# US 11,079,331 B2 · Inspection system

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- Number: US 11,079,331 B2
- Document ID: US11079331B2
- Status: Granted
- Kind: B2
- Application number: 15/772,346
- Filed: 2016-11-02
- Published: 2018-11-08
- Granted: 2021-08-03
- Earliest claimed: 2015-11-13
- Assignees: Konica Minolta, Inc.
- Applicants: Konica Minolta, Inc.
- Inventors: Masataka Matsuo; Tetsuya Noda
- Web page: https://patentgrep.com/patent/US11079331B2

## CPC

- G01N 21/648: {using evanescent coupling or surface plasmon coupling for the excitation of fluorescence}
- G01N 21/01: Arrangements or apparatus for facilitating the optical investigation
- G01N 21/0332: {with temperature control (control of temperature G05D23/00; cryostats F17C3/08)}
- G01N 21/05: Flow-through cuvettes (G01N21/09 takes precedence; handling fluid samples G01N1/10)
- G01N 21/11: Filling or emptying of cuvettes
- G01N 35/00: Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- 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)}
- C40B 30/04: by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
- C40B 40/10: Libraries containing peptides or polypeptides, or derivatives thereof
- G01N 21/49: within a body or fluid
- G01N 21/61: Non-dispersive gas analysers {(G01N21/3504 takes precedence)}
- G01N 21/77: by observing the effect on a chemical indicator
- G01N 33/53: Immunoassay; Biospecific binding assay; Materials therefor
- G01N 35/02: using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations {(G01N35/0098 and G01N35/0099 take precedence)}
- G01N 35/04: Details of the conveyor system {(G01N35/021 - G01N35/028 take precedence)}
- G01N 37/00: Details not covered by any other group of this subclass
- G01N 2021/6482: {Sample cells, cuvettes}
- 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)
- C40B: COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES (in silico combinatorial libraries of nucleic acids, proteins or peptides G16B35/00; in silico combinatorial chemistry G16C20/60)

## Abstract

To provide an inspection system capable of performing a target biological reaction under temperature conditions suitable for the reaction even with reciprocal liquid feeding. An inspection system including at least: a sensor chip with a flow path having a reaction site for performing biological reactions; a liquid feeder that causes reaction liquid to flow into and out of the flow path; and a first temperature adjuster that adjusts temperature of reaction liquid flowed in the flow path, where the system performs reciprocal liquid feeding by the liquid feeder where some of the reaction liquid flowed in the flow path is caused to flow out of the flow path and to flow in again. The inspection system includes a second temperature adjuster that, during reciprocal liquid feeding, adjusts temperature of the reaction liquid flowed outside the flow path through temperature adjustment of a liquid holding section of the liquid feeder.

## Claims

### Claim 1

An inspection system at least comprising:
a sensor chip equipped with a flow path having a reaction site for a biological reaction in at least part of the flow path;
a liquid feeder configured to pump a reaction-liquid used for the biological reaction to flow in and flow out of the flow path of the sensor chip;
a first temperature adjuster configured to adjust a temperature of the reaction liquid in the flow path;
a surface plasmon resonance device configured to receive and inspect the sensor chip after the biological reaction; and
a controller configured to control the operation of the inspection system,
wherein the liquid feeder is also configured to pump, at least some of the reaction liquid that has flowed in the flow path to flow out of the flow path and to flow in again, thereby moving the liquid reciprocally to cause reciprocal liquid feeding of the at least some of the reaction liquid into and out of the flow path of the sensor chip,
the inspection system further comprising: a second temperature adjuster configured to adjust, during the reciprocal liquid feeding, a temperature of the reaction liquid in a liquid holding section of the liquid feeder,
wherein the controller is further configured to monitor and adjust the temperature provided by the first temperature adjuster to maintain a predetermined temperature facilitating the biological reaction on the flow path,
wherein the controller is further configured to monitor and adjust the temperature provided by the second temperature adjuster to maintain the same predetermined temperature facilitating the biological reaction on the flow path, and
wherein a portion of the liquid holding section of the liquid feeder is covered with the second temperature adjuster, and the second temperature adjuster has an opening in a longitudinal wall to receive the portion of the liquid holding section of the liquid feeder.

