CN117813502A

CN117813502A - Apparatus and method for transferring a fluid sample from a fluid sample collection apparatus to a liquid sample analyzer

Info

Publication number: CN117813502A
Application number: CN202280055917.4A
Authority: CN
Inventors: J·考克斯; M·陈; J·戴维斯; J·德席尔瓦; M·沃恩; J·约瑟夫
Original assignee: Siemens Healthcare Diagnostics Inc
Current assignee: Siemens Healthcare Diagnostics Inc
Priority date: 2021-08-12
Filing date: 2022-08-05
Publication date: 2024-04-02

Abstract

Apparatus and methods for transferring a fluid sample from a fluid sample collection apparatus to a liquid sample analyzer. The apparatus includes a cartridge having a first end, a second end, a sidewall extending between the first end and the second end, an inner surface defining an interior chamber, and an outer surface defining at least a portion of a chromatography chamber in fluid communication with the interior chamber. The first end has an inlet opening, wherein the clot catcher extends across the inlet opening upstream of the channel and the second end has an outlet opening. The chromatography assay assembly is housed in a chromatography assay chamber for detecting the presence of free hemoglobin in a fluid sample.

Description

Apparatus and method for transferring a fluid sample from a fluid sample collection apparatus to a liquid sample analyzer

Cross Reference to Related Applications

U.S. provisional application No. 63/369,522 filed on day 27 of 7, 2022, as per 35USC 119 (e); U.S. provisional application No. 63/367,239, filed on day 29, 6, 2022; U.S. provisional application No. 63/366,558, filed on 6/17 of 2022; U.S. provisional application No. 63/244,987, filed on 9 and 16 days 2021; the benefits of U.S. provisional application No. 63/232,365 filed on 8/12 of 2021. The entire contents of the above-mentioned patent application are hereby expressly incorporated by reference.

Background

Blood sampling is a common healthcare procedure that is commonly used in hospital and laboratory settings to determine the physiological and biochemical condition of a patient. Blood sampling is critical for diagnosis and treatment of patients suspected of having a variety of conditions. The blood sample is analyzed by a fluid testing device, such as a blood analyzer, to detect clinically significant changes in blood constituents (e.g., plasma, red blood cells, white blood cells, and platelets) or other characteristics (e.g., blood gas conditions). Analysis of a blood sample for a blood gas condition provides information about the amount of oxygen and carbon dioxide in the blood and can also be used to determine the pH of the blood sample. An imbalance in oxygen, carbon dioxide or pH levels in a blood sample may indicate a particular pathological condition or stage of disease progression.

Blood samples are typically collected using a blood collection syringe having a hypodermic needle or a vacuum tube coupled to a needle assembly. However, blood collection syringes are prone to having bubbles of air or other gases within the syringe. Bubbles in the barrel and tip of the syringe may interfere with the analysis of the blood sample. With respect to blood gas analysis, bubbles trapped in the syringe may cause the blood analyzer to produce erroneous results. In order to obtain accurate results, the blood sample needs to be thoroughly mixed and all air must be vented before mixing. The air bubbles are typically expelled by tapping the side of the syringe to actuate air or gas to the top of the syringe. Once the air bubble reaches the top of the syringe, a piece of gauze or paper towel is placed on the top to encourage the expulsion of air (and some blood) from the syringe. This method not only carries a biohazard risk because the blood sample can freely flow out of the top of the syringe, but also carries an exposure risk because the tip of the syringe is still open to ambient air. A blood analyzer analyzing blood samples collected in this way runs the risk of producing erroneous results.

Furthermore, blood analyzers may not typically allow for direct sample input via a syringe or vacuum tube. There, the syringe and/or vacuum tube is simply an intermediate container of blood sample, and at least a portion of the blood sample must be removed and transferred to an auxiliary sample container that can be accommodated by the blood analyzer. Transferring the blood sample to the auxiliary sample container presents its own exposure risk and may increase the likelihood of obtaining erroneous results.

Clotting in blood samples can also lead to erroneous results, which can lead to improper treatment and to clogging within the blood analyzer, resulting in delayed results, analyzer damage, or the need to replace consumables, all of which can be expensive.

Detecting hemolysis in a blood sample is often time consuming. Typically, the user will have to centrifuge the sample and compare the plasma color to the hemolysis index. This requires the use of expensive equipment, such as a centrifuge, and takes time. On the other hand, testing without checking for hemolysis may lead to longer delays, as unexpectedly high potassium may make the whole test result problematic, leading to delays in treatment and increased costs while repeated samples are drawn and tested.

The auxiliary sample container is typically open (i.e., without a male fitting) and is therefore not compatible for use with the analyzer in a "hands-free" manner. That is, in prior art systems, the user had to hold the syringe during use with the analyzer (i.e., no hands free), or the syringe was not compatible and it was not feasible to use the adapter with the analyzer in a hands free attachment. There are many syringe accessories (e.g., adapters) and they are compatible with blood gas analyzers. However, these syringe accessories are not coupled or attached to the blood analyzer device in a "hands-free" manner, and the operator must remain at the analyzer and hold the syringe while the sample is being withdrawn. If an operator wishes to use the blood gas analyzer in a hands-free manner in prior art systems, the adapter must be removed from the syringe before such that the syringe is directly attached to the analyzer (without the adapter) during use of the analyzer. This alternative approach is sufficient for a defoamed adapter, but when using a clot catcher adapter, the benefits of the device are lost if the adapter is removed.

What is needed is an apparatus and a method that enable one or more of hemolysis detection, clot removal, hands-free connection of a blood collection device to a blood gas analyzer, and removal of air bubbles from a fluid sample. It is to such apparatuses and methods that the inventive concepts disclosed and claimed herein are directed.

Disclosure of Invention

The inventive concepts disclosed and claimed herein relate generally to an apparatus for transferring a fluid sample having a liquid portion and a gas portion from a fluid sample collection apparatus to a liquid sample analyzer. The apparatus includes a cartridge and a chromatography assembly. The cartridge has a first end, a second end opposite the first end, a sidewall extending between the first end and the second end, an inner surface defining an interior chamber, and an outer surface defining at least a portion of a chromatography chamber in fluid communication with the interior chamber via a passage through the outer surface of the cartridge. The first end of the cartridge has an inlet opening, wherein the clot catcher extends across the inlet opening upstream of the channel, and the second end has an outlet opening.

The chromatography assay assembly is housed in the chromatography assay chamber and is configured to detect the presence of free hemoglobin in the fluid sample. The chromatography assay assembly includes a sample application pad and a chromatography detection pad. The sample application pad is configured to receive a fluid sample from the internal chamber. The sample application pad is formed from a first layer of pre-filter material and a second layer of asymmetric polysulfone material, wherein the sample application pad is permeable to plasma and free hemoglobin and impermeable to red blood cells. The chromatographic detection pad is in fluid contact with the sample application pad and is configured to detect the presence of free hemoglobin.

In another aspect, the inventive concepts disclosed and claimed herein relate generally to a kit including the apparatus discussed above and a reference device comprising a plurality of reference colors. Each reference color corresponds to a different level of hemolysis.

In another aspect, the inventive concepts disclosed and claimed herein relate generally to a method of transferring a fluid sample having a liquid portion and a gas portion from a fluid sample collection device to a liquid sample analyzer having a sample probe. The method includes obtaining a device having a barrel with a first end, a second end, a sidewall extending between the first end and the second end, and an inner surface defining an interior chamber, the first end having an inlet opening, wherein a clot catcher extends across the inlet opening, and the second end having an outlet opening. At least a portion of the fluid sample is transferred from the fluid sample collection device to the interior chamber of the cartridge via the inlet opening, whereby the fluid sample passes through a clot catcher at the inlet opening to capture solids in the fluid sample. A portion of the fluid sample is transferred from the interior chamber of the cartridge to the chromatography measurement chamber and a chromatography measurement assembly housed in the chromatography measurement chamber. The chromatography chamber is in fluid communication with the interior chamber downstream of the clot catcher. The presence of free hemoglobin in the fluid sample is detected by a chromatographic assay assembly. The fluid sample is transferred from the internal chamber to the liquid sample analyzer using the sample probe.

Drawings

To assist one of ordinary skill in the relevant art in making and using the inventive concepts disclosed herein, reference is made to the drawings and schematic diagrams, which are not intended to be drawn to scale, and wherein like reference numerals are intended to refer to like or similar elements for consistency. For purposes of clarity, not every component may be labeled in every drawing. Certain features and certain views of the drawings may be exaggerated and not shown to scale or in schematic for clarity and conciseness. In the drawings:

fig. 1 is a side perspective view illustrating an exemplary embodiment of an apparatus for removing bubbles according to the inventive concepts disclosed herein as coupled to a sample receiving assembly.

Fig. 2A is a longitudinal cross-sectional view of the apparatus of fig. 1 coupled to a collection syringe illustrating positioning of a filter member and plunger assembly prior to removal of air bubbles from a fluid sample.

Fig. 2B is a longitudinal cross-sectional view of the device of fig. 1 coupled to a collection syringe illustrating positioning of the filter member and plunger assembly after removal of air bubbles from the fluid sample.

