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

Abstract

To provide a system that includes a fluid transfer device and a flow-based assay device.SOLUTION: A system includes a fluid transfer device and a lateral flow assay device. The fluid transfer device has an inlet fluidically coupleable to a bodily fluid source, an outlet fluidically coupleable to a sample reservoir, and a sequestration chamber configured to receive an initial volume of bodily fluid. The fluid transfer device can be transitioned between (1) a first state with the sequestration chamber in fluid communication with the inlet to receive the initial volume, (2) a second state with the outlet in fluid communication with the inlet to receive a subsequent flow of bodily fluid, and (3) a third state with the lateral flow assay device in fluid communication with the sequestration chamber to receive a portion of the initial volume of bodily fluid. The lateral flow assay device is configured to provide an indication associated with the presence of a target analyte in the bodily fluid.SELECTED DRAWING: Figure 1

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 the acquisition of bodily fluid samples and point-of-care diagnostic testing, and more specifically to bodily fluid transfer devices having integrated flow-based assay systems, such as lateral flow assays, that enable 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 bodily 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 commonly results from a bacterial infection (or, less commonly, a 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. An excessive inflammatory response is typically followed by a period of immunosuppression. During the immunosuppression period, there is multiple organ dysfunction, making patients susceptible to hospital-acquired infections. Patients with sepsis typically present with fatigue, fever, chills, and leukocytosis, which can prompt physicians to evaluate the presence of bacteria in such patients' bloodstreams, typically through bacterial culture tests.

[0004] As bacterial culture testing and / or other advanced diagnostic technologies develop and improve, the speed, accuracy (both sensitivity and specificity), and value of the information that can be provided to clinicians continue to improve. Examples of such diagnostic technologies 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 technologies may be prone to contamination, which can 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 extraneous contaminants, outside the intended sample source that are unintentionally included in the bodily 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] While such diagnostic techniques can provide sensitive and / or specific information from testing clean or unadulterated bodily fluids, the tests often take anywhere from six hours to about five days or more to obtain results. Furthermore, known diagnostic techniques are often performed using systems that require highly trained personnel and / or often employ culture protocols specifically tailored for the identification of various bacterial species. Therefore, such culture methods and / or diagnostic techniques are not suitable for the 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 patients, 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] Embodiments and methods described herein relate to bodily fluid transfer devices with integrated flow-based assays (e.g., lateral flow assays) that enable initial 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 quantity 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 quantity 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 quantity 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 first quantity of the portion of the bodily fluid. [Brief explanation 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. [Figure 2]

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

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

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

[0012] FIG. 1 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] FIG. 13 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] FIG. 10 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 state. [Figure 9B] 13 is a cross-sectional view of the fluid transfer and assay device (or system) of FIG. 12 shown in a second state. [Figure 9C] 13 is a cross-sectional view of the fluid transfer and assay device (or system) of FIG. 12 shown in a third state. [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 state. [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 the 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 state. [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 INVENTION

[0009] Detailed Description

[0024] Any of the fluid transfer devices described herein can 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 can 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 can 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 can be a fluid diversion and / or isolation device configured to accept and isolate an initial volume 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 can be configured to accept at least a portion of the initial volume of bodily fluid or at least a portion of a subsequent sample volume. The integrated device for rapid diagnostic testing can be, for example, a lateral flow assay and / or any other suitable diagnostic testing device. The integrated device for rapid diagnostic testing can be used to test a volume of bodily fluid and provide at least a qualitative result. The qualitative result can further be output at or by a device for visual inspection. In other cases, the test device may communicate data related to the results (e.g., via a wired or wireless network) to an electronic device, which 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 can be included or incorporated into a fluid transfer device (e.g., a sample collection device) and used to provide initial test results of an acquired bodily fluid. The initial test results can 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") can provide an approach for performing 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.), which can inform clinician decisions regarding treatment strategies. In some implementations, the initial test device can test for bacterial and / or other infections that may lead to and / or otherwise result in sepsis, thereby allowing clinicians to provide prompt 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") specimen analysis (e.g., NGS) and related techniques, morphokinetic cell analysis, and / or other current, advanced, or developing techniques used to characterize patient specimens and / or to detect, identify, type, classify, and / or characterize specific organisms, antibiotic sensitivity, etc.

[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 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.

[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 fluidly connected to 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 state 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 flow gas to flow through the isolation chamber when 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 a 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, wherein a flow controller of the fluid transfer device allows a flow of gas but not a flow of body fluid through the flow controller to vent the isolation chamber during the receiving. After the first amount of body fluid has been received into the isolation chamber, transitioning the fluid transfer device from a first state to a second state. In response to the fluid transfer device being in the second state, establishing fluid communication between the inlet and outlet of the fluid transfer device and allowing the second amount of body fluid to flow to a sample reservoir fluidly connected to 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 fluidly connected to a bodily fluid source, an outlet configured to be fluidly connected to a sample reservoir, and an isolation chamber configured to receive an initial amount of bodily fluid. The fluid transfer device is configured to transition 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 on.

[0016]

[0031] As used herein, "body fluid" can include any fluid obtained directly or indirectly from a patient's body. For example, "body fluid" includes, but is not limited to, blood, cerebrospinal fluid, urine, bile, lymph, 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 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, a predetermined and / or desired presample volume of a bodily fluid such as blood can be a drop of blood, several 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 thereof therebetween. In other cases, the presample volume can be greater than 50 mL or less than 0.1 mL. As a particular example, the predetermined and / or desired presample volume can 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 the flow path from a bodily fluid source to an initial collection chamber, section, 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. A "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, a desired sample volume of bodily fluid may be from about 10 mL to about 60 mL. In other cases, a desired sample volume of bodily fluid may be less than 10 mL or more than 60 mL. In still other cases, a 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 constituent material, 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, polyester, polycarbonate, polyacrylate, polysiloxane (silicone), 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] 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 understand that changes can 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] Fluid transfer and assay system 100 (also referred to herein as "system") may include at least a fluid transfer device 105 and a rapid diagnostic test device 170. In some implementations, 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 into the transfer device 105. Furthermore, 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, 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 transfer device 105 (or through one or more portions of transfer device 105), and then transfer such amount or volume to one or more devices coupled to or integrated with transfer device 105, such as one or more sample reservoirs, containers, bottles, etc. For example, 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 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 transfer device 105. In some embodiments, as described in further detail herein with reference to specific embodiments, transfer device 105 and / or the isolated portion of transfer device 105 may be configured to isolate the first amount of bodily fluid (e.g., within the isolated portion of 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 to 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, septa, 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 can be configured to receive a first quantity of bodily fluid from the transfer device 105 and perform one or more tests, assays, and / or diagnostic procedures using the first quantity of bodily fluid. For example, the rapid test device 170 can be a chromatographic lateral flow immunoassay capable of testing 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.). Generally, an LFA includes a series of capillary beds, such as porous paper strips, microstructured or sintered polymers, etc., that can be positioned at desired locations and / or arrangements on a substrate to guide the flow of a sample (e.g., at least a portion of the first quantity of bodily fluid) along a portion of the LFA.

[0029]

[0044] LFAs can be used in a wide range of applications where it is desirable to have a relatively fast, easy-to-use, and low-cost approach for rapid antigen detection. LFAs are typically performed with little or no 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 can 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 can further mean that such LFAs have relatively low sensitivity to contaminants (e.g., skin-resident microorganisms) that may be present in the first volume of bodily fluid drawn from the patient via transfer device 105.

[0030]

[0045] Typically, two types of LFAs are used depending on the size and / or number of binding sites for the target analyte. In particular, competitive LFAs are commonly used when testing small analytes, while sandwich LFAs are commonly used when testing large analytes. In this regard, 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 bodily fluid such as blood. While the embodiments described herein include and / or implement sandwich LFAs, it should be understood that the embodiments are not limited thereto. For example, any of the embodiments described herein can use and / or implement competitive LFAs and / or any other suitable rapid diagnostic testing device.

[0031]

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

[0032]

[0047] As shown, sample element 172 is generally disposed at one end of the substrate and configured to receive a sample volume. 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 homogeneous transfer of the sample to other components of the lateral flow test strip. Sample element 172 may be of any suitable shape, size, and / or configuration. Conjugate element 173 is disposed downstream adjacent to sample element 172. Conjugate element 173 includes a dry matrix (e.g., a salt-sugar matrix) configured to contain desired bioactive particles. The bioactive particles contained within the matrix include specific antibodies and / or affinity reagents (e.g., DNA aptamers, protein binders, etc.) immobilized on or within conjugate element 173. The antibodies and / or affinity reagents may be selected based on the target molecule (e.g., antigen or analyte) that LFA 170A is configured to detect. Additionally, the antibody and / or affinity reagent may be directly or indirectly conjugated to a molecule configured to allow detection. For example, the antibody may be labeled with a colored particle (e.g., latex for blue, colloidal gold for red, and / or any other suitable particle), a fluorescent particle, a magnetic particle, an enzyme for subsequent signal generation, etc. Thus, the labeled antibody can bind to the desired antigen or analyte, thereby generating a labeled or target analyte 177 that can be detected by other portions or by other elements of the LFA 170A.

[0033]

[0048] The capture element 174 is positioned 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] Control element 175 is positioned adjacent to and / or downstream from capture element 174. Control element 175 includes particles or molecules immobilized within or on control element 175. In contrast to capture element 174, the particles or molecules included within control element 175 may be configured to bind to a plurality of different particles, such as, for example, labeled analyte 177, labeled bioactive particles that do not bind to antigens, etc. Accordingly, control element 175 may be configured to bind to and / or otherwise immobilize labeled particles not immobilized within or on capture element 174. Accordingly, control element 175 may exhibit a colored portion or strip that can 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 was performed properly and that a negative result (no colored strip presented on or by capture element 174) indicates the condition of the sample volume and not a malfunction of LFA 170A. The wick 176 is positioned adjacent to and / or downstream of the control element 175 and is configured to absorb or soak up a portion of the sample that is not immobilized in or on the capture element 174 and / or in or on the 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 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 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 can be used in place of 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 specific inflammatory biomarkers, anti-inflammatory biomarkers, and / or any other suitable biomarkers, such as any of those described herein.

[0037] Lactate

[0052] In some implementations, any of the embodiments described herein can 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, rapid test device 170 can 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, rapid test device 170 can be an LFA (e.g., LFA 170A) configured to test for a blood (e.g., whole blood, serum, etc.) lactate biomarker (e.g., antigen). 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 according to serum lactate levels in septic patients requiring vasopressors (e.g., agents that cause vasoconstriction).

