# US 9,752,989 B2 · Sample analyzing method using sample analysis cartridge, sample analysis cartridge, and sample analyzer

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- Number: US 9,752,989 B2
- Document ID: US9752989B2
- Status: Granted
- Kind: B2
- Application number: 15/082,337
- Filed: 2016-03-28
- Published: 2016-11-03
- Granted: 2017-09-05
- Earliest claimed: 2015-04-30
- Assignees: Sysmex Corporation
- Applicants: Sysmex Corporation
- Inventors: Kazuyoshi Horii; Tomoyuki Nose; Tatsuya Kosako
- Web page: https://patentgrep.com/patent/US9752989B2

## CPC

- G01N 21/75: Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated (systems in which material is burnt in a flame or plasma G01N21/72, G01N21/73)
- B01F 33/451: wherein the mixture is directly exposed to an electromagnetic field without use of a stirrer, e.g. for material comprising ferromagnetic particles or for molten metal
- B01L 3/5023: {with a sample being transported to, and subsequently stored in an absorbent for analysis}
- B01L 3/50273: {characterised by the means or forces applied to move the fluids}
- B01L 3/502761: {specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules}
- B03C 1/02: acting directly on the substance being separated
- G01N 33/54326: {Magnetic particles}
- G01N 35/00029: {provided with flat sample substrates, e.g. slides (G01N35/028 takes precedence)}
- G01N 35/0098: {involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation (magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C)}
- B01L 7/00: Heating or cooling apparatus (autoclaves B01J3/04); Heat insulating devices
- B01L 2200/04: Exchange or ejection of cartridges, containers or reservoirs
- B01L 2200/0668: Trapping microscopic beads
- B01L 2200/10: Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
- B01L 2200/141: Preventing contamination, tampering
- B01L 2200/16: Reagents, handling or storing thereof
- B01L 2300/087: Multiple sequential chambers
- B01L 2300/0874: Three dimensional network
- B01L 2300/0883: Serpentine channels
- B01L 2300/0887: Laminated structure
- B01L 2300/1822: using Peltier elements
- B01L 2400/0406: capillary forces
- B01L 2400/0409: centrifugal forces
- B01L 2400/043: magnetic forces
- B01L 2400/0478: pistons
- B01L 2400/0487: fluid pressure, pneumatics
- B01L 2400/0688: surface tension valves, capillary stop, capillary break
- B81B 1/00: Devices without movable or flexible elements, e.g. microcapillary devices
- G01N 33/54333: {Modification of conditions of immunological binding reaction, e.g. use of more than one type of particle, use of chemical agents to improve binding, choice of incubation time or application of magnetic field during binding reaction}
- G01N 35/00069: {whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk}
- G01N 2035/00534: {Mixing by a special element, e.g. stirrer}
- Y10T 436/111666: Utilizing a centrifuge or compartmented rotor
- Y10T 436/25375: Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
- 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)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B03C: MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS (separating isotopes B01D59/00; combinations of magnetic or electrostatic separation with separation of solids by other means B03B, B07B)
- B81B: MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES (piezoelectric, electrostrictive or magnetostrictive elements per se H10N30/00, H10N35/00)
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

A sample analyzing method for suppressing an adverse effect on detection accuracy of a detection target substance is disclosed. In the sample analyzing method, a magnetic particle as a support of a detection target substance is transported by magnetic force to a second liquid container through a passage between a first liquid container storing a first liquid containing the magnetic particle and the second liquid container storing a second liquid containing a labeled substance to forma complex with the detection target substance and the magnetic particle. The complex formed in the second liquid container and containing the detection target substance, magnetic particle, and labeled substance is transported to a third liquid in a flow path, and the magnetic particle is transported to a detection tank for detecting the detection target substance, while being agitated in a mixed liquid of the complex and third liquid within the flow path.

## Claims

### Claim 1

A sample analyzing method using a sample analysis cartridge inserted into a sample analyzer that detects a detection target substance contained in a sample, comprising:
transporting a magnetic particle supporting the detection target substance by magnetic force from a first liquid container to a second liquid container through a passage disposed between the first and second liquid containers, the first liquid container storing a first liquid containing the magnetic particle to be a support of the detection target substance, the second liquid container storing a second liquid containing a labeled substance which is to form a complex together with the detection target substance and the magnetic particle;
transporting the complex, which is formed in the second liquid container, and contains the detection target substance, the magnetic particle, and the labeled substance, to a third liquid in a flow path; and
transporting the magnetic particle to a detection tank to detect the detection target substance, while agitating the magnetic particle in a mixed liquid of the complex and the third liquid within the flow path.

### Claim 2 (depends on 1)

The sample analyzing method using a sample analysis cartridge according to claim 1, wherein
the magnetic particle is transported while being agitated in the mixed liquid within the flow path by an air pressure.

### Claim 3 (depends on 1)

The sample analyzing method using a sample analysis cartridge according to claim 1, wherein
the magnetic particle is agitated in the mixed liquid in such a way that the mixed liquid is moved back and forth within the flow path by an air pressure.

