# US 2021/0275979 A1 · Method for removing interfering components of a liquid sample prior to dispensing same on a chemical reagent test slide

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- Number: US 2021/0275979 A1
- Document ID: US20210275979A1
- Status: Published application
- Kind: A1
- Application number: 17/194,713
- Filed: 2021-03-08
- Published: 2021-09-09
- Earliest claimed: 2020-03-09
- Assignees: IDEXX Laboratories, Inc.
- Applicants: IDEXX Laboratories, Inc.
- Inventors: Pamela Ann Cacavas; Lucius S. Fox; Robert W. Lachapelle; Wendy O'Malley LePage; Evan M. Peck; Dominic Pelletier; Eric Allen Steva; Murthy V.S.N. Yerramilli
- Web page: https://patentgrep.com/patent/US20210275979A1

## CPC

- B01L 3/5021: {Test tubes specially adapted for centrifugation purposes}
- G01N 1/34: Purifying; Cleaning {(processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003)}
- B01F 31/651: {Mixing by successively aspirating a part of the mixture in a conduit, e.g. a piston, and reinjecting it through the same conduit into the receptacle}
- B01J 20/103: {comprising silica}
- B01J 20/24: Naturally occurring macromolecular compounds, e.g. humic acids or their derivatives
- B01J 20/283: based on silica
- B01J 20/285: based on polymers
- B01J 20/286: Phases chemically bonded to a substrate, e.g. to silica or to polymers
- B01L 3/502: {with fluid transport, e.g. in multi-compartment structures}
- G01N 33/491: {by separating the blood components (G01N15/05 takes precedence)}
- G01N 35/10: Devices for transferring samples {or any liquids} to, in, or from, the analysis apparatus, e.g. suction devices, injection devices {(G01N35/0099 takes precedence)}
- A61B 2010/0061: {Alimentary tract secretions, e.g. biliary, gastric, intestinal, pancreatic secretions}
- B01F 2101/23: Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
- B01L 2200/026: Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L 2400/0475: specific mechanical means and fluid pressure
- G01N 2035/00564: {Handling or washing solid phase elements, e.g. beads}
- G01N 2035/103: {using disposable tips}
- G01N 2035/106: {by sucking and blowing}
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- B01F: MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING (mixing paints B44D3/06)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)

## Abstract

A method using a chemical analyzer for removing a component of a liquid sample which may interfere with a test performed on a test assay includes the steps of adding the liquid sample to a sample cup, transferring a volume of the liquid sample to a mixing cup containing an IMAC (Immobilized Metal Affinity Chromatography) resin containing porous beads to form a sample/resin solution in the mixing cup, using a pipette of the chemical analyzer to repeatedly aspirate the sample/resin solution into a disposable pipette tip of the pipette and expelling the sample/resin solution from the pipette tip into the mixing cup to achieve a mixed sample/resin solution in the mixing cup, and allowing the mixed sample/resin solution in the mixing cup to rest undisturbed so that the interfering component of the liquid sample adheres to the porous beads and the beads settle to a bottom portion of the mixing cup, resulting in a refined liquid sample devoid of the interfering component and occupying an upper portion of the mixing cup for later dispensing on the test assay.

## Claims

### Claim 1

A mixing cup used for mixing a liquid sample in a chemical analyzer, the mixing cup having an interior space, the mixing cup comprising:
a resin containing beads and used by the chemical analyzer for removing a component of the liquid sample which may interfere with a test performed on a test assay by the chemical analyzer, the resin being situated within the interior space of the mixing cup.

### Claim 2 (depends on 1)

A mixing cup as defined by claim 1, wherein the resin is an IMAC (Immobilized Metal Affinity Chromatography) resin.

### Claim 3 (depends on 1)

A mixing cup as defined by claim 1, wherein the mixing cup includes an interior side wall and a bottom wall;
wherein the resin is lyophilized; and
wherein the lyophilized resin coats at least one of at least a portion of the interior side wall of the mixing cup and at least a portion of the bottom wall of the mixing cup.