[0038] [Table 1]

[0039]

[0053] Lactate is the end product of the anaerobic breakdown of glucose in tissues and can dissociate into lactate (a hydroxymonocarboxylic acid anion, the conjugate base of lactic acid resulting from deprotonation of the carboxyl group). Lactate production in the body occurs when tissue energy demands are not met through 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 levels can lead to lactic acidosis. Clinically, causes of acidosis can be classified into type A disorders, which involve decreased tissue oxygenation, such as those caused by sepsis, and type B disorders, which are caused by certain drugs and / or toxins, particularly in conjunction with systemic disease. Medical evidence suggests that patients with persistently elevated lactate levels experience increased morbidity and mortality. Excess lactate in the body can also cause bleeding, respiratory failure, trauma, seizures, ischemia, kidney problems, liver disease, tissue hypoxia, shock, blood loss, and anemia, among other conditions. Therefore, lactate monitoring is of paramount importance for diagnosing and assessing health concerns that arise during anoxic conditions (i.e., conditions in which lactate levels in the body increase beyond acceptable limits). Blood lactate concentrations in healthy, unstressed individuals have been reported to be in the 0.1-1.0 millimolar (mM) range. In contrast, critically ill individuals, such as those with severe sepsis or septic shock, may exhibit 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] Alternatively, detection of lactate levels in biological fluids, including blood and / or plasma, can be achieved through the use of enzymes. These enzymes can 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 specific lactate chemical reaction, producing one or more species. The occurrence of one or more species can be monitored and correlated with the concentration of lactate. For example, L-lactate can be detected using enzymes such as L-lactate oxidase (LOD) and L-lactate dehydrogenase (LDH). LOD is a globular flavoprotein that can be obtained from various bacterial sources, such as Pediococcus, Aerococcus, viridans, and Mycobacterium. The source of LOD can affect the pH range 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 with glycolate oxidase, L-lactate monooxygenase, flavocytochrome b2, long-chain α-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 (HO) 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 an 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 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 approximately 7.2-7.4. LDH also catalyzes the conversion of L-lactate to pyruvate (PA) by its cofactor, nicotinic acid adenine dinucleotide (NAD) (oxidation of NAD). + During the reaction, LHD converts L-lactate to pyruvate (PA) and NAD to pyruvate (NADH). + is converted to NADH. As described above with reference to the detection of L-lactate by the LDH enzyme, the detection of lactate by the 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 enzymatic lactate oxidation relies on the conversion of lactate to one or more by-products, such as NADH and hydrogen peroxide (HO), 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, generating 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 between the enzyme and 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 bonding via 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, whereas an LOD enzyme immobilized in mesoporous silica using a polyvinyl alcohol (PVA) polymer matrix may exhibit 98% of its initial activity after nine months. Consequently, developing a sensor using an LOD enzyme to detect lactate requires identifying an appropriate immobilization technique, a suitable matrix support, and environmental conditions of use and / or storage so that the enzyme's activity or shell life can be maintained over an extended period of time.

[0046]

[0060] Electrochemical biosensors for lactate detection typically involve devices containing two or three electrode sensing platforms. Accurate measurement of lactate often involves the use of a reference electrode (typically made of Ag / AgCl) 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 current flow 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, a wide linear range, and a rapid response. However, their use presents limitations due to complex experimental setup, system passivation by fouling factors, and signal reduction and interference from competing reactions. For example, electrochemical quantification of hydrogen peroxide (HO) produced during the enzymatic oxidation of L-lactate by LOD enzymes requires a high oxidation potential, leading to interference from 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 assist in the diagnosis of sepsis. As described above with reference to FIG. 2, LFAs may be performed on a plastic-backed laminate or strip that includes one or more components assembled on a substrate 171. Components of an 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, sample element 172 may be a pad that provides a surface for receiving a blood and / or other biological fluid sample for analysis and promotes smooth, continuous, and uniform transfer of the sample to other components of the lateral flow test strip. Sample element 172 may be any suitable shape and / or size. In some embodiments, sample element 172 may be a rectangular strip configured to absorb and receive a volume of blood and / or other biological fluid sample. In other embodiments, sample element 172 may be a rectangular strip, one of whose ends includes a region having a dimension greater than the width of the strip to facilitate pipetting of a volume of blood and / or other biological fluid sample. For example, sample element 172 may be a rectangular strip that includes a circular region attached to one of its ends. The circular region of sample element 172 can provide a larger surface area for receiving a blood and / or other biological fluid sample via a micropipette. Alternatively, in some embodiments, sample element 172 may include a larger 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 assay replication for validation purposes.

[0049]

[0063] The sample element 172 can be disposed on a surface of the plastic backing laminate and provide mechanical support for the LFA. In some embodiments, the sample element 172 can 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 can be predetermined to allow the sample element to be disposed on the plastic backing laminate. The thickness of the sample element 172 can be selected to facilitate attachment of the sample element 172 to the plastic backing laminate while maintaining the mechanical structure of the pad. Furthermore, the thickness of the sample element 172 can be selected to accommodate a large volume 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 can be 0.18 mm to 0.34 mm.

[0050]

[0064] Sample element 172 may be made of cellulose, nitrocellulose, glass fiber, and / or any other suitable material. In some embodiments, sample element 172 may be made of cellulose membrane and / or chromatography paper configured to facilitate a linear flow rate of approximately 3-5 mm / min. 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 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, 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 an LFA assay. For example, in some embodiments, 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 sample element 172. In other embodiments, the blood separation region may be a pad located adjacent to sample element 172. In some cases, the blood separation pad may include one or more layers, such as a polyester matrix and a composite matrix, 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) in larger pores while allowing plasma to flow downstream through smaller-sized pores.

[0052]

[0066] The conjugate element 173 of an 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) containing a bioactive species capable of reacting with lactate to produce a species that can be detected colorimetrically. The conjugate element 173 can be configured to contain 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 fabricated in a single pad, positioned on opposite ends of the single pad, and optionally attached to the surface of a plastic backing laminate to provide mechanical support for the LFA. In yet another embodiment, the conjugate element 173 and the sample element 171 can be fabricated from a single pad comprising a rectangular strip, a first end of the strip including a region having a dimension greater than the width of the strip to provide an area for accommodating a bioactive species for lactate oxidation and colorimetric detection, 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 blood and / or other biological fluid sample. Alternatively, in some embodiments, the conjugate element 173 can comprise multiple rectangular strips radially joined to a larger diameter circular region configured to accommodate the sample element 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 assay replication for validation purposes.

[0053]

[0067] Conjugate element 173 may include a dry matrix configured to contain a desired bioactive species for detecting and quantifying lactate in a blood and / or other biological fluid sample. For example, in this embodiment, the conjugate element 173 matrix may include both a detection enzyme and a quantification enzyme. The detection enzyme may be configured to exhibit high activity and selectivity for catalytically oxidizing lactate, producing one or more byproducts. The one or more byproducts may be monitored by a secondary chemical reaction to quantify the concentration of lactate present in the sample. For example, in some embodiments, the conjugate element 173 matrix may include a detection enzyme such as L-lactate oxidase (LOD). In other embodiments, the conjugate element 173 matrix 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 so that they can be dissolved in a volume of blood and / or other biological fluid sample flowing from 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 a redox reaction with hydroperoxides, such as hydrogen peroxide (HO), that are produced during the oxidation of lactate. The heme-containing enzyme can be, for example, horseradish peroxidase. Horseradish peroxidase can catalyze the redox reaction of hydrogen peroxide (HO) 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, an LFA can 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 can be imaged by a camera on a peripheral device, such as a smartphone or dedicated optical detector, and the intensity of the image can 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 can 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 value range for the image is 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 drawbacks of lactate detection techniques that rely on electrochemical reactions to quantify the amount of hydrogen peroxide (HO) produced during lactate oxidation. As described above, the enzymatic reaction of hydrogen peroxide (HO) 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 lactate oxidation. Therefore, as further described herein, the use of additives in the dry matrix of LFAs 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 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, and reduced enzyme stability during storage.

[0058]

[0072] In some embodiments, the detection and quantification enzymes can be contained 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 can 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 equilibrium between the acidic species and its conjugate, maintaining the pH of the sample within a range where 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 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, LFAs can have a detectable lactate dynamic range of 2-6 mM and a lactate sensitivity of 0.5 mM or greater in buffer and / or serum samples. In some embodiments, LFAs can have cutoff 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 approximately 10 minutes. LFAs configured for lactate detection can remain relatively stable over long periods of 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 four 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 concentrations 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 116-amino acid peptide with an estimated molecular weight of 14.5 kDa and belongs to the calcitonin family of peptides. The PCT molecule contains three parts: 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 the peptide is not released into the blood in the absence of systemic inflammation. However, in cases of sepsis caused by bacterial infection, PCT synthesis is induced in tissues, making it 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. Additional conditions that can cause high levels of PCT in the body include recent major surgery, severe trauma, severe burns, prolonged cardiogenic shock, and chronic kidney disease.

[0064]

[0077] The inability of some tissues other than the thyroid gland to cleave PCT into its mature form, calcitonin, causes PCT to accumulate in the blood. Therefore, PCT can be used as a biomarker that relatively highly distinguishes between bacterial inflammation and viral inflammation, 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 methods for diagnosing sepsis due to bloodstream infection include culture of blood, urine, and cerebrospinal fluid samples from bronchial fluid. These testing methods typically require 24–48 hours to obtain results and often facilitate pathogen identification, providing information about the type of microorganism and its sensitivity to antibiotics. However, clinical symptoms may be evident even 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, makes it a suitable biomarker for bacterial infection.

[0066]

[0079] PCT can be quantified by immunoassays based on the sandwich ELISA principle. In these immunoassays, antibody-procalcitonin-antibody complexes are formed and quantified by one or more measurement methods, including chemiluminescence, enzymatic, fluorescent, and turbidimetric immunoassays. For example, a chemiluminescent assay for PCT uses a two-step sandwich technique. In this method, an anti-PCT monoclonal antibody conjugated with alkaline phosphatase is added to a 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 unconjugated materials by a magnet. A chemiluminescent substrate is added to the test, and light generated by the reaction is measured using a luminometer. Photon production 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 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 laser excitation causes non-radiative energy transfer 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 persists for several microseconds, long enough to be detected after decay of background fluorescence, which is 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 diagnosing sepsis. As described above with reference to FIG. 2, LFAs can be performed on strips that include one or more components assembled on a substrate 171. The components of an LFA configured to detect and quantify PCT in blood and / or other biological fluids can 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 for 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 for receiving a blood and / or other biological fluid sample for analysis and promotes smooth, continuous, and uniform transfer of the sample 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 blood and / or other biological fluid sample. The sample element 172 may be disposed on the surface of the substrate 171 and provide mechanical support for 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 so that the sample element can be placed 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 can be selected to accommodate a large volume of blood and / or other biological fluids, preventing oversaturation of the sample on the pad and channeling into the plastic backing laminate. The sample element 172 can be made of cellulose, nitrocellulose, glass fiber, and / or any other suitable material.

[0071]

[0084] As shown in FIG. 2 , the conjugate element 173 of an 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 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) containing bioactive particles and additives. The bioactive particles contained 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 can 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 nonionic 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 disinfectant reagents configured to promote an extended shelf life of the LFA by inhibiting a wide range of microorganisms. The disinfectant 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 conjugate element 173 may include one or more antibodies and / or affinity reagents conjugated to molecules 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, etc.

[0074]

[0087] The detection antibody can 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 can be used for capturing and quantifying PCT in blood and / or other biological fluid samples. In some embodiments, the detection antibody can be immobilized on gold nanoparticles. Gold nanoparticles and / or gold nanoshells can be functionalized with antibodies that exhibit specific binding activity for specific regions of the PCT molecule (e.g., bioconjugation). During bioconjugation, the surface of the gold nanoparticles can 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 binding. Physical interactions occur through spontaneous adsorption of the antibody onto the surface of the gold nanoparticles. In the case of ionic interactions, the positively charged group of the detection antibody is attracted to the negatively charged surface of the gold nanoparticles. 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 using physical methods include ease, simplicity, low cost, rapid production, and minimal use of additives and / or chemicals that can cause adverse toxic effects. However, certain disadvantages of physical methods 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 modality on 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 nonspecific binding sites, blocking regions of the antibody suitable for PCT capture. For example, in some cases, antibodies can be physically adsorbed onto the surface of gold nanoparticles through interactions between the constant region 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 can be physically adsorbed onto the surface of gold nanoparticles through interactions with the PCT antigen-binding site, thereby eliminating interaction between the antigen-binding site and PCT.

[0076]

[0089] Alternatively, in some embodiments, antibodies can be conjugated to gold nanoparticles by chemical methods involving covalent bonding, 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 a chemical reaction between gold and sulfur atoms, which generates 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 using, for example, bifunctional linkers that provide specific functionalization of the gold nanoparticle surface. For example, carboxylated polyethylene glycol (PEG) molecules (PEG-SH) functionalized with thiol groups can be used to functionalize the surface of gold nanoparticles. PEG molecules functionalizing gold nanoparticles can also contain carboxyl terminal groups. These carboxyl terminal groups can be modified with coupling agents, including water-soluble carbodiimides (EDC) and N-hydroxysuccinimide (NHS) compounds, to generate reactive functional groups that bind to primary amine groups on antibody molecules. The water-soluble carbodiimides react with the carboxylic acid moiety of the PEG containing the gold nanoparticles, generating intermediate activation groups that react with the N-hydroxysuccinimide compound to form reactive ester groups. When directly contacted with an 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 the addition of a spacer molecule between them.

