BLOOD ANALYSIS DEVICE FOR DETECTING HEMOLYSIS

Abstract

A blood test assembly and method are described. In the method, a blood test device, which includes a plasma separation membrane and a reagent, is connected to a syringe containing blood with blood cells and plasma. A blood sample is passed from the syringe through the plasma separation membrane within the blood test device to separate the plasma from the blood cells. A reagent is saturated with the plasma, and the reagent is then analyzed colorimetrically to determine the degree of hemolysis within the blood sample.

Description

This application claims the benefit under 35 USC§119(e) of U.S. Provisional Patent Application No. 62 / 817,144, filed on March 12, 2019. The entire contents of the aforementioned patent application are expressly incorporated herein by reference. Statement on federally sponsored research and development: Not applicable. BACKGROUND Point-of-care testing generally refers to medical tests performed at or near the patient's place of care, such as an emergency department. A desired outcome of such tests is often rapid and accurate laboratory results to determine the next course of action in the patient's care. Several of these point-of-care tests involve analyzing a sample of the patient's blood. Many of these tests use whole blood, plasma, or serum. These samples may contain residual ruptured blood cells as a result of hemolysis due to imperfections in sample collection, pre-analytical blood sample handling, clinical conditions (e.g., hemolytic anemia, poisons, or toxins), and the whole blood separation process. In some cases, materials released from hemolyzed cells or cell membrane fragments can interfere with the integrity of the analytical test results. For example, if hemolysis occurs, the resulting free hemoglobin in the sample can interfere with several tests, leading to reduced signal strength, decreased accuracy and precision of measurement, or, at the other end of the spectrum, false-positive results. On one hand, it has been found that the potassium concentration in a corresponding sample can increase significantly, causing a high risk of misdiagnosis in a diagnostic test for potassium levels. Hemolysis can also interfere with readings of albumin, amylase, bilirubin, calcium, magnesium, iron, phosphate, hemoglobin, haptoglobin, alkaline phosphatase, total protein, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, cardiac troponin T, HCHC, and platelet count. BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are incorporated herein and form a part of this specification, illustrate one or more implementations described herein and, together with the description, explain these implementations. In the drawings: Figure 1 is a side elevation view of an exemplary blood analysis assembly that includes a receptacle and a blood analysis device constructed according to the present description. Figure 2 is a side elevation view of the blood analysis device constructed according to one modality of the present description. Figure 3 is a top plan view of the blood analysis device of Figure 2 which has a color palette in the blood analysis device according to one modality of the present description. Figure 4 is a bottom plan view of the blood analysis device in Figure 2 showing a connector configured to connect the blood analysis device to the receptacle, such as a syringe, according to the present description. Figure 5 is an exploded view, top perspective, of the exemplary blood analysis device in Figure 2. Figure 6 is an exploded view, in bottom perspective, of the exemplary blood analysis device in Figure 2. Figure 7 is an exploded, perspective view of another modality of an exemplary blood analysis assembly constructed according to the present description. Figure 8 is a side elevation view of the blood analysis assembly modality depicted in Figure 7. DETAILED DESCRIPTION The following detailed description refers to the accompanying drawings. The same reference numbers on different drawings may identify identical or similar items. As used herein, the terms comprise, which comprises, include, which includes, has, which has, or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, article, or apparatus comprising a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent in such process, method, article, or apparatus. Furthermore, unless expressly stated otherwise, "or" refers to an inclusive "or" and not an exclusive "or." For example, a condition A or B is satisfied by any of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present). Furthermore, the use of "one" or "an" is employed to describe elements and components of the modalities in this document. This is done simply for convenience and to give a general sense of the inventive concept. This description should be read to include "one or more," and the singular also includes the plural unless it is obvious that otherwise. Furthermore, the use of the term plurality is intended to convey more than one unless expressly stated otherwise. As used herein, any reference to a modality or modality means that a particular element, feature, structure, or characteristic described in relation to the modality is included in at least one modality. Occurrences of the phrase "in a modality" in various places in the description do not necessarily refer to the same modality. As used herein, the term "substantially" means that the parameter, event, or circumstance described below occurs completely or that the parameter, event, or circumstance described below occurs to a large extent or degree. For example, the term substantially means that the parameter, event, or circumstance described below occurs at least 90% of the time, or at least 