A method of removing interfering components from a liquid sample prior to dispensing the liquid sample on a chemical reagent test slide

Abstract

A method of removing components of a liquid sample that can interfere with a test performed on a test assay using a chemical analyzer includes the steps of adding the liquid sample into a sample cup, transferring a volume of the liquid sample into a mixing cup containing an IMAC (immobilized metal affinity chromatography) resin containing porous beads to form a sample / resin solution in the mixing cup, repeatedly aspirating the sample / resin solution into and expelling the sample / resin solution from a disposable pipette tip of a pipettor of the chemical analyzer into the mixing cup to obtain a mixed sample / resin solution in the mixing cup, and allowing the mixed sample / resin solution to sit undisturbed in the mixing cup so that interfering components of the liquid sample attach to the porous beads, and the beads settle to the bottom of the mixing cup, to obtain a refined liquid sample free of the interfering components and occupying an upper portion of the mixing cup for later dispensing on the test assay.

Description

[0001] Cross-reference to related applications

[0002] This application relates to U.S. Provisional Patent Application No. 62 / 986,988, filed March 9, 2020, entitled “Method For Removing Interfering Components Of A Liquid Sample Prior To Dispensing Same On A Chemical Reagent Test Slide,” the disclosure of which is incorporated herein by reference and priority is hereby claimed.

[0003] This application is also related to U.S. Provisional Patent Application No. 62 / 987,077, filed March 9, 2020, entitled “Matrix And Associated Sample Or Mixing Cup Used For Removing Components Of A Liquid Sample,” filed by IDEXX Laboratories, Inc., the disclosure of which is incorporated herein by reference.

[0004] Background of the invention. Invention Field

[0005] This invention generally relates to techniques for dispensing liquid samples onto glass slides used in dry chemistry tests, and more particularly to methods for removing impurities from liquid samples. Even more specifically, this invention relates to a method for purifying liquid samples to remove components that can affect the accuracy of fluorescence or absorbance / reflectance measurements of liquid samples by automated chemical analyzers.

[0006] Description of the problem to be solved

[0007] When performing fluorescence or absorbance / reflectance tests on liquid samples, certain assays used in dry and wet chemistry analytical techniques may be susceptible to interference from the liquid sample's components. As an example, bile acid dry chemistry test slides are highly sensitive to hemoglobin interference primarily due to the interaction between hemoglobin and tetrazolium dyes on the slide. In this regard, reference should be made to the accompanying figures. Figure 1 It is a graph of the actual reflectance density (vertical axis) of bile acid measurement specimens for five undiluted blood samples with different hemoglobin (Hgb) concentrations in milligrams (mg) / dL (dL) versus time in seconds (horizontal axis). Figure 1The graph shows the effect of samples containing increasing hemoglobin concentrations on the instrument progress curve, and how such hemoglobin concentrations interfere with bile acid reflectance density measurements. This interference is caused by hemolysis of the blood samples. Figure 1 In the experiment, the sample was deposited on the test slide at time = 0. Figure 1 The curves overlap at time = 0, indicating that the baseline measurement of reflectance density is approximately 0.075, representing continuous readings on unspotted slides before sample distribution. Figure 1 The curve marked N in the graph represents the hypothetical bile acid reflectance density measurement assuming no interference from hemolysis of the blood sample (i.e., Hgb = 0 mg / dL). Many (if not most) commercially available bile acid measuring instruments are susceptible to hemoglobin interference.

[0008] One proposed way to overcome this problem is to design bile acid assay formulations that are unaffected or minimally affected by hemoglobin present in liquid samples, regardless of whether dry or wet chemistry is used. To the best of the inventors' knowledge, no such assay exists and would require significant time and expense to develop. Another approach to addressing hemolytic interference in bile acid measurements is to reduce hemoglobin levels in the sample before testing and to use existing, currently available bile acid assays, which is the approach taken by the inventors and described herein.

[0009] Purpose and Overview of the Invention

[0010] One object of the present invention is to provide a method for removing interfering components of a liquid sample before dispensing the sample onto a glass slide for a dry chemical reagent test.

[0011] Another object of the present invention is to provide a method for removing components from a liquid sample that may interfere with diagnostic measurements of the liquid sample.

[0012] Another object of the present invention is to provide a method for removing impurities from a liquid sample using functionalized particles before testing the sample.

[0013] A further object of the present invention is to provide a method for removing hemoglobin or other components from a liquid sample that may affect the accuracy of tests performed on the liquid sample.

[0014] A further object of the present invention is to provide a liquid sample mixing / dispensing technique that removes components from the sample that could interfere with the testing of the liquid sample and the resulting measurements.

[0015] Another object of the present invention is to provide a pretreated liquid sample having a minimized or negligible hemoglobin concentration before being dispensed onto a bile acid dry chemistry reagent test slide.

[0016] A further objective of the present invention is to use currently available automated chemical analyzers for analyzing reagent test slides to condition liquid samples so that the concentration of interfering components is reduced, which could otherwise affect the accuracy of fluorescence or absorbance / reflectance measurements obtained from tests performed on the liquid samples.

[0017] Another object of the present invention is to provide a method for removing interfering components from liquid samples using a conventional chemical analyzer and dispensing the liquid samples onto conventional unmodified dry chemical reagent test slides.

[0018] Another object of the present invention is to provide a method for pre-conditioning a liquid sample by removing or minimizing its interfering components before dispensing it onto a conventional reagent test slide. This method advantageously avoids the time and expense of developing test slide assays that are insensitive to interfering components.

[0019] According to one aspect of the invention, a sample for testing is prepared by removing components that could interfere with the testing of the sample. Such interfering components are advantageously removed using conventional, currently available automated chemical analyzers with pipetting capabilities. Furthermore, advantageously, the pre-conditioned liquid sample from which interfering components have been removed can now be tested using readily available test pieces, such as dry chemical reagent test slides. The test slide used to measure the liquid sample may still be sensitive to interfering components of the liquid sample, but since such components have been substantially removed from the sample, the slide assay does not need to be modified to make it insensitive to these components.

[0020] In a preferred embodiment of the invention, before dispensing the sample onto the test assay, interfering components are removed from the liquid sample or at least their concentration is minimized by mixing the functionalized particles with the liquid sample in a mixing cup. As an example, such functionalized particles may be in the form of agarose-based porous beads to which interfering components in the liquid sample adhere and are removed from the solution as the particles settle by gravity (although mild centrifugation is also considered to accelerate particle settling). The mixing of the functionalized particles and the liquid sample can be performed using a dispensing / pipette from a conventional chemical analyzer.

[0021] Once the functionalized particles and liquid sample are fully mixed in the mixing cup, the mixture is allowed to stand undisturbed for a first predetermined period of time, allowing the particles, along with any interfering components of the liquid sample attached to them, to settle to the bottom of the mixing cup by means of gravity, for example. Then, a predetermined volume of liquid sample is aspirated from the top of the mixing cup into a pipette tip using a pipette from the chemical analyzer. The liquid sample in the top of the mixing cup should be free of interfering components or have a reduced concentration of interfering components.

[0022] As a precautionary measure, and as an optional step in the method, the aspirated volume of liquid sample in the pipette tip may be allowed to stand undisturbed for a second predetermined time period, allowing any remaining functionalized particles (with or without interfering components attached) to the pipette tip to settle to the bottom section of the pipette tip by gravity. After this predetermined second time period has elapsed, a volume of liquid containing the settled particles and / or interfering sample components occupying the bottom section of the pipette tip is expelled or “spit out” from the pipette tip into a mixing cup. The remaining volume of liquid sample in the pipette tip, or a portion thereof—which should be substantially free of interfering components of the liquid sample or have a low concentration of interfering components of the liquid sample—can now be dispensed onto a chemical reagent test slide using the pipette of the chemical analyzer.

[0023] These and other objects, features and advantages of the present invention will become apparent from the following detailed description of its illustrative embodiments, which is read in conjunction with the accompanying drawings. Brief description of the attached diagram

[0025] Figure 1 It is a graph showing the measured actual reflectance density (vertical axis) of undiluted plasma samples with five different hemoglobin concentrations (Hgb) in milligrams (mg) per deciliter (dL) relative to time in seconds (horizontal axis).

[0026] Figure 2 This is a graph showing the absorption (ordinate) of 500 mg / dL hemoglobin (Hgb) in an untreated canine plasma sample relative to wavelength in nanometers (bb) compared to treatment with Ni IMAC (immobilized metal affinity chromatography) resin (33% resin, 66% sample) according to the method of the present invention. It also illustrates how treatment with the IMAC resin of the present invention for removing hemoglobin from the sample reduces hemoglobin from about 500 mg / dL to about 100 mg / dL.

[0027] Figure 3 This is an illustrated description of the sequence of steps taken in one form of a method according to the invention for removing interfering components from a liquid sample before dispensing the sample onto a test assay.

[0028] Figure 4A This is a cross-sectional view of the mixing cup used in the method of the present invention, which contains a mixture of 100 μL (µL) of liquid sample and 33 μL (µL) of porous beads, the porous beads being dried in the cup and rehydrated by the sample.

[0029] Figure 4B This is a cross-sectional view of the mixing cup used in the method of the present invention, which contains a mixture of 100 μL (µL) of liquid sample and 25 μL (µL) of porous beads, the porous beads being dried in the cup and rehydrated by the sample.

[0030] Figure 5 This is an illustration of the sequence of steps taken in another form of the method according to the invention for removing interfering components from a liquid sample before dispensing the sample onto a test assay, wherein any remaining interfering components of the liquid sample remaining in the tip of the sample metering pipette are allowed to settle in the tip and be expelled and “spit back” into the sample or mixing cup.

[0031] Figure 6 This is a cross-sectional view of a mixing cup formed according to the invention, having IMAC resin in the form of a physically stable cake located therein, but the presence of IMAC resin in liquid form within the mixing cup or in dry form on one or more walls of the mixing cup or as a physically stable cake as shown herein is within the scope of the invention.