[0078]

[0091] The capture element 174 of an LFA for detecting and quantifying PCT from blood and / or other biological fluid samples may be a pad positioned adjacent to and / or downstream of the conjugation element 173 and includes particles or molecules immobilized within 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 colored particles described above with reference to the conjugation 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 its surface. 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 its conjugated colored particles. In some embodiments, the capture antibody may be adsorbed onto the surface of the capture element 174.

[0079]

[0092] As described above with reference to detection antibodies, capture antibodies can include procalcitonin human antibodies, including monoclonal anti-PCT antibody 14A2cc, monoclonal anti-PCT antibody 796, PP3, and the like. The immobilized capture antibodies can be configured to bind to PCT molecules previously bound to detection antibodies (and their conjugated colored particles) within conjugate element 173. As a result, exposure of capture element 174 to a sample of blood and / or other biological fluid containing PCT that has previously flowed through conjugate element 173 can result in the accumulation of colored particles associated with the capture antibodies that bind to PCT molecules present in the sample. This accumulation of colored particles on capture element 174 can 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 capture element 174 can be determined by a standard lateral flow reader, such as the commercially available Leelu reader (LUMOS diagnostics), configured to detect colored particles, providing adequate optical sensitivity and dynamic range sufficient to cover a wide range of PCT 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 positioned 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 wick away 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, LFAs can have a detectable PCT dynamic range of 0.2 ng / mL to 2 ng / mL and a sensitivity of 0.1 ng / mL or greater in buffer and serum. In some embodiments, 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 results using an LFA configured for PCT detection can be approximately 10 minutes. LFAs configured for PCT detection can remain relatively stable during accelerated stability testing conducted at 37°C, without significant release of the conjugate through the lateral flow strip.

[0082]

[0095] While testing for serum lactate and / or serum PCT concentrations has been described above, it should be understood that testing blood (e.g., whole blood or other suitable fractions of blood) will yield similar or substantially the same results. While 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 biomarker 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 central 20-40 base variable region flanked by two constant regions containing binding sites at each end. Aptamers can fold into secondary structures and three-dimensional shapes through intermolecular hybridization. The equilibrium dissociation constant for aptamer-target binding is in the 1 picomolar (pM) to 1 nanomolar (nM) range. Aptamers can be generated for desired targets, such as toxic small molecules, non-immunogenic targets, or single molecules that have similar affinities to antibodies and do not bind to antibodies. Furthermore, aptamers can be reversibly denatured by heat or chemicals, a process that antibodies cannot.

[0084]

[0097] Aptamers are similar to antibodies in their range of target recognition and diverse applications. However, the use of aptamers may offer advantages over the use of antibodies. These advantages include, for example, their production through 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 to 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 via 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 non-immunogenic properties, allowing for safe use in vivo. In some cases, aptamers can have improved transport properties, enabling cell-specific targeting and improved tissue penetration.

[0085]

[0098] Aptamers can be tailored to specific targets using in vitro selection (SELEX: systematic evolution of ligands by exponential enrichment). This process involves three main steps: library generation, selection, and amplification. In the first step, a random library is designed and synthesized using combinatorial chemical synthesis to generate oligonucleotides containing variable regions of 20–40 bases, each flanked by upstream and downstream primer binding sites. The resulting library can contain 10 12–10 15 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 aptamer binds to the target to form an aptamer-target complex, while nonspecific sequences remain in the binding buffer. The aptamer-target complex can be recovered and washed several times with a wash buffer. The aptamer can then be separated from the aptamer-target complex 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 eliminated. In a third step, the sequences that escaped in the second step are amplified by PCR for DNA or by reverse transcriptase (RT)-PCR for RNA to generate a sublibrary for use in the second round of SELEX. 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, aptamer sequences that bind to the target with high sensitivity and specificity are identified and then cloned and sequenced. Several techniques can be used to improve the separation of unbound sequences from aptamer-target complexes. For example, in some cases, aptamer selection may involve 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 aptamer-target complexes and remove unbound oligonucleotide sequences based on size. Multiple micron-sized pores on the membrane's surface 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 use agarose beads packed on a column as the stationary phase. Magnetic beads are also used to immobilize targets through physical interactions or chemical reactions between specific tags and their ligands on the beads. Capillary electrophoresis and microfluidics-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 by the migration speed of the target, ligand, or a mixture of target-ligand complexes. Compared to other methods, capillary electrophoresis-based SELEX can be used to select aptamers in several rounds. Microfluidics-based SELEX is a technique that uses an automated and miniaturized platform that enables aptamer selection on a chip. To automatically perform the selection process, 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 in conjunction with SELEX 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 test results 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 test performance. In some such instances, a human visual inspection 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, 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 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 for detecting the strip. In some implementations, the strip reader may be configured to define data or a digital representation of the test result (strip), which 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 enabling 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 electronic device 190. Electronic device 190 may analyze, process, and / or otherwise use this data to generate one or more qualitative and / or quantitative test results. 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 pre-defined treatment plans, patient profiles, disease profiles, etc. Furthermore, electronic device 190 may be configured to transmit and / or receive data via a wired or wireless connection or network. In some embodiments, electronic device 190 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 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, electronic device 190 may be configured to provide a graphical and / or digital representation of the test results generated by rapid test device 170. Additionally, in some implementations, 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 quantity of bodily fluid to the rapid test device 170 and at least a portion of the second quantity 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 quantity 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 quantity of bodily fluid.

[0092]

[0105] In some embodiments, optional fluid collection device 195 can be any suitable device for at least temporarily containing a bodily fluid. For example, fluid collection device 195 can 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, fluid collection device can be substantially similar to or the same as known sample containers, such as, for example, 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 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., a Vacutainer®), a syringe, etc. In some implementations, the fluid collection device 195 may be physically and / or fluidically coupled to the transfer device 105 (e.g., an outlet or port) such that the 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 specific embodiments.

[0094]

[0107] In some embodiments, the fluid collection device 195 can include any suitable additives, media, substances, enzymes, oils, fluids, etc. For example, the fluid collection device 195 can be a sample or culture bottle containing, for example, aerobic or anaerobic media. The sample or culture bottle can be configured to receive a bodily fluid sample. The bodily fluid sample can 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 media yields a positive result, the media can then be tested using a nucleic acid-based system (e.g., a PCR-based system, hybridization probes, nucleic acid amplification tests (NAATs), etc.) to identify the specific organism. In some embodiments, the sample reservoir can include, for example, any suitable additives, etc., in addition to or instead of the media. Such additives may include, for example, heparin, citrate, ethylenediaminetetraacetic acid (EDTA), oxalate, sodium polyanetholesulfonate (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] While 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., blood constituent cells, 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 a 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 quantity of bodily fluid contained in the second or sampling portion of the transfer device 105 and / or contained in any one or more 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 quantity of bodily fluid from the second quantity of bodily fluid can isolate contaminants, etc., in the first quantity of bodily fluid and / or within the isolated portion of the transfer device 105. Isolation can further allow the second quantity of bodily fluid to remain substantially free of contaminants. Thus, the second portion or quantity of bodily fluid can 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, the system 100 can be configured to obtain a first quantity of bodily fluid that can be used in tests that are relatively less sensitive to contaminants and a second quantity of bodily fluid that can be used in tests that are relatively more sensitive to contaminants. In some cases, testing a first volume of bodily fluid can provide relatively quick initial results that can inform one or more treatment options, while testing a second volume of bodily fluid can provide more detailed test results that typically take longer to produce. Thus, for time-sensitive disease conditions (e.g., sepsis), early results from testing a first volume of bodily fluid can enable a physician or doctor to provide prompt initial treatment, while more detailed testing 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 a "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 into 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 a rapid diagnostic test device 270 and / or one or more fluid collection devices 295.

[0099]

[0112] Transfer device 205 includes a housing 210 and an actuator 250. The housing 210 of 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. Furthermore, 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] Housing 210 has and / or forms an inlet 212 and an outlet 213, defining at least one fluid flow path 215 between inlet 212 and outlet 213. Inlet 212 may 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. Inlet 212 is configured to fluidly couple housing 210 to a bodily fluid source (e.g., a patient). For example, inlet 212 may be coupled to a lumen-containing device configured to be percutaneously placed within a patient (e.g., a butterfly needle, an intravenous (IV) catheter, a peripherally inserted central catheter (PICC), a midline intermediate lumen-containing device, etc.). Thus, fluid may be transferred between housing 210 and a patient via inlet 212 and any lumen-containing device coupled between housing 210 and the patient. More specifically, as described in further detail herein, transfer device 205 may be configured to transfer bodily fluid from a patient and / or any other bodily fluid source through inlet 212 (and / or any lumen-containing device coupled thereto) and into housing 210 via 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 transfer device 205 and / or the housing 210 may be configured to transition between any number of states, operating modes, and / or configurations to selectively control the flow of bodily fluid through the one or more fluid flow paths 215. Furthermore, the transfer 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, tubing, 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 adhesive, a resistance fit, a mechanical fastener, a threaded connection, a drilled or punctured configuration, any number of mating recesses, and / or any other suitable connection, or a combination thereof. For example, in some embodiments, outlet 213 may include and / or be coupled to a fluid transfer adapter such as those described in U.S. Pat. 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 that described in U.S. Pat. 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 fluidly 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] Fluid collection device 295 may be any suitable device for at least temporarily containing bodily fluids (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 fluid collection device 195. In some embodiments, fluid collection device 295 may be a sample reservoir that includes a vacuum seal that can maintain a negative pressure (vacuum) within the sample reservoir and further facilitate the drawing of bodily fluids from the patient through transfer device 205 and into the sample reservoir by vacuum or suction. 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, direct, and / or otherwise facilitate selective flow of fluid through at least a portion of the housing 210 and / or at least a portion of 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, plunger, seal, membrane, bladder, flap, plate, rod, 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, 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, actuator 250 may be configured to automatically transition 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 melt or deform), etc. In still other implementations, actuator 250 may be mechanically and / or electrically actuated or transitioned (e.g., by a motor, spring release mechanism, etc.) 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 , actuator 250 may be configured to selectively establish fluid communication between inlet 212 and rapid diagnostic test device 270 when in a first state and to selectively establish fluid communication between inlet 212 and outlet 213 when in a second state. When in the first state, actuator 250 may be configured to allow bodily fluid to flow from inlet 212 through at least a portion of fluid flow path 215 to or within rapid diagnostic test device 270. In some embodiments, actuator 250 may be configured to isolate, separate, disconnect, and / or otherwise prevent fluid communication between outlet 213 and inlet 212, at least a portion of fluid flow path 215, and / or rapid diagnostic test 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 fluid collection device 295 fluidly coupled to outlet 213). Furthermore, 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, septa, 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 quantity of bodily fluid from the transfer device 205 and perform one or more tests, assays, and / or diagnostic procedures using the first quantity 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 specific analytes or biomarkers that can provide information used to diagnose a patient condition, such as sepsis and / or any other disease state. For example, the LFA may be configured to test for lactate and / or PCT biomarkers, which may be indicators 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, rapid test device 270 may be configured to output a test result associated with testing a quantity of bodily fluid transferred from transfer device 205 while transfer device 205 and / or 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 test result output by rapid test device 270 may be qualitative, semi-quantitative, and / or quantitative. Thus, rapid test device 270 may be structurally and / or functionally similar to or the same as rapid test device 170, described in detail above. Accordingly, it will not be described in further detail herein.

[0111]

[0124] As described above, system 200 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. For example, in some cases, a user, such as a doctor, physician, nurse, phlebotomist, technician, etc., may operate 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 operated 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 the bodily fluid source (e.g., a vein, an IV catheter, a PICC, etc.).