91%, or at least 92%, or at least 93%, or at least 94%, or at least 95%, or at least 96%, or at least 97%, or at least 98%, or at least 99% of the time, or means that the dimension or measure is within at least 90%, or at least 91%, or at least 92%, or at least 93%, or at least 94%, or at least 95%, or at least 96%, or at least 97%, or at least 98%, or at least 99% of the reference dimension or measure. Several tests have been developed to determine whether hemolysis has occurred. A common reagent used to determine hemoglobin (Hb) levels in a blood sample is called Drabkin's reagent. Drabkin's reagent comprises a mixture of sodium bicarbonate, potassium ferricyanide, and potassium cyanide that lyses red blood cells and quantitatively converts all the Hb in a sample into a form called cyanmethemoglobin, which is then measured in a spectrometer using a single wavelength. To process a sample with Drabkin's reagent, a spectrophotometer is set to 540 nm and the absorbance is measured using a water reference. Test tubes are prepared for both the water reference and the sample. Drabkin's solution (5 mL) is added to each test tube. The sample (20 µL) is added to the test tubes as needed and pipetted up and down several times to lyse the sample. The sample is allowed to stand for 15 minutes, depending on ambient conditions, to become MA / a / zuzi / uiur oo cyanmethemoglobin. The absorbance of the sample is then read at 540 nm after bleaching with water. The results are then interpreted using a calibration curve. Standard solutions may not need to be equilibrated for 15 minutes, but this will still take time and require manual handling and estimation of results. Drabkin's reagent does not provide a realistic picture of the amount of free hemoglobin present at a specific time in a sample, which is indicative of hemolysis. Drabkin's reagent also does not indicate whether a drawn blood sample has been lysed. Several rapid point-of-care tests for detecting hemolysis are described in patent publications. Document WO2015191450 describes techniques for detecting hemolysis using a chromatographic detection pad. U.S. Patent Application No. 20170248618 describes techniques for detecting hemolysis by using a membrane to separate blood from plasma and then determining the color of the plasma. An analyzer sold under the registered trademark Cholestech separates plasma from blood along a filter membrane (lateral flow) and then presses reagent pads onto a portion of the membrane to extract a sample. The analyzer sold under the Cholestech trademark does not detect hemolysis, but may provide an error message if the sample is hemolyzed. Techniques for detecting hemolysis are also described in the article Membrane-Based, Sedimentation-Assisted Plasma Separator for Point of Care Applications, Changchun Liu et al. Analytical Chemistry 2013 85(21), 10463-10470. However, the techniques described in this article require a large sample volume, a long waiting time, and secondary steps for the detection and quantification of hemolysis. U.S. Patents 7,896,818 and 8,444,621 describe a sampler cap that can be used to transfer a test sample to an analyzer without removing the sampler cap from a sampler. The sampler is a syringe, in a preferred embodiment. However, the sampler cap does not include any means of determining whether hemolysis has occurred in the sample. Therefore, when the sampler cap is used as specified in U.S. Patents 7,896,818 and 8,444,621 to transfer a blood sample from a patient to an analyzer, hemolyzed blood may be transferred to the analyzer, which can cause interference in various tests. There is a need for rapid point-of-care testing of a blood sample to determine if hemolysis has occurred that overcomes the shortcomings of current testing regimens. iviA / a / zuz ι / u iu / óo According to one aspect, devices, systems, and processes are provided for determining the presence of hemolysis in a sample suspected of having hemolysis (i.e., ruptured cell fragment, hemoglobin, etc.). Advantageously, the devices, systems, and processes described herein determine whether hemolysis has occurred in a sample based on a colorimetric evaluation of a portion of the sample. The sample may be one that could potentially create a false-positive result in a potassium assay by providing potassium levels that are significantly higher than the actual potassium levels of the associated subject in the absence of hemolysis. For example, potassium levels within red blood cells can be 25 times higher than in plasma. Therefore, if hemolysis occurs, the potassium value of the sample in question may increase significantly.When a person's potassium levels are not actually as high as indicated, a false-positive result can lead to misdiagnosis and inappropriate treatment of a disorder characterized by elevated potassium levels. For example, as a result of hemolysis, a person might be misdiagnosed with hyperkalemia or any other disorder or condition characterized by elevated potassium levels, such as Addison's disease or hemolytic anemia. Furthermore, a person may be misdiagnosed with elevated potassium levels as a side effect of taking medications such as diuretics or blood pressure medications and may be unnecessarily advised to discontinue these medications, to their detriment.Furthermore, a false-positive result could inadvertently lead to the unnecessary administration of agents to remove potassium from the intestines before it is absorbed, or other unnecessary treatments. Therefore, the blood test device described here can be advantageously used in a screening process for unacceptable levels of hemolysis prior to potassium level analysis or to confirm the accuracy of previously performed test