[0032] Figure 7 This is a cross-sectional view of a centrifuge cup formed according to the invention, having IMAC resin in the form of a physically stable cake located therein. However, it is within the scope of the invention to have the IMAC resin present in liquid form within the centrifuge cup, or coated in dry form onto one or more walls of the centrifuge cup, or as a component of a gel for separating components of whole blood samples during centrifugation, or as a physically stable cake as shown herein.

[0033] Figure 8A This is a cross-sectional view of another form of the mixing cup formed according to the invention, which has functionalized magnetic or iron-containing particles and a magnet located inside the cup, and shows how the components of a liquid sample, such as hemoglobin in a blood sample, attach to the functionalized magnetic or iron-containing particles in the mixing cup, which are thus attracted to the magnet along with the particles by magnetic attraction.

[0034] Figure 8BThis is a cross-sectional view of another form of the mixing cup formed according to the invention, which has functionalized magnetic or iron-containing particles and a magnet located outside the cup, and shows how the components of a liquid sample, such as hemoglobin in a blood sample, adhere to the functionalized magnetic or iron-containing particles in the mixing cup, and are thus attracted to the magnet along with the particles by magnetic attraction.

[0035] Detailed description of the preferred implementation scheme

[0036] Now you should refer to the attached diagram. Figure 2 , 3 4A, 4B, and 5-7. As previously mentioned, some assay pieces may be sensitive to components of liquid samples that can interfere with tests performed on liquid samples and may affect the accuracy of any measurements obtained. For example, if liver dysfunction is suspected, a bile acid test is performed on the subject, human, or animal. In the case of animals, a pre-meal blood sample is drawn, and a post-meal blood sample is collected after a predetermined time following the animal's feeding. Both samples are provided to the laboratory, and bile acid levels are tested using either a wet chemistry assay piece or a dry chemistry reagent test slide.

[0037] like Figure 1 As illustrated in the provided graphs and discussed previously, the problem with such bile acid assay pieces is their sensitivity to hemoglobin (Hgb), which interferes with bile acid testing of patient blood samples and can render any measurements obtained inaccurate. Therefore, the options for addressing this problem are to develop bile acid assay pieces that are insensitive to hemoglobin in blood samples, which may be an expensive and time-consuming approach, or to provide a method for substantially removing interfering components, in this case hemoglobin, from the blood sample before dispensing the sample onto the assay piece, or at least minimizing its concentration. The latter approach is the one adopted by the inventors and is described more fully herein. It should be understood, of course, that the method of the present invention described herein can be used to reduce the concentration of interfering components in liquid samples to which the assay piece may be sensitive, and should not be construed as limited to methods for removing hemoglobin from blood samples before dispensing the sample onto the assay piece. In fact, the method of the present invention can be used to remove other components from liquid samples, including proteins, or to reduce their concentration.

[0038] According to one form of the invention—wherein, by way of example only—a bile acid test slide sensitive to hemoglobin in a blood sample is used and the test is performed using a pipette equipped with disposable tips in an automated chemical analyzer with sample aspiration / dispensing capabilities. Functionalized particles are premixed in a mixing cup containing a blood sample (as used herein, "blood sample" generally refers to whole blood, diluted blood, plasma, serum, etc.). These functionalized particles cause interfering components of the blood sample, in this example hemoglobin, to attach to the particles, and the particles and the attached hemoglobin settle together to the bottom of the mixing cup by gravity.

[0039] Preferably, the functionalized particles envisioned for removing hemoglobin from blood samples are agarose-based porous beads. Such particles are used in immobilized metal affinity chromatography (IMAC) applications, where they are functionalized by linking ligands that subsequently coordinate with metal ions. For removing hemoglobin from blood samples used in bile acid tests, preferred particles have a chelating ligand based on nitrotriacetic acid (NTA) or an alternative iminodiacetic acid (IDA) and a nickel ion (Ni... 2+ ) or alternative cobalt (Co) 2+ ) or zinc (Zn 2+ ) ions. Porous beads in resin form are preferably of type (Part No.) 40 651 001 (for NTA and Ni +2 The porous beads and resin were purchased from Bio-Works Technologies AB, located in Uppsala, Sweden. For more information on such porous beads and resins, please refer to Bio-Works Data Sheet DS 40 650 010, the contents of which are incorporated herein by reference.

[0040] More specifically, the resin type manufactured by Bio-Works Technologies AB suitable for the method of the present invention is a cross-linked agarose resin containing either of two chelating groups, NTA or IDA, and carrying one of the four metal ions (nickel, cobalt, zinc, and possibly copper (Cu)) as described above. Preferably, the resin is packaged in water with a preservative before use, or the resin may be packaged in ethanol. The following resin grades from Bio-Works Technologies AB may be applicable: 40651 001 (Ni-NTA); 40 651 003 (Ni-NTA); 40 651 010 (Ni-NTA); 40 651 401 (Co-NTA); 40 651 403 (Co-NTA); 40 651 410 (Co-NTA); 40 651 301 (Cu-NTA); 40 651 303 (Cu-NTA); 40 651 310 (Cu-NTA); 40 651 501 (Zn-NTA); 40 651 503 (Zn-NTA); 40 651 510 (Zn-NTA); 40 650 001 (Ni-IDA); 40 650 003 (Ni-IDA); 40 650 010 (Ni-IDA); 40 650 401 (Co-IDA); 40 650 403 (Co-IDA); 40 650 410 (Co-IDA); 40 650 301 (Cu-IDA); 40 650 303 (Cu-IDA); 40 650 310 (Cu-IDA); 40 650 501 (Zn-IDA); 40 650 503 (Zn-IDA); and 40 650 510 (Zn-IDA). Beaded resins that constitute components of buffers or diluents added to liquid samples are also considered to be within the scope of this invention.

[0041] Furthermore, resins containing porous or non-porous beads can be used in the method according to the invention. For example, gels containing non-porous silica beads can be used. Suitable silica-based gels include, but are not limited to, those commonly referred to as “cleaner resins” manufactured by SiliCycle Inc. of Quebec City, Quebec, Canada, and further referred to as imidazole-silica, AMPA silica, DOTA silica, DMT silica, and TAAcOH silica, as well as mesoporous thiol-silica manufactured by Sigma-Aldrich, Inc. (now MilliporeSigma), owned by Merck KGaA of Darmstadt, Germany. Other materials that may be suitable for removing interfering components from blood samples, particularly hemoglobin, include the aforementioned IMAC resins, including NTA-Ni (and other metals such as Zn, Al, Mn, Co, etc.) resins, TALON™ resins (EDTA), such as those manufactured by Takara Bio USA, Inc. of Mountain View, California, and iminodiacetate-Ni resins; and other materials, including Fractogel®-Ni activation products manufactured by Merck KGaA of Darmstadt, Germany, TCEP immobilization resin products, ConA resin products, and protein depletion resins, each manufactured by Thermo Fisher Scientific Inc. of Waltham, Massachusetts.

[0042] Immobilized metal affinity chromatography (IMAC) is a common technique for purifying recombinant proteins tagged with histidine or multiple histidines. IMAC resin containing agarose-based porous beads is added to a disposable mixing cup as a sample preparation mitigation measure against hemolytic interference in bile acid assays. This is done by removing or reducing the amount of hemoglobin in blood samples before metering them onto bile acid test slides, as the hemoglobin in the sample is bound to immobilized metal ions in the IMAC resin.

[0043] Figure 2 The illustrations demonstrate the effectiveness of the method of the present invention, which will be described in more detail below. For example... Figure 2As can be seen in the graph depicted, the absorption spectrum of the hemoglobin content of the canine plasma sample without IMAC treatment is superimposed on the absorption spectrum of the same sample that has been IMAC treated according to the method of the present invention. It is evident from this graph that the hemoglobin content in the sample treated with this method is reduced by a factor of five; that is, after the blood sample is IMAC treated according to the method of the present invention, the hemoglobin (Hgb) in the exemplary sample has been reduced from approximately 500 mg / dL to approximately 100 mg / dL.

[0044] In the attached diagram Figure 3 The preferred sequence of steps according to the invention is shown, which is preferably implemented by an automated chemical analyzer 2 having a suction / dispensing pipette 4 with a disposable pipette tip 6 thereon, for processing the liquid sample 8 to remove interfering components or at least reduce their concentration. Furthermore, reference should be made to U.S. Patent No. 9,116,129 entitled "Chemical Analyzer" issued to Rich et al., August 25, 2015; U.S. Patent No. 9,797,916 entitled "Chemical Analyzer" issued to Connolly et al., October 24, 2017; and U.S. Patent No. 9,823,109 entitled "Chemical Analyzer" issued to Garrepy et al., November 21, 2017, which disclose chemical analyzers capable of implementing the steps of the method of the invention. The disclosures of each of the above patents are incorporated herein by reference. Each of the above patents is recorded and assigned to IDEXX Laboratories, Inc., Westbrook, Maine. Currently available chemical analyzers capable of implementing the methods of this invention are sold by IDEXX Laboratories, Inc. and are known in the industry by the names CatalystOne™ and Catalyst Dx™.

[0045] According to the sample processing and interfering component removal method of the present invention, a sample cup 10 containing a liquid sample 8, such as whole blood or diluted blood, serum, or plasma, is loaded into a chemical analyzer 2. Alternatively, the whole blood sample can be loaded into a centrifuge cup 12 of the whole blood separator 14 of the chemical analyzer 2, and after centrifugation, plasma or other separated components can be transferred to a consumable mixing cup 16 associated with the chemical analyzer 2 (for a description of the blood separator 14, centrifuge cup 12, and mixing cup 16, see the aforementioned U.S. Patent Nos. 9,116,129; 9,797,916; and 9,823,109). One or more reagent test slides 18, in this example bile acid test slides, are also loaded into the chemical analyzer 2. IMAC resin containing porous beads is stored in a consumable reagent cup, which can be used as the mixing cup 16 mentioned above.