[0112]

[0125] In some cases, the actuator 250 can 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). Accordingly, the transfer device 205 can be configured to transfer an initial amount of bodily fluid from the bodily fluid source (e.g., a patient) to the rapid test device 270. In some implementations, the initial amount of bodily fluid can flow passively (e.g., without user intervention and / or the 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 a portion thereof may be configured to create a negative pressure differential (e.g., a partial vacuum, a suction force, etc.) within at least a portion of the fluid flow path 215 that can initiate and / or maintain the flow of an initial amount of bodily fluid from the 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 may be transitioned from the storage state to the first state to initiate the flow of an initial amount of bodily fluid. In such cases, 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 operate in a manner similar to that described in U.S. Patent No. 8,535,241, entitled "Fluid Diversion Mechanism for Bodily-Fluid Sampling," filed October 22, 2012 (the "'241 Patent"), U.S. Patent No. 9,060,724, entitled "Fluid Diversion Mechanism for Bodily-Fluid Sampling," filed May 29, 2013 (the "'724 Patent"), U.S. Patent No. 9,155,495, entitled "Syringe-Based Fluid Diversion Mechanism for Bodily-Fluid Sampling," filed December 2, 2013 (the "'495 Patent"), U.S. Patent No. 9,155,495, entitled "Devices and Methods for Syringe-Based Fluid Transfer for Bodily-Fluid Sampling," filed June 23, 2016 (the "'495 Patent"). The negative pressure differential may be adapted to generate a negative pressure differential in a manner similar and / or substantially the same as any of those described in U.S. Patent Application Publication No. 2016 / 0361006 (the "'006 Publication"), entitled "Devices and Methods for Bodily Fluid Collection and Distribution," filed February 8, 2019 (the "'524 Publication"), and / or U.S. Patent Application Publication No. 2020 / 0253524 (the "'524 Publication"), entitled "Devices and Methods for Bodily Fluid Collection and Distribution," filed February 8, 2019 (the "Company"), the entire disclosures of each of which are incorporated herein by reference.In yet other implementations, as described in more 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 has been transferred to the rapid test device 270. In some embodiments, the initial amount may be related to and / or 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 be related to and / or 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 the 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 equilibrated 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 volume of bodily fluid once the initial volume has been 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 volume. In this manner, the initial volume of bodily fluid (whether alone or mixed with additional components) can flow through the rapid test device 270 (e.g., an LFA, such as those described above with reference to FIG. 2), and one or more tests or assays can be performed on the initial volume. 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 complete, the rapid test device 270 can be configured to output test results. As described in detail above, the test results 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 before 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 within 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 otherwise actuate the actuator 250 to transition the actuator 250 from its first state to its second state. In other embodiments, the actuator 250 may be transitioned automatically (e.g., without user intervention). Furthermore, 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) can sequester, disconnect, separate, and / or retain an initial volume of bodily fluid within the rapid test device 270. In other words, the actuator 250 can isolate and / or separate the rapid test device 270 from one or more portions of the inlet 212, outlet 213, and fluid flow path 215. As described in further 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, e.g., skin-resident microorganisms shed during a venipuncture event, bacterial flora of catheters and PICC lines used to collect samples, etc. Accordingly, such contaminants are sequestered in the initial volume. Furthermore, the configuration of the rapid test device 270 can 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 will not be affected by such contamination, as detailed above.

[0119]

[0132] In addition to isolating rapid test device 270 from inlet 212, outlet 213, and at least a portion of fluid flow path 215, placing actuator 250 in its second state also establishes fluid communication between inlet 212 and outlet 213 through at least a portion of fluid flow path 215. For example, in some embodiments, transitioning 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 simultaneously with the actuator 250 transitioning 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 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 volume of bodily fluid (e.g., within rapid test device 270) before collecting or obtaining one or more subsequent volumes of bodily fluid reduces and / or substantially eliminates the amount of contaminants in the one or more subsequent volumes. The subsequent volumes 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 an adverse result). In this manner, system 200 may be configured to obtain an initial volume of bodily fluid that may be used in tests with a relatively low sensitivity to contaminants and subsequent volumes of bodily fluid that may be used in tests with a relatively high sensitivity to contaminants. In some cases, testing the initial volume of bodily fluid (e.g., with rapid test device 270) may provide relatively quick initial results that may inform one or more treatment options, while testing subsequent volumes of bodily fluid may provide more detailed test results that typically take longer to produce.

[0121]

[0134] FIG. 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, which 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 to 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 into 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] Transfer device 305 includes a housing 310, a flow controller 340, and an actuator 350. The housing 310 of device 305 may be of any suitable shape, size, and / or configuration. For example, in some embodiments, housing 310 may be similar to and / or substantially the same as housing 210 described above with reference to FIG. 3 . In particular, housing 310 has and / or forms an inlet 312 and an outlet 313, defining at least one fluid flow path 315 between inlet 312 and outlet 313. Inlet 312 may be any suitable inlet or port and may be configured to establish fluid communication between housing 310 and a bodily fluid source (e.g., a patient). Outlet 313 may be any suitable outlet or port and may be configured to establish fluid communication between housing 310 and a fluid collection device 395. Furthermore, fluid collection device 395 may be similar to or substantially the same as fluid collection device 295 and 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, housing 310 may differ from housing 210 by including, forming, and / or being coupled to isolation chamber 330. As described in further detail herein, isolation chamber 330 is in selective fluid communication with fluid flow path 315. Furthermore, isolation chamber 330 may include, be coupled to, and / or otherwise be in fluid communication with rapid diagnostic testing device 370. As described in further detail herein, isolation chamber 330 may be configured to (1) receive a flow and / or quantity of bodily fluid from inlet 312, (2) isolate (e.g., separate, block, contain, retain, isolate, etc.) at least a portion of the flow and / or quantity of bodily fluid within isolation chamber 330, and (3) transport at least a portion of the flow and / or quantity 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 volume of bodily fluid from the inlet 312, thereby forming and / or functioning as the isolation chamber 330. While examples of isolation chambers are described herein, it should be understood that the transfer device 305 and / or housing 310 can have the isolation chamber arranged in any suitable manner, and thus, the isolation chamber 330 is not limited to what is 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 between about 0.1 mL and about 5.0 mL. In some embodiments, the isolation chamber 330 may have a volume measured in terms of the amount of bodily fluid configured to be transferred into the isolation chamber 330 (e.g., an initial or first amount of bodily fluid). 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 isolation chamber 330 can have a volume equal to at least some of the volume of one or more lumens that fluidly connect the isolation 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 isolation 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 is configured to control, direct, and / or otherwise facilitate the 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, etc., 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 ("'074 Publication"), filed September 12, 2018, entitled "Fluid Control Devices and Methods of Using the Same," U.S. Patent Application Publication No. 2019 / 0365303 ("'303 Publication"), filed May 30, 2019, entitled "Fluid Control Devices and Methods of Using the Same," and / or U.S. Patent Application Publication No. 2020 / 0289039 ("'039 Publication"), filed March 11, 2019, entitled "Fluid Control Devices and Methods of Using the Same," 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 can be configured to facilitate the displacement of air (or other fluid) through one or more portions of the transfer device 305. This may, in some cases, enable or create a pressure differential and / or pressure equalization in one or more portions of the housing 310. Furthermore, 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 fluid flow. 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 liquid (e.g., body fluid) 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 can be configured to transition from a first state to a second state in response to application of a negative pressure differential and / or suction force across at least a portion of the flow controller 340. For example, the flow controller 340 can include one or more valves, membranes, diaphragms, etc. For example, the flow controller 340 can be in a first state (e.g., a storage or non-use state) prior to use of the device 305, and the flow controller 340 can 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 defining or configured to define a negative pressure and / or suction force). In some embodiments, the flow controller 340 can be a bladder configured to transition or "convert" from a first state to a second state in response to application of a negative pressure differential and / or suction force across a surface of the bladder, as detailed in the '380 and / or '477 applications.

[0132]

[0145] In some embodiments, the size, shape, arrangement, and / or materials of construction of flow controller 340 may be configured and / or otherwise selected to transition 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 flow controller 340 transitions from the first state to the second state can further control and / or adjust the rate at which bodily fluid flows into isolation chamber 330 and / or the magnitude of the suction force generated within isolation chamber 330 that serves to draw an initial amount of bodily fluid into isolation chamber 330. Although not shown in FIG. 4 , in some embodiments, housing 310 and / or flow controller 340 may include any suitable members, features, openings, etc. configured to adjust the suction force acting on or within flow controller 340 and further adjust the rate at which flow controller 340 transitions from the first state to the second state. In some cases, controlling the rate at which flow controller 340 transitions and / or the magnitude of the pressure differential and / or suction force generated within 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 flow controller 340 and / or the pressure differential generated within isolation chamber 330 can at least partially control the amount or volume of bodily fluid transferred to isolation chamber 330 (i.e., can control the volume of the initial amount of bodily fluid).

[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, while specific flow controllers are described herein, it should be understood that fluid flow 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, direct, 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., user actuation, automatic actuation, mechanical actuation, electronic actuation, chemical actuation, etc.). For example, the actuator 350 may be similar to and / or substantially the same as any of those described above with reference to the actuator 250.

[0135]

[0148] 4 , actuator 350 may be configured to selectively establish fluid communication between inlet 312 and isolation chamber 330 when in a first state and to selectively establish fluid communication between inlet 312 and outlet 313 when in a second state. When in the first state, actuator 350 may be configured to allow bodily fluid to flow from inlet 312 through at least a portion of fluid flow path 315 to or within isolation chamber 330. In some embodiments, actuator 350 may be configured to isolate, separate, disconnect, and / or otherwise prevent fluid communication between outlet 313 and inlet 312, at least a portion of fluid flow path 315, and / or isolation chamber 330. As described in further detail herein, when in the second state, 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 inlet 312 through at least a portion of fluid flow path 315 to outlet 313 (and / or a fluid collection device 395 fluidly coupled to outlet 313). Furthermore, when in the second state, actuator 350 may be configured to isolate, separate, disconnect, and / or otherwise prevent fluid communication between isolation chamber 330 and at least a portion of inlet 312, outlet 313, and / or fluid flow path 315. In the embodiment shown in FIG. 4, as described in further detail herein, transfer device 305 is such that actuator 350 and 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, septa, 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 quantity of bodily fluid from the transfer device 305 and perform one or more tests, assays, and / or diagnostic procedures using the first quantity 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 those 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. Accordingly, 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 can be used to obtain one or more quantities of bodily fluid from a patient, which can 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., can operate device 305 to establish fluid communication between inlet 312 and a bodily fluid source (e.g., a patient's vein, cerebrospinal fluid (CSF) from the spinal cavity, collected urine, etc.). In some cases, actuator 350 can be in a first state when inlet 312 is in fluid communication with a bodily fluid source (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 the bodily fluid source (e.g., a portion of the 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 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 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 functions 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 flow controller 340 is a diaphragm, flap, valve, sleeve, etc., the configuration of flow controller 340 and actuator 350 may be such that a portion and / or surface of flow controller 340 is in fluid communication with outlet 313 (e.g., via a portion of fluid flow path 315). Thus, negative pressure and / or suction may act on a portion and / or surface of flow controller 340, which may further function to transition flow controller 340 from its first state, in which isolation chamber 330 has a first volume, to its second state, in which isolation chamber 330 has a second volume greater than the first volume. Isolation chamber 330 may be such that an increase in volume causes a decrease in pressure within isolation chamber 330, creating a negative pressure differential that functions to draw body fluid into isolation chamber 330. Thus, as detailed in the '380 and / or '477 applications, 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 can 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 can remain in the first state or configuration until a predetermined and / or desired amount (e.g., an initial amount) of bodily fluid has been transferred to the isolation chamber 330. In some embodiments, the initial amount can be related to and / or at least partially based on the 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 can 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 can 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, transfer device 305 can be configured to transfer a flow of bodily fluid (e.g., an initial amount) to isolation chamber 330 until flow controller 340 transitions to its second configuration. In other words, in some embodiments, transferring the initial amount of bodily fluid to isolation chamber 330 can function to place flow controller 340 in its second state or configuration. For example, in embodiments in which flow controller 340 is a selectively permeable member, as detailed in the '117 and / or '380 applications, transferring the initial amount of bodily fluid to isolation chamber 330 can be such that at least a portion of the initial amount wets and / or saturates flow controller 340, thereby further placing 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 can 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 separates isolation chamber 330 from outlet 313 such that the negative pressure and / or suction force created 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, etc.