Fig. 2C is a longitudinal cross-sectional view of the device of fig. 1 coupled to a collection syringe illustrating insertion of a probe into the device after removal of a bubble from a fluid sample.

Fig. 3A is a longitudinal cross-sectional view of the apparatus of fig. 1, illustrating the position of the filter member prior to removing air bubbles from the fluid sample.

Fig. 3B is a longitudinal cross-sectional view of the apparatus of fig. 1, illustrating the position of the filter member after removing air bubbles from the fluid sample.

Fig. 3C is a longitudinal cross-sectional view of the device of fig. 1, illustrating the insertion of a probe into the device after removal of a bubble from a fluid sample.

Fig. 4A is a perspective view of the device.

Fig. 4B is a cross-sectional view taken along line 4B-4B of fig. 4A.

Fig. 5 is an exploded cross-sectional view of the apparatus.

Fig. 6A is a perspective view of an exemplary embodiment of a filter member according to the inventive concepts disclosed herein.

Fig. 6B is a cross-sectional view taken along line 6B-6B of fig. 6A.

Fig. 7 is a perspective view of another embodiment of a filter member according to the inventive concepts disclosed herein.

Fig. 8A is a perspective view of another embodiment of a filter member according to the inventive concepts disclosed herein.

Fig. 8B is a cross-sectional view taken along line 8B-8B of fig. 8A.

Fig. 9 is a perspective view of another exemplary embodiment of an apparatus according to the inventive concepts disclosed herein.

Fig. 10A is a cross-sectional view taken along line 10A-10A of fig. 9.

Fig. 10B is a cross-sectional view taken along line 10B-10B of fig. 9.

Fig. 10C is a cross-sectional view taken along line 10C-10C of fig. 9.

Fig. 10D is a cross-sectional view taken along line 10D-10D of fig. 9.

Fig. 11 is a longitudinal cross-sectional view of a portion of the apparatus of fig. 9 shown coupled to a collection syringe.

Fig. 12 is a partially exploded perspective view of the apparatus of fig. 9 illustrated with the chromatography assembly removed.

Fig. 13A is a perspective view of a non-limiting embodiment of a chromatography assay assembly constructed in accordance with the inventive concepts disclosed herein.

Fig. 13B contains a perspective view illustrating a workflow for using the chromatography assay assembly of fig. 13A.

Fig. 14 is a cross-sectional view taken along line 14-14 of fig. 9.

FIG. 15 schematically depicts one non-limiting embodiment of a reference device for use with a chromatography assay assembly constructed according to the present disclosure.

Detailed Description

Before explaining at least one embodiment of the inventive concept in detail with the aid of the example drawings, experiments, results and laboratory procedures, it is to be understood that the inventive concept is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings, experiments and/or results. The inventive concept is capable of other embodiments or of being practiced or of being carried out in various ways. Language used herein is intended to be given the broadest possible scope and meaning; and the embodiments are intended to be exemplary rather than exhaustive. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.

Unless defined otherwise, scientific and technical terms used in connection with the presently disclosed and claimed inventive concepts should have meanings commonly understood by one of ordinary skill in the art. Furthermore, unless the context requires otherwise, singular terms shall include the plural and plural terms shall include the singular. The foregoing techniques and procedures are generally performed according to conventional methods well known in the art and as described in various general and more specific references cited and discussed throughout the present specification. Nomenclature used in connection with the analytical chemistry, synthetic organic chemistry, and medical and pharmaceutical chemistry described herein, and the laboratory procedures and techniques therefor, are those well known and commonly employed in the art. Standard techniques are used for chemical synthesis and chemical analysis.

In view of the present disclosure, all articles, compositions, and/or methods disclosed and claimed herein can be made and executed without undue experimentation. Although the articles, compositions, and methods of the present inventive concept have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the articles, compositions, and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the inventive concept. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.

As used in this disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings:

the use of the terms "a," an, "or" the "when used in conjunction with the term" comprising "in the claims and/or specification may mean" one, "but it is also consistent with the meaning of" one or more, "" at least one, "and" one or more than one.

The use of the term "or" in the claims is intended to mean "and/or" unless explicitly indicated to mean only alternatives or that the alternatives are mutually exclusive, but the disclosure supports definitions of only alternatives and "and/or".

Throughout this application, the term "about" is used to indicate that the value includes inherent variations in the device, error in the method used to determine the value, or variations that exist between subjects.

The use of the term "at least one" will be understood to include one as well as any amount of more than one, including but not limited to 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 100, etc. The term "at least one" may extend up to 100 or 1000 or more, depending on the term it is associated with; in addition, the 100/1000 amount should not be considered limiting, as higher limits may also yield satisfactory results. In addition, the use of the term "at least one of X, Y and Z" will be understood to include any combination of X alone, Y alone, and Z alone, and X, Y and Z.

As used in this specification and claims, the terms "comprises" (and any form of comprising, such as "comprises" and "comprises"), "having" (and any form of "having, such as" has "and" has ")," including "(and any form of containing, such as" include "and" include ") or" containing "(and any form of containing, such as" contain "and" contain ") are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.

The term "or a combination thereof" as used herein refers to all permutations and combinations of items listed before the term. For example, "A, B, C or a combination thereof" is intended to include at least one of the following: A. b, C, AB, AC, BC or ABC, and BA, CA, CB, CBA, BCA, ACB, BAC or CAB if the order is important in a particular context. Continuing with this example, explicitly included are repeated combinations comprising one or more items or terms, such as BB, AAA, MB, BBC, AAABCCCC, CBBAAA, CABABB, etc. The skilled artisan will appreciate that there is generally no limit to the number of items or terms in any combination, unless otherwise apparent from the context.

For example, as used herein, the term "sample" and variations thereof is intended to include biological tissue, biological fluids, chemical fluids, chemicals, suspensions, solutions, slurries, mixtures, agglomerates, tinctures, slides, powders, or other preparations of biological tissue or fluids, synthetic analogs of biological tissue or fluids, bacterial cells (prokaryotic or eukaryotic), viruses, unicellular organisms, lysed biological cells, immobilized biological tissue, cell cultures, tissue cultures, genetically engineered cells and tissues, genetically engineered organisms, and combinations thereof.

In the following detailed description of embodiments of the inventive concept, numerous specific details are set forth in order to provide a more thorough understanding of the inventive concept. It will be apparent, however, to one skilled in the art that the inventive concepts within this disclosure may be practiced without these specific details. In other instances, well-known features have not been described in detail so as not to unnecessarily complicate the present disclosure.

Finally, as used herein, any reference to "one embodiment" or "an embodiment" means that a particular element, feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment.

Described herein and shown in the drawings are several non-limiting embodiments of the apparatus of the presently claimed and disclosed inventive concepts that can be used in conjunction with a collection syringe and a liquid sample analyzer for removing bubbles of air or other gases from a fluid sample for analysis by the liquid sample analyzer. The fluid sample is typically from a biological source. "fluid" refers to any substance that does not have a fixed shape and is susceptible to external pressure.

Referring now to the drawings, and more particularly to fig. 1-5, there is illustrated an exemplary embodiment of a device 10 constructed in accordance with the inventive concepts disclosed and claimed herein, the device 10 for transferring a fluid sample from a liquid sample collection device to a liquid sample analyzer, and for removing air bubbles from the fluid sample. The apparatus 10 includes a cartridge 12, a nozzle cap 14, and a filter member 16.

The cartridge 12 includes a first end 18, a second end 20, a sidewall 22, and an inner surface 24. The cartridge 12 may be of any suitable size and shape and formed of any suitable material, such as, but not limited to, plastics, such as polycarbonate, polystyrene, polyacrylate, and polyurethane, or medical grade polymers. A sidewall 22 of the barrel 12 extends between the first end 18 and the second end 20 of the barrel 12. The inner surface 24 of the barrel 12 defines an interior chamber 26. The first end 18 has an inlet opening 28 and the second end 20 has an outlet opening 30.

The interior chamber 26 may have any suitable size and shape to accommodate the fluid sample 32. The fluid sample 32 may be a liquid biological sample such as blood, serum, plasma, or other bodily fluid. The fluid sample 32 may include a gas portion and a liquid portion. For example, the gaseous portion of the fluid sample 32 may be air or other gas. A portion of the gas portion may form bubbles in the fluid sample.