results. In certain modalities, the sample is a whole blood sample that includes a quantity of complete blood cells, including red blood cells, white blood cells, and platelets. Within the sample, the extent of hemolysis can be correlated with the amount of hemoglobin it contains. As used in this document, the term hemoglobin is understood to refer to each and every hemoglobin molecule obtained from drawn blood. Hemoglobin is commonly known as the oxygen-carrying pigment and the predominant protein in red blood cells. Hemoglobin is composed of four protein chains, two alpha chains and two beta chains, each with a ring-shaped heme group containing an iron atom. Oxygen binds reversibly to these iron atoms. In its oxygenated state, hemoglobin can In its reduced state, hemoglobin can be called oxyhemoglobin and is characterized by a bright red color. In its reduced state, hemoglobin can be called deoxyhemoglobin and is characterized by a purplish-blue color. According to another aspect, devices, systems and processes are provided for a blood collection assembly that has a hemolysis indicator feature. According to another aspect, devices, systems, accessories and blood analysis processes are provided that have a plasma separation feature. According to another aspect, devices, systems, accessories and blood analysis processes are provided that have a hemolysis indicator feature. With reference to the figures, and in particular Figure 1, a schematic view of a blood analysis assembly 10 constructed according to the present description is shown. In general, the blood analysis assembly 10 includes a receptacle 12 containing a blood sample and a blood analysis device 14. The receptacle 12 has a port 16 configured to transfer the blood out of the receptacle 12. The blood analysis device 14 has a housing 20 constructed of a fluid-impermeable material. The housing 20 has an internal space 22, shown with dashed lines in Figure 2. The housing 20 may also include a vent 24 configured to allow gas to escape from the internal space 22 and prevent liquid (i.e., plasma) from escaping from the internal space 22. In another embodiment, the housing 20 may be without the vent 24.This can be achieved by pressurizing the internal space 22 within the housing 20 below atmospheric pressure (e.g., a vacuum) so that the housing 20 draws the blood sample into the internal space 22. The housing 20 has a top wall 25, a bottom wall 26, and a side wall 27 extending between the top wall 25 and the bottom wall 26. The vent 24 extends from the bottom wall 26. The blood analysis device 14 also includes a receptacle connector 30 extending from the top wall 25, which is connected to the housing 20, and to port 16 of the receptacle 12. The receptacle connector 30, in one embodiment, is a tubular member forming a passage from port 16 (outside the housing 20) to the internal space 22 so that at least a portion (e.g., 0.5–1 ml) of the blood sample can be transferred from the receptacle to the interior space 22.Smaller blood volumes are possible depending on the design of the housing 20. In one embodiment, receptacle 12 is a syringe and receptacle connector 30 is a device known in the art as a Luer lock. It should be understood that receptacle 12 and receptacle connector 30 may have other forms. For example, receptacle 12 may be a device known in the art as a “vacutainer” that can be used to collect and transport blood for analysis. In another embodiment, the The receptacle 12 can be simultaneously connected to an instrument, such as a blood gas analyzer, and to the blood analysis device 14. For example, the housing 20 and vent 24 can be constructed as described to form the hollow body, and the analyzer connector 162 (in U.S. Patent No. 7,896,818) can be used to provide a venting mechanism (e.g., a vent duct) and an analyzer connector for attachment to an analyzer. This allows the analyzer connector of the blood analysis device 14 to be connected to the analyzer and used to transfer the sample from the receptacle 12 to the analyzer via the blood analysis device 14. In one embodiment, the analyzer can have an analyzer probe that extends through the analyzer connector and into the receptacle 12 to obtain a sample directly from the receptacle 12.The full text of U.S. Patent No. 7,896,818 is incorporated herein by reference. Blood may be drawn from an animal, such as a human, or from a non-human (such as a cat, dog, cow, horse, fish, or similar). Figure 2 shows a side elevation view of an exemplary blood analysis device 14 constructed according to the present description. The housing 20 is constructed of fluid-impermeable material so that it can retain and contain a blood sample containing blood cells suspended within the plasma. The housing 20 is shown as cylindrical, but it should be understood that it can be provided in any shape, such as square, round, rectangular, offset rectangular, triangular, offset triangular, or similar. The housing 20 includes a window 34 (see Figure 3) constructed of an optically transparent material configured to allow bidirectional passage of light from the outside of the housing 20 to the interior space 22, and from the interior space 22 to the outside of the housing 20.In one embodiment, the light is in a visible part of the electromagnetic spectrum to allow a user to look through the window 34 and into the interior space 22 of the housing 20. As shown in Figure 3, the window 34 can be a transparent portion of the bottom wall 26, although in other embodiments the window can be located in the side wall 27 of the housing 20. The blood analysis device 14 is also provided with a separator 40 (Figure 5) within the housing 20, and a reagent 42 (Figure 5). The separator 40 is configured