[0146]

[0159] In some embodiments, as described in detail above with reference to rapid test device 270, transferring a portion of the initial volume of bodily fluid to rapid test device 370 can initiate a test and / or assay of or relating to the initial volume 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, upon completion of a test or assay, rapid test device 370 can be configured to output test results. The test results can be detected and / or evaluated by a person 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., placing the transfer device 305 in 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 results 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 described above, isolating an initial quantity of bodily fluid (e.g., within rapid test device 370) before 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 system 100 and / or system 200, system 300 may be configured to obtain an initial quantity of bodily fluid that may be used in a rapid test that is relatively less sensitive to contamination and subsequent quantities of bodily fluid that may be used in a test that is 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 to and / or substantially the same as 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] Transfer device 405 includes at least a housing 410 and an actuator 450. The housing 410 of device 405 may be of any suitable shape, size, and / or configuration. For example, in some embodiments, housing 410 may be similar to and / or substantially the same as housing 210 and / or housing 310 described above. In particular, 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 inlet 412 and outlet 413. Inlet 412 may be any suitable inlet or port and may be configured to establish fluid communication between housing 410 and a bodily fluid source (e.g., a patient). Outlet 413 may be any suitable outlet or port and may be configured to establish fluid communication between 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 described above with reference to housing 310, housing 410 shown in FIGS. 5A and 5B includes, forms, and / or couples to isolation chamber 430 configured to be selectively fluidly connected to fluid flow path and / or at least inlet 412. Furthermore, isolation chamber 430 includes, couples to, and / or is otherwise configured to be fluidly connected to rapid diagnostic testing device 470. Isolation chamber 430 may have any suitable shape, size, and / or configuration. For example, in some embodiments, isolation chamber 430 may have a volume and / or fluid capacity of about 0.1 mL to about 5.0 mL. In some embodiments, 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 isolation chamber 430 and / or tested by 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 with and / or formed with the absorbent material 431. As shown in FIGS. 5A and 5B , the isolation chamber 430 can be positioned such that the sampling portion 435 of the isolation chamber 430 is downstream of the absorbent material 431 (e.g., temporarily fluidly coupled to the inlet 412 for a portion of the isolation chamber 430). In this manner, the absorbent material 431 can be configured to receive and / or absorb a first portion or portions of an initial amount of bodily fluid transferred to the isolation chamber 430. In some implementations, the absorbent material 431 can 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 can flow to the sampling portion 435. As described in further detail herein, the sampling portion 435 of the isolation chamber 430 can be in fluid communication with a rapid diagnostic test device 470 to transfer a portion of the initial amount of bodily fluid disposed in the sampling portion 435 to the rapid diagnostic test 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 can 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 body fluid is transferred into 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 within the isolation chamber 430 that may restrict and / or prevent the flow of body 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 body 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 portions 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 walls of isolation chamber 430.

[0155]

[0168] Actuator 450 of device 405 can be of any suitable shape, size, and / or configuration. In some embodiments, actuator 450 and / or aspects or portions thereof can be similar to and / or substantially the same as actuators 150, 250, and / or 350, described in detail above. In some embodiments, actuator 450 can be at least partially disposed within and / or partially formed by housing 410. As described above, actuator 450 can be configured to control, direct, and / or otherwise facilitate selective flow of fluid through at least a portion of housing 410 and / or at least a portion of one or more fluid flow paths. In some embodiments, actuator 450 can 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-activated, automatic, mechanically activated, electronically activated, chemically activated, etc.).

[0156]

[0169] 5A and 5B, actuator 450 may be configured to transition between a first state (FIG. 5A) in which inlet 412 is in fluid communication with isolation chamber 430 and a second state (FIG. 5B) in which inlet 412 is in fluid communication with outlet 413. In some embodiments, when actuator 450 is in the first state, it may be configured to isolate, separate, disconnect, and / or otherwise prevent fluid communication between outlet 413 and inlet 412 and / or outlet 413 and isolation chamber 430. In contrast, when in the second state, 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 inlet 412 through one or more fluid flow paths (not shown in FIGS. 5A and 5B) to outlet 413 (and / or a fluid collection device fluidically coupled to outlet 413). Furthermore, when in the second state, actuator 450 may be configured to isolate, separate, disconnect, and / or otherwise prevent fluid communication between isolation chamber 430 and inlet 412, isolation chamber 430 and outlet 413, and / or at least a portion of the fluid flow path extending between isolation chamber 430 and inlet 412 and outlet 413. Actuator 450 may therefore be structurally and / or functionally similar to 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 to 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 may 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 may 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 quantity 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 quantity 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 those 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. Accordingly, the rapid test device 470 and / or aspects or portions thereof will not be described in further detail herein.

[0159]

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

[0160]

[0173] 5A and 5B, the initial amount of body 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 body fluid is first absorbed by the absorbent material 431 until the absorbent material 431 is saturated, and then the remaining portion of the initial amount of body fluid may flow to and / or fill the sampling portion 435 of the isolation chamber 430. In some implementations, the sequential filling of 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 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 isolation chamber 430, actuator 450 may be transitioned from its first state ( FIG. 5A ) to its second state ( FIG. 5B ). For example, in some embodiments, actuator 450 may be moved, slid, switched, rotated, and / or otherwise transitioned relative to inlet 412 and outlet 413. In some embodiments, transitioning and / or moving actuator 450 may include transitioning and / or moving at least a portion of housing 410. In other embodiments, actuator 450 may be moved relative to housing 410 (e.g., housing 410 need not be transitioned and / or moved).

[0162]

[0175] 5B , transitioning the actuator 450 from the first state to the 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 actuator 450 can be positioned such that transitioning the actuator 450 to the second state creates and / or increases an air gap between the portion of the isolation chamber 430 that includes the absorbent material 431 and the portion of the isolation chamber 430 that includes, forms, and / or defines the sampling portion 435. The air gap can facilitate the 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). Furthermore, in instances where contaminants are contained in 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 in 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 can 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 can be automatic. In other implementations, the transfer of the portion of the initial amount can be in response to one or more user inputs, or the like. In some implementations, transitioning the actuator 450 to the second state can 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 rapid test device 270, transfer of a portion of the initial volume of bodily fluid to rapid test device 470 can initiate testing and / or assays of or relating to the initial volume of bodily fluid. In some cases, as shown in FIG. 5B , 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 initial volume of bodily fluid. Rapid test device 470 can be configured to perform any suitable test and / or assay. For example, as described in detail above with reference to rapid test devices 170, 270, and / or 370, rapid test device 470 can be configured to output test results upon completion of the test or assay. The test results can be detected and / or evaluated by a person and / or one or more electronic devices.

[0165]

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

[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 placed in fluid communication with a fluid collection device before or after the actuator is placed in its second 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 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 quantity of bodily fluid in isolation chamber 430 before 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, and / or 300, system 400 may be configured to obtain an initial quantity of bodily fluid that may be used in one or more rapid testing processes and a subsequent quantity 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] 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, test device 570 and / or aspects or portions thereof may be substantially similar to rapid test devices 170 (and / or LFA 170A), 270, 370, and / or 470, described in detail above. Accordingly, 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, rapid test device 570 may be an LFA, such as described in detail above with reference to LFA 170A shown in FIG. 2. Rapid test device 570 includes a substrate 571 having a capillary bed, etc., of any suitable configuration, as described in detail above. Rapid test device 570 further includes a coupling member 578, which may be coupled to substrate 571 via attachment mechanism 579. Coupling member 578 may be any suitable coupling member configured to establish fluid communication with an interior volume of transfer device 505 in response to rapid test device 570 being coupled to transfer device 505. For example, as shown in FIGS. 6A and 6B, rapid test device 570 and / or its coupling member 578 may be configured to couple to transfer device 505 via port 525 (e.g., any suitable port, vent, coupler, opening, valve, junction, etc.). In some embodiments, coupling member 578 may be, for example, a piercing member, needle, tube, etc., capable of piercing and / or otherwise advancing within port 525. In some embodiments, coupling member 578 may be a capillary member or the like configured to transfer 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 (e.g., a sample portion, element, and / or capillary bed) of substrate 571. 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 may be coupled to the transfer device 505, and the coupling portion 578 may 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 may 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 may be decoupled from the transfer device 505, and the attachment mechanism 579 may be transitioned from its first state to its second state.

[0173]

[0186] For example, in some embodiments, attachment mechanism 579 can be a living hinge or the like that can bend, fold, deform, and / or otherwise reconfigure. As shown in FIG. 6D , when attachment mechanism 579 is in the second state, coupling member 578 can be in fluid communication with a portion of substrate 571 (e.g., a sample portion, an element, and / or a capillary bed). Thus, a volume of bodily fluid contained in coupling member 578 can be transferred to the portion of substrate 571. Furthermore, in some implementations, when attachment mechanism 579 is in the second state, buffer 581 and / or any other suitable solution can be transferred to substrate 571. Buffer 581 can be transferred to substrate 571 via coupling member 578, any suitable portion of attachment mechanism 579, and / or any other suitable portion of rapid test device 570. Thus, as described in detail above, buffer 581 can be mixed with a volume of bodily fluid, and the mixture can flow along substrate 571 for testing. In some implementations, 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, as described in detail above with reference to rapid test devices 170, 270, 370, and / or 470, upon completion of the test or assay, rapid test device 570 may be configured to output test results, which may be detected and / or evaluated by a person 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 to 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] Transfer device 605 includes at least a housing 610 and an actuator 650. The housing 610 of device 605 may be of any suitable shape, size, and / or configuration. For example, in some embodiments, housing 610 may be similar to and / or substantially the same as housings 210, 310, and / or 410 described above. In particular, housing 610 may have and / or form an inlet 612 and an outlet 613, defining a fluid flow path 615 between inlet 612 and outlet 613. Inlet 612 may be any suitable inlet or port and may be configured to establish fluid communication between housing 610 and a bodily fluid source (e.g., a patient). Outlet 613 may be any suitable outlet or port and may be configured to establish fluid communication between 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 shown in FIGS. 7A-7D includes, forms, and / or couples to isolation chamber 630 configured to be selectively fluidly connected to 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] Port 625 is coupled to housing 610 and / or isolation chamber 630 and is in fluid communication with the interior volume of isolation chamber 630. More specifically, as shown in FIGS. 7A-7D , port 625 is included in and / or coupled to housing 610 and is in fluid communication with sampling portion 635 of isolation chamber 630. In some embodiments, as described in detail above with reference to vent 424, port 625 and / or at least a portion thereof can be configured to vent and / or otherwise allow a flow of air or gas to exit isolation chamber 630 when an initial amount of bodily fluid is transferred to isolation chamber 630. Sampling portion 635 of isolation chamber 630 can be in fluid communication with rapid diagnostic test device 670 to transfer a portion of the initial amount of bodily fluid disposed in sampling portion 635 to rapid diagnostic test device 670. In the embodiment shown in Figures 7A-7D, for example, the rapid diagnostic test device 670 may be in fluid communication with 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] Actuator 650 of device 605 can be of any suitable shape, size, and / or configuration. In some embodiments, actuator 650 and / or aspects or portions thereof can be similar to and / or substantially the same as actuators 150, 250, 350, and / or 450, described in detail above. In some embodiments, actuator 650 can be at least partially disposed within and / or partially formed by housing 610. As described above, actuator 650 can be configured to control, direct, and / or otherwise facilitate selective flow of fluid through at least a portion of housing 610 and / or at least a portion of one or more fluid flow paths. Actuator 650 can 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-activated, automatic, mechanically activated, electronically activated, chemically activated, 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 being 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 630 and the remainder of isolation chamber 630, as described in further detail herein.