The inlet opening 28 and the outlet opening 30 may have a cross-section of any suitable geometry, including but not limited to circular, elliptical, square, or rectangular. The inlet opening 28 and the outlet opening 30 may be molded or cut into the barrel 12 or otherwise prefabricated. The inlet opening 28 may be formed to capture clots as the fluid sample 32 enters the interior chamber 26 via the inlet opening 28. The cartridge 12 may include a clot catcher 33 (fig. 5) disposed across the inlet opening 28 so as to define a plurality of apertures 35 sized and shaped to allow fluid to pass into the interior chamber 26, but to capture or prevent solids (i.e., clots) greater than a predetermined size from passing into the interior chamber 26. Solids that may be captured by clot catcher 33 and prevented from flowing into interior chamber 26 may include clots and other solids present in fluid sample 32 having a predetermined size, for example, of at least about 0.17+/-0.05mm in diameter or greater. In one non-limiting embodiment, clot catcher 33 is star-shaped (e.g., as illustrated in fig. 10C and 10D as clot catcher 133) so as to cooperate with inlet opening 28 to define five apertures 35 (only one of which is numbered in fig. 5) through which fluid enters interior chamber 26. In this non-limiting embodiment, five apertures 35 are formed between the five arms of the star-shaped clot catcher 33, wherein the arms may be sized and shaped to act as a capture element to capture and prevent a clot from entering the interior chamber 26 (e.g., as shown in fig. 10C as clot catcher 133 with apertures 135).

The outlet opening 30 may be provided with a nozzle cap 14. The nozzle cap 14 includes an annular wall 36 and a tubular portion 38, the tubular portion 38 having an aperture 40 extending therethrough. The tubular portion 38 may be in the form of a male luer (luer) for frictional engagement with a portion of the fluid analyzer 68 (fig. 1). The liquid sample analyzer 68 includes a sample input port 70 for frictionally receiving the tubular portion 38 and a sample probe 72 (fig. 2C and 3C). The sample probe 72 is axially slidable relative to the sample input port 70. The aperture 40 may have a cross-section of any suitable geometry including, but not limited to, circular, oval, square, or rectangular. The aperture 40 may be sized to have a diameter suitable for slidably axially receiving a sample probe. The base of the tubular portion 38 flares outwardly and merges with the annular wall 36 at a rim 42, the annular wall 36 tapering downwardly to form an inverted frusto-conical profile. The nozzle cap 14 may be releasably coupled to the outlet opening 30 such that the bore 40 is aligned with the outlet opening 30, thereby allowing fluid communication with the interior chamber 26.

The filter member 16 is disposed within the interior chamber 26 such that the filter member 16 defines an inlet side 44 and an outlet side 46 of the interior chamber 26. The filter member 16 may be positioned between a first end 18 and a second end 20 of the cartridge 12. The filter member 16 includes at least one gas permeable, liquid impermeable membrane 48. The filter member 16 may be of any suitable shape and size to sealingly engage the inner surface 24 of the cartridge 12. The filter member 16 may be formed of any suitable material such as, but not limited to, rubber, elastomer, polyolefin-based resin, fluorine-based resin, or polyester-based resin. For example, the elastomer may comprise a polyvinyl chloride-based elastomer, a polyolefin-based elastomer, a styrene-based elastomer, a polyester-based elastomer, a polyamide-based elastomer, a polyurethane-based elastomer, or a mixture thereof.

Referring now to fig. 6A and 6B, perspective and cross-sectional views of an exemplary embodiment of the filter member 16 are shown, respectively. The filter member 16 includes a body 50 having a first end 52, a second end 54, and a sidewall 56 extending from the first end 52 to the second end 54. The side wall 56 of the body 50 defines a passage 58 extending through the body 50 from the first end 52 to the second end 54. The sidewall 56 of the body 50 may have at least two annular protrusions 60 extending radially outward that slidably seal contact the inner surface 24 of the barrel 12. As shown in fig. 6A and 6B, the body 50 may have two annular protrusions 60 spaced apart from each other. The annular projection 60 may include male or female features.

The filter member 16 also includes a gas permeable, liquid impermeable membrane 48 extending across the entire channel 58. In one embodiment, the gas permeable, liquid impermeable membrane 48 is secured to the body 50 adjacent the second end 54 of the body 50, as shown in fig. 6B.

Referring now to fig. 7, there is shown a perspective view of another embodiment of a filter member 16a constructed in accordance with the inventive concepts disclosed and claimed herein. Similar to the previously described embodiment, the filter member 16a includes a body 50a having a first end 52a, a second end 54a, and a sidewall 56a extending from the first end 52a to the second end 54 a. The side wall 56a of the body 50a defines a channel 58a (not shown) extending through the body 50a from the first end 52a to the second end 54 a. As in fig. 6A and 6B of the previous embodiments, the body 50a may have at least two annular protrusions 60B extending radially outwardly that slidably sealingly contact the inner surface 24 of the barrel 12. As shown in fig. 7, the body 50a may have three annular protrusions 60a spaced apart from each other. The filter member 16a also includes a gas permeable, liquid impermeable membrane 48 extending across the entire channel 58 a. In this embodiment, the gas permeable, liquid impermeable membrane 48 is secured to the body 50a adjacent the second end 54a of the body.

Referring now to fig. 8A and 8B, a perspective view and a cross-sectional view of another embodiment of a filter member 16B are shown, respectively. The filter member 16b includes a body 50b having a first end 52b, a second end 54b, and a sidewall 56b extending from the first end 52b to the second end 54 b. Similar to the previously described embodiments, the body 50b may have at least two radially outwardly extending annular projections 50b that slidably sealingly contact the inner surface 24 of the barrel 12. The side wall 56b of the body 50b defines a plurality of channels 58b extending through the body 50b from the first end 52b to the second end 54 b. In this embodiment, the plurality of channels 58B may be in parallel relationship to one another, as shown in FIG. 8B. Further, the filter member 16b may include a plurality of gas permeable, liquid impermeable membranes 48b, wherein at least one of the gas permeable, liquid impermeable membranes 48b extends across each of the plurality of channels 58b of the body 50 b. The filter member 16B may also include a plurality of porous filter materials 62 positioned between the first end 52B of the body 50B and each of the plurality of gas-permeable, liquid-impermeable membranes 48B to prevent solid particles from contacting the plurality of gas-permeable, liquid-impermeable membranes 48B, as shown in fig. 8B.

The at least one gas permeable, liquid impermeable membrane 48 may be formed of any suitable material such as, but not limited to, polytetrafluoroethylene, polyvinylidene fluoride, polyvinyl chloride, polyolefins such as polypropylene, polyethylene, polymethylpentene, polyamides, polysulfones, polyetheretherketones, polycarbonates, and combinations including any one of these. In one embodiment, the gas permeable, liquid impermeable membrane 48 is formed from a material including at least one of polytetrafluoroethylene, polypropylene, and polyethylene. The at least one gas permeable, liquid impermeable membrane 48 may have a thickness suitable to allow penetration upon application of a mechanical force. The at least one gas permeable, liquid impermeable membrane 48 may allow at least a portion of the gas portion of the bubble-forming fluid sample 32 to pass through the filter member 16 from the inlet side 44 to the outlet side 46 of the interior chamber 26. The at least one gas permeable, liquid impermeable membrane 48 also provides a fluid tight seal across the filter member 16 to prevent the liquid portion of the fluid sample 32 from passing from the inlet side 44 to the outlet side 46 to separate at least a portion of the gas portion of the fluid sample 32 from the liquid portion as the fluid sample 32 enters the interior chamber 26 via the inlet opening 28. The filter member 16 is pierceable so that the sample probe 72 can pass through the filter member 16 from the outlet side 46 to the inlet side 44 to draw the liquid portion of the fluid sample 32 from the inlet side 44 of the interior chamber 26.

As shown in fig. 1, the device 10 may be used in conjunction with a fluid sample collection device, such as a collection syringe 66 and a liquid sample analyzer 68, for transferring a fluid sample from the collection syringe 66 to the liquid sample analyzer 68 and removing bubbles from the fluid sample 32 having a liquid portion and a gas portion. Although fig. 1 shows apparatus 10 associated with collection syringe 66 and liquid sample analyzer 68, those skilled in the art will understand and appreciate that apparatus 10 may be independently associated with collection devices other than collection syringe 66, such as a vacuum tube, and medical devices other than liquid sample analyzer 68. The liquid sample analyzer 68 may be any suitable fluid testing device such as, but not limited to, a microfluidic device, a blood gas analyzer, a blood analyzer, a urine chemistry analyzer, and the like.

The liquid sample analyzer 68 includes a sample input port 70 and a sample probe 72 (fig. 2C and 3C). Sample input port 70 may be sized to frictionally receive and detachably secure at least a portion of nozzle cap 14 (e.g., a female luer fitting), as shown in fig. 1, to allow for "hands-free" operation of liquid sample analyzer 68 such that a fluid sample in device 10 may be drawn into liquid sample analyzer 68 via sample probe 72 without requiring a user to hold device 10.

Sample probe 72 may extend through filter member 16 from outlet side 46 to inlet side 44 of interior chamber 26 to draw at least a portion of fluid sample 32 from inlet side 44 of interior chamber 26 into liquid sample analyzer 68, as shown in fig. 2C and 3C. The sample probe 72 may have a length compatible with sampling from the inlet side 44 of the interior chamber 26.