### Claim 2 (depends on 1)

The inspection system according to claim 1, wherein the liquid feeder comprises:
a pump for feeding or sucking the reaction liquid to and from the flow path of the sensor chip; and
a pipette tip as the liquid holding section attached to the pump,
wherein the portion of the longitudinal periphery of the pipette tip to be covered is covered with a heat block serving as the second temperature adjuster.

### Claim 3 (depends on 2)

The inspection system according to claim 2, wherein the heat block has the opening in a longitudinal wall to receive the portion of the pipette tip to be covered.

### Claim 4 (depends on 2)

The inspection system according to claim 2, wherein
the sensor chip has a liquid discharger/suction unit that is provided with a space that communicates with the flow path and houses the tip end of the pipette tip upon insertion into the space of the liquid discharger/suction unit, and
only the portion of the longitudinal periphery of the pipette tip is covered with the heat block so that at least the tip end of the pipette tip, which is inserted in the space of the liquid discharger/suction unit, is exposed.

### Claim 5 (depends on 1)

The inspection system according to claim 1, further comprising:
a liquid reservoir that reserves the reaction liquid; and
a third temperature adjuster configured to adjust a temperature of the reaction liquid that is reserved in the liquid reservoir before liquid feeding,
wherein the third temperature adjuster, monitored and adjusted by the controller, adjusts the temperature provided by the third temperature adjuster to the same predetermined temperature as adjusted by the first temperature adjuster.

### Claim 6 (depends on 1)

The inspection system according to claim 1, further comprising:
a liquid feed reaction chamber in which the liquid feeder, sensor chip, and the first and second temperature adjusters are arranged inside for performing the biological reaction and temperature adjustments by the first and second temperature adjusters,
an optical measurement chamber in which the surface plasmon resonance device configured to receive the sensor chip after the biological reaction is arranged, the surface plasmon resonance device including (i) a light-emitting unit configured to irradiate the reaction site of the sensor chip with excitement light, and (ii) a light-receiving unit configured to detect light emitted from the irradiated sensor chip arranged inside the optical measurement chamber, the light-receiving unit being further configured to perform optical measurement based on the detected light, and
a partition positioned intermediate the liquid feed reaction chamber and the optical measurement chamber, the partition being configured to open and close an opening that makes the liquid feed reaction chamber and the optical measurement chamber to communicate with each other allowing the transfer of the sensor chip,
wherein the partition closes the opening during the temperature adjustment or the optical measurement.

### Claim 7 (depends on 6)

The inspection system according to claim 6, wherein the controller adjusts a temperature of a space inside the optical measurement chamber to be set lower than a temperature of a space inside the liquid feed reaction chamber during the biological reaction.

### Claim 8 (depends on 2)

The inspection system according to claim 2, further comprising:
a liquid reservoir that reserves the reaction liquid; and
a third temperature adjuster configured to adjust a temperature of the reaction liquid that is reserved in the liquid reservoir before liquid feeding,
wherein the third temperature adjuster, monitored and adjusted by the controller, adjusts the temperature provided by the third temperature adjuster to the same predetermined temperature as adjusted by the first temperature adjuster.

### Claim 9 (depends on 3)

The inspection system according to claim 3, further comprising:
a liquid reservoir that reserves the reaction liquid; and
a third temperature adjuster configured to adjust a temperature of the reaction liquid that is reserved in the liquid reservoir before liquid feeding,
wherein the third temperature adjuster, monitored and adjusted by the controller, adjusts the temperature provided by the third temperature adjuster to the same predetermined temperature as adjusted by the first temperature adjuster.

### Claim 10 (depends on 4)

The inspection system according to claim 4, further comprising:
a liquid reservoir that reserves the reaction liquid; and
a third temperature adjuster configured to adjust a temperature of the reaction liquid that is reserved in the liquid reservoir before liquid feeding,
wherein the third temperature adjuster, monitored and adjusted by the controller, adjusts the temperature provided by the third temperature adjuster to the same predetermined temperature as adjusted by the first temperature adjuster.