[0181]

[0194] The second member 660 of the actuator 650 can be of any suitable shape, size, and / or configuration. For example, in the embodiment shown in FIGS. 7A-7D , the second member 660 can be disposed around and / or over 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 can include a set of three seals. As shown, the second member 660 can 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 the 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 first member 651 and the second member 660 of the actuator are arranged such that a portion of the isolation chamber 630 (e.g., a portion other than the sampling portion 635) is disposed and / or defined between, for example, an end portion of the first member 651 and a first end portion of the second member 660. Furthermore, 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 first end portion of the second member 660 and a seal 661 included therein isolate and / or fluidly isolate the isolation chamber 630 from the fluid flow path 615.

[0183]

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

[0184]

[0197] 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, rapid test device 670 may be an LFA, such as those described in detail above with reference to LFA 170A shown in FIG. 2. In some implementations, test device 670 and / or aspects or portions thereof may be substantially similar to rapid test devices 170, 270, 370 and / or 470, described in detail above. Accordingly, 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 can be configured to engage or couple to the housing 610 via port 625. In some embodiments, for example, the port 625 can 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 place the rapid test device 670 in fluid communication with the sampling portion 635 of the isolation chamber 630. For example, the rapid test device 670 can 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 can 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 can be substantially similar to the coupling member 578 described above with reference to FIGS. 6A-6D . In some embodiments, port 625 may be self-healing, allowing port 625 to seal when coupling portion 678 of test device 670 is removed from port 625. As shown in FIG. 7D , coupling portion 678 of test device 670 may be coupled to substrate 671 of test device 670 (e.g., coupled directly to substrate 671 and / or coupled via an attachment mechanism such as attachment mechanism 579). In this manner, coupling portion 678 can transfer a volume of bodily fluid from sampling portion 635 of isolation chamber 630 to test device 670. In response, test device 670 can perform one or more tests, assays, and / or diagnostic procedures using the volume of bodily fluid.

[0186]

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

[0187]

[0200] In some cases, actuator 650 may be transitioned from its first state to its second state when inlet 612 is placed in fluid communication with a source of bodily fluid. For example, as shown in FIG. 7B , first member 651 may be transitioned or moved relative to inlet 612 and second member 660, which in turn increases the volume of the portion of isolation chamber 630 disposed between first member 651 and second member 660. Furthermore, the transition and / or movement of first member 651 may reduce the volume of sampling portion 635 of isolation chamber 630, and the location of port 625 may be such that it may allow air or gas contained within sampling portion 635 to exit and / or flow out of 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 body fluid may be any suitable amount of body fluid, such as any of the volumes or amounts described above. In some implementations, once the initial amount of body fluid is transferred to the isolation chamber 630, the flow of body fluid may stop and / or the pressure differential may be substantially equalized, slowing or stopping the flow of body 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 body fluid may be the amount of body 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 serve to stop the flow to the isolation chamber 630.

[0189]

[0202] Actuator 650 can be transitioned from its second state to its third state once an initial amount of bodily fluid is contained within isolation chamber 630. As shown in FIG. 7C , transitioning actuator 650 to the third state can include transitioning and / or moving second member 660 relative to inlet 612 and first member 651 of actuator 650. The transition and / or movement of second member 660 transitions and / or moves a first end portion of the second member from the second side of inlet 612 to the first side of inlet 612, thereby isolating and / or fluidly decoupling isolation chamber 630 from inlet 612. Additionally, the transition and / or movement of second member 660 relative to first member 651 can reduce the volume of the portion of isolation chamber 630 disposed between first member 651 and second member 660. In some implementations, as shown in FIG. 7C, the reduction in the volume of the portion of the isolation chamber 630 results in an increase in pressure that can 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 initial portion of the bodily fluid may be automatic. In other implementations, the transfer of the initial portion of the bodily fluid may be in response to one or more user inputs (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, testing and / or assaying of or relating to the initial portion of the bodily fluid may begin upon transfer of the initial portion of the bodily fluid to the rapid test device 670. 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, upon completion of the test or assay, rapid test device 670 may be configured to output test results. The test results may be detected and / or evaluated by a person and / or one or more electronic devices.

[0191]

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

[0192]

[0205] 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, outlet 613 can be fluidly connected to a fluid collection device (not shown in FIGS. 7A-7D ) before or after actuator 650 is placed in its third state. As described in detail above, the fluid collection device can be configured to define and / or generate a negative pressure and / or suction force that can 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 can flow from inlet 612, through fluid flow path 615, through outlet 613, and into the fluid collection device. As described above, isolating an initial quantity of bodily fluid in isolation chamber 630 before 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 in a rapid test that is relatively less sensitive to contamination and a subsequent amount of bodily fluid that may be used in a test that is relatively more sensitive to contamination.

[0194]

[0207] 8 and 9A-9D illustrate 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 to and / or substantially the same as 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] Transfer device 705 includes at least a housing 710 and an actuator 750. The housing 710 of device 705 may be of any suitable shape, size, and / or configuration. For example, in some embodiments, housing 710 may be similar to and / or substantially the same as at least housing 610 described above. In particular, housing 710 may have and / or form an inlet 712 and an outlet 713, defining a fluid flow path 715 between inlet 712 and outlet 713. Inlet 712 may be any suitable inlet or port and may be configured to establish fluid communication between housing 710 and a bodily fluid source (e.g., a patient). Outlet 713 may be any suitable outlet or port and may be configured to establish fluid communication between 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 housing 610, housing 710 shown in FIGS. 8-9D includes, forms, and / or couples to a fluid flow path and / or isolation chamber 730 configured to be selectively fluidly connected to at least inlet 712. Additionally, as described in further detail herein, the housing defines an opening 721 and / or port configured to receive a portion of a rapid diagnostic test device 770. Isolation chamber 730 may have any suitable shape, size, and / or configuration. For example, in some embodiments, isolation chamber 730 and / or at least a portion thereof may be substantially similar in form and / or function to isolation chambers 330, 430, and / or 630, described in detail above. Accordingly, portions and / or aspects of isolation chamber 730 will not be described in further detail herein.

[0198]

[0211] Actuator 750 of device 705 may be of any suitable shape, size, and / or configuration. In some embodiments, actuator 750 and / or aspects or portions thereof may be similar to and / or substantially the same as actuators 150, 250, 350, 450, and / or 650, described in detail above. In some embodiments, actuator 750 may be at least partially disposed within and / or partially formed by housing 710. As described above, actuator 750 may be configured to control, direct, and / or otherwise facilitate selective flow of fluid through at least a portion of housing 710 and / or at least a portion of one or more fluid flow paths. 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-activated, automatic, mechanically activated, electronically activated, chemically activated, etc.).

[0199]

[0212] More specifically, as shown in FIGS. 9A-9D , actuator 750 includes a first member 751, a second member 760, and a third member 765. First member 751 of actuator 750 may be of any suitable shape, size, and / or configuration. For example, first member 751 may be similar in form and / or function to first member 651 of actuator 650, described in detail above. First member 751 includes at least one seal 752 disposed at a first end portion of first member 751. Seal 752 may be configured such that seal 752 engages and / or contacts an inner surface of housing 710 to form and / or define a substantially fluid-tight seal between seal 752 and the inner surface of 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 a flow of air or gas 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. Furthermore, 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 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] 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, tab, button, knob, and / or any other suitable engagement member. As described in further 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 movement 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 can be of any suitable shape, size, and / or configuration. As shown in FIGS. 9A-9D , the second member 760 can 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 can 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, also having the outer seal 761. As such, the second member 760 can be similar to 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 an external portion of a portion of the housing 710 and / or a 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 or the like having an open end and a substantially closed end. 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, some of the transitions 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 first member 751 and the second member 760 of the actuator 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. Furthermore, 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. Accordingly, a seal 761 included in the first end portion and the second end portion of the second member 760 isolates and / or fluidly isolates the isolation chamber 730 from the fluid flow path 715.

[0205]

[0218] 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 Figures 9A-9D, regardless of the state of actuator 750, a first end portion of first member 751 and a seal 752 included in the first end portion of first member 751 are positioned and maintained on a first side of inlet 712 and a first side of outlet 713. Similarly, regardless of the state of actuator 750, a second end portion of second member 760 and a seal member 761 included in the second end portion of second member 760 are positioned and maintained on a second side (opposite the first side) of inlet 712 and a second side (opposite the first side) of 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 path 715.

[0206]

[0219] 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, rapid test device 770 may be an LFA, such as those described in detail above with reference to LFA 170A shown in FIG. 2. In some implementations, test device 770 and / or aspects or portions thereof may be substantially similar to rapid test devices 170, 270, 370, 470, 570 and / or 670, described in detail above. Accordingly, rapid test device 770 and / or aspects or portions thereof will not be described in further detail herein.

[0207]

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

[0208]

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

[0209]

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

[0210]

[0223] 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 isolation chamber 730. As described above with reference to transfer device 605, the transition of actuator 750 from the second state to the third state may be in response to an initial amount of bodily fluid being placed within 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 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] 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 positioned relative to the second member 760 such that an opening, port, valve, etc. (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 can 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 can 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 actuator 750 transitions to the fourth state, engagement member 755 disengages from and / or moves relative to engagement surface 766. In some embodiments, 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 engagement member 755 and / or engagement surface 766, and / or any other suitable force). In other words, third member 765 may move relative to 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 and 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. Furthermore, as described in further 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 the sampling channel 735 to be vented.

[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 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 a portion of the initial quantity of bodily fluid, as described in detail above with reference to the rapid test device 270. Furthermore, in some cases, venting the sampling channel 735 via the opening 754 may enable a desired pressure differential within the sampling channel 735 that may facilitate the transfer of the bodily fluid from the sampling channel 735 to the rapid test device 770. Rapid test device 770 may be configured to perform any suitable test and / or assay (e.g., test for the presence of lactate and / or PCT), such as any of those described in detail above. Furthermore, upon completion of a test or assay, rapid test device 770 may be configured to output test results, as described in detail above with reference to rapid test devices 170, 270, 370, 470, 570 and / or 670. Test results may be detected and / or evaluated by a person and / or one or more electronic devices.

[0216]

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

[0217]

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

[0218]

[0231] In some implementations, the outlet 713 may be placed 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 before 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 in a rapid test that is relatively less sensitive to contamination and a subsequent amount of bodily fluid that may be used in a test that is relatively more sensitive to contamination.

[0219]

[0232] 10, 11, and 12A-12D illustrate a fluid transfer and assay system 800 according to one embodiment. 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 fluid transfer device 805 and / or rapid diagnostic test device 870 may be similar to and / or substantially the same as 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] Transfer device 805 includes at least a housing 810 and an actuator 850. The housing 810 of device 805 may be of any suitable shape, size, and / or configuration. For example, in some embodiments, housing 810 may be similar to and / or substantially the same as any of housings 210, 310, 410, 510, 610, and / or 710 described above. In particular, housing 810 has and / or forms an inlet 812 and an outlet 813. Housing 810 may form and / or define an actuator chamber 814, a fluid flow path 815, and an isolation chamber 830. Inlet 812 may be any suitable inlet or port and may be configured to establish fluid communication between housing 810 and a bodily fluid source (e.g., a patient). As shown in FIG. 11 , inlet 812 is in fluid communication with actuator chamber 814, which in turn is in fluid communication with fluid flow path 815 and 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. Furthermore, outlet 813 is configured for 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 volume of bodily fluid from inlet 812 and isolate (e.g., separate, block, contain, retain, isolate, etc.) at least a portion of the flow and / or volume 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 is 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] Flow controller 840 may be of any suitable shape, size, and / or configuration. In some embodiments, flow controller 840 may be similar to and / or substantially the same as flow controller 340, described in detail above with reference to FIG. 4. For example, 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, flow controller 840 may be a member or device formed of an absorbent or semi-permeable material that is 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, flow controller 840 and / or aspects or portions thereof will not be described in further detail herein.