The collection syringe 66 includes a syringe body 74 having a front end 76, a rear end 78, and a plunger 80. The syringe body 74 defines a reservoir 82 within which the fluid sample 32 may be received and then discharged through a dispensing opening 84 at the front end 76 of the syringe body 74. The rear end 78 of the syringe body 74 may be open and provided with a body flange 85 to facilitate collection and discharge of the fluid sample 32. The syringe body 74 may be any suitable size or shape for collecting a fluid sample, such as a cylindrical shape. The syringe body 74 may also include a collar 77 formed in a cylindrical shape concentric with the dispensing opening 84 to surround the dispensing opening 84. Collar 77 may include an inner peripheral surface in which is formed a threaded engagement portion 79 for engaging apparatus 10. The syringe body 74 may be constructed of any suitable material, such as glass or plastic. The syringe body 74 may have an outer diameter adapted to slide coaxially within the first end 18 of the device 10.

Plunger 80 may include a shaft 86 terminating at one end in a plunger flange 88 to facilitate collection and drainage of fluid sample 32. For example, the shaft 86 may have a cylindrical shape or a cylindrical shape, and may have a cross-section of a polygonal shape, such as a square, pentagon, hexagon, or cross shape. Plunger 80 may also include a plunger seal 90 secured to shaft 86 opposite plunger flange 88. Plunger 80 may be removably disposed within syringe body 74 and selectively movable within reservoir 82. Plunger seal 90 has a diameter that allows plunger seal 90 to form a fluid-tight seal when positioned within reservoir 82 such that liquid sample 32 is not movable past plunger seal 90. In addition, the plunger seal 90 prevents ambient air from moving from the rear end 78 of the syringe body 74 in a direction past the plunger seal 90. The plunger 80 is axially displaceable relative to the syringe body 74. Movement of the plunger 80 from the rear end 78 to the front end 76 of the syringe body 74 may cause at least a portion of the fluid sample 32 to be expelled from the reservoir 82 and introduced into the inlet opening 28 of the device 10 via the dispensing opening 84. Plunger 80 may be constructed of any suitable polymeric material known in the art.

To remove the gaseous portion (i.e., the air bubbles) of the fluid sample 32 from the liquid portion, a collection syringe 66 containing a volume of the fluid sample 32 within a reservoir 82 is releasably attached to the first end 18 of the cartridge 12, as shown in fig. 2A. As shown in fig. 2A-2C, the forward end 76 of the syringe body 74 may be interlockingly engaged with the device 10 by means of a threaded engagement portion 79.

As shown in fig. 4A and 4B, the cartridge 12 may include a cartridge connecting portion 94. In one embodiment, the threaded engagement portion 79 of the syringe body 74 is a male luer connector and the barrel connection portion 94 is a female luer connector, which in one exemplary embodiment includes a pair of threaded lugs 95 extending radially from the exterior of the barrel 12 and having a pitch, size, and geometry corresponding to the threaded engagement portion 79 of the syringe body 74. As shown in fig. 2A-2C, threaded engagement portion 79 may interlockingly engage cartridge connecting portion 94 such that significant relative movement between collection syringe 66 and device 10 is prevented to allow for "hands-free" operation of the liquid sample analyzer such that fluid sample from collection syringe 66 may be drawn into the liquid sample analyzer via device 10 without requiring a user to hold collection syringe 66 or device 10. It will be appreciated that other suitable connectors, such as luer slip connectors, may be utilized between the device 10 and the collection syringe 66. The first end 18 of the barrel 12 may include a female luer 96 (fig. 3A and 5).

In use, the collection syringe 66 and the device 10 are positioned in an upright orientation with the device 10 above the collection syringe 66 and the air bubbles in the fluid sample rising to the top of the fluid sample. The plunger 80 of the collection syringe 66 is axially displaced a distance along the reservoir 82 from the rear end 78 toward the front end 76 of the syringe body 74, as shown in fig. 2A. Movement of plunger 80 within reservoir 82 causes at least a portion of the gaseous portion (i.e., the bubbles) of fluid sample 32 to be expelled from reservoir 82 and through filter member 16 into interior chamber 26 of device 10 via inlet opening 28 and clot catcher 33. The gaseous portion of the fluid sample 32 passes through the filter member 16 and is then eventually expelled from the interior chamber 26 of the apparatus 10. Once at least a portion of the gaseous portion of fluid sample 32 has been removed from reservoir 82, plunger 80 experiences an initial resistance.

When sufficient force is applied to overcome this initial resistance, plunger 80 is advanced further into reservoir 82 toward front end 76 of syringe body 74, as shown in fig. 2B, thereby increasing the internal pressure of reservoir 82. As the internal pressure of reservoir 82 increases, it generates a force sufficient to expel at least a portion of the liquid portion of fluid sample 32 from reservoir 82 and into interior chamber 26 of cartridge 12 via inlet opening 28 and clot catcher 33. The fluid sample 32 entering the interior chamber 26 may cause the filter member 16 to be axially displaced along the interior chamber 26 toward the second end 20 of the cartridge 12, as shown in fig. 2B and 3B. The filter member 16 may be displaced such that it becomes disposed adjacent to the outlet opening 30. This arrangement prevents ambient air from entering the interior chamber 26 and prevents the fluid sample 32 from exiting the interior chamber 26 via the outlet opening 30. In some embodiments, the plunger 80 may extend partially into the reservoir 82, so less than all of the fluid sample 32 is transferred from the reservoir 82 into the interior chamber 26.

Once the liquid portion of the fluid sample 32 has been expelled from the reservoir 82 and contained within the interior chamber 26 of the apparatus 10, the sample probe 72 of the liquid sample analyzer 68 may be extended from the sample input port 70 and through the filter member 16 to extract the liquid portion of the fluid sample 32 from the inlet side 44 of the interior chamber 26, as shown in fig. 2C and 3C. In one embodiment, the sample probe 72 pierces the gas permeable, liquid impermeable membrane 48 of the filter member 16 to obtain fluid access to the inlet side 44 of the interior chamber 26.

No additional support is required when the fluid sample is drawn into the liquid sample analyzer 68 after the user initially inserts the device 10 into the sample input port 70. The connection between the collection syringe 66, the device 10 and the liquid sample analyzer 68 is sufficiently rigid to prevent gravity from tilting downward or to impart undue stress on the combination of connected elements so that hands-free operation can be performed without additional support structure to hold the connected elements together in proper alignment. In one non-limiting embodiment and as shown in fig. 1 and 2C, the connection between collection syringe 66, device 10, and liquid sample analyzer 68 is sufficiently rigid to support collection syringe 66 and device 10 in axially aligned relation with sample probe 72 of liquid sample analyzer 68. As such, the user need not remain at the liquid sample analyzer 68 and need not hold the device 10 and/or the collection syringe 66 while the fluid sample in the device 10 is drawn into the liquid sample analyzer 68 via the sample probe 72.

Referring now to fig. 9-11, another exemplary embodiment of an apparatus 100 constructed in accordance with the inventive concepts disclosed and claimed herein is shown. The apparatus 100 is similar to the apparatus 10 described above, except as described below. The apparatus 100 includes a cartridge 112 and a nozzle cap 114. The apparatus 100 is shown without the filter member 16, the filter member 16 being optional.

The barrel 112 includes a first end 118, a second end 120, a sidewall 122, and an inner surface 124. The barrel 112 may be of any suitable size and shape and formed of any suitable material, such as, but not limited to, plastics, such as polycarbonate, polystyrene, polyacrylate, and polyurethane, or medical grade polymers. A sidewall 122 of the barrel 112 extends between the first end 118 and the second end 120 of the barrel 112. The inner surface 124 of the barrel 112 defines an interior chamber 126. The first end 118 has an inlet opening 128 and the second end 120 has an outlet opening 130.

The interior chamber 126 may have any suitable size and shape to accommodate a fluid sample (e.g., the fluid sample 32 shown in fig. 2A-2C). For example, the fluid sample may be blood, serum, plasma, or other bodily fluids. The fluid sample may comprise a gas portion and a liquid portion. For example, the gaseous portion of the fluid sample may be air or other gas. A portion of the gas portion may form bubbles in the fluid sample.

The inlet opening 128 and the outlet opening 130 may have a cross-section of any suitable geometry, including but not limited to circular, elliptical, square, or rectangular. The inlet opening 128 and the outlet opening 130 may be molded or cut into the barrel 112 or otherwise prefabricated. The inlet opening 128 may be formed to capture clots as the fluid sample 32 enters the interior chamber 126 via the inlet opening 128. The cartridge 112 may include a clot catcher 133 disposed across the inlet opening 28 so as to define a plurality of apertures 135 sized and shaped to allow fluid to pass into the interior chamber 126, but to catch or prevent solids (i.e., clots) greater than a predetermined size from passing into the interior chamber 126. Solids that may be captured by the clot catcher 133 and prevented from flowing into the interior chamber 126 may include clots and other solids present in the fluid sample 32 having a predetermined size, for example, of at least about 0.17+/-0.05mm in diameter or greater. In one non-limiting embodiment, the clot catcher 133 is star-shaped (e.g., as illustrated in fig. 10C and 10D as clot catcher 133) so as to cooperate with the inlet opening 128 to define five apertures 135 (only one of which is numbered in fig. 10C and 10D) through which fluid enters into the interior chamber 126. In this non-limiting embodiment, five apertures 135 are formed between the five arms of the star-shaped clot catcher 133, wherein the arms may be sized and shaped to act as a capture element to capture and prevent a clot from entering the interior chamber 126 (e.g., as shown in fig. 10C as a clot catcher 133 with apertures 135).

