# US 2021/0278431 A1 · Matrix and associated sample or mixing cup used for removing components of a liquid sample

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- Number: US 2021/0278431 A1
- Document ID: US20210278431A1
- Status: Published application
- Kind: A1
- Application number: 17/195,020
- Filed: 2021-03-08
- Published: 2021-09-09
- Earliest claimed: 2020-03-09
- Assignees: IDEXX Laboratories, Inc.
- Applicants: IDEXX Laboratories, Inc.
- Inventors: Jesse Daniel Faller; Robert W. Lachapelle; Dominic Pelletier
- Web page: https://patentgrep.com/patent/US20210278431A1

## CPC

- G01N 1/34: Purifying; Cleaning {(processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003)}
- G01N 35/1072: {with provision for selective pipetting of individual channels}
- G01N 1/38: Diluting, dispersing or mixing samples
- G01N 1/40: Concentrating samples
- G01N 1/405: {by adsorption or absorption}
- 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)}
- G01N 35/1011: {Control of the position or alignment of the transfer device}
- G01N 2001/383: {collecting and diluting in a flow of liquid}
- G01N 2030/525: {surface properties, e.g. porosity}
- G01N 2030/528: {Monolithic sorbent material}
- G01N 2035/00564: {Handling or washing solid phase elements, e.g. beads}
- G01N 2035/1013: {Confirming presence of tip}
- G01N 2035/1058: {for mixing}
- 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)

## Abstract

An insert mounted in a mixing cup and used by an automated chemical analyzer for removing a targeted component of a liquid sample includes a porous matrix formed of or carrying in an immobilized state functionalized particles having properties such that the targeted component of the liquid sample adheres to the functionalized particles. When the liquid sample is expelled from a disposable tip fitted on the end of a pipette forming part of the automated chemical analyzer into the mixing cup, the liquid sample is drawn into the matrix of the insert by capillary action, whereupon the targeted component of the liquid sample adheres to the immobilized functionalized particles of the matrix.

## Claims

### Claim 1

An insert mounted or insertable in a mixing cup and used by an automated chemical analyzer for removing a targeted component of a liquid sample, the automated chemical analyzer including a sample metering device having a pipette fitted with a disposable pipette tip and a pump operatively connected to the pipette for aspirating the liquid sample into the pipette tip and expelling the liquid sample therefrom, the insert comprising:
a porous matrix formed of or carrying in an immobilized state functionalized particles having properties such that the targeted component of the liquid sample adheres to the functionalized particles, the porous matrix having a predetermined porosity that allows the liquid sample to flow therethrough;
wherein, when the liquid sample is expelled from the pipette tip, the liquid sample is drawn into the matrix of the insert by capillary action or forced into the matrix by positive hydraulic or pneumatic pressure exerted thereon by the pump of the sample metering device, whereupon the targeted component of the liquid sample adheres to the immobilized functionalized particles of the matrix; and
wherein, under negative hydraulic or pneumatic pressure exerted on the liquid sample within the matrix by the pump of the sample metering device, liquid sample free of the targeted component or having a reduced concentration thereof is drawn from the matrix of the insert and aspirated into the pipette tip for subsequent testing by the automated chemical analyzer.

### Claim 2 (depends on 1)

An insert as defined by claim 1, wherein the insert has one or more side walls, a top wall and a bottom wall disposed opposite the top wall, the one or more side walls extending between the top wall and the bottom wall; and
wherein the insert has formed in the one or more side walls one or more liquid flow channels, the one or more liquid flow channels extending longitudinally along at least a portion of the one or more side walls, the one or more channels being in fluid communication with the matrix of the insert.

### Claim 3 (depends on 1)

An insert as defined by claim 1, wherein the insert has one or more side walls, a top wall and a bottom wall disposed opposite the top wall, the one or more side walls extending between the top wall and the bottom wall; and
wherein the insert has formed axially therein a central bore, the central bore passing through the insert from the top wall thereof to the bottom wall thereof, the bore being dimensioned to at least partially receive the pipette tip of the sample metering device.

### Claim 4 (depends on 3)

An insert as defined by claim 3, wherein the top wall of the insert has formed therein a funnel-shaped entry port, the funnel-shaped entry port being in alignment and fluid communication with the central bore.

### Claim 5 (depends on 1)

An insert as defined by claim 1, wherein the insert has one or more side walls, a top wall and a bottom wall disposed opposite the top wall, the one or more side walls extending between the top wall and the bottom wall; and
wherein the insert includes at least one standoff, the at least one standoff extending outwardly from the bottom wall of the insert a predetermined distance, the at least one standoff helping to define between the bottom wall of the insert and the mixing cup a chamber for receiving the liquid sample when the insert is received by the mixing cup.