### Claim 4 (depends on 3)

A mixing cup as defined by claim 3, which further comprises:
a bottom portion and an upper portion situated above the bottom portion;
wherein the lyophilized resin is resuspended in a liquid form when the liquid sample is added to the mixing cup to form a sample/resin solution therein, wherein, when the sample/resin solution in the mixing cup is mixed, a mixed sample/resin solution is achieved, and wherein, when the mixed sample/resin solution in the mixing cup is allowed to rest undisturbed for a predetermined period of time, at least a portion of the interfering component of the liquid sample adheres to the beads of the resin and at least some of the beads with or without the interfering component adhering thereto settle in the mixing cup and occupy the bottom portion thereof, the result of the settling of the beads having the interfering component adhered thereto being the formation of a refined liquid sample devoid or having a lower concentration of the interfering component than the liquid sample and occupying an upper portion of the mixing cup, the refined liquid sample occupying the upper portion of the mixing cup being provided for later dispensing of a selected volume of the refined liquid sample devoid or having the lower concentration of the interfering component onto the test assay.

### Claim 5 (depends on 4)

A mixing cup as defined by claim 4, wherein the predetermined period of time which the mixed sample/resin solution in the mixing cup is allowed to rest undisturbed is between about one minute and about fifteen minutes.

### Claim 6 (depends on 4)

A mixing cup as defined by claim 4, wherein the resin includes at least one of agarose-based beads and silica-based beads.

### Claim 7 (depends on 4)

A mixing cup as defined by claim 4, wherein the test assay is a bile acid assay; and
wherein the interfering component of the liquid sample is hemoglobin.

### Claim 8 (depends on 3)

A mixing cup as defined by claim 3, wherein the resin is lyophilized in a solution of between about two percent (2%) and about ten percent (10%) dextran and between about two percent (2%) and about ten percent (10%) sucrose.

### Claim 9 (depends on 3)

A mixing cup as defined by claim 3, wherein the resin is lyophilized in a solution of about two percent (2%) to about fourteen percent (14%) dextran/sucrose.

### Claim 10 (depends on 1)

A mixing cup as defined by claim 1, wherein the resin is lyophilized and forms a physically stable cake, the resin cake being situated within the interior space of the mixing cup.

### Claim 11 (depends on 10)

A mixing cup as defined by claim 10, which further comprises:
a bottom portion and an upper portion situated above the bottom portion;
wherein the resin cake is resuspended in a liquid form when the liquid sample is added to the mixing cup to form a sample/resin solution therein, wherein, when the sample/resin solution in the mixing cup is mixed, a mixed sample/resin solution is achieved, and wherein, when the mixed sample/resin solution in the mixing cup is allowed to rest undisturbed for a predetermined period of time, at least a portion of the interfering component of the liquid sample adheres to the beads of the resin and at least some of the beads with or without the interfering component adhering thereto settle in the mixing cup and occupy the bottom portion thereof, the result of the settling of the beads having the interfering component adhered thereto being the formation of a refined liquid sample devoid or having a lower concentration of the interfering component than the liquid sample and occupying an upper portion of the mixing cup, the refined liquid sample occupying the upper portion of the mixing cup being provided for later dispensing of a selected volume of the refined liquid sample devoid or having the lower concentration of the interfering component onto the test assay.

### Claim 12 (depends on 11)

A mixing cup as defined by claim 11, wherein the resin is lyophilized in a solution of between about two percent (2%) and about ten percent (10%) dextran and between about two percent (2%) and about ten percent (10%) sucrose.

### Claim 13 (depends on 11)

A mixing cup as defined by claim 11, wherein the resin is lyophilized in a solution of about two percent (2%) to about fourteen percent (14%) dextran/sucrose.

### Claim 14 (depends on 11)

A mixing cup as defined by claim 11, wherein the predetermined period of time which the mixed sample/resin solution in the mixing cup is allowed to rest undisturbed is between about one minute and about fifteen minutes.

### Claim 15 (depends on 11)

A mixing cup as defined by claim 11, wherein the resin includes at least one of agarose-based beads and silica-based beads.

### Claim 16 (depends on 11)

A mixing cup as defined by claim 11, wherein the test assay is a bile acid assay; and
wherein the interfering component of the liquid sample is hemoglobin.