The outlet opening 130 may be provided with a nozzle cap 114. The nozzle cap 114 includes a cap portion 136 and a tubular portion 138, the tubular portion 138 having an aperture 140 extending therethrough. The tubular portion 138 may be in the form of a male luer for frictional engagement with the sample input port 70 (fig. 1) of the fluid analyzer 68 to allow for "hands-free" operation of the fluid sample analyzer 68 such that the fluid sample in the device 100 may be drawn into the fluid sample analyzer 68 without requiring the user to hold the device 100.

The aperture 140 may have a cross-section of any suitable geometry including, but not limited to, circular, oval, square, or rectangular. The aperture 140 may be sized to have a diameter suitable for slidably axially receiving the sample probe 72. The base of the tubular portion 138 flares outwardly and merges with the cap portion 136. Nozzle cap 114 may be coupled to the second end of barrel 112 in a suitable manner such that aperture 140 is aligned with outlet opening 130 to allow fluid communication with interior chamber 126.

A gas permeable, liquid impermeable membrane 149 (fig. 10A) may be secured to the cartridge 112 adjacent the second end 120 of the cartridge 112 to provide a fluid tight seal across the outlet opening 130 to prevent the liquid portion of the fluid sample from entering from the interior chamber 126 into the outlet opening 130. The gas-permeable, liquid-impermeable membrane 149 is pierceable so that the sample probe 72 can pass through the gas-permeable, liquid-impermeable membrane 149 to withdraw the liquid portion of the fluid sample from the interior chamber 126.

The gas permeable, liquid impermeable membrane 149 may be formed of any suitable material such as, but not limited to, polytetrafluoroethylene, polyvinylidene fluoride, polyvinyl chloride, polyolefins such as polypropylene, polyethylene, polymethylpentene, polyamides, polysulfones, polyetheretherketones, polycarbonates, and combinations including any one of these. In one embodiment, the gas permeable, liquid impermeable membrane 149 is formed from a material including at least one of polytetrafluoroethylene, polypropylene, and polyethylene. The gas permeable, liquid impermeable membrane 149 may have a thickness suitable to allow penetration upon application of a mechanical force.

Similar to device 10, device 100 may be used in conjunction with collection syringe 66 and liquid sample analyzer 68.

To establish fluid communication between collection syringe 66 and device 100, collection syringe 66, which contains a volume of fluid sample within reservoir 82, may be interlockingly engaged with first end 118 of barrel 112. As shown in fig. 11, the forward end 76 of the syringe body 74 may be interlockingly engaged with the device 100 by means of a threaded engagement portion 79. As shown in fig. 9 and 10B, the cartridge 112 may include a cartridge connecting portion 194. In one embodiment, the threaded engagement portion 79 of the syringe body 74 is a male luer connector and the barrel connection portion 194 is a female luer connector, which in one exemplary embodiment includes a pair of threaded lugs 195, the threaded lugs 195 extending radially from the exterior of the barrel 112 and having a pitch, size, and geometry corresponding to the threaded engagement portion 79 of the syringe body 74. As shown in fig. 11, the threaded engagement portion 79 may interlockingly engage the cartridge connecting portion 194 such that significant relative movement between the collection syringe 66 and the device 100 is prevented to allow for "hands-free" operation of the liquid sample analyzer 68 such that a fluid sample from the collection syringe 66 may be drawn into the liquid sample analyzer 68 via the device 100 without requiring a user to hold the collection syringe 66 or the device 100. It will be appreciated that other suitable connectors, such as luer slip connectors, may be utilized between the device 100 and the collection syringe 66. The first end 118 of the barrel 112 may include a female luer 196 (fig. 10A).

Referring now to fig. 12-15, the apparatus 100 may further include a chromatography assembly 200 for detecting free hemoglobin in a fluid sample, such as the fluid sample 32. The chromatography measurement assembly 200 is housed in a chromatography measurement chamber 211 (fig. 12 and 14) of the cartridge 112. In one non-limiting embodiment, the chromatography assay chamber 211 may be formed in part by a portion of the outer surface of the sidewall 122 of the cartridge 112 and the cap 212. The chamber 211 is in fluid communication with the interior chamber 126 of the cartridge 112 via a channel 210 downstream of the clot catcher 133 and upstream of the membrane 149, as shown in fig. 14. The chromatography assay chamber 211 is configured to hold the chromatography assay assembly 200 such that at least a portion of the fluid sample in the interior chamber 126 of the cartridge 112 enters the chromatography assay chamber 211 and contacts the chromatography assay assembly 200.

The cap 212 may be formed entirely or partially from the same material as the material from which the barrel 112 is formed. For example, the cover 212 may be formed of any suitable material, such as, but not limited to, plastics, such as polycarbonate, polystyrene, polyacrylate, and polyurethane, or medical grade polymers. The cover 212 may be transparent or formed with a transparent window for viewing the chromatography assembly 200. In a manner to be described below, the cover 212 may include a fill panel 212a for observing when a sufficient volume of the fluid sample 32 has entered the chamber 211, and a read panel 212b for assessing the level of hemolysis, as shown in fig. 12 and 14. In one non-limiting embodiment, the fill pane 212a and the read pane 212b may be defined by the remainder of the cover 212 by reducing the thickness of the cover 212 so as to define the fill pane 212a and the read pane 212b. In another embodiment, the fill pane 212a and the read pane 212b may be formed of a transparent material, such as glass, that is different from the material used to form the cover 212. In another embodiment, the fill pane 212a and the read pane 212b may be voids or openings through the cover 212.

As shown in fig. 13A, 13B and 14, the chromatography assay assembly 200 includes a sample application pad 214 in fluid contact with a chromatography detection pad 216. Sample application pad 214 is configured for applying a portion of fluid sample 32 to chromatographic assay assembly 200. The sample application pad 214 may receive and absorb (a portion of) the fluid sample 32, and the fluid sample 32 from the internal chamber 126 via the channel 210 may then be absorbed from the sample application pad 214 into the chromatographic detection pad 216.

Referring to fig. 13A, the sample application pad 214 may be formed of two layers having different sizes and dimensions, and do not completely overlap each other. The sample application pad 214 includes a first layer 230 formed of a pre-filter material, such as a fiberglass material, and a second layer 232 formed of a different filter material, such as an asymmetric polysulfone material. The first layer 230 has a first end 240, a second end 242, an upper surface 244, and a lower surface 246. The second layer 232 has a first end 247, a second end 249, an upper surface 252, and a lower surface 254. At least a portion of the first layer 230 adjacent its second end 242 overlaps a portion of the second layer 232 between its first and second ends 247, 249. The overlapping portions of the first layer 230 and the second layer 232 may be attached to each other, or the overlapping portions of the first layer 230 may simply be laminated on the second layer 232 such that a portion of the lower surface 246 of the first layer 230 is in contact with a portion of the upper surface 252 of the second layer 232.

The lower surface 246 of the first layer 230 is aligned with and in fluid communication with the channel 210 and is positioned to receive the fluid sample 32 from the interior chamber 126 of the cartridge 112.

Thus, the first layer 230 and the second layer 232 of the sample application pad 214 may partially overlap each other to form an overlapping portion and a non-overlapping portion. Referring to the workflow shown in fig. 13B of the chromatography assembly 200, the non-overlapping portion of the first layer 230 (at the lower surface 246) may receive and absorb a portion of the fluid sample 32 (shown in the second figure of fig. 13B) from the interior chamber 126 via the channel 210. The fluid sample 32 may then be absorbed into the chromatographic detection pad 216 from the overlapping portion of the sample application pad 214 (shown in the third and fourth figures of fig. 13B). In particular, when the fluid sample 32 is absorbed or saturated throughout the first layer 230 (which may be seen through the fill pane 212a shown in fig. 12), then the fluid sample 32 may be filtered or passed from the overlapping portion of the first layer 230 (at the lower surface 246) to the overlapping portion of the second layer 232 (at the upper surface 252), as shown in the third figure of fig. 13B. When the fluid sample 32 is absorbed or saturated throughout the second layer 232, the fluid sample 32 may then be filtered or passed from the second layer 232 (at the lower surface 254) to the sample application site 248 of the chromatographic detection pad 216 (at the portion of its upper surface that overlaps the lower surface 254 of the second layer 232), as shown in the third and fourth figures of fig. 13B. The components of the fluid sample 32 (i.e., plasma and free hemoglobin, if present) absorbed by the chromatographic detection pad 216 then flow from the sample application site 248 via capillary action to the detection site 250 on the chromatographic detection pad 216 for detection of free hemoglobin indicative of hemolysis (as shown in the fourth figure).