[0046] More specifically, and in a preferred form, the IMAC resin is freeze-dried in a solution of about 7% dextran / sucrose, more specifically about 3.5% dextran and about 3.5% sucrose, which forms physically stable aggregates 20. The dextran / sucrose solution holds the freeze-dried resin aggregates 20 at the bottom of the mixing cup 16.

[0047] Liquid sample 8, such as blood, serum, or plasma, is then transferred to mixing cup 16 via pipette 4 of the chemical analyzer 2—by aspirating a predetermined volume of liquid sample 8 from sample cup 10 into pipette tip 6 and discharging that volume, or a portion thereof, from pipette tip 6 into mixing cup 16 containing dried resin clumps 20. If a diluted blood sample is required, sample 8 is mixed with a preferred diluent that acts on the resin to bring it to an optimal state for binding with interfering components (e.g., hemoglobin in the case of bile acid assays). This dilution step occurs before or during the addition of blood sample 8 to mixing cup 16 containing IMAC resin. For example, pipette tip 6 may first aspirate a first predetermined volume of dilution buffer, then aspirate a second predetermined volume of blood sample 8 from sample cup 10, depositing the sample / buffer mixture into mixing cup 16 containing resin clumps 20. Alternatively, a certain volume of liquid sample 8 can be aspirated first and deposited into mixing cup 16, followed by aspirating dilution buffer and depositing it into mixing cup 16 to avoid contact between the dilution buffer and the liquid sample 8 in sample cup 10 in the pipette tip 6. The liquid sample 8 added to the resin clump 20 located in mixing cup 16 dissolves the clump 20 in mixing cup 16 into a resuspension of IMAC resin containing porous beads.

[0048] Then, the liquid sample 8 and the IMAC resin beads are mixed using the pipette 4 of the chemical analyzer 2—by aspirating the combined sample / resin solution into the pipette tip 6 and then expelling the solution from the pipette tip 6 back into the mixing cup 16, the aspiration and subsequent expulsion steps are repeated multiple times to ensure that the resuspended resin and sample 8 are thoroughly mixed.

[0049] Now, the sample / resin solution in mixing cup 16 is allowed to stand (i.e., incubate) undisturbed for a predetermined period of time, such as about 5 minutes or less than about 10 minutes, or longer. This time depends primarily on the time required for the particles to settle from the liquid portion so that pipette 4 can subsequently aspirate cleanly or substantially cleanly. Denser particles will settle faster than less dense particles, therefore the predetermined period for particle settling in mixing cup 16 can vary from about 1 minute to about 15 minutes. The interaction between the particles and hemoglobin appears to occur relatively quickly, making an incubation (settling) time of less than or equal to about 2 minutes to about 3 minutes sufficient. During this incubation time, hemoglobin or other target interfering components in the liquid sample will adhere to the porous beads of the IMAC resin, and beads with hemoglobin adhering to them, as well as unadhered beads, will... Figure 4A and 4B The sample settles to the lower bottom portion 22 of the mixing cup 16, leaving a certain volume of liquid sample without hemoglobin or with a minimal amount of hemoglobin occupying the upper portion 24 of the mixing cup 16.

[0050] Some mixing cups 16 used in the automated analyzer and instrument 2 have unique geometries, and these geometries should be taken into account when the liquid sample 8, free of interfering components and occupying the upper 24 of the mixing cup 16, is aspirated into the pipette tip 6 via the pipette 4 for dispensing the sample 8 onto the test piece 18. For example, see the attached figure. Figure 4A and 4B The cross-sectional view illustrates the particularly preferred truncated conical shape of the mixing cup 16 for use with the Catalyst One™ and Catalyst Dx™ IDEXX Laboratories instruments mentioned above.

[0051] exist Figure 4A In the illustration, mixing cup 16 is shown to contain 100 μL (µL) of sample and 33 μL (µL) of resin, the resin being dry and rehydrated by the sample, and... Figure 4B In the diagram, the same mixing cup 16 is shown as containing, as... Figure 4A The samples shown are of the same volume, but the resin volume is smaller, i.e., 100 μL of sample and 25 μL of resin. The resin is dried and rehydrated by the sample. Figure 4A and 4BIn each example of the mixing cup 16 shown, the volume of particles is lyophilized before the addition of 100 μL (µL) of sample, such that the total volume of the sample / bead mixture is equal to approximately 100 μL (µL) in any example. In other words, once the liquid sample 8 is added to the mixing cup 16, the resin is rehydrated by the sample 8 to near its original hydration volume. Therefore, as Figure 4A and 4B As shown, after a predetermined incubation time to allow beads and hemoglobin or other interfering components to settle to the lower 22 of the mixing cup 16, the controller of the analyzer 2 should be programmed to lower the pipette tip 6 into the mixing cup 16 until only the upper 24 of the mixing cup 16 is aspirated (in... Figure 4A and 4B The liquid sample 8 (marked as "top space") is placed at the required depth (i.e., the vertical height above the inner bottom of the cup) to avoid aspirating the sediment bead / hemoglobin mixture 26 located in the lower part 22 of the mixing cup 16 into the pipette tip 6.

[0052] For example, the Catalyst One™ and Catalyst Dx™ instruments used and displayed in IDEXX Laboratories Figure 4A and 4B Under the specific geometry of mixing cup 16, for a 100 μL (µL) mixture of sample and 33 µL of rehydrated beads, and after the incubation time, the automated instrument 2 should be programmed so that pipette 4 aspirates part or all of the sample 8 occupying a 2.50 mm (mm) vertical “top space” A, which is located above the 3.40 mm (mm) bead and hemoglobin sedimentation solution 26 (see [link to instrumentation]). Figure 4A For a 100 μL mixture of sample and 25 µL of rehydrated beads, and after the incubation period, the automated instrument 2 should be programmed so that pipette 4 aspirates part or all of the sample occupying a 3.20 mm vertical “top space” C, which is located above the 2.70 mm D beads and the sedimentation solution 26 of hemoglobin (see...). Figure 4B In other words, Figure 4A The mixing cup 16 shown contains approximately 67 μL of usable liquid (for testing) and approximately 33 μL of rehydrated resin particles for a total volume of approximately 100 μL. Figure 4B The mixing cup 16 shown also contains approximately 75 μL (μL) of usable liquid (for testing) and approximately 25 μL (μL) of rehydrated resin particles for a total volume of approximately 100 μL (μL).

[0053] After allowing the solution to settle in the mixing cup 16 to remove hemoglobin or other target interfering components and any remaining unattached beads, the pipette 4 of the analyzer 2 preferably aspirates the required volume of liquid sample 8 only from the upper part 24 (i.e., the “headspace”) of the mixing cup 16 into a new (clean) pipette tip 6 mounted thereon, in order to avoid or to the minimum aspiration of settled beads and hemoglobin—each of which can interfere with the measurements obtained on the test piece 18.

[0054] As a precautionary measure, and as an optional step in the method of the present invention, the liquid sample solution 8 aspirated into the pipette tip 6 may be allowed to stand undisturbed for a second predetermined incubation period, i.e., about 1 minute to about 15 minutes, or about 5 minutes or less to about 10 minutes or longer, or less than or equal to about 2 minutes to about 3 minutes (especially for the sedimentation of particles attached to hemoglobin), such that if any beads (any remaining interfering components of the liquid sample 8 attached or not attached to the aspirated sample solution 8) are present in the aspirated sample solution 8, they will settle to the discharge end of the pipette tip 6. After the time for any beads to settle in pipette tip 6 has elapsed, the controller of analyzer 2 removes and “re-feeds” a small volume of solution (e.g., from about 10 μL to about 50 μL, including the settled contents which may contain relatively high concentrations of beads or beads with hemoglobin attached thereto) from pipette tip 6 into mixing cup 16 to ensure that almost all beads and / or residual hemoglobin are removed from the remaining solution in pipette tip 6. Finally, the remaining solution is dispensed onto bile acid test slide 18. This sequence of steps is shown in the attached figures. Figure 5 Although the bile acid test measuring element 18 to which the sample solution is metered remains sensitive to hemoglobin, there is little or no hemoglobin in the solution finally dispensed onto the test measuring element 18 that interferes with the bile acid test and the measurements obtained by the chemical analyzer 2.

[0055] It should be noted that although the consumable mixing cup 16 with pre-loaded beads / resin clumps 20 described herein and shown in the accompanying drawings is preferably used for carrying out the method of the present invention for removing interfering components from liquid sample 8, it is considered within the scope of the invention that resin in dry or liquid form is pre-loaded in the centrifuge cup 12 of the whole blood separator of a chemical analyzer, or that resin is added to the centrifuge cup 12 after centrifugation, after which hemoglobin settles from liquid sample 8 to the bottom 28 of centrifuge cup 12, and a volume of sample occupying the upper 30 of centrifuge cup 12 is aspirated by pipette 4 into pipette tip 6 for dispensing onto test specimen 18. As described above, the sample aspirated by pipette 4 is allowed to settle in pipette tip 6, such as... Figure 5As shown, this allows any remaining beads to be expelled from the pipette tip 6 before the sample is metered onto the test piece 18. Furthermore, although the resin containing beads is described herein as a physically stable aggregate 20 located in the mixing cup 16, it is also contemplated that the resin may be located in liquid form in the sealed mixing cup 16, with the seal broken by downward movement of the pipette tip, or may be located in a separate sealed cup and transferred to the mixing cup 16 via the pipette 4.

[0056] Methods for removing interfering components from liquid samples 8, such as blood samples (e.g., diluted, undiluted, whole blood, serum, plasma, etc.), will now be further described.