to receive blood containing blood cells and plasma, separate the blood cells from the plasma, and direct the plasma to an inspection zone 44 within the inner space 22. The reagent 42 is positioned within the inspection zone 44 and adjacent to the window 34 so that the reagent 42 is visible through the window 34. The reagent 42 is configured to change color in the presence of hemoglobin within the plasma. MA / a / zuzi / uiur oo provide an indication of a state of blood hemolysis. When the blood analysis device 14 is configured with an analyzer connector set to couple to the analyzer discussed above, the analyzer inlet probe can approach the separator 40 and penetrate the separator 40 to gain access to the sample within the receptacle 12. In one embodiment, reagent 42 includes a pad 43 (see Figure 5) that changes color due to the amount of hemoglobin in the plasma. The pad 43 may be a hydrophilic membrane to effect a flickering / pinking color change so that a user or an external reading device can colorimetrically analyze and correlate the color change with a color reference (e.g., visual). The pad 43 may be white or another color. In some embodiments, the pad 43 may be made of cellulose, nitrocellulose, carboxymethylcellulose, or another material that will tend to retain proteins. The color change of pad 43 is visible through window 34 to allow a user or external reading device to view reagent 42 and compare its color to regions 50a-f of a color palette 52. Each of the 50af regions has a different color that has been correlated with reagent 42 to indicate a different state of hemolysis, for example, the amount of hemoglobin within the plasma. The user can determine the amount of hemoglobin by comparing the color of reagent 42 to regions 50a-f on the color palette 52. As discussed below, the color palette 52 can be a sticker / label with a bonding material connecting a transparent substrate to the bottom wall 26 and surrounding the vent 24. In one configuration, regions 50a-f are provided in a circular pattern coaxial with the vent 24.It should be understood, however, that other configurations of regions 50a-f are possible. Additionally, the sticker may have an opening aligned with window 34 to allow the user to view reagent 42. In another example, window 34 may be a transparent region of the sticker. In this configuration, housing 20 (or a portion thereof) may be opaque and have an opening aligned with pad 43. The sticker may be attached to housing 20 to form a fluid-tight seal. In this configuration, a user or external reader may view pad 43 through the transparent region of the sticker and the opening. MA / a / ZUZl / UlU / ÓO The 42 reagent samples that can be used and the resulting color changes are shown below in Table 1. Purpose of the test (and simplified formula) Approximate TTR Membrane (color change) 30 seconds Blood: This test is based on the peroxidase-like activity of hemoglobin, which catalyzes the reaction of diisopropylbenzene dihydroperoxide (6.8% w / w) and 3,3',5,5'-tetramethylbenzidine (4% w / w). The resulting color ranges from orange to green. Very high levels may continue the color development to blue. <60 seconds Low Protein (Albumin): This test is based on dye binding using a high-affinity sulfonephthalein dye. At a constant pH, any color development ranges from pale green to aqua blue. Ingredients: 1.9% w / w bis(3',3-diiodo4',4-dihydroxy-5',5-dinitrophenyl)-3,4,5,6-tetrabromosulfonephthalein <50 seconds High Protein: This test is based on the protein error principle of indicators. At a constant pH, the development of any green color is due to the presence of proteins. Controls range from yellow, light green, green, and blue-green. Ingredients: 0.3% w / w tetrabromphenol blue <50 seconds Tab a 1. With reference now to Figures 5 and 6, exploded views of the exemplary embodiment of the blood analysis device 14 are shown. In this example, the housing 20 is provided with a housing top 60 and a housing bottom 62 that are connected together to enclose the interior space 22. The housing top 60 includes the upper wall 25. The housing top 60 can be integrally formed as a unitary structure, or it can be formed from separate components that are joined by any suitable method, such as sonic welding or a bonding material, such as an adhesive or a cohesive. MA / a / zuzi / uiur oo The top wall 25 is provided with an inner surface 64 and an outer surface 66 generally opposite the inner surface 64. The top wall 25 is also provided with an opening 70 that communicates with the receptacle connector 30 to allow blood to enter the inner space 22 of the housing 20. In one embodiment, the opening 70 can be located in a central region of the top wall 25 as shown in Figure 5. It should be understood that the opening 70 can be placed in other parts of the top wall 25 provided that the opening 70 communicates with the receptacle connector 30. The inner surface 64 is configured to diffuse the blood from the opening 70 over a separation area 71 which, in this example, covers a substantial portion of the inner surface 64. For example, the inner surface 64 can be configured to include a plurality of channels 72 and ribs 74.The upper housing portion 60 also includes a side wall portion 76 that extends from the top wall 25 and forms a portion of the side wall 27 when the upper housing portion 60 and the lower housing portion 62 are connected. The inner surface 64 and the side wall portion 76 are cup-shaped, forming a recess 80. The inner surface 64 may also be provided with a perimeter region 82 surrounding the separation area 71. As discussed below, the perimeter region 82 is shaped to match the separator 40. For example, the perimeter region 82 and the