### Claim 6 (depends on 1)

An insert as defined by claim 1, wherein the insert has one or more side walls, a top wall and a bottom wall disposed opposite the top wall, the one or more side walls extending between the top wall and the bottom wall; and
wherein the insert is formed with a generally frusto-conical shape and includes a generally circular upper portion having a first diameter and situated at or near the top wall thereof, a tapered middle portion of decreasing diameter, extending from the upper portion, and a generally cylindrical lower portion extending from the middle portion and situated at or near the bottom wall thereof, the lower portion having a second diameter which is less than the first diameter of the upper portion.

### Claim 7 (depends on 1)

An insert as defined by claim 1, wherein the insert has one or more side walls, a top wall and a bottom wall disposed opposite the top wall, the one or more side walls extending between the top wall and the bottom wall; and
wherein the insert is formed with a generally cylindrical shape.

### Claim 8 (depends on 1)

An insert as defined by claim 1, wherein the mixing cup defines an interior cavity for receiving the liquid sample and includes an interior bottom surface; and
wherein the insert is received by the mixing cup and positioned within the interior cavity of the mixing cup such that the bottom wall of the insert is spaced from the interior bottom surface of the mixing cup to define therewith a chamber for receiving the liquid sample.

### Claim 9 (depends on 1)

An insert as defined by claim 1, wherein the matrix of the insert is formed of a medium which holds in an immobilized state functionalized particles.

### Claim 10 (depends on 9)

An insert as defined by claim 9, wherein the functionalized particles are IMAC (Immobilized Metal Affinity Chromatography) beads.

### Claim 11 (depends on 10)

An insert as defined by claim 10, wherein the IMAC beads are at least one of agarose-based beads and silica-based beads.

### Claim 12 (depends on 9)

An insert as defined by claim 9, wherein the functionalized particles are nanobeads.

### Claim 13 (depends on 1)

An insert as defined by claim 1, wherein the matrix of the insert is formed of functionalized particles.

### Claim 14 (depends on 13)

An insert as defined by claim 13, wherein the functionalized particles are IMAC (Immobilized Metal Affinity Chromatography) beads.

### Claim 15 (depends on 14)

An insert as defined by claim 14, wherein the IMAC beads are at least one of agarose-based beads and silica-based beads.

### Claim 16 (depends on 15)

An insert as defined by claim 15, wherein the functionalized particles are nanobeads.

### Claim 17 (depends on 1)

An insert as defined by claim 1, wherein the matrix is formed from a glass fiber-based material that contains a plastic binder.

### Claim 18 (depends on 1)

An insert as defined by claim 1, wherein the matrix is formed from a porous material selected from the group consisting of: natural, synthetic, or naturally occurring or synthetically modified materials; fibrous materials; membranes of cellulose materials, including paper, cellulose, and cellulose derivatives, including cellulose acetate and nitrocellulose, fiberglass, glass fiber, cloth, both naturally occurring, including cotton, and synthetic, including nylon; porous gels, including silica gel, agarose, dextran and gelatin; porous fibrous matrices; starch based materials; cross-linked dextran chains; ceramic materials; olefin and thermoplastic materials, including films of polyvinyl chloride, polyethylene, polyvinyl acetate, polyamide, polycarbonate, polystyrene, copolymers of vinyl acetate and vinyl chloride and combinations of polyvinyl chloride-silica.

### Claim 19 (depends on 1)

An insert as defined by claim 1, wherein the matrix is selected from the group of materials consisting of: sintered polyethylene beads; nitrocellulose; glass fibers; and paper.

### Claim 20

In combination:
a mixing cup, the mixing cup defining an interior cavity for receiving a liquid sample; and
an insert mounted within the interior cavity of the mixing cup, the mixing cup and the insert being used by an automated chemical analyzer for removing a targeted component of the liquid sample received by the mixing cup, the automated chemical analyzer including a sample metering device having a pipette fitted with a disposable pipette tip for aspirating the liquid sample into the pipette tip and expelling the liquid sample therefrom;
wherein the insert includes a porous matrix formed of or carrying in an immobilized state functionalized particles having properties such that the targeted component of the liquid sample adheres to the functionalized particles, the porous matrix having a predetermined porosity that allows the liquid sample to flow therethrough;
wherein, when the liquid sample is expelled from the pipette tip, the liquid sample is drawn into the matrix of the insert by capillary action or forced into the matrix by positive hydraulic or pneumatic pressure exerted thereon by the pump of the sample metering device, whereupon the targeted component of the liquid sample adheres to the immobilized functionalized particles of the matrix; and
wherein, under negative hydraulic or pneumatic pressure exerted on the liquid sample within the matrix by the pump of the sample metering device, liquid sample free of the targeted component or having a reduced concentration thereof is drawn from the matrix of the insert and aspirated into the pipette tip for subsequent testing by the automated chemical analyzer.