[0225]

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

[0226]

[0239] While the rapid test devices included in the previously described embodiments are shown and / or described as being coupled to housing 810, in the embodiment shown in FIGS. 10-12D , rapid test device 870 is disposed within and / or incorporated into housing 810. 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, rapid test device 870 and / or aspects or portions thereof may be substantially similar to rapid test devices 170, 270, 370, 470, 570, 670, and / or 770, described in detail above. In some implementations, rapid test device 870 may be an LFA, such as described in detail above with reference to LFA 170A shown in FIG. 2 .

[0227]

[0240] 11 , rapid test device 870 includes at least a sample element 872 disposed on an end portion of substrate 871, a conjugate element 873 disposed on substrate 871 downstream from sample element 872, a capture element 874 disposed on substrate 871 downstream from conjugate element 873, and a control element 875 disposed on substrate 871 downstream from capture element 874. Rapid test device 870 may be disposed within housing 810 such that capture element 874 and control element 875 can be observed from outside housing 810, such as through observation opening 819. Furthermore, housing 810 and / or rapid test device 870 include and / or are coupled to buffer actuator 880 that contains a quantity of buffer solution 881. In some embodiments, 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] System 800 can be used to obtain one or more quantities of bodily fluid from a patient, which can be used in one or more tests, assays, and / or diagnostic procedures. As described above, for example, inlet 812 can be in fluid communication with a bodily fluid source. As shown in FIG. 11 , when inlet 812 is in fluid communication with a bodily fluid source (e.g., a portion of a patient), actuator 850 can be in a first state, thereby establishing fluid communication between inlet 812 and isolation chamber 830. More specifically, when actuator 850 is in the first state, inlet 812 and isolation chamber 830 can be in fluid communication with a portion of actuator chamber 814 defined between two of the seals 852 of actuator 850. For example, a first seal 852 (e.g., an end seal) located at or near an end portion of the actuator 850 may be positioned within the actuator chamber 814 at a location between the rapid test device 870 and the isolation chamber 830, and a second seal 852 adjacent to (or closest to) the first or end seal 852 may be positioned within 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] 10-12D, once inlet 812 is fluidly connected to a source of bodily fluid (e.g., a portion of a patient), 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 a syringe that is operated to generate a negative pressure. Thus, coupling the fluid collection device to outlet 813 selectively exposes at least a portion of fluid flow path 815 to negative pressure and / or suction 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 connects the outlet 813 to portions of the actuator chamber 814 that are isolated and / or fluidly 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 flow controller 840 (e.g., selectively permeable member) may be such that air or gas flow is permitted through flow controller 840 between outlet 813 (and / or fluid flow path 815) and isolation chamber 830, but liquid (e.g., body fluid) flow is not permitted through flow controller 840. As a result, as described in detail above with reference to 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 isolation chamber 830, and further function to draw an initial amount of body fluid from the body fluid source through inlet 812, a portion of actuator chamber 814 defined between two corresponding seals 852, and into isolation chamber 830.

[0232]

[0245] The initial amount of bodily fluid can be any suitable amount of bodily fluid, such as any of the volumes or amounts described above. For example, in some cases, actuator 850 and / or transfer device 805 can 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 isolation chamber 830. In some embodiments, the initial amount can be related to and / or based at least in part on the volume of isolation chamber 830 or a portion thereof (e.g., an amount sufficient to fill isolation chamber 830 or a desired portion of isolation chamber 830). In some embodiments, transfer device 805 can be configured to transfer a flow of bodily fluid (e.g., an initial amount) to isolation chamber 830 until flow controller 840 transitions to its second configuration. In other words, in some embodiments, transferring the initial amount of bodily fluid to isolation chamber 830 can function to place 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 flow controller 840 transitions to its second state and / or configuration, flow controller 840 isolates and / or fluidly disconnects isolation chamber 830 from outlet 813. Thus, negative pressure and / or suction generated by the fluid collection device no longer acts on or within isolation chamber 830. In some cases, this may allow the pressure differential between isolation chamber 830 and inlet 812 to substantially equalize and / or reduce below a desired threshold. In some cases, the pressure equalization may be such that the flow of bodily fluid into isolation chamber 830 ceases.

[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 described above with reference to transfer device 605, the transition of actuator 850 from the first state to the second state may be in response to an initial amount of bodily fluid being placed 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, actuator 850 can be positioned within actuator chamber 814 such that seal 852 is in a desired position relative to rapid test device 870, isolation chamber 830, inlet 812, and fluid flow path 815. For example, isolation chamber 830 is in fluid communication with a portion of actuator chamber 814 that is disposed between seal 852 disposed between rapid test device 870 and isolation chamber 830 and seal 852 disposed between isolation chamber 830 and inlet 812. Thus, when flow controller 840 is in its second state and actuator 850 is transitioned to its second state, isolation chamber 830 is isolated and / or fluidly decoupled from other portions of transfer device 805 (see, e.g., FIGS. 12B-12D). In other words, actuator 850 (and flow controller 840) can isolate and / or decouple isolation chamber 830 from inlet 812, outlet 813, fluid flow path 815, and rapid test device 870. In some cases, isolating an initial volume of bodily fluid within isolation chamber 830 can also isolate contaminants within the initial volume.

[0236]

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

[0237]

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

[0238]

[0251] In some embodiments, a test and / or assay of or on a bodily fluid can 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 870. Furthermore, rapid test device 870 can be configured to perform any suitable test and / or assay. In some embodiments, buffer solution 881 can be based at least in part on the test to be performed. For example, in some cases, rapid test device 870 can be configured to test for the presence of lactate and / or PCT, as described in detail above. Furthermore, upon completion of the test or assay, rapid test device 870 can be configured to output test results, which can be detected and / or evaluated. For example, in some cases, a person may observe capture element 874 and / or control element 875 through viewing opening 819 defined by housing 810. In other embodiments, an electronic device can 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 into 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 rapid test device 870 may be such that the tests and / or assays performed by rapid test device 870 are not susceptible to such contamination. This means that the accuracy of the test results output by rapid test device 870 will not be affected by contamination that may be present in the initial volume 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 volume of bodily fluid that may be used in a rapid test that is relatively less sensitive to contamination and subsequent volumes of bodily fluid that may be used in a test that is relatively more sensitive to contamination.

[0240]

[0253] 13-16 illustrate 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 to 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, transfer device 905 includes at least a housing 910 and an actuator 950. Housing 910 has and / or forms an inlet 912 and an outlet 913. Inlet 912 may be any suitable inlet or port and may be configured to establish fluid communication between housing 910 and a bodily fluid source (e.g., a patient). Outlet 913 may be any suitable outlet or port and may be configured to establish fluid communication between housing 910 and a fluid collection device (not shown in FIGS. 13-16 ), such as any of those described in detail above. Additionally, housing 910 includes and / or defines port 925, which may be configured to establish fluid communication between at least a portion of housing 910 and / or one or more reservoirs or chambers disposed within housing 910, such as a rapid diagnostic test device 970. In some embodiments, port 925 may be substantially similar in form and / or function to port 525 described above with reference to FIGS. 6A-6D . As such, housing 910 and / or portions or aspects thereof may be similar to and / or substantially the same as any of housings 210, 310, 410, 510, 610, 710 and / or 810 described above and will not be described in further detail herein.

[0243]

[0256] Actuator 950 is at least partially disposed within housing 910. Actuator 950 of device 905 may be of any suitable shape, size, and / or configuration. For example, actuator 950 may be a member or device configured to transition between two or more states to control, direct, and / or otherwise facilitate selective flow of fluid through at least a portion of housing 910. Furthermore, 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 , actuator 950 may be transitioned between at least a first state and a second state. When in the first state, actuator 950 may be configured to allow an initial amount of bodily fluid to flow from inlet 912 into an initial or first portion of housing 910, such as an isolation chamber, such as those described in detail above with reference to 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 in the second state, the actuator 950 may be configured to isolate, separate, disconnect, and / or otherwise prevent fluid communication between the initial or first portion of the housing 910 and the inlet 912, the outlet 913, and / or one or more other portions of the 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] 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, test device 970 and / or aspects or portions thereof may be substantially similar to rapid test devices 170, 270, 370, 470, 570, 670, 770, and / or 870, described in detail above. In some implementations, rapid test device 970 may be an LFA, such as described in detail above with reference to LFA 170A shown in FIG. 2. For example, rapid test device 970 includes at least a sample element 972 disposed on an end portion of substrate 971, a conjugate element 973 disposed on substrate 971 downstream of sample element 972, a capture element 974 disposed on substrate 971 downstream of conjugate element 973, and a control element 975 disposed on substrate 971 downstream of 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, tubing, 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 then coupled and / or assembled at the time of use. In some implementations, the modular configuration of the test device 970 may allow various styles of test device 970 to fit into the transfer device 905, with each style 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 can be of any suitable shape, size, and / or configuration. In some embodiments, the housing 983 of the inspection device 970 can be configured to couple 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 can facilitate fluid flow through the inspection device 970 (e.g., along the substrate 971). Additionally, the housing 983 includes and / or defines a viewing opening 984. As shown in FIGS. 14 and 15 , the inspection device 970 can 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 viewing 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 or the like, which may include a piercing member 987. 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 when the testing device actuator 986 is in a first state (see, for example, Figure 15), the puncturing member 987 is positioned on a first side of the septum 988 and within the housing 983 of the testing device 970, and when the testing device actuator 986 is in a second state (not shown in Figures 13 to 16), the puncturing member 987 extends through the septum 988 and out of the housing 983 of the testing device 970.

[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 can 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 can 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 can be mixed with a volume of bodily fluid, and the mixture can flow along the substrate 971 for testing, as described in detail above. In some implementations, the rapid test device 970 can be configured to test for the presence of lactate and / or PCT, which can indicate a patient condition, such as sepsis. Furthermore, upon completion of the test or assay, the rapid test device 970 can be configured to output test results. The test results can be detected and / or evaluated. For example, in some cases, a person may view the capture element 974 and / or control element 975 through a viewing opening 984 defined by the housing 983 of the test device 970. In other embodiments, an electronic device can perform one or more scans of the capture element 974 and / or control element 975 through the viewing opening 984. In other embodiments, one or more electronic devices may be incorporated into and / or positioned within housing 910 without the need for human observation of capture element 974 and / or 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 can be used in a rapid test (e.g., relatively less sensitive to contamination) and subsequent quantities of bodily fluid that can be used in subsequent tests (e.g., relatively more sensitive to contamination).

[0251]

[0264] 17-20 illustrate various examples of fluid transfer and assay systems and / or devices according to various embodiments. For example, FIG. 17 illustrates 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. While 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, bodily fluid flow through a rapid test device coupled to a transfer device of system 1000 may be substantially counter-directional relative to bodily fluid flow through rapid test device 970 described above with reference to FIGS. 13-17.

[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 in and / or coupled to the inlet tubing, the outlet tubing, and / or any other suitable portion of the system 1100. In some implementations, the in-line rapid test device included in the system may accept a flow of bodily fluid and 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 accepting 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, 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 , system 1200 can include a rapid diagnostic test device that can be coupled to any appropriate portion of the syringe and fluidically connected to 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. In this manner, 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, 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, system 1300 may include a fluid transfer device configured to draw an initial amount of bodily fluid into 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. Furthermore, 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, system 1300 may be similar in form and / or function to any of the systems detailed herein.

