In some cases, such tests may be, for example, tests for sepsis and / or any other disease condition.

[0267]

[0280] Examples of electronic devices and / or components thereof are provided below. While specific devices and / or components are described, it should be understood that they are presented by way of example only and not limitation. Any other suitable electronic device having any other suitable components capable of implementing the processes, procedures, and / or methods described herein may be used.

[0268]

[0281] The electronic devices described herein may be, for example, a mobile electronic device (e.g., a smartphone, a tablet, a laptop, and / or any other mobile or wearable device), a PC, a workstation, a server device or a distributed network of server devices, a virtual server or machine, a virtual private server running and / or operated as an instance or guest of a physical server or server group, etc., and / or any other suitable device. In some implementations, the electronic device may be configured to provide a graphical and / or digital representation of a test result generated by any of the rapid test devices described herein. Furthermore, in some implementations, the electronic device may be configured to determine and graphically or digitally present, based on data related to and / or indicative of the test result, one or more diagnoses, one or more treatment plans, one or more simulations, and / or any other suitable data related to the body fluid sample, the patient, and / or the patient's treatment.

[0269]

[0282] The components of the electronic device may be contained within a single housing or machine, or may be distributed within and / or among multiple physical machines, and / or any combination thereof. In some embodiments, the electronic device may be stored, operated, executed, and / or otherwise implemented in a cloud computing environment. In some embodiments, the electronic device may include and / or may collectively be formed by client or mobile devices (e.g., smartphones, tablets, wearable devices, etc.) and server or host devices that can communicate over one or more networks. Furthermore, the electronic device and / or any of its components may be included, housed, and / or incorporated in any of the fluid transfer devices and / or rapid diagnostic test devices described herein, or any suitable combination thereof.

[0270]

[0283] An electronic device included in the embodiments described herein may include at least a memory, a processor, and a communication interface. The memory, processor, and communication interface may be connected and / or electrically coupled (e.g., via a system bus, etc.) such that electrical and / or electronic signals may be transmitted between the memory, processor, and communication interface. As described in more detail herein, the electronic device may also include and / or be otherwise operatively coupled to a database and / or one or more user interfaces or input / output (I / O) devices.

[0271]

[0284] In some embodiments, the memory may be, for example, a random access memory (RAM), a memory buffer, a hard drive, a read only memory (ROM), an erasable programmable read only memory (EPROM), an electrically erasable read only memory (EEPROM), a flash memory, etc., or a suitable combination thereof. In some implementations, the memory may be physically contained and / or stored within or by the electronic device, or may be operatively coupled to the electronic device and / or at least its processor. In such implementations, for example, the memory may be included in and / or distributed across one or more devices, such as, for example, server devices, cloud-based computing devices, network computing devices, etc. The memory may be configured to store one or more software modules and / or code, which may include instructions that may cause the processor to perform, for example, one or more processes, functions, etc. (e.g., processes, functions, etc. associated with storing, analyzing, and / or presenting data associated with the fluid transfer and / or rapid diagnostic testing systems and methods described herein).

[0272]

[0285] The memory and / or at least a portion thereof may include and / or communicate with one or more data storage structures, such as, for example, one or more databases. The database may be any suitable data storage structure, such as, for example, a table, a repository, a relational database, an object-oriented database, an object-relational database, a Structured Query Language (SQL) database, an Extensible Markup Language (XML) database, etc. In some embodiments, the database may be located in a housing, a rack, and / or other physical structure that includes at least a memory, a processor, and / or a communication interface. In other embodiments, the electronic device may include and / or be operatively coupled to any number of databases. In some implementations, the database may be configured to store data related to the fluid transfer and / or rapid diagnostic testing systems and methods described herein.

[0273]

[0286] In some embodiments, the processor may be a hardware-based integrated circuit (IC) and / or any other suitable processing device configured to operate or execute a set of instructions and / or code stored, for example, in a memory. For example, the processor may be a general-purpose processor, a central processing unit (CPU), an accelerated processing unit (APU), an application specific integrated circuit (ASIC), a network processor, a front-end processor, a field programmable gate array (FPGA), a programmable logic array (PLA), etc. The processor may communicate with the memory (and any other components of the electronic device) via any suitable interconnect, system bus, circuitry, etc. The processor may include any number of engines, processing units, cores, etc. configured to execute codes, instructions, modules, processes, and / or functions associated with the fluid transfer and / or rapid diagnostic testing systems and methods described herein.

[0274]

[0287] In some embodiments, the communication interface may be any suitable hardware-based device that communicates with the processor and the memory and / or any suitable software stored in the memory and executed by the processor. In some implementations, the communication interface may be configured to communicate with a network and / or any suitable device that communicates with the network. The communication interface may include one or more wired and / or wireless interfaces, such as, for example, a network interface card (NIC), a universal serial bus (USB) card, and / or any other suitable communication and / or peripheral card or device. For example, in some implementations, a NIC may include, for example, one or more Ethernet interfaces, optical carrier (OC) interfaces, asynchronous transfer mode (ATM) interfaces, one or more wireless radios (e.g., WiFi® radios, Bluetooth® radios, near field communication (NFC) radios, etc.), and the like. In some implementations, the communications interface may be configured to transmit data to and / or receive data from (e.g., via one or more networks) any suitable portion or device included in the fluid transfer and / or assay devices and / or systems described herein, one or more peripheral components (e.g., readers, scanners, cameras, analyzers, detectors, input / output devices, etc.), a user or client device (e.g., a smartphone, tablet, wearable electronic device, PC, etc.), etc.