### Claim 4 (depends on 1)

The sample analyzing method using a sample analysis cartridge according claim 1, wherein
the flow path meanders, and
the magnetic particle is agitated in the mixed liquid in such a way that the mixed liquid is moved in the meandering flow path.

### Claim 5 (depends on 4)

The sample analyzing method using a sample analysis cartridge according to claim 4, wherein
the mixed liquid is moved within the flow path also in a thickness direction of the sample analysis cartridge.

### Claim 6 (depends on 1)

The sample analyzing method using a sample analysis cartridge according to claim 1, wherein
a fourth liquid containing a substrate that facilitates light emission by reacting with the complex is transported to the detection tank by an air pressure.

### Claim 7 (depends on 6)

The sample analyzing method using a sample analysis cartridge according to claim 6, wherein
the fourth liquid is transported to a position in the detection tank near a position to which the mixed liquid is transported from the flow path.

### Claim 8

A sample analysis cartridge to be inserted into a sample analyzer that detects a detection target substance contained in a sample, comprising:
a first liquid container that stores a first liquid containing a magnetic particle to be a support of the detection target substance;
a second liquid container that stores a second liquid containing a labeled substance which is to form a complex together with the detection target substance and the magnetic particle;
a passage that is disposed between the first liquid container and the second liquid container, and that transports the magnetic particle supporting the detection target substance to the second liquid container by magnetic force; and
a first flow path that transports the complex, which is formed in the second liquid container and contains the detection target substance, the magnetic particle, and the labeled substance, to a third liquid, wherein the magnetic particle is transported to a detection tank to detect the detection target substance, and the magnetic particle is configured to be agitated in a mixed liquid of the complex and the third liquid in the first flow path while being transported to the detection tank.

### Claim 9 (depends on 8)

The sample analysis cartridge according to claim 8, wherein
the magnetic particle is transported while being agitated in the mixed liquid in the first flow path by an air pressure.

### Claim 10 (depends on 8)

The sample analysis cartridge according to claim 8, further comprising:
an air chamber that transports the magnetic particle to the detection tank while agitating the magnetic particle in the mixed liquid in the first flow path by an air pressure.

### Claim 11 (depends on 10)

The sample analysis cartridge according to claim 10, wherein
the air chamber is alternately deformed between an initial state and a contracted state, thereby moving the mixed liquid back and forth in the first flow path and agitating the magnetic particle in the mixed liquid.

### Claim 12 (depends on 8)

The sample analysis cartridge according to claim 8, wherein
the first flow path is formed in a meandering shape.

### Claim 13 (depends on 8)

The sample analysis cartridge according to claim 8, wherein
a volume of the first flow path is larger than a volume of the mixed liquid.

### Claim 14 (depends on 12)

The sample analysis cartridge according to claim 12, wherein
the first flow path is formed to also extend in a thickness direction of the sample analysis cartridge.

### Claim 15 (depends on 14)

The sample analysis cartridge according to claim 14, wherein
the first flow path includes a first portion and a second portion disposed at positions lower than the detection tank in the thickness direction,
the first portion is formed to extend in a direction perpendicular to the thickness direction, and
the second portion is formed to extend in the thickness direction and to include a first end connected to the first portion and a second end connected to the detection tank.

### Claim 16 (depends on 8)

The sample analysis cartridge according to claim 8, wherein
the first flow path is disposed on an extension of the passage in a transportation direction of the magnetic particle in the passage.

### Claim 17 (depends on 8)

The sample analysis cartridge according to claim 8, further comprising:
an air chamber that transports the magnetic particle to the detection tank while agitating the magnetic particle in the mixed liquid in the first flow path by an air pressure, the air chamber being a first air chamber that transports the mixed liquid to the detection tank from the first flow path; and
a second air chamber that transports a fourth liquid to the detection tank by an air pressure, the fourth liquid containing a substrate that facilitates light emission by reacting with the complex.

### Claim 18 (depends on 17)

The sample analysis cartridge according to claim 17, further comprising a second flow path that is connected to the detection tank and that transports the fourth liquid to the detection tank,
wherein the second flow path is connected to a portion of the detection tank near the first flow path connected to the detection tank.

### Claim 19

A sample analyzer that performs a sample analysis using a sample analysis cartridge, comprising:
a first liquid container that stores a first liquid containing a magnetic particle to be a support of a detection target substance;
a second liquid container that stores a second liquid containing a labeled substance which is to form a complex together with the detection target substance and the magnetic particle;
a passage that is disposed between the first liquid container and the second liquid container, and that transports the magnetic particle supporting the detection target substance to the second liquid container by magnetic force; and
a flow path that transports the complex formed in the second liquid container, and contains the detection target substance, the magnetic particle, and the labeled substance, to a third liquid, wherein the sample analysis is performed using the sample analysis cartridge in which the magnetic particle is transported from inside of the flow path to a detection tank to detect the detection target substance, and the magnetic particle is configured to be agitated in a mixed liquid of the complex and the third liquid within the flow path while being transported to the detection tank.

### Claim 20 (depends on 19)

The sample analyzer according to claim 19, wherein
the sample analysis is performed using the sample analysis cartridge in which the magnetic particle is transported while being agitated in the mixed liquid within the flow path by an air pressure.
