IP Library Granted Patent US 12,038,385
Granted Patent B2
US 12,038,385 · App. 17/541,622 · Granted Jul 16, 2024

Examination method, system, and computer-readable medium

Inventor: Tadashi Hirata (Tokyo, JP)
Assignee: Evident Corporation
G01N21/80C12M41/26C12M41/32C12M41/36
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Quick Facts
Patent No.
US 12,038,385
App. No.
17/541,622
Granted
Jul 16, 2024
Kind
B2
Abstract

A method for examining a culture solution containing a pH indicator and accommodated in a culture container includes: measuring, as a baseline intensity, an intensity of light that has passed through a solution and the culture container; measuring, as a measurement intensity, an intensity of light that has passed through the culture solution and the culture container; obtaining light source information including first information pertaining to the light source that is provided when measuring the baseline intensity and second information pertaining to the light source that is provided when measuring the measurement intensity; and on the basis of the baseline intensity, the measurement intensity, and the light source information, calculating an absorbance of the pH indicator at at least one wavelength included in emitted light from the light source.

Claims (111)

1. A method for examining a culture solution containing a pH indicator and accommodated in a culture container, the method comprising:

causing a processor of a control apparatus to control one or more photodetectors to:

measure, as a baseline intensity, an intensity of light that is a portion of emitted light from a light source and has passed through a solution not containing the pH indicator and the culture container;

measure, as an auxiliary baseline intensity, an intensity of light that is a portion of emitted light from the light source and does not pass through the solution;

after measuring the baseline intensity and the auxiliary baseline intensity, measure, as a measurement intensity, an intensity of light that is a portion of emitted light from the light source and has passed through the culture solution containing the pH indicator and the culture container; and

after measuring the baseline intensity and the auxiliary baseline intensity, measure, as an auxiliary measurement intensity, an intensity of light that is a portion of emitted light from the light source and does not pass through the culture solution; and

on the basis of the baseline intensity, the auxiliary baseline intensity, the measurement intensity, and the auxiliary measurement intensity, calculating an absorbance of the pH indicator at at least one wavelength included in emitted light from the light source.

2. The method according to claim 1 ,

wherein causing the processor to control the one or more photodetectors to measure the baseline intensity comprises controlling the one or more photodetectors to:

measure, as a first baseline intensity, an intensity of light that has passed through the solution and the culture container, and has a first wavelength at which the absorbance of the pH indicator is pH-dependent; and

measure, as a second baseline intensity, an intensity of light that has passed through the solution and the culture container and has a second wavelength at which the absorbance of the pH indicator is not pH-dependent,

wherein causing the processor to control the one or more photodetectors to measure the measurement intensity comprises controlling the one or more photodetectors to:

measure, as a first measurement intensity, an intensity of light that has the first wavelength and has passed through the culture solution and the culture container; and

measure, as a second measurement intensity, an intensity of light that has the second wavelength and has passed through the culture solution and the culture container,

wherein causing the processor to control the one or more photodetectors to measure the auxiliary baseline intensity comprises controlling the one or more photodetectors to measure, as the auxiliary baseline intensity, the intensity of the light from the light source that has the first wavelength and the intensity of the light from the light source that has the second wavelength when measuring the baseline intensity,

wherein causing the processor to control the one or more photodetectors to measure the auxiliary measurement intensity comprises controlling the one or more photodetectors to measure, as the auxiliary baseline intensity, the intensity of the light from the light source that has the first wavelength and the intensity of the light from the light source that has the second wavelength when measuring the baseline intensity, and

wherein calculating the absorbance of the pH indicator comprises calculating the absorbance of the pH indicator at the first wavelength on the basis of the first baseline intensity, the second baseline intensity, the first measurement intensity, the second measurement intensity, the auxiliary baseline intensity and the auxiliary measurement intensity.

3. The method according to claim 2 ,

wherein causing the processor to control the one or more photodetectors to measure the baseline intensity comprises controlling the one or more photodetectors to measure, as a third baseline intensity, an intensity of light that has passed through the solution and the culture container, and has a third wavelength at which the absorbance of the pH indicator is pH-dependent, the third wavelength being different from the first wavelength,

wherein causing the processor to control the one or more photodetectors to measure the measurement intensity comprises controlling the one or more photodetectors to measure, as a third measurement intensity, an intensity of the light from the light source that has the third wavelength and has passed through the culture solution and the culture container,

wherein causing the processor to control the one or more photodetectors to measure the auxiliary baseline intensity comprises controlling the one or more photodetectors to measure, as the auxiliary baseline intensity, an intensity of the light from the light source that has the third wavelength and an intensity of the light from the light source that has the second wavelength when measuring the baseline intensity,

wherein causing the processor to control the one or more photodetectors to measure the auxiliary measurement intensity comprises controlling the one or more photodetectors to measure, as the auxiliary measurement intensity, the intensity of the light from the light source that has the third wavelength and the intensity of the light from the light source that has the second wavelength when measuring the measurement intensity,

wherein method further comprises calculating an absorbance of the pH indicator at the third wavelength on the basis of the third baseline intensity, the second baseline intensity, the third measurement intensity, the second measurement intensity, the auxiliary baseline intensity and the auxiliary measurement intensity,

wherein calculating the absorbance of the pH indicator further comprises calculating the absorbance of the pH indicator at the third wavelength on the basis of the third baseline intensity, the second baseline intensity, the third measurement intensity, the second measurement intensity, the third information, and the fourth information, and

wherein the method further comprises calculating a pH of the culture solution on the basis of the absorbance of the pH indicator at the first wavelength and the absorbance of the pH indicator at the third wavelength.