[0275]

[0288] In some implementations, the network may be any type of network, such as, for example, a local area network (LAN), a wireless local area network (WLAN), a virtual network such as a virtual local area network (VLAN), a wide area network (WAN), a metropolitan area network (MAN), a Worldwide Interoperability for Microwave Access (WiMAX), a telephone network (such as a public switched telephone network (PSTN) and / or a public land mobile network (PLMN)), an intranet, the Internet, a fiber optic (or fiber optic) based network, a cellular network, and / or any other suitable network. Furthermore, the network and / or one or more portions thereof may be implemented as a wired and / or wireless network. For example, the network may include one or more networks of any type, such as, for example, a wired or wireless LAN and the Internet. In some implementations, the network may be any suitable combination of devices connected and / or otherwise communicating via wired or wireless connections (e.g., a USB connection, an Ethernet connection, a WiFi network, a Bluetooth network, an NFC network, etc.).

[0276]

[0289] In some embodiments, the user interface may be a display or screen, such as, for example, a cathode ray tube (CRT) monitor, a liquid crystal display (LCD) monitor, a light emitting diode (LED) monitor, or the like. In some cases, the display may be a touch-sensitive display, or the like (e.g., a touch-sensitive display of a smartphone, a tablet, a wearable device, a PC, or the like). In some cases, the display may provide a user interface for a software application (e.g., a mobile application, a PC application, an Internet web browser, or the like) that may enable a user to operate the electronic device. In some implementations, the user interface may include any suitable type of human machine interface device, human computer interface device, batch interface, graphical user interface (GUI), or the like. In some implementations, the user interface may be any other suitable user interface and / or input / output (I / O) device, such as, for example, a holographic display, a wearable device such as a contact lens display, an optical head mounted display, a virtual reality display, an augmented reality display, a mouse, a keyboard, or the like, or a combination thereof. Thus, the electronic devices described herein can receive, process, define, and / or store data such as, for example, one or more diagnostic test results, test criteria for measuring result data, predetermined and / or predefined treatment regimens, patient profiles, disease profiles, etc. Additionally, the electronic devices can present (e.g., on its display) one or more qualitative and / or quantitative test results associated with any of the rapid diagnostic testing methods described herein (e.g., rapid diagnostic tests for sepsis and / or any other disease condition).

[0277]

[0290] Some embodiments described herein relate to computer storage products having a non-transitory computer-readable medium (e.g., a memory or one or more memories) having instructions or computer code for performing various computer-implemented operations. The computer-readable medium (or processor-readable medium) is non-transitory in the sense that it is essentially free of transient propagating signals (e.g., electromagnetic waves carrying information propagating through a transmission medium such as space or a cable). The medium and computer code (which may...

Claims

1. A flow-based assay device; a fluid transfer device having an inlet configured to be in fluid communication with a body fluid source and an outlet configured to be in fluid communication with a sample reservoir, the fluid transfer device including a sequestration chamber and a port in fluid communication with the sequestration chamber; Including, The isolation chamber is configured to be fluidly connected to the inlet via a first fluid flow path to receive a first amount of bodily fluid when the fluid transfer device is in a first state, the outlet is configured to be fluidly connected to the inlet via a second fluid flow path different from the first fluid flow path to receive a second amount of bodily fluid when the fluid transfer device is in a second state, the flow-based assay device is configured to be coupled to the port via a third fluid flow path different from the first and second fluid flow paths to receive a portion of the first amount of bodily fluid when the fluid transfer device is in a third state, and the flow-based assay device is configured to provide an indication related to the presence of a target analyte in the portion of the first amount of bodily fluid. system.

2. The system of claim 1 , wherein the first amount is isolated from the first fluid flow path when the fluid transfer device is in the second state.

3. The system of claim 2 , wherein the second amount of bodily fluid flows through the second fluid flow path, thereby bypassing the isolation chamber and the first amount of bodily fluid isolated within the isolation chamber.

4. The system of claim 1 , wherein the port is configured to transition from a closed state to an open state to place the fluid transfer device in the third state.

5. The system of claim 4 , wherein coupling the flow-based assay device to the port is operable to transition the port from the closed state to the open state.

6. The system of claim 1 , wherein the flow-based assay device is one of a sandwich lateral flow assay device or a competitive lateral flow assay device.

7. The system of claim 1 , wherein the bodily fluid is blood and the target analyte is a biomarker for detecting sepsis in the blood.

8. The system of claim 7 , wherein the biomarker is procalcitonin.

9. The system of claim 7 , wherein the biomarker is lactate.

10. The system of claim 9 , wherein the flow-based assay device comprises a conjugate element comprising a matrix of at least one of an enzyme, an antibody, or an aptamer.

11. The system of claim 10 , wherein the matrix comprises chitosan.

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