[0057] More specifically, and according to one form of the invention, a method is disclosed herein for removing components from a liquid sample 8 that may interfere with a test performed on a test piece 18 using a chemical analyzer 2. The chemical analyzer 2 has a sample cup 10, a mixing cup 16, and a vertically movable pipette 4 associated thereto, the pipette 4 being equipped with a disposable pipette tip 6 and capable of aspirating and dispensing the liquid sample 8 into and from the pipette tip 6 and dispensing the liquid sample 8 onto the test piece 18. The method includes the following steps: adding a liquid sample 8 containing interfering components to a sample cup 10; transferring the liquid sample 8 containing interfering components from the sample cup 10 to a mixing cup 16, the mixing cup 16 containing IMAC (immobilized metal affinity chromatography) resin with porous beads, the liquid sample 8 and the IMAC resin forming a sample / resin solution in the mixing cup 16; mixing the sample / resin solution in the mixing cup 16 using a pipette 4 of the chemical analyzer 2 to obtain a mixed sample / resin solution—by aspirating the sample / resin solution into a pipette tip 6 and then discharging the sample / resin solution from the pipette tip 6 into the mixing cup 16, repeating the aspiration and discharging steps if or necessary to thoroughly mix the sample / resin solution in the mixing cup 16 and obtain a mixed sample / resin solution; allowing the... The mixed sample / resin solution is allowed to stand undisturbed in mixing cup 16 for a predetermined time period, the predetermined time period being selected so that at least a portion of the interfering component of the liquid sample 8 adheres to the porous beads of the IMAC resin, and so that at least a portion of the porous beads with or without the interfering component adhering thereto settle in the mixing cup and occupy its bottom 22. The result of the settling of the porous beads with the interfering component adhering thereto is the formation of a purified liquid sample, which is free of interfering components or has a lower concentration of interfering components than the liquid sample and occupies the upper part 24 of mixing cup 16; and a predetermined volume of the purified liquid sample occupying the upper part 24 of mixing cup 16 is aspirated from mixing cup 16 into pipette tip 6 so that a selected volume of the purified liquid sample free of interfering components or having a lower concentration of interfering components can be dispensed onto test piece 18 later.

[0058] The predetermined time period mentioned above is preferably about 5 minutes to about 10 minutes. Furthermore, the IMAC resin preferably comprises agarose-based porous beads.

[0059] Even more preferably, the IMAC resin is lyophilized in a solution of about 2% to about 14% dextran / sucrose, or more preferably about 7% dextran / sucrose. More specifically, the IMAC resin is lyophilized in a solution of about 2% to about 10% dextran and about 2% to about 10% sucrose, or more preferably about 3.5% dextran and about 3.5% sucrose.

[0060] In one form, the IMAC resin is formed as physically stable aggregates 20 and located at the bottom 22 of the mixing cup 16.

[0061] Although the method of the present invention can be used to remove interfering components from many different types of liquid samples 8 to be analyzed, in one particular application, when the bile acid assay is performed by the chemical analyzer 2, the interfering component removed from the liquid sample 8 is hemoglobin.

[0062] In another form of the invention, a method is disclosed for removing components from a liquid sample 8 that may interfere with a test performed on a test piece 18 using a chemical analyzer 2, wherein the chemical analyzer 2 has a sample cup 10, a mixing cup 16, and a vertically movable pipette 4, the pipette 4 being equipped with a disposable pipette tip 6 having an outlet end and being able to aspirate the liquid sample 8 into and out of the pipette tip 6 and dispense the liquid sample 8 onto the test piece 18. The method includes the following steps: adding a liquid sample 8 containing interfering components to a sample cup 10; transferring the liquid sample 8 containing interfering components from the sample cup 10 to a mixing cup 16, the mixing cup 16 containing IMAC (immobilized metal affinity chromatography) resin with porous beads, the liquid sample 8 and the IMAC resin forming a sample / resin solution in the mixing cup 16; mixing the sample / resin solution in the mixing cup 16 using a pipette 4 of the chemical analyzer 2 to obtain a mixed sample / resin solution—by aspirating the sample / resin solution into a pipette tip 6 and then discharging the sample / resin solution from the pipette tip 6 into the mixing cup 16, repeating the aspiration and discharging steps if necessary. The sample / resin solution is thoroughly mixed in mixing cup 16 to obtain a mixed sample / resin solution; and the mixed sample / resin solution is allowed to stand undisturbed in mixing cup 16 for a first predetermined time period, the first predetermined time period being selected to allow at least a portion of the interfering components of liquid sample 8 to adhere to the porous beads of IMAC resin, and to allow at least a portion of the porous beads with or without the interfering components attached thereto to settle in mixing cup 16 and occupy its bottom 22, the result of the settling of the porous beads with the interfering components attached thereto is the formation of a first-stage refined liquid sample, which contains no interfering components or has a first lower concentration of interfering components than liquid sample 8 and occupies the upper part 24 of mixing cup 16.

[0063] The method further includes the following steps: aspirating a predetermined volume of a first-stage purified liquid sample occupying the upper part 24 of a mixing cup 16 from the mixing cup 16 into a pipette tip 6; allowing the first-stage purified liquid sample aspirated into the pipette tip 6 to stand undisturbed for a second predetermined time period; selecting the second predetermined time period to allow any remaining interfering components of the liquid sample in the first-stage purified liquid sample in the pipette tip 6 to adhere to any porous beads of the remaining IMAC resin in the first-stage purified liquid sample in the pipette tip 6; and allowing at least a portion of the remaining porous beads, with or without interfering components attached thereto, to settle in the pipette tip 6 and form a portion of the pipette tip near its discharge end. The sedimentation solution 32 at the bottom 34 of pipette tip 6, with and without the adhering interfering components of porous beads, results in the formation of sedimentation solution 32 and a second-stage refined liquid sample, which is free of interfering components or has a second lower concentration of interfering components than the first-stage refined liquid sample and occupies the upper 36 of pipette tip 6; and the sedimentation solution 32 occupying the bottom 34 of pipette tip 6 is discharged from pipette tip 6 into mixing cup 16 to leave the second-stage refined liquid sample in pipette tip 6 so that a selected volume of the second-stage refined liquid sample, free of interfering components or with a second lower concentration of interfering components, can be dispensed onto test piece 18 later.

[0064] In the above method, the first predetermined time period is preferably about 5 minutes to about 10 minutes, and the second predetermined time period is preferably between about 5 minutes and about 10 minutes; the IMAC resin may include agarose-based porous beads; the IMAC resin is preferably lyophilized in a solution of about 7% dextran / sucrose; even more preferably, the IMAC resin is lyophilized in a solution of about 3.5% dextran and about 3.5% sucrose, wherein the IMAC resin forms physically stable clumps 20 and is located at the bottom 22 of the mixing cup 16; and wherein the method is used to remove hemoglobin as an interfering component that may affect the test performed on the bile acid test measuring piece 18.

[0065] According to another form of the method of the present invention for removing components from blood sample 8 that may interfere with the test performed on test piece 18, the chemical analyzer 2 is used again. The chemical analyzer 2 has a blood separator 14 and a centrifuge cup 12, a mixing cup 16 and a vertically movable pipette 4, the pipette 4 being equipped with a disposable pipette tip 6 and capable of aspirating liquid into and out of the pipette tip 6 and dispensing liquid onto test piece 18. The method includes the following steps: adding a blood sample 8 containing interfering components to a centrifuge cup 12; centrifuging the blood sample in the centrifuge cup 12 using a blood separator 14 of a chemical analyzer 2 to provide separated blood components containing interfering components in the centrifuge cup 12; transferring the separated blood components containing interfering components from the centrifuge cup 12 to a mixing cup 16 containing IMAC (immobilized metal affinity chromatography) resin with porous beads, the separated blood components and IMAC resin forming a blood component / resin solution in the mixing cup 16; mixing the blood component / resin solution in the mixing cup 16 using a pipette 4 of the chemical analyzer 2 to obtain a mixed blood component / resin solution—by aspirating the blood component / resin solution into a pipette tip 6 and then discharging the blood component / resin solution from the pipette tip 6 into the mixing cup 16, repeating the aspiration and discharging steps if necessary. The blood component / resin solution is thoroughly mixed in mixing cup 16 to obtain a mixed blood component / resin solution; the mixed blood component / resin solution is allowed to stand undisturbed in mixing cup 16 for a predetermined time period, the predetermined time period being selected so that at least a portion of the interfering component of the blood component adheres to the porous beads of IMAC resin, and at least a portion of the porous beads with or without the interfering component adhering thereto settle in mixing cup 16 and occupy its bottom 22, the result of the settling of the porous beads with the interfering component adhering thereto is the formation of a purified blood component, which is free of interfering components or has a lower concentration of interfering components than the blood component and occupies the upper part 24 of mixing cup 16; and a predetermined volume of the purified blood component occupying the upper part of mixing cup 16 is aspirated from mixing cup 16 into pipette tip 6 so that a selected volume of purified blood component free of interfering components or having a lower concentration of interfering components can be dispensed onto test specimen 18 later.

[0066] According to the above method, the predetermined time period is preferably about 5 minutes to about 10 minutes; the IMAC resin may include agarose-based porous beads; the IMAC resin is preferably lyophilized in a solution of about 7% dextran / sucrose; even more preferably, the IMAC resin is lyophilized in a solution of about 3.5% dextran and about 3.5% sucrose, wherein the IMAC resin forms physically stable clumps 20 and is located at the bottom 22 of the mixing cup 16; and wherein the method is used to remove hemoglobin as an interfering component that may affect the test performed on the bile acid test measuring piece 18.