separator 40 may both be flat. The upper part of housing 60 may be made of any suitable liquid-impermeable material that is also inert to at least hemoglobin. For example, without limitation, the upper part of housing 60 may be made of a material comprising polystyrene, polyethylene, polycarbonate, polypropylene, fluoropolymer, polyester, glass, metals, ceramics, suitable composite materials, and combinations thereof, as will be appreciated by those skilled in the art. In addition, the upper part of housing 60 may be made of a material that is opaque to light in the visible portion of the electromagnetic spectrum. The separator 40 can be provided with one or more stacked filters. In the example shown, the separator 40 is provided with a first filter 90 and a second filter 92 that are aligned and stacked one on top of the other. The first filter 90 and the second filter 92 can be the same size and shape; for example, in this case, both the first filter 90 and the second filter 92 are circular. In other embodiments, the first filter 90 and the second filter 92 can be of different sizes and / or shapes. In the described embodiment, the first filter 90 is positioned and attached to the inner surface 64, and the second filter 92 is positioned and attached to the first filter 90. MA / a / zuzi / uiur oo The first filter 90 can be designed to separate blood cells from the plasma and then pass the plasma to the second filter 92. For example, in the embodiment shown in Figure 5, the first filter 90 can isolate plasma and hemolysis products, e.g., hemoglobin, from whole blood cells in a sample such as a whole blood sample. In one embodiment, the first filter 90 comprises a plasma separation membrane as commercially available in the art. In certain embodiments, the plasma separation membrane comprises an asymmetric material capable of retaining a plurality of whole blood cells while allowing plasma and small molecules / complexes to pass through. Several different plasma separation membranes are commercially available and may be suitable for use in the blood analysis device 14.For example, the plasma separation membrane may comprise an asymmetric polysulfone material as commercially available from Pall Corporation (currently under the trademark VividMR). Alternatively, the first filter 90 may comprise any other suitable material or device capable of providing a sample comprising plasma and hemolysis components (if present) thereon. The plasma separated by the first filter 90 is fed to the second filter 92. The second filter 92 is provided with a predetermined color and forms a background or environment for reagent 42. The second filter 92 is placed over reagent 42. In one configuration, reagent 42 is positioned between the second filter 92 and the window 34 so that the second filter 92 provides a background color for reagent 42. When blood suspected of having hemolysis is fed into the inner space 22 through the receptacle connector 30 and the opening 70, the blood diffuses through the separation area 71 and passes through the first filter 90. The first filter 90 separates the blood cells and platelets from the plasma and then passes the plasma to the second filter 92. The plasma saturates the second filter 92 and passes through it to reagent 42. Reagent 42 reacts with the plasma and may change color to indicate a state of hemolysis or an unacceptable level. of hemolysis.The second filter 92 provides a uniform background color and thus aids in the colorimetric comparison of reagent 42. In one example, the second filter 92 is black filter paper, although it should be understood that other colors could be used. In one modality, the first filter 90 may be a predetermined color to provide a uniform background color. In this modality, the second filter 92 may be transparent or omitted. As discussed previously, vent 24 is designed to allow gas to pass through it, but prevents fluid from passing through. In one embodiment, vent 24 is a tubular member having an internal opening 100. Vent 24 includes an overflow plug 102 positioned inside and blocking the internal opening 100. The overflow plug 102 is constructed of a material capable of venting gas from the internal space 22, while preventing fluid from passing through. MA / a / ZUZl / UlU / ÓO through vent 24. Exemplary materials for making overflow plug 102 include starch, cellulose, and Teflon. The lower part of housing 62 includes the lower wall 26. The lower wall 26 is provided with an inner surface 110 and an outer surface 112 generally opposite the inner surface 110. The lower wall 26 is also provided with an opening 114 that communicates with the inner opening 100 of the vent 24 to allow gas and fluid to enter the inner opening 100 from the interior space 22 of the housing 20. In one embodiment, the opening 114 can be located in a central region of the lower wall 26 as shown in Figure 6. It should be understood that the opening 114 can be placed in other parts of the lower wall 26 provided that the opening 114 communicates with the inner opening 100 of the vent 24. The inner surface 110 is configured to diffuse the plasma from the second filter 92 over a reagent saturation area 120 which, in this example, covers a substantial portion of the interior surface 110.For example, the inner surface 110 can be configured to include a plurality of channels 122 and ribs 124. The lower casing portion 62 also includes a side wall portion 130 that extends from the lower wall 26 and forms a portion of the side wall 27 when the upper casing portion 60 and the lower casing portion 62 are connected. The inner surface 110 and the side wall portion 130 can be cup-shaped, forming a recess 132. The inner surface 110 can also be provided