### Claim 21 (depends on 20)

A combination as defined by claim 20, wherein the insert has one or more side walls, a top wall and a bottom wall disposed opposite the top wall, the one or more side walls extending between the top wall and the bottom wall; and
wherein the insert has formed in the one or more side walls one or more liquid flow channels, the one or more liquid flow channels extending longitudinally along at least a portion of the one or more side walls, the one or more channels being fluid communication with the matrix of the insert.

### Claim 22 (depends on 20)

A combination as defined by claim 20, wherein the insert has one or more side walls, a top wall and a bottom wall disposed opposite the top wall, the one or more side walls extending between the top wall and the bottom wall; and
wherein the insert has formed axially therein a central bore, the central bore passing through the insert from the top wall thereof to the bottom wall thereof, the bore being dimensioned to at least partially receive the pipette tip of the sample metering device.

### Claim 23 (depends on 22)

A combination as defined by claim 22, wherein the top wall of the insert has formed therein a funnel-shaped entry port, the funnel-shaped entry port being in alignment and communication with the central bore.

### Claim 24 (depends on 20)

A combination as defined by claim 20, wherein the insert has one or more side walls, a top wall and a bottom wall disposed opposite the top wall, the one or more side walls extending between the top wall and the bottom wall;
wherein the mixing cup includes an interior bottom surface; and
wherein the insert includes at least one standoff, the least one standoff extending outwardly from the bottom wall of the insert a predetermined distance and engages the interior bottom surface of the mixing cup, the at least one standoff helping to define between the bottom wall of the insert and the interior bottom surface of the mixing cup a chamber for receiving the liquid sample.

### Claim 25 (depends on 20)

A combination as defined by claim 20, wherein the insert has one or more side walls, a top wall and a bottom wall disposed opposite the top wall, the one or more side walls extending between the top wall and the bottom wall; and
wherein the insert is formed with a generally frusto-conical shape and includes a generally circular upper portion having a first diameter and situated at or near the top wall thereof, a tapered middle portion of decreasing diameter, extending from the upper portion, and a generally cylindrical lower portion extending from the middle portion and situated at or near the bottom wall thereof, the lower portion having a second diameter which is less than the first diameter of the upper portion.

### Claim 26 (depends on 20)

A combination as defined by claim 20, wherein the insert has one or more side walls, a top wall and a bottom wall disposed opposite the top wall, the one or more side walls extending between the top wall and the bottom wall; and
wherein the insert is formed with a generally cylindrical shape.

### Claim 27 (depends on 20)

A combination as defined by claim 20, wherein the insert has one or more side walls, a top wall and a bottom wall disposed opposite the top wall, the one or more side walls extending between the top wall and the bottom wall; and
wherein the mixing cup includes an interior bottom surface; and
wherein the insert is positioned within the interior cavity of the mixing cup such that the bottom wall of the insert is spaced from the interior bottom surface of the mixing cup to define therewith a chamber for receiving the liquid sample.

### Claim 28 (depends on 20)

A combination as defined by claim 20, wherein the matrix of the insert is formed of a medium which holds in an immobilized state functionalized particles.

### Claim 29 (depends on 28)

A combination as defined by claim 28, wherein the functionalized particles are IMAC (Immobilized Metal Affinity Chromatography) beads.

### Claim 30 (depends on 29)

A combination as defined by claim 29, wherein the IMAC beads are at least one of agarose-based beads and silica-based beads.

### Claim 31 (depends on 28)

A combination as defined by claim 28, wherein the functionalized particles are nanobeads.

### Claim 32 (depends on 20)

A combination as defined by claim 20, wherein the matrix of the insert is formed of functionalized particles.

### Claim 33 (depends on 32)

A combination as defined by claim 32, wherein the functionalized particles are IMAC (Immobilized Metal Affinity Chromatography) beads.

### Claim 34 (depends on 33)

A combination as defined by claim 33, wherein the IMAC beads are at least one of agarose-based beads and silica-based beads.

### Claim 35 (depends on 34)

A combination as defined by claim 34, wherein the functionalized particles are nanobeads.

### Claim 36 (depends on 20)

A combination as defined by claim 20, wherein the matrix is formed from a glass fiber-based material that contains a plastic binder.

### Claim 37 (depends on 20)

A combination as defined by claim 20, wherein the matrix is formed from a porous material selected from the group consisting of: natural, synthetic, or naturally occurring or synthetically modified materials; fibrous materials; membranes of cellulose materials, including paper, cellulose, and cellulose derivatives, including cellulose acetate and nitrocellulose, fiberglass, glass fiber, cloth, both naturally occurring, including cotton, and synthetic, including nylon; porous gels, including silica gel, agarose, dextran and gelatin; porous fibrous matrices; starch based materials; cross-linked dextran chains; ceramic materials; olefin and thermoplastic materials, including films of polyvinyl chloride, polyethylene, polyvinyl acetate, polyamide, polycarbonate, polystyrene, copolymers of vinyl acetate and vinyl chloride and combinations of polyvinyl chloride-silica.