[0255]

[0268] While 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, while 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 configurations of the various components may also be varied. For example, the size and specific shape of the various components may differ from the illustrated embodiments while still providing the functionality described herein. In some embodiments, changing 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 device's functionality. 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 an adult patient who is presumed to be healthy may be configured to obtain a first amount of bodily fluid, while a device configured for use in or with, for example, a critically 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 from one or more parts, features, structures, etc. When referring to such components, it should be understood that the component may be formed by a single part having any number of sections, regions, portions, and / or characteristics, or may be formed by multiple parts or features. For example, when referring to a structure such as a wall or chamber, the structure may be considered a single structure having multiple portions, multiple substructures joined to form the structure, etc. Thus, a monolithically constructed structure may include, for example, a series of substructures. Such a series of substructures may include multiple portions that are either contiguous or discontinuous with one another. A series of substructures may also be fabricated from multiple articles or components that are fabricated 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, a sample reservoir, vessel, container, bottle, adapter, dish, vial, syringe, and / or device (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 device, transfer adapter, 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 require physical and / or mechanical isolation of 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 transfer device is in a second state, one or more features and / or geometric shapes of the transfer device can result in 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) that fluidly communicates with the isolation chamber. In some such embodiments, the port may be configured to couple to and / or accept 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 all of a volume of bodily fluid into the isolation chamber, channel, reservoir, etc., allowing that volume of bodily fluid (e.g., a pre-sample volume) to 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) integrated into the chamber, allowing at least a portion of the initial volume of bodily fluid to be used for that testing. In still other embodiments, the isolation chamber and / or rapid test device coupled to or forming a portion of the isolation chamber may be removable and may be designed, sized, and configured to fit with 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 isolated 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 quantity 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 device described above with reference to system 800. While rapid test device 870 is shown as being disposed or contained within 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 bypass the isolation chamber (or rapid test device) and into the collection 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. Furthermore, certain events and / or steps can be performed sequentially as described above, as well as simultaneously in parallel processes where possible. Certain steps can be partially completed or omitted before proceeding to the next step.

[0265]

[0278] For example, while some devices are described herein as transitioning from a first state to a second state, such as in a separate operation, 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, in some cases, be relatively gradual. For example, in some cases, the device can begin transitioning from the first state to the second state as the final portion of an initial amount of bodily fluid (e.g., the initial or isolated portion) 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 final 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 isolate 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 in and / or associated with the fluid transfer and / or rapid diagnostic testing systems and methods described herein. The electronic devices 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 pre-defined treatment regimens, patient profiles, disease profiles, etc. In some cases, the 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 a test may be, for example, a test for sepsis and / or any other disease condition.

[0267]

[0280] Examples of electronic devices and / or components thereof are provided below. While particular devices and / or components are described, it should be understood that they are shown 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, mobile electronic devices (e.g., smartphones, tablets, laptops, and / or any other mobile or wearable devices), PCs, workstations, server devices or distributed networks of server devices, virtual servers or machines, virtual private servers running and / or operated as instances or guests of physical servers or server groups, etc., and / or any other suitable devices. In some implementations, the electronic devices may be configured to provide a graphical and / or digital representation of test results generated by any of the rapid test devices described herein. Furthermore, in some implementations, the electronic devices 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 body fluid sample, the patient, and / or the patient's treatment based on data related to and / or indicative of the test results.

[0269]

[0282] The components of an 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 be collectively 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 in, housed within, and / or incorporated into 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 further 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, 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 within and / or stored by an electronic device, or may be operatively coupled to an 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 a 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 series 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), a high-speed 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 component 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 communications interface may be any suitable hardware-based device that communicates with a processor and memory and / or any suitable software stored in the memory and executed by the processor. In some implementations, the communications interface may be configured to communicate with a network and / or any suitable device that communicates with a network. The communications 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 communications 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., Wi-Fi radios, Bluetooth radios, near field communications (NFC) radios, etc.), etc. In some implementations, the communication interface may be configured to transmit data to and / or receive data from (e.g., via one or more networks) any suitable part 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.), user or client devices (e.g., smartphones, tablets, wearable electronic devices, PCs, 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, etc. In some cases, the display may be a touch-sensitive display, etc. (e.g., a touch-sensitive display of a smartphone, a tablet, a wearable device, a PC, etc.). 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, etc.) 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), etc. 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, etc., 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 pre-defined treatment regimens, patient profiles, disease profiles, etc. Additionally, the electronic devices can present (e.g., on their 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 state).

[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 space or a transmission medium such as a cable). The medium and computer code (which may also be referred to as code) may be designed and constructed for a specific purpose or purposes. Examples of non-transitory computer-readable media include, but are not limited to, magnetic storage media such as hard disks, floppy disks, and magnetic tape; optical storage media such as compact discs / digital video discs (CDs / DVDs), compact disc read-only memories (CD-ROMs), and holographic devices; magneto-optical storage media such as optical discs; carrier wave signal processing modules; and hardware devices specially configured to store and execute program code, such as ASICs, ROM devices, RAM devices, and / or programmable logic devices (PLDs). Other embodiments described herein relate to computer program products that may include, for example, instructions and / or computer code described herein.

[0278]

[0291] Some embodiments and / or methods described herein may be implemented by software (executed on hardware), hardware, or a combination thereof. Hardware modules may include, for example, a general-purpose processor, a CPU, an FPGA, an ASIC, etc. Software modules (executed on hardware) may be expressed in various software languages (e.g., computer code), including C, C++, Java™, Ruby, Visual Basic™, Python™, and / or other object-oriented, procedural, or other programming languages and development tools. Examples of computer code include, but are not limited to, microcode or microinstructions, e.g., machine instructions generated by a compiler, code used to create web services, and files containing high-level instructions executed by a computer using an interpreter. For example, embodiments may be implemented using an imperative programming language (e.g., C, FORTRAN, etc.), a functional programming language (Haskell, Erlang, etc.), a logic programming language (e.g., Prolog), an object-oriented programming language (e.g., Java, C++, etc.), or other suitable programming languages and / or development tools, and / or a combination thereof (e.g., Python™). Further examples of computer code include, but are not limited to, control signals, encryption code, and compression code.

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 in fluid communication with 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 in fluid communication with 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, 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 when the fluid transfer device is in the second state, the first quantity is isolated from a fluid flow path between the inlet and the outlet.

3. 3. The system of claim 2, wherein the second amount of bodily fluid flows through the fluid flow path between the inlet and the outlet, 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. 10. 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. 11. The system of claim 10, wherein the matrix comprises a combination of chitosan and trehalose enzymes configured to stabilize at least a portion of the matrix.

12. 1. 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 quantity of bodily fluid, and a port in at least temporary fluid communication with the isolation chamber, the fluid transfer device configured to transition between a first state in which the isolation chamber is in fluid communication with the inlet to receive a 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 allowing a flow of gas through the isolation chamber when the isolation chamber receives the first amount of bodily fluid; a flow-based assay device configured to be coupled to the fluid transfer device in the second state, a portion of the flow-based assay device engaging the port when coupled to the fluid transfer device to allow a portion of the first quantity of bodily fluid to be transferred from the isolation chamber to the flow-based assay device, the flow-based assay device configured to provide an indication related to the presence of a target analyte in the portion of the initial quantity of bodily fluid; Including, the system.

13. The system of claim 12 , wherein when the fluid transfer device is in the second state, the first quantity is isolated from a fluid flow path between the inlet and the outlet.

14. 14. The system of claim 13, wherein the second amount of bodily fluid flows through the fluid flow path between the inlet and the outlet, thereby bypassing the isolation chamber and the first amount of bodily fluid isolated within the isolation chamber.

15. 13. The system of claim 12, wherein the flow-based assay device is one of a sandwich lateral flow assay device or a competitive lateral flow assay device.

16. 13. The system of claim 12, wherein the bodily fluid is blood and the target analyte is a biomarker for detecting sepsis in the blood.

17. 17. The system of claim 16, wherein the biomarker is one of procalcitonin or lactate.

18. The system of claim 12, wherein the portion of the flow-based assay device that engages with the port when the flow-based assay device is coupled to the fluid transfer device is operable to transition the port from a closed state to an open state.

19. 13. The system of claim 12, wherein the flow-based assay device comprises a conjugate element comprising a labeled antibody configured to bind to the target analyte, and a capture element configured to immobilize the target analyte and the labeled antibody, wherein an accumulation of immobilized labeled antibody along the capture element is configured to provide a visual indication related to the presence of the target analyte in the portion of the first quantity of bodily fluid.

20. 13. The system of claim 12, wherein the fluid transfer device forms a channel extending into the isolation chamber, a first end portion of the channel defining an opening operable to allow at least the portion of the first quantity of bodily fluid to flow into the channel, and the port is coupled to a second end portion of the channel.

21. 21. The system of claim 20, wherein the fluid transfer device has a third state between the first state and the second state, and the opening is configured to fluidly connect the channel to the isolation chamber when the fluid transfer device is in the third state.

22. 22. The system of claim 21, wherein placing the fluid transfer device in the third state temporarily limits the transition of the fluid transfer device from the first state to the second state.

23. placing an inlet of the fluid transfer device in fluid communication with a body fluid source; receiving a first amount of bodily fluid from the inlet into an isolation chamber of the fluid transfer device, wherein a flow controller of the fluid transfer device passes a flow of gas but not a flow of bodily fluid through the flow controller to vent the isolation chamber during the receiving; transitioning the fluid transfer device from the first state to a second state after the first amount of bodily fluid is received in the isolation chamber; In response to the fluid transfer device being in a second state: establishing fluid communication between the inlet and outlet of the fluid transfer device and allowing a second amount of bodily fluid to flow to a sample reservoir in fluid communication with the outlet; transporting a portion of the first quantity of bodily 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.

24. 24. The method of claim 23, wherein when the fluid transfer device is in the second state, the first amount is isolated from the fluid flow path between the inlet and the outlet.

25. 25. The method of claim 24, wherein the second amount of bodily fluid flows through the fluid flow path between the inlet and the outlet, thereby bypassing the isolation chamber and the first amount of bodily fluid isolated within the isolation chamber.

26. The isolation chamber is at least partially disposed within a housing of the fluid transfer device, and the method comprises: further comprising removably coupling the flow-based assay device to the housing of the fluid transfer device such that the isolation chamber is in fluid communication with a sample element of the flow-based assay device.

24. The method of claim 23.

27. 24. The method of claim 23, wherein the fluid transfer device includes a housing, and wherein the isolation chamber and the flow-based assay device are each at least partially disposed within the housing.

28. transitioning the fluid transfer device from the first state to the second state includes moving an actuator from a first position to a second position; the actuator in the first position is configured to define a portion of a first fluid flow path between the inlet and the isolation chamber; 24. The method of claim 23, wherein the actuator in the second position is configured to define (i) a second fluid flow path between the inlet and the outlet, and (ii) a third fluid flow path configured to enable the transport of the portion of the first quantity of bodily fluid to the sample element of the flow-based assay device.

29. The flow-based assay device is a lateral flow assay device, and the method comprises: performing a lateral flow assay on said portion of said first quantity of bodily fluid; providing an output associated with the results of the lateral flow assay; 24. The method of claim 23, further comprising:

30. 30. The method of claim 29, wherein the lateral flow assay device is one of a sandwich lateral flow assay device or a competitive lateral flow assay device.

31. 30. The method of claim 29, wherein the bodily fluid is blood and the target analyte is a biomarker for detecting sepsis in the blood.

32. The lateral flow assay device comprises: a conjugate element comprising a labeled aptamer configured to bind to the target analyte; a capture element configured to immobilize the target analyte and the labeled aptamer bound to the target analyte; Including, an accumulation of the immobilized labeled aptamer along the capture element configured to provide an indication related to the presence of the target analyte in the portion of the first quantity of bodily fluid; 32. The method of claim 31 .

33. 32. The method of claim 31, wherein the biomarker is one of procalcitonin or lactate.

34. The lateral flow assay device comprises: a conjugate element comprising a labeled antibody configured to bind to one of the procalcitonin or the lactate, respectively; a capture element configured to immobilize the one of the procalcitonin or the lactate, respectively, and the labeled antibody bound to the one of the procalcitonin or the lactate, respectively; Including, an accumulation of the immobilized labeled antibody along the capture element configured to provide an indication related to the presence of the one of the procalcitonin or the lactate, respectively, in the portion of the first quantity of bodily fluid.

34. The method of claim 33.

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