4. The method according to claim 3 ,

wherein the calculating the absorbance of the pH indicator further comprises:

calculating the absorbance of the pH indicator for the first wavelength based on:

a ratio that is attained when measuring an intensity of light of the first wavelength of the auxiliary baseline intensity and an intensity of light of the second wavelength of the auxiliary baseline intensity; and

a ratio that is attained when measuring an intensity of light of the first wavelength of the auxiliary measurement intensity and an intensity of light of the second wavelength of the auxiliary measurement intensity.

5. The method according to claim 4 ,

wherein the calculating the absorbance of the pH indicator further comprises:

calculating the absorbance of the pH indicator for the third wavelength based on:

a ratio that is attained when measuring an intensity of light of the third wavelength of the auxiliary baseline intensity and an intensity of light of the second wavelength of the auxiliary baseline intensity; and

a ratio that is attained when measuring an intensity of light of the third wavelength of the auxiliary measurement intensity and an intensity of light of the second wavelength of the auxiliary measurement intensity.

6. A system comprising:

an image capturing apparatus configured to have a culture container placed thereon and to capture an image of a sample cultured within the culture container; and

a control apparatus configured to control the image capturing apparatus,

wherein the image capturing apparatus comprises:

a light source; and

one or more photodetectors, and

wherein the control apparatus is configured to control the one or more photodetectors to:

measure, as a baseline intensity, an intensity of light that is a portion of emitted light from the light source and has passed through a solution not containing a pH indicator and the culture container;

measure, as an auxiliary baseline intensity, an intensity of light that is a portion of emitted light from the light source and does not pass through the solution;

after measuring the baseline intensity and the auxiliary baseline intensity, measure, as a measurement intensity, an intensity of light that is a portion of emitted light from the light source and has passed through a culture solution containing the pH indicator and the culture container; and

after measuring the baseline intensity and the auxiliary baseline intensity, measure, as an auxiliary measurement intensity, an intensity of light that is a portion of emitted light from the light source and does not pass through the culture solution; and

wherein the control apparatus is configured to, on the basis of the baseline intensity, the auxiliary baseline intensity, the measurement intensity, and the auxiliary measurement intensity, calculate an absorbance of the pH indicator at at least one wavelength included in emitted light from the light source.

7. The system of claim 6 ,

wherein the control apparatus is configured to control a display apparatus to display information indicating a history of the pH of the culture solution.

8. The system of claim 6 ,

wherein the control apparatus is configured to:

control a drive mechanism to move the one or more photodetectors to a first position on which light that is a portion of emitted light from the light source and has passed through the culture container is incident;

control the one or more photodetectors to measure the baseline intensity and the measurement intensity at the first position;

control the drive mechanism to move the one or more photodetectors to a second position on which light that is a portion of emitted light from the light source and does not pass through the culture solution is incident; and

control the one or more photodetectors to measure the auxiliary baseline intensity and the auxiliary measurement intensity at the second position.

9. The system of claim 8 ,

wherein the image capturing apparatus further comprises a housing having a placement surface on which the culture container is placed,

wherein the one or more photodetectors and the light source are provided within the housing, and

wherein the light source is configured to move together with the one or more photodetectors within the housing.

10. The system of claim 8 ,

wherein the image capturing apparatus further comprises a housing having a placement surface on which the culture container is placed,

wherein the one or more photodetectors are provided within the housing, and

wherein the light source is fixed at a higher position than the placement surface.

11. The system of claim 10 ,

wherein the image capturing apparatus further comprises a deflection element configured to deflect emitted light from the light source toward the one or more photodetectors.

12. The system of claim 10 ,

wherein the image capturing apparatus further comprises a light diffusion element between the light source and the one or more photodetectors.

13. The system of claim 10 ,

wherein the light source is disposed outward of a region obtained by upwardly extending a region of an image projected onto the culture container placed on the placement surface.

14. The system of claim 6 ,

wherein the image capturing apparatus is configured to capture an image of the sample on the basis of light that is a portion of emitted light from the light source and has been detected by the one or more photodetectors.

15. The system of claim 6 ,

wherein the image capturing apparatus is configured to capture an image of the sample on the basis of light detected by the photodetector.