[0067] According to another form of the method of the present invention for removing components from blood sample 8 that may interfere with the test performed on test piece 18, a chemical analyzer 2 is used, which has a blood separator 14 and a centrifuge cup 12, a mixing cup 16 and a vertically movable pipette 4, the pipette 4 being equipped with a disposable pipette tip 6 having an outlet end and being able to aspirate liquid into and out of the pipette tip 6 and to dispense liquid onto test piece 18. The method includes the following steps: adding a blood sample 8 containing interfering components to a centrifuge cup 12; centrifuging the blood sample 8 in the centrifuge cup 12 using a blood separator 14 of a chemical analyzer 2 to provide separated blood components containing interfering components in the centrifuge cup 12; transferring the separated blood components containing interfering components from the centrifuge cup 12 to a mixing cup 16 containing IMAC (immobilized metal affinity chromatography) resin with porous beads, the separated blood components and IMAC resin forming a blood component / resin solution in the mixing cup 16; mixing the blood component / resin solution in the mixing cup 16 using a pipette 4 of the chemical analyzer 2 to obtain a mixed blood component / resin solution—by aspirating the blood component / resin solution into a pipette tip 6 and then... The resin solution is discharged from pipette tip 6 into mixing cup 16. If necessary, the aspiration and discharge steps are repeated to fully mix the blood component / resin solution in mixing cup 16 and obtain a mixed blood component / resin solution. The mixed blood component / resin solution is allowed to stand undisturbed in mixing cup 16 for a first predetermined time period, the first predetermined time period being selected to allow at least a portion of the interfering component of the blood component to adhere to the porous beads of IMAC resin, and to allow at least a portion of the porous beads with or without the interfering component attached thereto to settle in mixing cup 16 and occupy its bottom 22. The result of the settling of the porous beads with the interfering component attached thereto is the formation of a first-stage purified blood component, which contains no interfering component or has a first lower concentration of interfering component than the blood component and occupies the upper part 24 of mixing cup 16.

[0068] The method further includes the following steps: aspirating a predetermined volume of a first-stage purified blood component occupying the upper part 24 of a mixing cup 16 from the mixing cup 16 into a pipette tip 6; allowing the first-stage purified blood component aspirated into the pipette tip 6 to stand undisturbed for a second predetermined time period; selecting the second predetermined time period to allow any remaining interfering components of the blood component in the first-stage purified blood component in the pipette tip 6 to adhere to any porous beads of the remaining IMAC resin in the first-stage purified blood component in the pipette tip 6; and allowing at least a portion of the remaining porous beads, with or without interfering components attached thereto, to settle in the pipette tip 6 and form a pipette tip near its discharge end. The sedimentation solution 32 at the bottom 34 of pipette tip 6, with and without the adhering interfering components, results in the formation of a second-stage refined blood component, which is free of interfering components or has a second lower concentration of interfering components than the first refined blood component, and occupies the upper 36 of pipette tip 6; and the sedimentation solution 32 occupying the bottom 34 of pipette tip 6 is discharged from pipette tip 6 into mixing cup 16 to leave the second-stage refined blood component in pipette tip 6 so that a selected volume of the second-stage refined blood component, free of interfering components or with a second lower concentration of interfering components, can be dispensed onto test piece 18 later.

[0069] According to the above method, the first predetermined time period is preferably about 5 minutes to about 10 minutes, and the second predetermined time period is preferably about 5 minutes to about 10 minutes; the IMAC resin may include agarose-based porous beads; the IMAC resin is preferably lyophilized in a solution of about 7% dextran / sucrose; even more preferably, the IMAC resin is lyophilized in a solution of about 3.5% dextran and about 3.5% sucrose, wherein the IMAC resin forms physically stable clumps 20 and is located at the bottom 22 of the mixing cup 16; and wherein the method is used to remove hemoglobin as an interfering component that may affect the test performed on the bile acid test measuring piece 18.

[0070] The present invention also relates to an IMAC (immobilized metal affinity chromatography) resin containing porous beads for use in a chemical analyzer 2 to remove components from a liquid sample 8 that could interfere with tests performed by the chemical analyzer 2 on a test piece 18. The IMAC resin is lyophilized in a solution of about 3.5% dextran and about 3.5% sucrose to form physically stable aggregates 20.

[0071] The present invention further relates to, for example, a method for mixing liquid samples 8 in a chemical analyzer 2. Figure 6The mixing cup 16 shown has an internal space 38. The mixing cup 16 includes IMAC (immobilized metal affinity chromatography) resin containing porous beads and used by the chemical analyzer 2 to remove components from the liquid sample 8 that could interfere with the test performed by the chemical analyzer 2 on the test piece 18. The IMAC resin is located within the internal space 38 of the mixing cup 16.

[0072] Even more preferably, the mixing cup 16 for mixing the liquid sample 8 in the chemical analyzer 2 includes a bottom 22 and an upper portion 24 located above the bottom 22, and an IMAC (immobilized metal affinity chromatography) resin containing porous beads, which is used by the chemical analyzer 2 to remove components from the liquid sample 8 that could interfere with the tests performed by the chemical analyzer 2 on the test piece 18. The IMAC resin is lyophilized in a solution of approximately 3.5% dextran and approximately 3.5% sucrose to form physically stable aggregates 20, which are located at the bottom 22 of the mixing cup 16. When liquid sample 8 is added to mixing cup 16, resin clumps 20 are resuspended in liquid form to form a sample / resin solution therein. A mixed sample / resin solution is obtained when the sample / resin solution in mixing cup 16 is mixed. At least a portion of the interfering component of liquid sample 8 adheres to the porous beads of IMAC resin when the mixed sample / resin solution in mixing cup 16 is allowed to stand undisturbed for a predetermined period of time. At least a portion of the porous beads with or without the interfering component adhering to them settles in mixing cup 16 and occupies its bottom 22. The settling of the porous beads with the adhering interfering component results in the formation of a refined liquid sample, which is free of interfering components or has a lower concentration of interfering components than liquid sample 8, and occupies the upper 24 of mixing cup 16. The refined liquid sample occupying the upper 24 of mixing cup 16 is provided for later dispensing a selected volume of the refined liquid sample, free of interfering components or with a lower concentration of interfering components, onto the test piece 18.

[0073] Specifically, the mixing cup 16 for mixing the liquid sample 8 in the chemical analyzer 2 includes an internal space 38 and further includes a resin containing beads that the chemical analyzer 2 uses to remove components from the liquid sample 8 that could interfere with the tests performed by the chemical analyzer 2 on the test piece 18. This resin is located within the internal space 38 of the mixing cup 16. Preferably, the resin is an IMAC (Immobilized Metal Affinity Chromatography) resin.

[0074] In one embodiment, the mixing cup 16 includes an inner sidewall 21 and a bottom wall 23, and the resin is lyophilized. The lyophilized resin is coated on at least a portion of the inner sidewall 21 of the mixing cup 16 and / or at least a portion of the bottom wall 23 of the mixing cup 16.

[0075] In another embodiment, the mixing cup 16 further includes a bottom 22 and an upper portion 24 located above the bottom 22. When the liquid sample 8 is added to the mixing cup 16, the lyophilized resin is resuspended in liquid form to form a sample / resin solution therein. A mixed sample / resin solution is obtained when the sample / resin solutions in the mixing cup 16 are mixed. At least a portion of the interfering components of the liquid sample 8 adhere to the resin beads when the mixed sample / resin solution in the mixing cup 16 is allowed to stand undisturbed for a predetermined period of time. At least a portion of the beads with or without the interfering components adhering to them settle in the mixing cup 16 and occupy its bottom 22. The settling of the beads with the adhering interfering components results in the formation of a refined liquid sample that is free of interfering components or has a lower concentration of interfering components than the liquid sample 8 and occupies the upper portion 24 of the mixing cup 16. The refined liquid sample occupying the upper portion 24 of the mixing cup 16 is provided for later dispensing a selected volume of the refined liquid sample free of interfering components or having a lower concentration of interfering components onto the test piece 18.

[0076] Preferably, the predetermined time period during which the mixed sample / resin solution in mixing cup 16 is allowed to stand undisturbed is from about 1 minute to about 15 minutes. Furthermore, the resin preferably includes at least one of agarose-based beads and silica-based beads. Additionally, the test assay 18 is preferably a bile acid assay, and the interfering component of the liquid sample is hemoglobin.

[0077] Alternatively, the resin is freeze-dried in a solution of about 2% to about 10% dextran and about 2% to about 10% sucrose, or the resin is freeze-dried in a solution of about 2% to about 14% dextran / sucrose.

[0078] In another embodiment of the invention, the resin in the mixing cup 16 is freeze-dried and forms physically stable aggregates 20, which are located within the internal space 38 of the mixing cup 16. Furthermore, the mixing cup 16 further includes a bottom 22 and an upper portion 24 located above the bottom 22. When liquid sample 8 is added to mixing cup 16, resin clumps 20 are resuspended in liquid form to form a sample / resin solution therein, wherein a mixed sample / resin solution is obtained when the sample / resin solution in mixing cup 16 is mixed, and wherein when the mixed sample / resin solution in mixing cup 16 is allowed to stand undisturbed for a predetermined period of time, at least a portion of the interfering component of liquid sample 8 adheres to the resin beads, and at least a portion of the beads with or without the interfering component adhering thereto settles in mixing cup 16 and occupies its bottom 22. The result of the settling of the beads with the interfering component adhering thereto is the formation of a refined liquid sample, which is free of interfering components or has a lower concentration of interfering components than liquid sample 8 and occupies the upper 24 of mixing cup 16. The refined liquid sample occupying the upper 24 of mixing cup 16 is provided for later dispensing a selected volume of refined liquid sample free of interfering components or having a lower concentration of interfering components onto test specimen 18.

[0079] Preferably, the resin is freeze-dried in a solution of about 2% to about 10% dextran and about 2% to about 10% sucrose, or the resin is freeze-dried in a solution of about 2% to about 14% dextran / sucrose.

[0080] Furthermore, the predetermined time period during which the mixed sample / resin solution in the mixing cup 16 is allowed to stand undisturbed is from about 1 minute to about 15 minutes, and the resin includes at least one of agarose-based beads and silica-based beads.