with a perimeter region 134 surrounding the reagent saturation area 120. As discussed below, the perimeter region 134 is shaped to match the separator 40. For example, the perimeter region 134 can be flat. The lower portion of housing 62 may be made of any suitable liquid-impermeable material that is also inert to at least hemoglobin. For example, without limitation, the upper portion of housing 60 may be made of a material comprising polystyrene, polyethylene, polycarbonate, polypropylene, fluoropolymer, polyester, glass, metals, ceramics, suitable composite materials, and combinations thereof, as will be appreciated by those skilled in the art. Furthermore, a portion of the lower portion of housing 62 that forms the window 34 is constructed of a material that is transparent to light in the visible part of the electromagnetic spectrum. In operation, a blood sample to be analyzed is placed inside receptacle 12. The receptacle connector 30 of the blood analysis device 14 can be connected to port 16 of receptacle 12, and a quantity of blood is transferred through port 16 and receptacle connector 30 into the inner space 22 of the blood analysis device 14. As the blood is transferred to inner space 22, air within inner space 22 is directed through vent 24. When the blood enters inner space 22, the Blood diffuses through channels 72 and ribs 74 and is applied to the first filter 90. The first filter 90 separates the blood cells and platelets from the plasma and passes the plasma to the second filter 92. The plasma saturates the second filter 92 and passes the plasma to the reagent saturation area 120 so that the plasma can come into contact with and saturate reagent pad 43. The saturated reagent pad 43 may then change color or not, depending on the state of hemolysis of the blood. In either case, the user can see the color of reagent pad 43 and determine whether the blood has hemolysis by comparing the color of reagent pad 43 with regions 50a-f of the color palette 52. The blood test device 14 can then be removed from the receptacle 12 and disposed of.When the blood sample does not have an unacceptable level of hemolysis, the blood sample can be analyzed using conventional techniques, such as providing the blood sample in a blood gas analyzer cartridge. Figure 7 is an exploded perspective view of another embodiment of a blood test assembly 10a constructed according to the present description. The blood test assembly 10a includes a receptacle 12a and a blood test assembly 14a. Similar components between receptacles 12 and 12a shall be labelled with the same part numbers. Likewise, similar components between blood test assemblies 14 and 14a shall be labelled with the same part numbers. Receptacle 12a and blood sample assembly 14a are similar in construction and function to receptacle 12 and blood sample assembly 14 described above, except that receptacle 12a and blood sample assembly 14a are integrated into a single device, which in this example is a syringe. In this respect, receptacle 12a has a side wall 140, a first port 142, and a second port 144 (which in some embodiments may be the same as port 16 described above). In the embodiment shown, the side wall 140 and a top wall 25a of the blood sample device 14a are integrally formed as a unitary structure.The side wall 140 and the top wall 25a include the first port 142 formed through the side wall 140 and the top wall 25a to allow a sample, e.g., blood, to flow from the receptacle 12a into the inner space 22 of the blood analysis device 14a. Apart from being integrally formed with the side wall 140, the top wall 25a is identical to the top wall 25 in construction and function. The sample flow from receptacle 12a to the inner space 22 of the blood analysis device 14a can be implemented in several ways. For example, port 142 can be designed to establish capillary action between receptacle 12a and inner space 22. In this configuration, after a sample is drawn through port 144 with port 142 (or vent 102) closed by a valve, the valve MA / a / zuzi / uiur jo can be opened and the blood sample can displace the gas in the inner space 22 of the housing 20 through capillary action. In this case, the sample volume is limited by a volume of the inner space 22 that is not filled by the first membrane 90, the second membrane 92 and the reagent pad 43. In any implementation, any overfilling should be stopped by the overflow plug 102. Figure 8 is a side elevation view of the blood test assembly modality 10a depicted in Figure 7. The operation of blood test assembly 10a is identical to the operation of blood test assembly 10 described above, except that blood test assembly 14a does not have a receptacle connector 30 that must be connected to port 16 of receptacle 12 because receptacle 12a and blood test assembly 14a are integral and a single device. Additionally, in embodiments that include a valve positioned within the first port 142, operation may include opening the valve to allow the sample to flow through the first port 142 and into the interior space 22, and closing the valve to prevent further sample from flowing through the first port 142. From the foregoing description, it is clear that the inventive concepts described herein are well suited to accomplish the objectives and achieve the advantages mentioned herein, as well as those inherent in the inventive concepts described herein. While currently preferred embodiments of the inventive concepts described herein have been outlined for the purposes of this description, it is understood that numerous modifications can be readily suggested to those skilled in the art and are achievable within the scope and coverage of the inventive concepts described and claimed herein.