The sample application pad 214 is permeable to plasma and free hemoglobin present in the fluid sample 32, but impermeable to red blood cells, so that red blood cells present in the fluid sample 32 are retained within the two layers 230 and 232 of the sample application pad 214 and are thereby prevented from flowing therethrough to the chromatographic detection pad 216. Thus, the sample application pad 214 acts as a filter to filter the fluid sample 32 received through the channel 210 such that red blood cells present in the fluid sample 32 (received from the interior chamber 126 via the channel 210) are filtered out and retained within the two layers 230 and 232, while plasma and free hemoglobin present in the fluid sample 32 may pass through the pores of the sample application pad 214 and be received by and absorbed into the chromatographic detection pad 216.

The multi-layer or dual-layer sample application pad 214 advantageously provides improved red blood cell removal or filtration and hemolysis detection (by detecting the presence of free hemoglobin on the chromatographic detection pad 216) because, for example, the first layer 230 of the sample application pad 214 is capable of retaining at least a portion of the red blood cells and other larger cellular components in the fluid sample 32 (without lysing the cells) and thereby reducing the amount of red blood cells and other larger cellular components flowing into the second layer 232 of the sample application pad 214 so as not to overburden the filtration that occurs at the second layer 232. In particular, but not by way of limitation, the first layer 230 and/or the second layer 232 have varying pore sizes that decrease in size as one moves from the first layer 230 to the lower surface 254 of the second layer 232 (i.e., in a direction toward the chromatographic detection pad).

The chromatographic detection pad 216 defines a path for capillary fluid flow. The components of fluid sample 32 that are capable of flowing through sample application pad 214 then flow through chromatographic detection pad 216 (which may also be referred to as capillary flow) by capillary action. The chromatographic test pad 216 has a first end portion and a second end portion. The chromatographic test pad 216 can be made of any suitable material that allows blood plasma and free hemoglobin from the fluid sample 32 to freely flow through it by capillary action. As one non-limiting example, the chromatographic detection pad 216 may be a nitrocellulose membrane. The chromatographic test pad 216 may have small holes through which certain components of the fluid sample 32 move by capillary action. Most of the apertures of chromatographic detection pad 216 may all be of substantially the same size or fall within a range of values.

Referring to fig. 13A, a first end portion of chromatographic test pad 216 is in fluid contact with the lower surface 254 of the second layer 232 of sample application pad 214 and forms a sample application site 248 on chromatographic test pad 216. As shown in fig. 13A-13B, chromatographic detection pad 216 also has a detection site 250 spaced apart from (and, in certain non-limiting embodiments, downstream of) the first end portion/sample application site 248, wherein detection site 250 is disposed between or substantially adjacent to or closer to the second end portion than the first end portion.

Sample application pad 214 covers only the portion of chromatographic detection pad 216 adjacent its first end portion and sample application site 248, but does not cover its detection site 250; in this way, the flow of sample through chromatographic detection pad 216 into its detection site 250 can be seen via the reading pane 212b of the lid 212 (as shown in fig. 12 and 14).

Referring to fig. 13A, the chromatography assay assembly 200 may also include a backing material 218 to which the lower surface of the chromatography detection pad 216 is attached or otherwise associated (e.g., without limitation, via double-sided tape).

When a fluid sample 32 (such as, but not limited to, a whole blood sample, urine, or other liquid sample containing red blood cells) is applied to the chromatographic assay assembly 200, free hemoglobin flows through the sample application pad 214 into the chromatographic test pad 216 and then from the sample application site 248 of the chromatographic test pad 216 to the test site 250 thereof. In this way, free hemoglobin (indicative of hemolysis) can be detected at the detection site 250 by a color change due to the red color of the free hemoglobin. The chromatographic detection pad 216 may be formed of a material that is white in color, allowing for visual reading or detection of hemolysis via a color change of the chromatographic detection pad 216 at the detection site 250 through the reading pane 212b of the cover 212.

While one specific non-limiting embodiment of a chromatography assay 200 is shown in fig. 13A and 13B, it should be understood that the design and construction of the chromatography assay 200 shown is for illustrative purposes only. The scope of the present disclosure includes adjusting the design and construction of the chromatography assay of the present disclosure so long as the chromatography assay is still capable of functioning in accordance with the present disclosure.

For example, and without limitation, it will be appreciated that the first layer 230 (of pre-filter material) and the second layer 232 (of asymmetric polysulfone material) of the sample application pad 214 need not be symmetrical to each other (i.e., they may differ from each other in size, length, width, and/or thickness). In addition, the first layer 230 and the second layer 232 of the sample application pad 214 need not conform to each other, and thus each layer may have a region that does not overlap with the other layer. The only requirement is that at least a portion of the first layer 230 must overlap with a sufficient portion of the second layer 232 so that the sample can flow through the first layer 230 into the second layer 232 and then from the second layer 232 into the sample application site 248 of the chromatographic detection pad 216.

In use, the collection syringe 66 is interlockingly engaged with the device 100 and both are positioned in an upright orientation with the device 100 above the collection syringe 66. When the apparatus 100 does not include a filter member 16, a user may remove bubbles from the fluid sample in a conventional manner as described above. The plunger 80 of the collection syringe 66 is axially displaced a distance along the reservoir 82 from the rear end 78 toward the front end 76 of the syringe body 74. Movement of plunger 80 within reservoir 82 causes at least a portion of the fluid sample to be expelled from reservoir 82 and into interior chamber 126 of device 100 via inlet opening 128 and through clot catcher 133. Any gaseous portion of the fluid sample passes through a gas permeable, liquid impermeable membrane 149.

A portion of the fluid sample enters the chromatography assay chamber 211 via channel 210 and contacts the sample application pad 214. Fig. 13B illustrates the workflow of the chromatography assembly 200. A fluid sample 32 (e.g., a blood sample) is applied to the lower surface 246 of the first layer 230 of the sample application pad 214 and into the first layer 230, as shown in the second drawing of fig. 13B. The fluid sample 32 saturates the first layer 230 and flows through the overlap into the second layer 222 (third figure). Saturation of the first layer 230 may be determined by observing the first layer 230 through a fill pane 212a of the cover 212, the fill pane 212a being aligned with at least a portion of the sample application pad 214.

When the first layer 230 is saturated, plasma and free hemoglobin (if present) from the blood sample 32 then passes through the second layer 232 and into the chromatographic detection pad 216 and flows from the sample application site 248 to its detection site 250 in order to detect any hemolysis present (fourth figure). A control line may be present at or near the detection site 250 on the chromatographic detection pad 216. In one non-limiting embodiment, plasma reaching the detection site 250 changes the control line from yellow to blue, indicating that the chromatography assembly 200 is ready to be read through the reading pane 212b aligned with the detection site 250.

Fig. 15 illustrates one non-limiting embodiment of a reference device 260, which reference device 260 may be used with the chromatography assembly 200 to visually determine the level of hemolysis in the fluid sample 32. The reference device 260 contains a plurality of reference colors (such as, but not limited to, reference colors 262, 264, 266, 268, and 270, wherein color 262 has the white/default color of the chromatographic detection pad 16 and serves as a negative control, and colors 264, 266, 268, and 270 are various pink/red hues with increased intensity/hue, wherein darker intensities/hues are associated with higher amounts/degrees of hemolysis); the five reference colors shown are for illustrative purposes only). In addition, the reference device 260 also includes a legend 272 that correlates each of the reference colors 262, 264, 266, 268, and 270 with a particular concentration of free hemoglobin. That is (and for purposes of illustration only), color 262 of legend 272 is a negative control, while color 264 indicates that 0mg/dL of free hemoglobin is present, color 266 indicates that 100mg/dL of free hemoglobin is present, color 268 indicates that 250mg/dL of free hemoglobin is present, and color 270 indicates that 500mg/dL of free hemoglobin is present. In this manner, an individual may determine the level of hemolysis in a liquid biological sample in any environment, including but not limited to point of care or home environments, by comparing the color at the detection site 250 to the reference colors 264-270 of the reference device 260.

The design and construction of the reference device 260 of fig. 15 is shown for illustrative purposes only; it will be appreciated that the reference device 260 may have fewer than five reference colors or more than five reference colors disposed thereon (e.g., without limitation, two, three, four, five, six, seven, eight, nine, ten, or more reference colors disposed thereon). In addition, the shape and arrangement of the reference colors may be different. Furthermore, legend 272 may also be provided with different shapes/arrangements than shown in fig. 15. The design and configuration of each of the components of the reference device 260 (such as, but not limited to, the reference color and legend 272) can be readily modified by one of ordinary skill in the art to possess any design and configuration that will allow the reference device 260 to function in accordance with the present disclosure. Alternatively, a medical diagnostic device may be used to optically detect the level of hemolysis in the fluid sample, such as by reading pane 212b, wherein the medical diagnostic device comprises an optical sensor, a processor, and a light source directed at detection site 250. The medical diagnostic device may be a liquid sample analyzer 68 or a different device.