[0081] In addition, the test specimen 18 can be a bile acid test specimen, and the interfering component of the liquid sample 8 can be hemoglobin.

[0082] In another embodiment of the invention, the mixing cup 16 for mixing the liquid sample 8 in the chemical analyzer 2 includes an internal space 38, a bottom 22, and an upper portion 24 located above the bottom 22, as well as a resin containing beads and used by the chemical analyzer 2 to remove components from the liquid sample 8 that could interfere with the tests performed by the chemical analyzer 2 on the test specimen 18. The resin is located within the internal space 38 of the mixing cup 16. Preferably, the resin is an IMAC (Immobilized Metal Affinity Chromatography) resin.

[0083] Preferably, the resin is freeze-dried in a solution of about 2% to about 10% dextran and about 2% to about 10% sucrose, or a solution of about 2% to about 14% dextran / sucrose, to form physically stable aggregates 20. The resin aggregates 20 are located at the bottom 22 of the mixing cup 16. When the liquid sample 8 is added to the mixing cup 16, the resin aggregates 20 are resuspended in liquid form to form a sample / resin solution therein. A mixed sample / resin solution is obtained when the sample / resin solutions in the mixing cup 16 are mixed, and the mixed sample / resin solution in the mixing cup 16 is allowed to stand undisturbed for a predetermined period of time. At that time, at least a portion of the interfering component of liquid sample 8 adheres to the resin beads, and at least a portion of the beads with or without the interfering component adhering thereto settle in the mixing cup 16 and occupy its bottom 22. The result of the settling of the beads with the interfering component adhering thereto is the formation of a refined liquid sample, which contains no interfering component or has a lower concentration of interfering component than liquid sample 8 and occupies the upper 24 of mixing cup 16. The refined liquid sample occupying the upper 24 of mixing cup 16 is provided for later dispensing a selected volume of refined liquid sample containing no interfering component or having a lower concentration of interfering component onto the test piece 18.

[0084] The present invention also relates to a centrifuge cup 12 of a blood separator 14, which forms part of a chemical analyzer 2 and is used to centrifuge the blood sample 8 contained therein to provide separated blood components in the centrifuge cup 12, the centrifuge cup 12 having an internal space 40. Preferably, the centrifuge cup 12 comprises an IMAC (immobilized metal affinity chromatography) resin containing porous beads and used by the chemical analyzer 2 to remove components from the blood sample 8 that could interfere with tests performed by the chemical analyzer 2 on a test piece 18, the IMAC resin being located within the internal space 40 of the centrifuge cup 12. As will be described below, the IMAC resin may be present in liquid form, in a dry form adhering to one or more walls of the centrifuge cup 12, or as physically stable clumps 20 within the internal space 40 of the centrifuge cup 12.

[0085] More specifically, the centrifuge cup 12 of the blood separator 14 includes an IMAC (immobilized metal affinity chromatography) resin containing porous beads, which is used by the chemical analyzer 2 to remove components from the separated blood fraction that could interfere with the tests performed by the chemical analyzer 2 on the test piece 18. The IMAC resin is lyophilized in a solution of about 3.5% dextran and about 3.5% sucrose to form physically stable aggregates 20, which are located in the internal space 40 of the centrifuge cup 12. When the separated blood components are present in centrifuge cup 12, the resin clumps 20 are resuspended in liquid form to form a blood component / resin solution therein. A mixed blood component / resin solution is obtained when the blood component / resin solution in centrifuge cup 12 is mixed. At least a portion of the interfering components of the blood components adhere to the porous beads of the IMAC resin when the mixed blood component / resin solution in centrifuge cup 12 is allowed to stand undisturbed for a predetermined period of time. At least a portion of the porous beads with or without the interfering components attached to them will settle in centrifuge cup 12 and occupy the bottom 28 of the internal space 40 of centrifuge cup 12. The settling of the porous beads with the attached interfering components results in the formation of a purified blood component, which is free of interfering components or has a lower concentration of interfering components than the blood sample 8, and occupies the upper 30 of centrifuge cup 12. The purified blood component occupying the upper 30 of centrifuge cup 12 is provided for later dispensing a selected volume of purified blood component free of interfering components or with a lower concentration of interfering components onto the test piece 18.

[0086] Figure 8A and 8B This diagram illustrates another method for removing interfering components from a liquid sample according to the present invention. The functionalized beads or particles 41 may be formed to have magnetic properties, or to have an iron-containing component, or more generally, may be as follows: Figure 8A The permanent magnet 42 shown is located in the lower part 22 of the mixing cup 16, or as shown in the figure. Figure 8B The permanent magnet or electromagnet 44 shown is located outside the cup 16 and preferably below the bottom of the cup 16, exhibiting magnetic attraction. The cup 16, formed of a non-magnetic, preferably thermoplastic, material, will not interfere with the magnetic attraction between the functionalized magnetic particles or beads 41 and the magnets or electromagnets 42, 44 placed inside or outside the cup 16 and close to them. As described above and as shown in the figures... Figure 6 As shown, the functionalized particles 41 may be in a dry form and coated on the wall of the mixing cup 16, or they may be in a physically stable form 20 and located in the cup 16.

[0087] When liquid sample 8 is added to mixing cup 16, functionalized magnetic particles 41 are rehydrated and mixed with liquid sample 8 in solution. Interfering components of liquid sample 8 to be removed adhere to the functionalized magnetic particles 41, which are then magnetically attracted and drawn to magnets 42, 44 located in the lower part 22 of cup 16 or below and close to the bottom of cup 16. Thus, particles or beads 41 with or without attached interfering components occupy the lower part 22 of cup 16 by attraction from magnets 42, 44, leaving a certain volume of liquid sample 8 without interfering components or with reduced concentration occupying the upper part 24 of mixing cup 16, where it can be easily aspirated into pipette tip 6 for subsequent deposition on chemical reagent test slide 18.

[0088] Suitable functionalized particles with such magnetic properties are beads of model number 88831 distributed by Thermo Fisher Scientific Inc., Waltham, MA.

[0089] Although this document primarily describes placing a gel containing functionalized particles in a mixing cup 16 used by an automated chemical analyzer 2, it is contemplated that the gel be placed in a sample cup, reagent cup, centrifuge cup, or any other type of cup or liquid container that can be used to remove interfering components from the liquid sample 8 or reduce their concentration in the liquid sample 8, and it should be understood that the term "mixing cup" as used herein and in the claims should be interpreted to include all of the aforementioned cups and containers.

[0090] Although illustrative embodiments of the invention have been described herein with reference to the accompanying drawings, it is to be understood that the invention is not limited to these exact embodiments, and various other changes and modifications may be made therein by those skilled in the art without departing from the scope or spirit of the invention.

Claims

1. A mixing cup for mixing liquid samples in a chemical analyzer, wherein the mixing cup comprises: Interior space; Inner wall and bottom wall; and A resin containing beads is used by the chemical analyzer to remove interfering components from the liquid sample that could interfere with tests performed by the chemical analyzer on a test piece, wherein the resin is located within the internal space of the mixing cup. The resin mentioned therein is freeze-dried; The freeze-dried resin is applied to at least a portion of the inner sidewall of the mixing cup and / or at least a portion of the bottom wall of the mixing cup; and When the liquid sample is added to the mixing cup, the lyophilized resin is resuspended in liquid form to form a sample / resin solution.

2. The mixing cup according to claim 1, wherein the resin is an immobilized metal affinity chromatography resin.

3. The mixing cup according to claim 1, further comprising: The bottom and the upper part located above the bottom; When the sample / resin solution in the mixing cup is mixed, a mixed sample / resin solution is obtained. When the mixed sample / resin solution in the mixing cup is allowed to stand undisturbed for a predetermined period of time, at least a portion of the interfering component of the liquid sample adheres to the resin beads, and at least a portion of the beads settle in the mixing cup and occupy its bottom. The settling of the beads with the attached interfering component results in the formation of a refined liquid sample, which contains no interfering component or has a lower concentration of interfering component than the liquid sample and occupies the upper part of the mixing cup. The refined liquid sample occupying the upper part of the mixing cup is provided for later dispensing a selected volume of the refined liquid sample, which contains no interfering component or has a lower concentration of interfering component, onto the test specimen.

4. The mixing cup according to claim 3, wherein the predetermined time period during which the mixed sample / resin solution in the mixing cup is allowed to stand undisturbed is from about 1 minute to about 15 minutes.

5. The mixing cup according to claim 3, wherein the resin comprises at least one of agarose-based beads and silica-based beads.

6. The mixing cup according to claim 3, wherein the test element is a bile acid test element; and The interfering component of the liquid sample is hemoglobin.

7. The mixing cup according to claim 1, wherein the resin is freeze-dried in a solution of about 2% to about 10% dextran and about 2% to about 10% sucrose.

8. The mixing cup according to claim 1, wherein the resin is freeze-dried in a solution of about 2% to about 14% dextran / sucrose.

9. The mixing cup according to claim 1, wherein the resin is freeze-dried and forms physically stable clumps within the internal space of the mixing cup.

10. The mixing cup according to claim 9, wherein the resin is an immobilized metal affinity chromatography resin.

11. The mixing cup according to claim 9, further comprising: The bottom and the upper part above the bottom; When the liquid sample is added to the mixing cup, the physically stable aggregates are resuspended in liquid form to form a sample / resin solution therein, and a mixed sample / resin solution is obtained when the sample / resin solution in the mixing cup is mixed, and at least a portion of the interfering components of the liquid sample adhere to the resin beads when the mixed sample / resin solution in the mixing cup is allowed to stand undisturbed for a predetermined period of time, and at least a portion of the beads with or without the interfering components adhering thereto settle in the mixing cup and occupy its bottom, the settling of the beads with the interfering components adhering thereto results in the formation of a refined liquid sample, which is free of interfering components or has a lower concentration of interfering components than the liquid sample and occupies the upper part of the mixing cup, the refined liquid sample occupying the upper part of the mixing cup is provided for later dispensing a selected volume of the refined liquid sample, which is free of interfering components or has a lower concentration of interfering components, onto the test specimen.