### Claim 17 (depends on 1)

A mixing cup as defined by claim 1, which further comprises:
a bottom portion and an upper portion situated above the bottom portion;
wherein the resin is lyophilized in a solution of between about two percent (2%) and about ten percent (10%) dextran and between about two percent (2%) and about ten percent (10%) sucrose, or of about two percent (2%) to about fourteen percent (14%) dextran/sucrose, to form a physically stable cake, the resin cake residing in the bottom portion of the mixing cup, the resin cake being resuspended in a liquid form when the liquid sample is added to the mixing cup to form a sample/resin solution therein, wherein, when the sample/resin solution in the mixing cup is mixed, a mixed sample/resin solution is achieved, and wherein, when the mixed sample/resin solution in the mixing cup is allowed to rest undisturbed for a predetermined period of time, at least a portion of the interfering component of the liquid sample adheres to the beads of the resin and at least some of the beads with or without the interfering component adhering thereto settle in the mixing cup and occupy the bottom portion thereof, the result of the settling of the beads having the interfering component adhered thereto being the formation of a refined liquid sample devoid or having a lower concentration of the interfering component than the liquid sample and occupying an upper portion of the mixing cup, the refined liquid sample occupying the upper portion of the mixing cup being provided for later dispensing of a selected volume of the refined liquid sample devoid or having the lower concentration of the interfering component onto the test assay.

### Claim 18

A method using a chemical analyzer for removing a component of a liquid sample which may interfere with a test performed on a test assay, the chemical analyzer having a sample cup, a mixing cup, a pipette fitted with a disposable pipette tip and capable of aspirating and expelling liquid sample into and from the pipette tip and capable of dispensing the liquid sample onto the test assay, the method comprising the steps of:
adding the liquid sample containing the interfering component to the sample cup;
transferring the liquid sample containing the interfering component from the sample cup to the mixing cup, the mixing cup containing a resin containing beads, the liquid sample and resin forming a sample/resin solution in the mixing cup;
mixing the sample/resin solution in the mixing cup using the pipette of the chemical analyzer to achieve a mixed sample/resin solution by aspirating the sample/resin solution into the pipette tip and then expelling the sample/resin solution from the pipette tip into the mixing cup, the aspirating and expelling steps being repeated, if or as necessary, to thoroughly mix the sample/resin solution in the mixing cup and achieve the mixed sample/resin solution;
allowing the mixed sample/resin solution in the mixing cup to rest undisturbed for a predetermined period of time, the predetermined period of time being selected to allow at least a portion of the interfering component of the liquid sample to adhere to the beads of the resin and to allow at least some of the beads with or without the interfering component adhering thereto to settle in the mixing cup and to occupy a bottom portion thereof, the result of the settling of the beads having the interfering component adhered thereto being the formation of a refined liquid sample devoid or having a lower concentration of the interfering component than the liquid sample and occupying an upper portion of the mixing cup; and
aspirating into the pipette tip from the mixing cup a predetermined volume of the refined liquid sample occupying the upper portion of the mixing cup for later dispensing of a selected volume of the refined liquid sample devoid or having the lower concentration of the interfering component onto the test assay.

### Claim 19 (depends on 18)

A method for removing an interfering component of a liquid sample as defined by claim 18, wherein the predetermined period of time is between about one minute and about fifteen minutes.

### Claim 20 (depends on 18)

A method for removing an interfering component of a liquid sample as defined by claim 18, wherein the resin includes at least one of agarose-based beads and silica-based beads.

### Claim 21 (depends on 18)

A method for removing an interfering component of a liquid sample as defined by claim 18, wherein the resin is lyophilized in a solution of about two percent (2%) to about fourteen percent (14%) dextran/sucrose.

### Claim 22 (depends on 18)

A method for removing an interfering component of a liquid sample as defined by claim 18, wherein the resin is lyophilized in a solution of between about two percent (2%) and about ten percent (10%) dextran and between about two percent (2%) and about ten percent (10%) sucrose.

### Claim 23 (depends on 18)

A method for removing an interfering component of a liquid sample as defined by claim 18, wherein the resin is formed as a physically stable cake and resides in the bottom portion of the mixing cup.

### Claim 24 (depends on 18)

A method for removing an interfering component of a liquid sample as defined by claim 18, wherein the resin is an IMAC (Immobilized Metal Affinity Chromatography) resin.

### Claim 25 (depends on 18)

A method for removing an interfering component of a liquid sample as defined by claim 18, wherein the test assay is a bile acid assay; and
wherein the interfering component of the liquid sample is hemoglobin.

### Claim 26 (depends on 18)

A method for removing an interfering component of a liquid sample as defined by claim 18, wherein the interfering component of the liquid sample is a protein.