### Claim 38 (depends on 20)

A combination as defined by claim 20, wherein the matrix is selected from the group of materials consisting of: sintered polyethylene beads; nitrocellulose; glass fibers; and paper.

### Claim 39

A method using an automated chemical analyzer for removing a targeted component of a liquid sample, the automated chemical analyzer including a sample cup, and a sample metering device having a pipette fitted with a disposable pipette tip and a pump operatively connected to the pipette for aspirating the liquid sample into the pipette tip and expelling the liquid sample therefrom, the method comprising the steps of:
aspirating into the pipette tip a volume of the liquid sample contained in the sample cup;
positioning the pipette tip containing the volume of the liquid sample over a mixing cup, the mixing cup defining an interior cavity for receiving the liquid sample and having an interior bottom surface, the mixing cup further having an insert mounted within the interior cavity thereof, wherein the insert includes a porous matrix formed of or carrying in an immobilized state functionalized particles having properties such that the targeted component of the liquid sample adheres to the functionalized particles, the porous matrix having a predetermined porosity that allows the liquid sample to flow therethrough, the insert further having one or more side walls, a top wall and a bottom wall disposed opposite the top wall, the one or more side walls extending between the top wall and the bottom wall, the insert having formed axially therein a central bore, the central bore passing through the insert from the top wall thereof to the bottom wall thereof, the bore being dimensioned to at least partially receive the pipette tip of the sample metering device;
lowering the pipette tip into the mixing cup such that the pipette tip is at least partially received by the central bore of the insert disposed within the mixing cup;
expelling the volume of liquid sample from the pipette tip into the insert, wherein the liquid sample expelled from the pipette tip is drawn into the matrix of the insert by capillary action or forced into the matrix by positive hydraulic or pneumatic pressure exerted thereon by the pump of the sample metering device, whereupon the targeted component of the liquid sample adheres to the immobilized functionalized particles of the matrix; and
applying, using the pipette tip in the at least partially received position within the central bore of the insert, a negative hydraulic or pneumatic pressure on the liquid sample within the matrix by the pump of the sample metering device, whereby liquid sample free of the targeted component or having a reduced concentration thereof is drawn from the matrix of the insert and aspirated into the pipette tip for subsequent testing by the automated chemical analyzer.

### Claim 40 (depends on 39)

A method as defined by claim 39, which further comprises the steps of:
expelling from the pipette tip into the insert for at least a second time the liquid sample drawn from the matrix of the insert and aspirated into the pipette tip, whereby the expelled liquid sample flows into the matrix of the insert for at least a second time; and
applying, using the pipette tip in the at least partially received position within the central bore of the insert, for at least a second time a negative hydraulic or pneumatic pressure on the liquid sample within the matrix by the pump of the sample metering device, whereby liquid sample free of the targeted component or having a reduced concentration thereof is drawn from the matrix of the insert for at least a second time and re-aspirated into the pipette tip.

### Claim 41 (depends on 39)

A method as defined by claim 39, wherein the insert has formed in the one or more side walls one or more liquid flow channels, the one or more liquid flow channels extending longitudinally along at least a portion of the one or more side walls, the one or more channels being in fluid communication with the matrix of the insert; and
wherein the step of expelling the volume of liquid sample from the pipette tip into the insert includes the sub-step of forcing the liquid sample expelled from the pipette tip into the one or more liquid flow channels.

### Claim 42 (depends on 39)

A method as defined by claim 39, wherein the insert is positioned within the interior cavity of the mixing cup such that the bottom wall of the insert is spaced from the interior bottom surface of the mixing cup to define therewith a chamber for receiving the liquid sample; and
wherein the step of expelling the volume of liquid sample from the pipette tip into the insert includes the sub-step of forcing the liquid sample expelled from the pipette tip into the liquid sample receiving chamber.

### Claim 43 (depends on 39)

A method as defined by claim 39, wherein the step of lowering the pipette tip into the mixing cup such that the pipette tip is at least partially received by the central bore of the insert includes the sub-step of forming a substantially liquid tight seal between the pipette tip and the inner wall of the insert that defines the central bore thereof.

### Claim 44 (depends on 39)

A method as defined by claim 39, wherein the central bore of the insert is dimensioned to provide an annular space between at least a portion of an inner wall of the insert defining the central bore and at least a portion of the pipette tip when the pipette tip is at least partially received by the central bore of the insert, the annular space being in fluid communication with the matrix of the insert; and
wherein the step of expelling the volume of liquid sample from the pipette into the insert includes the sub-step of forcing the liquid sample expelled from the pipette tip into the annular space.