A method for optically testing a fluid sample for hemolysis may include: as described above, after a portion of the liquid sample 32 has been applied to the sample application pad 214 and free hemoglobin has flowed from the sample application site 248 through the sample application pad 214 and into the chromatographic detection pad 216 to the detection site 250, the characteristics of the light reflected by the detection site 250 of the chromatographic assay assembly 200 are measured. The measured amounts of, for example, red, orange, green and/or blue light may then be used to determine the level of free hemoglobin by, for example, comparing the measured amounts to one or more reference values. In an exemplary embodiment, the method for hemolyzing a test fluid sample may be performed optically by a medical diagnostic device (not shown) or visually by a medical provider. For example, the medical provider may visually compare the completed chromatography assay 200 with a reference device (such as, but not limited to, reference device 260 shown in fig. 15) that contains a plurality of reference colors that each correspond to a different level of hemolysis to visually determine hemolysis of liquid sample 32.

The method may detect hemoglobin levels that exceed a predetermined interference value (e.g., the manufacturer's interference level). If the sample is above the interference value, the sample will be marked to inform the end user (i.e., the relevant healthcare provider) that the sample has been hemolyzed and thus compromised and not applied for further testing.

If the level of hemolysis determined in the sample (by visual and/or optical detection of free hemoglobin levels as discussed above) is below a predetermined threshold, the sample is not compromised and can undergo further testing. To subject the undamaged sample to further testing, the apparatus 100 is engaged with a test instrument, such as a liquid sample analyzer 68, with the collection syringe 66 engaged with the apparatus 100. The sample probe 72 (fig. 3C) of the liquid sample analyzer 68 may then be extended from the sample input port 70 and through the gas permeable, liquid impermeable membrane 149 to withdraw the liquid portion of the fluid sample from the interior chamber 126 in a "hands-free" manner without requiring the user to hold the collection syringe 66 or device 100.

No additional support is required when the fluid sample is drawn into the liquid sample analyzer 68 after the user initially inserts the device 100 into the sample input port 70. The connection between collection syringe 66, device 100 and liquid sample analyzer 68 is sufficiently rigid to prevent gravity from tilting downward or to impart undue stress on the combination of connected elements so that hands-free operation can be performed without additional support structure to hold the connected elements together in proper alignment. Similar to that shown with reference to apparatus 10 in fig. 2C, the connection between collection syringe 66, apparatus 100 and liquid sample analyzer 68 is sufficiently rigid to support collection syringe 66 and apparatus 100 in axially aligned relation with sample probe 72 of liquid sample analyzer 68. As such, the user need not remain at the liquid sample analyzer 68 and need not hold the device 100 and/or the collection syringe 66 while the fluid sample in the device 100 is drawn into the liquid sample analyzer 68 via the sample probe 72.

From the above description, it is apparent that the inventive concepts disclosed herein are well-suited to carry out the objects and obtain the advantages mentioned herein as well as the advantages inherent in the inventive concepts disclosed herein. Although exemplary embodiments of the inventive concepts disclosed herein have been described for purposes of this disclosure, it will be understood that many modifications may be made which will be readily apparent to those skilled in the art, and which may be made without departing from the scope of the inventive concepts disclosed herein and defined in the appended claims.

The following is a list of non-limiting illustrative embodiments of the inventive concepts disclosed herein:

illustrative embodiment 1 an illustrative apparatus for transferring a fluid sample having a liquid portion and a gas portion from a fluid sample collection apparatus to a liquid sample analyzer, comprising:

a cartridge having a first end, a second end opposite the first end, a sidewall extending between the first end and the second end, an inner surface defining an interior chamber, and an outer surface defining at least a portion of a chromatography chamber in fluid communication with the interior chamber via a channel passing through the outer surface of the cartridge, the first end having an inlet opening with a clot catcher extending across the inlet opening upstream of the channel, and the second end having an outlet opening; and

A chromatography assay assembly housed in the chromatography assay chamber, the chromatography assay assembly configured to detect the presence of free hemoglobin in the fluid sample, the chromatography assay assembly comprising:

a sample application pad configured to receive the fluid sample from the interior chamber, wherein the sample application pad is formed from a first layer of pre-filter material and a second layer of asymmetric polysulfone material, wherein the sample application pad is permeable to plasma and the free hemoglobin and impermeable to red blood cells; and

a chromatographic detection pad in fluid contact with the sample application pad, the chromatographic detection pad configured to detect the presence of the free hemoglobin.

Illustrative embodiment 2 the illustrative apparatus of illustrative embodiment 1 wherein the chromatography chamber is defined by a portion of the exterior surface of the cartridge and a cap having: a transparent fill pane aligned with the sample application pad for viewing the flow of the fluid sample through the sample application pad; and a transparent reading pane aligned with a detection site of the chromatographic detection pad for viewing the detection site.

Illustrative embodiment 3 the illustrative device of any of the preceding illustrative embodiments, wherein the first end of the cartridge has a cartridge connecting portion engageable with a portion of the fluid sample collection device, and wherein the second end of the cartridge has a tubular portion configured to engage with the liquid sample analyzer, whereby the combination of the fluid sample collection device and the cartridge can be attached to the liquid sample analyzer without additional support.

Illustrative embodiment 4 the illustrative device of any of the preceding illustrative embodiments, wherein the cartridge connecting portion comprises at least one threaded lug extending radially outward from the sidewall of the cartridge so as to be interlockingly engageable with a portion of the fluid sample collection device.

Illustrative embodiment 5 the illustrative device of any of the preceding embodiments, wherein the cartridge connecting portion comprises a pair of threaded lugs extending radially outwardly from the sidewall of the cartridge so as to be interlockingly engageable with the fluid sample collection device.

Illustrative embodiment 6. The illustrative apparatus of any of the preceding illustrative embodiments, wherein the barrel connection portion is a female luer connector.

Illustrative embodiment 7. The illustrative device of any of the foregoing illustrative embodiments, wherein the tubular portion of the cartridge is a male luer connector configured to engage with the liquid sample analyzer.

Illustrative embodiment 8. The illustrative apparatus of any of the preceding illustrative embodiments, further comprising a gas permeable, liquid impermeable membrane secured to the cartridge adjacent the second end of the cartridge, the gas permeable, liquid impermeable membrane being pierceable, whereby the sample probe is configured to pass through the gas permeable, liquid impermeable membrane to the interior chamber.

Illustrative embodiment 9. The illustrative apparatus of any of the preceding illustrative embodiments, wherein the gas permeable, liquid impermeable membrane is formed from a material comprising at least one of polytetrafluoroethylene, polypropylene, and polyethylene.

The illustrative apparatus of any of the preceding illustrative embodiments, further comprising:

a filter member disposed within the interior chamber, whereby the filter member defines an inlet side and an outlet side of the interior chamber, and whereby the filter member is positionable between the first end and the second end of the cartridge, the filter member having at least one gas permeable, liquid impermeable membrane configured to permit at least a portion of the gas portion of the fluid sample to pass through the filter member from the inlet side to the outlet side of the interior chamber, and to provide a fluid-tight seal across the filter member to prevent the liquid portion of the fluid sample from passing from the inlet side to the outlet side to separate at least a portion of the gas portion of the fluid sample from the liquid portion when the fluid sample enters the interior chamber via the inlet opening,

Wherein the filter member is pierceable, whereby a probe is configured to pass through the filter member from the outlet side to the inlet side to draw the liquid portion of the fluid sample from the inlet side of the interior chamber.

Illustrative embodiment 11. The apparatus of any of the foregoing illustrative embodiments, wherein the filter member is slidably disposed in the interior chamber of the cartridge.

Illustrative embodiment 12 an illustrative kit comprising:

the apparatus of any of the preceding illustrative embodiments; and

a reference device comprising a plurality of reference colors, wherein each reference color corresponds to a different level of hemolysis.

Illustrative embodiment 13. An illustrative method of transferring a fluid sample having a liquid portion and a gas portion from a fluid sample collection device to a liquid sample analyzer having a sample probe, the method comprising:

obtaining a device having a cartridge with a first end, a second end, a sidewall extending between the first end and the second end, and an inner surface defining an interior chamber, the first end having an inlet opening, wherein a clot catcher extends across the inlet opening, and the second end having an outlet opening;

Transferring at least a portion of the fluid sample from the fluid sample collection device to the interior chamber of the cartridge via the inlet opening, whereby the fluid sample passes through the clot catcher at the inlet opening to capture solids in the fluid sample;

transferring a portion of the fluid sample from the interior chamber of the cartridge to a chromatography assay chamber and a chromatography assay assembly housed in the chromatography assay chamber, the chromatography assay chamber in fluid communication with the interior chamber downstream of the clot catcher;

detecting the presence of free hemoglobin in the fluid sample by the chromatography assembly; and

transferring the fluid sample from the internal chamber to the liquid sample analyzer using the sample probe.

Illustrative embodiment 14. The illustrative method of embodiment 13, wherein the detecting step comprises:

applying the fluid sample to a sample application pad of the chromatography assay assembly and allowing plasma and the free hemoglobin present in the fluid sample to flow through the sample application pad to a chromatography detection pad while retaining red blood cells present in the fluid sample in the sample application pad;

Flowing the plasma and the free hemoglobin from the sample application site of the chromatographic test pad to the test site of the chromatographic test pad by capillary action; and

the color change at the detection site is visually compared to a reference device comprising a plurality of reference colors, wherein each reference color corresponds to a different level of hemolysis.