Claims

CLAIMS 1. A blood analysis assembly, characterized in that it comprises: a receptacle containing blood and having a port configured to transfer the blood out of the receptacle; a blood analysis device, comprising: a housing constructed of a fluid-impermeable material, the housing having an interior space in fluid communication with the port, and a window constructed of an optically transparent material configured to pass light bidirectionally from the outside of the housing to the interior space, and from the interior space to the outside of the housing, the light being in a visible part of an electromagnetic spectrum; a separator within the housing, the separator configured to receive blood having blood cells and plasma, separate the blood cells from the plasma, and direct the plasma to an inspection zone within the interior space;a reagent within the inspection zone and adjacent to the window so that the reagent is visible through the window, the reagent configured to change color in the presence of hemoglobin within the plasma to provide an indication of a state of hemolysis of the blood.; 2. The blood analysis assembly of claim 1, characterized in that the separator includes a plasma separation membrane.

3. The blood analysis assembly of claim 2, characterized in that the plasma separation membrane is provided with a predetermined color to form a background for the reagent.

4. The blood analysis assembly of claim 1, characterized in that the separator includes a first filter and a second filter that are arranged adjacently and overlapping, one of the first filter and the second filter being a plasma separation membrane, and the other of the first filter and the second filter being of a predetermined color to form a background for the reagent.

