# US 10,502,752 B2 · Reaction method including pipette height detection and correction

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- Number: US 10,502,752 B2
- Document ID: US10502752B2
- Status: Granted
- Kind: B2
- Application number: 15/772,558
- Filed: 2016-10-27
- Published: 2019-03-28
- Granted: 2019-12-10
- Earliest claimed: 2015-11-13
- Assignees: Konica Minolta, Inc.
- Applicants: Konica Minolta, Inc.
- Inventors: Tetsuya Noda; Masataka Matsuo; Youichi Aoki
- Web page: https://patentgrep.com/patent/US10502752B2

## CPC

- G01N 35/1011: {Control of the position or alignment of the transfer device}
- B01L 3/0237: {Details of electronic control, e.g. relating to user interface}
- G01N 1/00: Sampling; Preparing specimens for investigation
- G01N 21/648: {using evanescent coupling or surface plasmon coupling for the excitation of fluorescence}
- 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)}
- G01N 1/14: Suction devices, e.g. pumps; Ejector devices
- 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)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

A reaction method includes a reaction step of reacting two or more substances with each other by using a pipette tip, attached to a pipette nozzle, for sucking or discharging a liquid to supply a liquid to a reaction field and remove the liquid from the reaction field a plurality of times. The reaction method further includes: a first process of, prior to the reaction step, detecting an end height of the pipette tip and setting a reference height of the pipette nozzle on the basis of the end height of the pipette tip; and a second process of correcting, in a course of the reaction step, the height of the pipette nozzle from the reference height so as to cancel out variation in the end height of the pipette tip due to a change in the temperature of the pipette tip.

## Claims

### Claim 1

A reaction method comprising reacting two or more substances with each other by using a pipette tip, attached to a pipette nozzle, for sucking or discharging a liquid to supply a liquid to a reaction field and remove the liquid from the reaction field a plurality of times, the reaction method further comprising:
prior to the reacting, detecting an end height of the pipette tip and setting a reference height of the pipette nozzle based on the end height of the pipette tip; and
correcting, in a course of the reaction step, the height of the pipette nozzle from the reference height so as to cancel out variation in the end height of the pipette tip due to a change in the temperature of the pipette tip.

### Claim 2 (depends on 1)

The reaction method according to claim 1, wherein the correcting includes correcting the height of the pipette nozzle from the reference height so as to make the height of the pipette nozzle higher with respect to the reaction field.

### Claim 3 (depends on 1)

The reaction method according to claim 1, wherein the second process includes correcting includes correcting the height of the pipette nozzle from the reference height in accordance with an elapsed time of the reaction step reacting.

### Claim 4 (depends on 3)

The reaction method according to claim 3, wherein the correcting includes
estimating a variation of the end height of the pipette tip based on:
a length of the pipette tip between an end and a portion fitting with the pipette nozzle;
a linear expansion coefficient of the pipette tip;
a variation of a temperature of the pipette tip with time; and
an elapsed time of the reacting, and
correcting the height of the pipette nozzle from the reference height based on the estimated variation.

### Claim 5 (depends on 4)

The reaction method according to claim 4, wherein a variation rate of the end height of the pipette tip decreases with time.

### Claim 6 (depends on 4)

The reaction method according to claim 4, wherein the detecting further includes measuring a temperature around the pipette tip when the pipette tip is attached to the pipette nozzle by a first temperature measurement means measurer, and correcting the height of the pipette nozzle from the reference height in accordance with a maximum change amount of the temperature of the pipette tip estimated based on a measured value.

### Claim 7 (depends on 4)

The reaction method according to claim 4, wherein the detecting further includes measuring a temperature of the pipette tip by a second temperature measurement means measurer, and correcting the height of the pipette nozzle from the reference height in accordance with a maximum change amount of the temperature of the pipette tip estimated based on the measured value.

### Claim 8 (depends on 1)

The reaction method according to claim 1, wherein
the detecting further includes measuring a temperature of the pipette tip by a second temperature measurer, and
the correcting further includes measuring the temperature of the pipette tip by the second temperature measurer, as well as correcting the height of the pipette nozzle from the reference height in accordance with a difference between the temperature of the pipette tip measured by the second temperature measurer in the detecting at a time when the end height of the pipette tip is detected and the temperature of the pipette tip measured by the second temperature measurer in the reacting.

### Claim 9 (depends on 8)

The reaction method according to claim 8, wherein
the correcting includes correcting the reference height of the pipette nozzle based on:
a length of the pipette tip between an end and a portion fitting with the pipette nozzle;
a linear expansion coefficient of the pipette tip; and
a difference between the temperature of the pipette tip further measured by the second temperature measurer, the temperature of the pipette tip being the temperature at the time when the end height of the pipette tip is detected, measured by the second temperature measurer in the detecting and the temperature of the pipette tip measured by the second temperature measurer in the reacting.

### Claim 10 (depends on 1)

The reaction method according to claim 1, wherein
the pipette tip is formed of resin, and
a linear expansion coefficient of the pipette tip is 5.8×10−5/° C. or more.

### Claim 11 (depends on 1)

The reaction method according to claim 1, wherein a temperature of the pipette tip is adjusted by a temperature adjuster.

### Claim 12 (depends on 1)

The reaction method according to claim 1, wherein the correcting is performed after the liquid is supplied to the reaction field and before the liquid is removed from the reaction field.

### Claim 13 (depends on 1)

The reaction method according to claim 1, wherein
the reaction field is arranged at a bottom surface of a flow path or at a bottom surface of a well, capable of storing a liquid, and
the reacting includes an immune reaction in the reaction field.

### Claim 14 (depends on 2)

The reaction method according to claim 2, wherein the correcting includes correcting the height of the pipette nozzle from the reference height in accordance with an elapsed time of the reacting.

### Claim 15 (depends on 2)

The reaction method according to claim 2, wherein
the detecting further includes measuring a temperature of the pipette tip by a second temperature measurer, and
the correcting further includes measuring the temperature of the pipette tip by the second temperature measurer, as well as correcting the height of the pipette nozzle from the reference height in accordance with a difference between the temperature of the pipette tip measured by the second temperature measurer in the detecting at a time when the end height of the pipette tip is detected and the temperature of the pipette tip measured by the second temperature measurer in the reacting.

### Claim 16 (depends on 2)

The reaction method according to claim 2, wherein
the pipette tip is formed of resin, and
a linear expansion coefficient of the pipette tip is 5.8×10−5/° C. or more.

### Claim 17 (depends on 2)

The reaction method according to claim 2, wherein a temperature of the pipette tip is adjusted by a temperature adjuster.

### Claim 18 (depends on 2)

The reaction method according to claim 2, wherein the correcting is performed after the liquid is supplied to the reaction field and before the liquid is removed from the reaction field.

### Claim 19 (depends on 2)

The reaction method according to claim 2, wherein
the reaction field is arranged at a bottom surface of a flow path or at a bottom surface of a well, capable of storing a liquid, and
the reacting includes an immune reaction in the reaction field.

### Claim 20 (depends on 3)

The reaction method according to claim 3, wherein
the detecting further includes measuring a temperature of the pipette tip by a second temperature measurer, and
the correcting further includes measuring the temperature of the pipette tip by the second temperature measurer, as well as correcting the height of the pipette nozzle from the reference height in accordance with a difference between the temperature of the pipette tip measured by the second temperature measurer in the detecting at a time when the end height of the pipette tip is detected and the temperature of the pipette tip measured by the second temperature measurer in the reacting.