### Claim 27

A method using a chemical analyzer for removing a component of a liquid sample which may interfere with a test performed on a test assay, the chemical analyzer having a sample cup, a mixing cup, a pipette fitted with a disposable pipette tip having a discharge end and capable of aspirating and expelling liquid sample into and from the pipette tip and capable of dispensing the liquid sample onto the test assay, the method comprising the steps of:
adding the liquid sample containing the interfering component to the sample cup;
transferring the liquid sample containing the interfering component from the sample cup to the mixing cup, the mixing cup containing a resin containing beads, the liquid sample and resin forming a sample/resin solution in the mixing cup;
mixing the sample/resin solution in the mixing cup using the pipette of the chemical analyzer to achieve a mixed sample/resin solution by aspirating the sample/resin solution into the pipette tip and then expelling the sample/resin solution from the pipette tip into the mixing cup, the aspirating and expelling steps being repeated, if or as necessary, to thoroughly mix the sample/resin solution in the mixing cup and achieve the mixed sample/resin solution;
allowing the mixed sample/resin solution in the mixing cup to rest undisturbed for a first predetermined period of time, the first predetermined period of time being selected to allow at least a portion of the interfering component of the liquid sample to adhere to the beads of the resin and to allow at least some of the beads with or without the interfering component adhering thereto to settle in the mixing cup and to occupy a bottom portion thereof, the result of the settling of the beads having the interfering component adhered thereto being the formation of a first stage refined liquid sample devoid or having a first lower concentration of the interfering component than the liquid sample and occupying an upper portion of the mixing cup;
aspirating into the pipette tip from the mixing cup a predetermined volume of the first stage refined liquid sample occupying the upper portion of the mixing cup;
allowing the first stage refined liquid sample aspirated into the pipette tip to rest undisturbed for a second predetermined period of time, the second predetermined period of time being selected to allow any remaining interfering component of the liquid sample in the first stage refined liquid sample in the pipette tip to adhere to any beads of the resin remaining in the first stage refined liquid sample in the pipette tip and to allow at least some of the remaining beads with or without the interfering component adhering thereto to settle in the pipette tip and to form a settled solution occupying a bottom portion of the pipette tip near the discharge end thereof, the result of the settling of the beads having the interfering component adhered thereto and unattached beads being the formation of the settled solution and a second stage, more refined liquid sample devoid or having a second lower concentration of the interfering component than the first stage refined liquid sample and occupying an upper portion of the pipette tip; and
expelling from the pipette tip the settled solution occupying the bottom portion of the pipette tip into the mixing cup, leaving the second stage, more refined liquid sample in the pipette tip for later dispensing of a selected volume of the second stage, more refined liquid sample devoid or having the second lower concentration of the interfering component onto the test assay.

### Claim 28 (depends on 27)

A method for removing an interfering component of a liquid sample as defined by claim 27, wherein the first predetermined period of time is between about one minute and about fifteen minutes.

### Claim 29 (depends on 27)

A method for removing an interfering component of a liquid sample as defined by claim 27, wherein the second predetermined period of time is between about one minute and about fifteen minutes.

### Claim 30 (depends on 27)

A method for removing an interfering component of a liquid sample as defined by claim 27, wherein the resin includes at least one of agarose-based beads and silica-based beads.

### Claim 31 (depends on 27)

A method for removing an interfering component of a liquid sample as defined by claim 27, wherein the resin is lyophilized in a solution of about two percent (2%) to about fourteen percent (14%) dextran/sucrose.

### Claim 32 (depends on 27)

A method for removing an interfering component of a liquid sample as defined by claim 27, wherein the resin is lyophilized in a solution of between about two percent (2%) and about ten percent (10%) dextran and between about two percent (2%) and about ten percent (10%) sucrose.

### Claim 33 (depends on 27)

A method for removing an interfering component of a liquid sample as defined by claim 27, wherein the resin is formed as a physically stable cake and resides in the bottom portion of the mixing cup.

### Claim 34 (depends on 27)

A method for removing an interfering component of a liquid sample as defined by claim 27, wherein the resin is an IMAC (Immobilized Metal Affinity Chromatography) resin.

### Claim 35 (depends on 27)

A method for removing an interfering component of a liquid sample as defined by claim 27, wherein the test assay is a bile acid assay; and
wherein the interfering component of the liquid sample is hemoglobin.

### Claim 36 (depends on 27)

A method for removing an interfering component of a liquid sample as defined by claim 27, wherein the interfering component of the liquid sample is a protein.

### Claim 37

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