### Claim 11 (depends on 2)

The inspection system according to claim 2, further comprising:
a liquid feed reaction chamber in which the liquid feeder, sensor chip, and the first and second temperature adjusters are arranged inside for performing the biological reaction and temperature adjustments by the first and second temperature adjusters,
an optical measurement chamber in which the surface plasmon resonance device configured to receive the sensor chip after the biological reaction is arranged, the surface plasmon resonance device including (i) a light-emitting unit the reaction site of the sensor chip with excitement light, and (ii) a light-receiving unit configured to detect light emitted from the irradiated sensor chip arranged inside the optical measurement chamber, the light-receiving unit being further configured to perform optical measurement based on the detected light, and
a partition positioned intermediate the liquid feed reaction chamber and the optical measurement chamber, the partition being configured to open and close an opening that makes the liquid feed reaction chamber and the optical measurement chamber to communicate with each other allowing the transfer of the sensor chip,
wherein the partition closes the opening during the temperature adjustment or the optical measurement.

### Claim 12 (depends on 3)

The inspection system according to claim 3, further comprising:
a liquid feed reaction chamber in which the liquid feeder, sensor chip, and the first and second temperature adjusters are arranged inside for performing the biological reaction and temperature adjustments by the first and second temperature adjusters,
an optical measurement chamber in which the surface plasmon resonance device configured to receive the sensor chip after the biological reaction is arranged, the surface plasmon resonance device including (i) a light-emitting unit configured to irradiate the reaction site of the sensor chip with excitement light, and (ii) a light-receiving unit configured to detect light emitted from the irradiated sensor chip arranged inside the optical measurement chamber, the light-receiving unit being further configured to perform optical measurement based on the detected light, and
a partition positioned intermediate the liquid feed reaction chamber and the optical measurement chamber, the partition being configured to open and close an opening that makes the liquid feed reaction chamber and the optical measurement chamber to communicate with each other allowing the transfer of the sensor chip,
wherein the partition closes the opening during the temperature adjustment or the optical measurement.

### Claim 13 (depends on 4)

The inspection system according to claim 4, further comprising:
a liquid feed reaction chamber in which the liquid feeder, the sensor chip, and the first and second temperature adjusters are arranged inside for performing the biological reaction and temperature adjustments by the first and second temperature adjusters,
an optical measurement chamber in which the surface plasmon resonance device configured to receive the sensor chip after the biological reaction is arranged, the surface plasmon resonance device including (i) a light-emitting unit configured to irradiate the reaction site of the sensor chip with excitement light, and (ii) a light-receiving unit configured to detect light emitted from the irradiated sensor chip arranged inside the optical measurement chamber, the light-receiving unit being further configured to perform optical measurement based on the detected light, and
a partition positioned intermediate the liquid feed reaction chamber and the optical measurement chamber, the partition being configured to open and close an opening that makes the liquid feed reaction chamber and the optical measurement chamber to communicate with each other allowing the transfer of the sensor chip,
wherein the partition closes the opening during the temperature adjustment or the optical measurement.

### Claim 14 (depends on 5)

The inspection system according to claim 5, further comprising:
a liquid feed reaction chamber in which the liquid feeder, the sensor chip, and the first and second temperature adjusters are arranged inside for performing the biological reaction and temperature adjustments by the first and second temperature adjusters,
an optical measurement chamber in which the surface plasmon resonance device configured to receive the sensor chip after the biological reaction is arranged, the surface plasmon resonance device including (i) a light-emitting unit configured to irradiate the reaction site of the sensor chip with excitement light, and (ii) a light-receiving unit configured to detect light emitted from the irradiated sensor chip arranged inside the optical measurement chamber, the light-receiving unit being further configured to perform optical measurement based on the detected light, and
a partition positioned intermediate the liquid feed reaction chamber and the optical measurement chamber, the partition being configured to open and close an opening that makes the liquid feed reaction chamber and the optical measurement chamber to communicate with each other allowing the transfer of the sensor chip,
wherein the partition closes the opening during the temperature adjustment or the optical measurement.