Illustrative embodiment 15 the illustrative method of any of the preceding embodiments, wherein the sample application pad comprises a first layer and a second layer, and wherein the applying step further comprises saturating the first layer with the fluid sample, and transferring the fluid sample from the first layer to the second layer to saturate the second layer with the fluid sample.

The illustrative embodiment 16. The illustrative method combination of any of the foregoing illustrative embodiments, wherein the chromatography assay chamber is defined by a portion of an outer surface of the cartridge and a cap having a fill pane aligned with the sample application pad and a read pane aligned with the detection site of the chromatography detection pad, and wherein the applying step further comprises observing the sample application pad through the fill pane of the cap to determine whether sample application is saturated with the fluid sample.

Illustrative embodiment 17 the illustrative method of any of the preceding illustrative embodiments, wherein the visually comparing step comprises viewing the detection site through the reading pane of the cover.

Illustrative embodiment 18. The illustrative method of any of the foregoing illustrative embodiments, wherein the step of transferring at least a portion of the fluid sample from the fluid sample collection device further comprises engaging the first end of the cartridge with a portion of the fluid sample collection device, and wherein the step of transferring the fluid sample from the interior chamber to the liquid sample analyzer further comprises engaging the second end of the cartridge with the liquid sample analyzer, whereby the combination of the fluid sample collection device and the cartridge is attached to the liquid sample analyzer without additional support.

Illustrative embodiment 19 the illustrative method of any one of the preceding illustrative embodiments, wherein the hemolysis detection of the visual comparison step is determined to be below a predetermined hemolysis threshold prior to transferring the fluid sample from the internal chamber to the liquid sample analyzer.

Illustrative embodiment 20. The illustrative method of any of the preceding illustrative embodiments, wherein the step of engaging the first end further comprises threading the first end of the cartridge with the portion of the fluid sample collection device to interlockingly engage the cartridge with the fluid sample collection device.

The illustrative method of any of the preceding illustrative embodiments, wherein the first end of the barrel has a barrel connection portion that is a male luer connector, wherein the portion of the fluid sample collection device has a female luer connector, and wherein the step of engaging the first end further comprises engaging the male luer connector of the barrel with the female luer connector of the fluid sample collection device.

The illustrative embodiment 22. The illustrative method of any of the preceding illustrative embodiments, wherein the second end of the cartridge has a tubular portion that is a male luer connector, and wherein the step of engaging the second end comprises engaging the male luer connector of the cartridge within a sample input port of the liquid sample analyzer.

Illustrative embodiment 23. The method of any of the foregoing illustrative embodiments, wherein the steps of engaging the first end and engaging the second end further comprise axially aligning the fluid sample collection device and the cartridge with the sample probe.

Illustrative embodiment 24. The illustrative method of any of the preceding illustrative embodiments, wherein the apparatus further comprises a gas permeable, liquid impermeable membrane secured to the barrel adjacent the second end of the barrel, and wherein the step of transferring the fluid sample from the interior chamber of the barrel further comprises passing the sample probe through the gas permeable, liquid impermeable membrane to the interior chamber of the barrel.

Illustrative embodiment 25 the illustrative method of any one of the preceding illustrative embodiments, further comprising:

contacting the fluid sample with a filter member disposed within the interior chamber, the filter member defining an inlet side and an outlet side of the interior chamber, the filter member having a gas permeable, liquid impermeable membrane;

separating at least a portion of the gaseous portion of a liquid sample from the liquid portion of the fluid sample by contacting the fluid sample with the gas permeable, liquid impermeable membrane such that at least a portion of the gaseous portion of the fluid sample passes through the filter member from the inlet side to the outlet side of the internal chamber and thereby prevents the liquid portion of the fluid sample from passing from the inlet side to the outlet side; and

At least a portion of the liquid portion of the fluid sample is collected from the inlet side of the interior chamber.

Illustrative embodiment 26. The method of any of the foregoing illustrative embodiments, wherein the step of collecting the fluid sample from the interior chamber of the cartridge further comprises passing the sample probe through the gas permeable, liquid impermeable membrane to the inlet side of the interior chamber of the cartridge.

Claims

1. An apparatus for transferring a fluid sample having a liquid portion and a gas portion from a fluid sample collection apparatus to a liquid sample analyzer, comprising:

2. The apparatus of claim 1, wherein the chromatography chamber is defined by a portion of the outer surface of the cartridge and a cover having: a transparent fill pane aligned with the sample application pad for viewing the flow of the fluid sample through the sample application pad; and a transparent reading pane aligned with a detection site of the chromatographic detection pad for viewing the detection site.

3. The device of claim 1, wherein the first end of the cartridge has a cartridge connection portion engageable with a portion of the fluid sample collection device, and wherein the second end of the cartridge has a tubular portion configured to engage with the liquid sample analyzer, whereby the combination of the fluid sample collection device and the cartridge is attachable to the liquid sample analyzer without additional support.

4. A device according to claim 3, wherein the cartridge connecting portion comprises at least one threaded lug extending radially outwardly from the sidewall of the cartridge so as to be interlockingly engageable with a portion of the fluid sample collection device.

5. A device according to claim 3, wherein the cartridge connecting portion comprises a pair of threaded lugs extending radially outwardly from the side wall of the cartridge so as to be interlockingly engageable with the fluid sample collection device.

6. The apparatus of claim 3, wherein the cartridge connecting portion is a female luer connector.

7. The apparatus of claim 3, wherein the tubular portion of the cartridge is a male luer connector configured to engage with the liquid sample analyzer.

8. The apparatus of claim 1, further comprising a gas permeable, liquid impermeable membrane secured to the cartridge adjacent the second end of the cartridge, the gas permeable, liquid impermeable membrane being pierceable, whereby a sample probe is configured to pass through the gas permeable, liquid impermeable membrane to the interior chamber.

9. The apparatus of claim 8, wherein the gas permeable, liquid impermeable membrane is formed from a material comprising at least one of polytetrafluoroethylene, polypropylene, and polyethylene.

10. The apparatus of claim 1, further comprising:

11. The apparatus of claim 10, wherein the filter member is slidably disposed in the interior chamber of the cartridge.

12. A kit, comprising:

the apparatus of claim 1; and

13. A method of transferring a fluid sample having a liquid portion and a gas portion from a fluid sample collection device to a liquid sample analyzer having a sample probe, the method comprising:

14. The method of claim 13, wherein the detecting step comprises:

15. The method of claim 14, wherein the sample application pad comprises a first layer and a second layer, and wherein the applying step further comprises saturating the first layer with the fluid sample, and transferring the fluid sample from the first layer to the second layer to saturate the second layer with the fluid sample.

16. The method of claim 14, wherein the chromatography chamber is defined by a portion of an outer surface of the cartridge and a cover having a fill pane aligned with the sample application pad and a read pane aligned with the detection site of the chromatography detection pad, and wherein the applying step further comprises observing the sample application pad through the fill pane of the cover to determine whether sample application is saturated with the fluid sample.

17. The method of claim 16, wherein the visual comparison step includes viewing the detection site through the reading pane of the cover.

18. The method of claim 13, wherein transferring at least a portion of the fluid sample from the fluid sample collection device further comprises engaging the first end of the cartridge with a portion of the fluid sample collection device, and wherein transferring the fluid sample from the interior chamber to the liquid sample analyzer further comprises engaging the second end of the cartridge with the liquid sample analyzer, whereby the combination of the fluid sample collection device and the cartridge is attached to the liquid sample analyzer without additional support.

19. The method of claim 18, wherein the hemolysis detection of the visual comparison step is determined to be below a predetermined hemolysis threshold prior to transferring the fluid sample from the internal chamber to the liquid sample analyzer.

20. The method of claim 18, wherein the step of engaging the first end further comprises threading the first end of the cartridge with the portion of the fluid sample collection device to interlockingly engage the cartridge with the fluid sample collection device.

21. The method of claim 20, wherein the first end of the barrel has a barrel connection portion that is a male luer connector, wherein the portion of the fluid sample collection device has a female luer connector, and wherein the step of engaging the first end further comprises engaging the male luer connector of the barrel with the female luer connector of the fluid sample collection device.

22. The method of claim 20, wherein the second end of the cartridge has a tubular portion that is a male luer connector, and wherein the step of engaging the second end comprises engaging the male luer connector of the cartridge within a sample input port of the liquid sample analyzer.

23. The method of claim 18, wherein the steps of engaging the first end and engaging the second end further comprise axially aligning the fluid sample collection device and the cartridge with the sample probe.

24. The method of claim 17, wherein the apparatus further comprises a gas permeable, liquid impermeable membrane secured to the barrel adjacent the second end of the barrel, and wherein the step of transferring the fluid sample from the interior chamber of the barrel further comprises passing the sample probe through the gas permeable, liquid impermeable membrane to the interior chamber of the barrel.

25. The method of claim 18, further comprising:

26. The method of claim 25, wherein the step of collecting the fluid sample from the interior chamber of the cartridge further comprises passing the sample probe through the gas permeable, liquid impermeable membrane to the inlet side of the interior chamber of the cartridge.