5. The blood analysis assembly of claim 2, characterized in that the separator includes a first filter that is the plasma separation membrane, and a second filter stacked with the first filter, the second filter being between the first filter and the reagent, and MA / a / zuzi / uiur jo superimposed on the reagent to form a background for the reagent when the reagent is viewed through the window.

6. The blood analysis assembly of claim 1, characterized in that it further comprises a color palette having a plurality of regions having a correlated reagent color to indicate a predetermined state of hemolysis of a blood sample, the color palette being in the housing.

7. The blood test assembly of claim 6, characterized in that the color palette is a sticker having a bonding material connecting a substrate to the housing, the colored regions being supported by the substrate.

8. The blood analysis assembly of claim 6, characterized in that the color palette surrounds the vent.

9. The blood analysis assembly of claim 1, characterized in that it further comprises a receptacle connector connected to the housing and to the receptacle port, the receptacle connector forming a passage from the port, outside the housing, to the interior space.

10. The blood analysis assembly of claim 1, characterized in that the housing includes an analysis connector configured to connect the housing to an analyzer.

11. The blood analysis assembly of claim 1, characterized in that the housing comprises a vent configured to allow gas to escape from the interior space and prevent liquid from escaping from the interior space.

12. A blood analysis device, characterized in that it comprises: a housing constructed of a fluid-impermeable material, the housing having an interior space, and a window constructed of an optically transparent material configured to allow light to pass bidirectionally from the outside of the housing to the interior space, and from the interior space to the outside of the housing, the light being in a visible part of an electromagnetic spectrum; a separator within the housing, the separator configured to receive blood having blood cells and plasma, separate the blood cells from the plasma, and direct the plasma to an inspection zone within the interior space;a reagent within the inspection zone and adjacent to the window so that the reagent is visible through the window, the reagent configured to change color in the presence of hemoglobin within the plasma to provide an indication of a state of hemolysis of the blood.; 13. The blood analysis device according to claim 12, characterized in that the separator includes a plasma separation membrane. MA / a / zuzi / uiur oo 14. The blood analysis assembly of claim 13, characterized in that the plasma separation membrane is provided with a predetermined color to form a background for the reagent.

15. The blood analysis assembly of claim 12, characterized in that the separator includes a first filter and a second filter that are arranged adjacently and overlapping, one of the first filter and the second filter being a plasma separation membrane, and the other of the first filter and the second filter being of a predetermined color to form a background for the reagent.

16. The blood analysis device of claim 12, characterized in that the separator includes a first filter stacked with a second filter, the first filter being a plasma separation membrane, the second filter being between the first filter and the reagent, and superimposed on the reagent so as to form a background for the reagent when the reagent is viewed through the window.

17. The blood analysis device of claim 12, characterized in that it further comprises a color palette having a plurality of regions having a correlated reagent color to indicate a predetermined state of hemolysis of a blood sample, the color palette being in the housing.

18. The blood analysis device of claim 17, characterized in that the color palette is a sticker having a bonding material connecting a substrate to the housing, the colored regions being supported by the substrate.

19. The blood analysis device of claim 17, characterized in that the color palette surrounds the vent.

20. The blood analysis device of claim 12, characterized in that it further comprises a receptacle connector connected to the housing and to the receptacle port, the receptacle connector forming a passage from the port, outside the housing, to the interior space.

21. The blood analysis device of claim 12, characterized in that the housing includes an analysis connector configured to connect the housing to an analyzer.

22. The blood analysis device of claim 12, characterized in that the housing comprises a vent configured to allow gas to escape from the interior space and to prevent liquid from escaping from the interior space.

23. A method, characterized in that it comprises: connecting a blood testing device having a plasma separation membrane and a reagent to a syringe containing blood having blood cells and plasma; passing a blood sample from the syringe through a plasma separation membrane within the blood testing device to separate the plasma from the blood cells; saturating the reagent with the plasma; and colorimetrically analyzing the reagent to determine a degree of hemolysis within the blood sample.

24. The method of claim 21, characterized in that it further comprises obtaining a sample of the blood sample by means of an analyzer through the blood analysis device.

25. The method of claim 22, characterized in that obtaining the sample includes penetrating the plasma separation membrane with an analyzer inlet probe of an analyzer.