12. The mixing cup of claim 11, wherein the resin is freeze-dried in a solution of about 2% to about 10% dextran and about 2% to about 10% sucrose.

13. The mixing cup of claim 11, wherein the resin is freeze-dried in a solution of about 2% to about 14% dextran / sucrose.

14. The mixing cup of claim 11, wherein the predetermined time period during which the mixed sample / resin solution in the mixing cup is allowed to stand undisturbed is from about 1 minute to about 15 minutes.

15. The mixing cup of claim 11, wherein the resin comprises at least one of agarose-based beads and silica-based beads.

16. The mixing cup of claim 11, wherein the test element is a bile acid test element; and The interfering component of the liquid sample is hemoglobin.

17. The mixing cup according to claim 1, further comprising: The bottom and the upper part located above the bottom; The resin is freeze-dried in a solution of about 2% to about 10% dextran and about 2% to about 10% sucrose, or a solution of about 2% to about 14% dextran / sucrose, to form physically stable aggregates. These physically stable aggregates are located at the bottom of the mixing cup and are resuspended in liquid form when the liquid sample is added to the mixing cup to form a sample / resin solution therein. A mixed sample / resin solution is obtained when the sample / resin solutions in the mixing cup are mixed. The mixed sample / resin solution in the mixing cup is allowed to remain undisturbed. During a predetermined settling period, at least a portion of the interfering components of the liquid sample adhere to the resin beads, and at least a portion of the beads settle in the mixing cup and occupy its bottom. The settling of the beads with the interfering components attached thereto results in the formation of a refined liquid sample, which contains no interfering components or has a lower concentration of interfering components than the liquid sample and occupies the upper part of the mixing cup. The refined liquid sample occupying the upper part of the mixing cup is provided for later dispensing a selected volume of the refined liquid sample, which contains no interfering components or has a lower concentration of interfering components, onto the test specimen.

18. A method for removing interfering components from a liquid sample that may interfere with a test performed on a test piece using a chemical analyzer, the chemical analyzer having a sample cup, a mixing cup, and a pipette, the pipette being equipped with a disposable pipette tip and capable of aspirating the liquid sample into and out of the pipette tip and dispensing the liquid sample onto the test piece, the method comprising the following steps: Add the liquid sample containing the interfering component to the sample cup; A liquid sample containing interfering components is transferred from the sample cup to the mixing cup, the mixing cup having an internal space and a bottom and an upper part located above the bottom, the mixing cup containing bead-containing resin, the resin being freeze-dried and formed as physically stable clumps located within the internal space of the mixing cup, and wherein the physically stable clumps are resuspended in liquid form to form a sample / resin solution when the liquid sample is added to the mixing cup; The sample / resin solution is mixed in the mixing cup using the pipette of the chemical analyzer to obtain a mixed sample / resin solution—by aspirating the sample / resin solution into the pipette tip and then discharging the sample / resin solution from the pipette tip into the mixing cup, repeating the aspiration and discharging steps if or necessary, to fully mix the sample / resin solution in the mixing cup and obtain a mixed sample / resin solution; The mixed sample / resin solution is allowed to stand undisturbed in the mixing cup for a predetermined time period, the predetermined time period being selected so that at least a portion of the interfering component of the liquid sample adheres to the resin beads, and at least a portion of the beads settle in the mixing cup and occupy its bottom. The result of the settling of the beads with the interfering component attached thereto is the formation of a refined liquid sample, which contains no interfering component or has a lower concentration of interfering component than the liquid sample and occupies the upper part of the mixing cup. and A predetermined volume of purified liquid sample occupying the upper part of the mixing cup is aspirated from the mixing cup into a pipette tip so that a selected volume of purified liquid sample free of interfering components or with a low concentration of interfering components can be dispensed onto the test specimen later.

19. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 18, wherein the predetermined time period is from about 1 minute to about 15 minutes.

20. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 18, wherein the resin comprises at least one of agarose-based beads and silica-based beads.

21. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 18, wherein the resin is lyophilized in a solution of about 2% to about 14% dextran / sucrose.

22. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 18, wherein the resin is freeze-dried in a solution of about 2% to about 10% dextran and about 2% to about 10% sucrose.

23. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 18, wherein the resin is an immobilized metal affinity chromatography resin.

24. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 18, wherein the test element is a bile acid analyzer; and The interfering component of the liquid sample is hemoglobin.

25. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 18, wherein the interfering component of the liquid sample is a protein.

26. A method for removing interfering components from a liquid sample that may interfere with a test performed on a test piece using a chemical analyzer, the chemical analyzer having a sample cup, a mixing cup, and a pipette equipped with a disposable pipette tip having a discharge end and capable of aspirating the liquid sample into and out of the pipette tip and dispensing the liquid sample onto the test piece, the method comprising the following steps: Add the liquid sample containing the interfering component to the sample cup; A liquid sample containing interfering components is transferred from the sample cup to the mixing cup, the mixing cup having an internal space and a bottom and an upper part located above the bottom, the mixing cup containing bead-containing resin, the resin being freeze-dried and formed as physically stable clumps located within the internal space of the mixing cup, and wherein the physically stable clumps are resuspended in liquid form to form a sample / resin solution when the liquid sample is added to the mixing cup; The sample / resin solution is mixed in the mixing cup using the pipette of the chemical analyzer to obtain a mixed sample / resin solution—by aspirating the sample / resin solution into the pipette tip and then discharging the sample / resin solution from the pipette tip into the mixing cup, repeating the aspiration and discharging steps if or necessary, to fully mix the sample / resin solution in the mixing cup and obtain a mixed sample / resin solution; The mixed sample / resin solution is allowed to stand undisturbed in the mixing cup for a first predetermined time period, the first predetermined time period being selected to allow at least a portion of the interfering components of the liquid sample to adhere to the resin beads, and to allow at least a portion of the beads to settle in the mixing cup and occupy its bottom. The result of the settling of the beads with the interfering components attached thereto is the formation of a first-stage refined liquid sample, which contains no interfering components or has a first lower concentration of interfering components than the liquid sample and occupies the upper part of the mixing cup. A predetermined volume of the first-stage refined liquid sample, occupying the upper part of the mixing cup, is aspirated from the mixing cup into the pipette tip; The first-stage refined liquid sample aspirated into the pipette tip is allowed to stand undisturbed for a second predetermined time period, the second predetermined time period being selected to allow any remaining interfering components of the liquid sample in the first-stage refined liquid sample in the pipette tip to adhere to any beads of the remaining resin in the first-stage refined liquid sample in the pipette tip, and to allow at least a portion of the remaining beads to settle in the pipette tip and form a settling solution occupying the bottom of the pipette tip near its discharge end, wherein the settling of at least a portion of the remaining beads with the interfering components attached thereto and at least a portion of the remaining beads without attachment results in the formation of a settling solution and a second, more refined liquid sample, which contains no interfering components or has a second lower concentration of interfering components than the first-stage refined liquid sample and occupies the upper part of the pipette tip. and The sedimentation solution occupying the bottom of the pipette tip is expelled from the pipette tip into the mixing cup to leave a second-stage refined liquid sample in the pipette tip so that a selected volume of a second-stage refined liquid sample with or without interfering components at a lower concentration can be dispensed onto the test specimen later.

27. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 26, wherein the first predetermined time period is from about 1 minute to about 15 minutes.

28. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 26, wherein the second predetermined time period is from about 1 minute to about 15 minutes.

29. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 26, wherein the resin comprises at least one of agarose-based beads and silica-based beads.

30. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 26, wherein the resin is lyophilized in a solution of about 2% to about 14% dextran / sucrose.

31. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 26, wherein the resin is freeze-dried in a solution of about 2% to about 10% dextran and about 2% to about 10% sucrose.

32. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 26, wherein the resin is an immobilized metal affinity chromatography resin.

33. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 26, wherein the test specimen is a bile acid test specimen; and The interfering component of the liquid sample is hemoglobin.

34. The method for removing interfering components from a liquid sample using a chemical analyzer according to claim 26, wherein the interfering component of the liquid sample is a protein.

35. A method for removing interfering components from a blood sample that may interfere with a test performed on a test piece using a chemical analyzer, the chemical analyzer having a blood separator and centrifuge cup, mixing cup, and pipette equipped with disposable pipette tips and capable of aspirating liquid into and out of the pipette tips and dispensing liquid onto the test piece, the method comprising the following steps: Add the blood sample containing interfering components to the centrifuge cup; The blood sample is centrifuged in the centrifuge cup using the blood separator of the chemical analyzer to provide separated blood components in the centrifuge cup, the separated blood components containing interfering components; The separated blood component containing interfering components is transferred from the centrifuge cup to the mixing cup, the mixing cup having an internal space and a bottom and an upper part above the bottom, the mixing cup containing bead-containing resin, the resin being freeze-dried and formed as physically stable clumps within the internal space of the mixing cup, and wherein the physically stable clumps are resuspended in liquid form to form a blood component / resin solution when the separated blood component is added to the mixing cup; The blood component / resin solution is mixed in the mixing cup using the pipette of the chemical analyzer to obtain a mixed blood component / resin solution—by aspirating the blood component / resin solution into the pipette tip and then dispensing the blood component / resin solution from the pipette tip into the mixing cup, repeating the aspiration and dispensing steps if or necessary, to fully mix the blood component / resin solution in the mixing cup and obtain a mixed blood component / resin solution; The mixed blood component / resin solution is allowed to stand undisturbed in the mixing cup for a predetermined time period, the predetermined time period being selected so that at least a portion of the interfering component of the blood component adheres to the resin beads, and at least a portion of the beads settle in the mixing cup and occupy its bottom. The result of the settling of the beads with the interfering component attached thereto is the formation of a refined blood component, which contains no interfering component or has a lower concentration of interfering component than the blood component and occupies the upper part of the mixing cup. and A predetermined volume of purified blood, occupying the upper part of the mixing cup, is aspirated from the mixing cup into a pipette tip so that a selected volume of purified blood, free of interfering components or with a low concentration of interfering components, can later be dispensed onto the test specimen.

36. The method for removing interfering components from a blood sample using a chemical analyzer according to claim 35, wherein the predetermined time period is from about 1 minute to about 15 minutes.

37. The method for removing interfering components from a blood sample using a chemical analyzer according to claim 35, wherein the resin comprises at least one of agarose-based beads and silica-based beads.

38. The method for removing interfering components from a blood sample using a chemical analyzer according to claim 35, wherein the resin is lyophilized in a solution of about 2% to about 14% dextran / sucrose.

39. The method for removing interfering components from a blood sample using a chemical analyzer according to claim 35, wherein the resin is freeze-dried in a solution of about 2% to about 10% dextran and about 2% to about 10% sucrose.

40. The method for removing interfering components from a blood sample using a chemical analyzer according to claim 35, wherein the resin is an immobilized metal affinity chromatography resin.

41. The method for removing interfering components from a blood sample using a chemical analyzer according to claim 35, wherein the test element is a bile acid analyzer; and The interfering component in the blood sample is hemoglobin.

42. The method for removing interfering components from a blood sample using a chemical analyzer according to claim 35, wherein the interfering component of the blood sample is protein.

43. A method for removing interfering components from a blood sample that may interfere with a test performed on a test piece using a chemical analyzer, the chemical analyzer having a blood separator, a centrifuge cup, a mixing cup, and a pipette equipped with a disposable pipette tip having a discharge end and capable of aspirating liquid into and out of the pipette tip and dispensing liquid onto the test piece, the method comprising the following steps: Add the blood sample containing interfering components to the centrifuge cup; The blood sample is centrifuged in the centrifuge cup using the blood separator of the chemical analyzer to provide separated blood components in the centrifuge cup, the separated blood components containing interfering components; The separated blood component containing interfering components is transferred from the centrifuge cup to the mixing cup, the mixing cup having an internal space and a bottom and an upper part above the bottom, the mixing cup containing bead-containing resin, the resin being freeze-dried and formed as physically stable clumps within the internal space of the mixing cup, and wherein the physically stable clumps are resuspended in liquid form to form a blood component / resin solution when the separated blood component is added to the mixing cup; The blood component / resin solution is mixed in a mixing cup using the pipette of the chemical analyzer to obtain a mixed blood component / resin solution—by aspirating the blood component / resin solution into the pipette tip and then dispensing the blood component / resin solution from the pipette tip into the mixing cup, repeating the aspiration and dispensing steps if or necessary to fully mix the blood component / resin solution in the mixing cup and obtain a mixed blood component / resin solution; The mixed blood component / resin solution is allowed to stand undisturbed in the mixing cup for a first predetermined time period, the first predetermined time period being selected so that at least a portion of the interfering component of the blood component adheres to the resin beads, and at least a portion of the beads settle in the mixing cup and occupy its bottom. The result of the settling of the beads with the interfering component attached thereto is the formation of a first-stage refined blood component, which contains no interfering component or has a first lower concentration of interfering component than the blood component and occupies the upper part of the mixing cup. A predetermined volume of the first-stage refined blood component, occupying the upper part of the mixing cup, is aspirated from the mixing cup into the pipette tip; The first-stage refined blood component aspirated into the pipette tip is allowed to stand undisturbed for a second predetermined time period, the second predetermined time period being selected so that any remaining interfering components of the blood component in the first-stage refined blood component in the pipette tip adhere to any beads of the remaining resin in the first-stage refined blood component in the pipette tip, and at least a portion of the remaining beads settle in the pipette tip and form a settling solution occupying the bottom of the pipette tip near its discharge end, and wherein the settling of at least a portion of the remaining beads with the interfering components attached thereto and at least a portion of the remaining beads without attachment results in the formation of a settling solution and a second-stage more refined blood component, which contains no interfering components or has a second lower concentration of interfering components than the first refined blood component and occupies the upper part of the pipette tip; and The sedimentation solution occupying the bottom of the pipette tip is expelled from the pipette tip into the mixing cup to leave a second-stage refined blood component in the pipette tip so that a selected volume of a second, lower concentration of the second-stage refined blood component, either free of interfering components or containing interfering components, can be dispensed onto the test specimen later.

44. The method for removing interfering components from a blood sample using a chemical analyzer according to claim 43, wherein the first predetermined time period is from about 1 minute to about 15 minutes.

45. The method for removing interfering components from a blood sample using a chemical analyzer according to claim 43, wherein the second predetermined time period is from about 1 minute to about 15 minutes.

46. ​​The method for removing interfering components from a blood sample using a chemical analyzer according to claim 43, wherein the resin comprises at least one of agarose-based beads and silica-based beads.

47. The method for removing interfering components from a blood sample using a chemical analyzer according to claim 43, wherein the resin is lyophilized in a solution of about 2% to about 14% dextran / sucrose.

48. The method for removing interfering components from a blood sample using a chemical analyzer according to claim 43, wherein the resin is freeze-dried in a solution of about 2% to about 10% dextran and about 2% to about 10% sucrose.

49. The method for removing interfering components from a blood sample using a chemical analyzer according to claim 43, wherein the resin is an immobilized metal affinity chromatography resin.

50. The method for removing interfering components from a blood sample using a chemical analyzer according to claim 43, wherein the test element is a bile acid analyzer; and The interfering component in the blood sample is hemoglobin.

51. The method for removing interfering components from a blood sample using a chemical analyzer according to claim 43, wherein the interfering component of the blood sample is a protein.

52. A mixing cup for mixing liquid samples in a chemical analyzer, the mixing cup comprising: The bottom and the upper part located above the bottom; and A resin containing beads, used by the chemical analyzer to remove interfering components from a liquid sample that could interfere with tests performed by the chemical analyzer on a test piece, is lyophilized in a solution of about 2% to about 10% dextran and about 2% to about 10% sucrose, or a solution of about 2% to about 14% dextran / sucrose, to form physically stable aggregates. These resin aggregates are located at the bottom of the mixing cup and are resuspended in liquid form when a liquid sample is added to the mixing cup to form a sample / resin solution therein. A mixed sample / resin solution is obtained when the sample / resin solutions in the mixing cup are mixed, and wherein, when the mixing is allowed... When the mixed sample / resin solution in the mixing cup is left to stand undisturbed for a predetermined period of time, at least a portion of the interfering component of the liquid sample adheres to the resin beads, and at least a portion of the beads with or without the interfering component adhering to them settle in the mixing cup and occupy its bottom. The result of the settling of the beads with the interfering component adhering to them is the formation of a refined liquid sample, which contains no interfering component or has a lower concentration of interfering component than the liquid sample and occupies the upper part of the mixing cup. The refined liquid sample occupying the upper part of the mixing cup is provided for later dispensing a selected volume of the refined liquid sample containing no interfering component or having a lower concentration of interfering component onto the test specimen.

53. The mixing cup according to claim 52, wherein the resin is an immobilized metal affinity chromatography resin.

54. A centrifuge cup for a blood separator, which forms part of a chemical analyzer and is used to centrifuge a blood sample contained therein to provide separated blood components in the centrifuge cup, wherein the centrifuge cup comprises: Interior space; Inner wall and bottom wall; and A resin containing beads is used by the chemical analyzer to remove interfering components from blood samples that may interfere with tests performed by the chemical analyzer on test pieces, wherein the resin is located within the internal space of the centrifuge cup. The resin mentioned therein is freeze-dried; The freeze-dried resin is applied to at least a portion of the inner wall of the centrifuge cup and / or at least a portion of the bottom wall of the centrifuge cup; and When the blood sample is added to the centrifuge cup, the lyophilized resin is resuspended in liquid form to form a sample / resin solution.

55. The centrifuge cup according to claim 54, wherein the resin is an immobilized metal affinity chromatography resin.

56. A centrifuge cup for a blood separator, which forms part of a chemical analyzer and is used to centrifuge a blood sample contained therein to provide separated blood components in the centrifuge cup, the centrifuge cup having an internal space, the centrifuge cup comprising: A resin containing beads, used by the chemical analyzer to remove interfering components from the separated blood components that could interfere with tests performed by the chemical analyzer on a test piece, is freeze-dried in a solution of about 2% to about 10% dextran and about 2% to about 10% sucrose, or a solution of about 2% to about 14% dextran / sucrose, to form physically stable clumps. These resin clumps are located within the internal space of the centrifuge cup. When the separated blood components are present in the centrifuge cup, the resin clumps are resuspended in liquid form to form a blood component / resin solution therein. When the blood component / resin solutions in the centrifuge cup are mixed, a mixed blood component / resin solution is obtained. When the mixed blood component / resin solution in the centrifuge cup is allowed to stand undisturbed for a predetermined period of time, at least a portion of the interfering component of the blood component adheres to the resin beads, and at least a portion of the beads with or without the interfering component adhering thereto settle in the centrifuge cup and occupy the bottom of the centrifuge cup. The result of the settling of the beads with the interfering component adhering thereto is the formation of a purified blood component, which is free of interfering components or has a lower concentration of interfering components than the blood sample and occupies the upper part of the centrifuge cup. The purified blood component occupying the upper part of the centrifuge cup is provided for later dispensing a selected volume of purified blood component free of interfering components or having a lower concentration of interfering components onto the test specimen.

57. The centrifuge cup according to claim 56, wherein the resin is an immobilized metal affinity chromatography resin.

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