16. The system of claim 6 ,

wherein the one or more photodetectors comprise:

a first photodetector disposed at a first position on which light that is a portion of emitted light from the light source and passes through the culture solution is incident; and

a second photodetector disposed at a second position on which light that is a portion of emitted light from the light source and does not pass through the culture solution is incident, the second photodetector being different from the first photodetector, and

wherein the control apparatus is configured to control the first photodetector to measure the measurement intensity, and

wherein the control apparatus is configured to control the second photodetector to measure the auxiliary measurement intensity.

17. The system of claim 16 ,

wherein the first photodetector is configured to acquire light that passes through the culture solution and the culture container, and

wherein the second photodetector is configured to acquire light that passes through the culture container without passing through the culture solution.

18. The system of claim 16 ,

wherein the first position is lower than the placement surface,

wherein the second position is higher than the placement surface, and

wherein the control apparatus is configured to control the second photodetector to detect light reflected by a liquid surface of the culture solution or light reflected by a top plate of the culture container.

19. The system according to claim 6 ,

wherein, to measure the baseline intensity, the processor is configured to control the one or more photodetectors to:

measure, as a first baseline intensity, an intensity of light that has passed through the solution and the culture container, and has a first wavelength at which the absorbance of the pH indicator is pH-dependent; and

measure, as a second baseline intensity, an intensity of light that has passed through the solution and the culture container and has a second wavelength at which the absorbance of the pH indicator is not pH-dependent,

wherein, to measure the measurement intensity, the processor is configured to control the one or more photodetectors to:

measure, as a first measurement intensity, an intensity of light that has the first wavelength and has passed through the culture solution and the culture container; and

measure, as a second measurement intensity, an intensity of light that has the second wavelength and has passed through the culture solution and the culture container,

wherein, to measure the auxiliary baseline intensity, the processor is configured to control the one or more photodetectors to measure, as the auxiliary baseline intensity, the intensity of the light from the light source that has the first wavelength and the intensity of the light from the light source that has the second wavelength when measuring the baseline intensity,

wherein, to measure the auxiliary measurement intensity, the processor is configured to control the one or more photodetectors to measure, as the auxiliary baseline intensity, the intensity of the light from the light source that has the first wavelength and the intensity of the light from the light source that has the second wavelength when measuring the baseline intensity, and

wherein, to calculate the absorbance of the pH indicator, the processor is configured to calculate the absorbance of the pH indicator at the first wavelength on the basis of the first baseline intensity, the second baseline intensity, the first measurement intensity, the second measurement intensity, the auxiliary baseline intensity and the auxiliary measurement intensity.

20. The system according to claim 19 ,

wherein, to control the one or more photodetectors to measure the baseline intensity, the processor is configured to control the one or more photodetectors to measure, as a third baseline intensity, an intensity of light that has passed through the solution and the culture container, and has a third wavelength at which the absorbance of the pH indicator is pH-dependent, the third wavelength being different from the first wavelength,

wherein, to control the one or more photodetectors to measure the measurement intensity, the processor is configured to control the one or more photodetectors to measure, as a third measurement intensity, an intensity of the light from the light source that has the third wavelength and has passed through the culture solution and the culture container,

wherein, to control the one or more photodetectors to measure the auxiliary baseline intensity, the processor is configured to control the one or more photodetectors to measure, as the auxiliary baseline intensity, an intensity of the light from the light source that has the third wavelength and an intensity of the light from the light source that has the second wavelength when measuring the baseline intensity,

wherein, to control the one or more photodetectors to measure the auxiliary measurement intensity, the processor is configured to control the one or more photodetectors to measure, as the auxiliary measurement intensity, the intensity of the light from the light source that has the third wavelength and the intensity of the light from the light source that has the second wavelength when measuring the measurement intensity,

wherein the processor is further configured to calculate an absorbance of the pH indicator at the third wavelength on the basis of the third baseline intensity, the second baseline intensity, the third measurement intensity, the second measurement intensity, the auxiliary baseline intensity and the auxiliary measurement intensity,

wherein, to calculate the absorbance of the pH indicator, the processor is configured to calculate the absorbance of the pH indicator at the third wavelength on the basis of the third baseline intensity, the second baseline intensity, the third measurement intensity, the second measurement intensity, the third information, and the fourth information, and

wherein the processer is configured to calculate a pH of the culture solution on the basis of the absorbance of the pH indicator at the first wavelength and the absorbance of the pH indicator at the third wavelength.

21. A non-transitory computer-readable medium having stored therein a program for causing a computer to perform a process comprising:

controlling one or more photodetectors to:

measure, as a baseline intensity, an intensity of light that is a portion of emitted light from a light source and has passed through a solution not containing a pH indicator and a culture container;

measure, as an auxiliary baseline intensity, an intensity of light that is a portion of emitted light from the light source and does not pass through the solution;

after measuring the baseline intensity and the auxiliary baseline intensity, measure, as a measurement intensity, an intensity of light that is a portion of emitted light from the light source and has passed through a culture solution containing the pH indicator and the culture container; and

after measuring the baseline intensity and the auxiliary baseline intensity, measure, as an auxiliary measurement intensity, an intensity of light that is a portion of emitted light from the light source and does not pass through the culture solution; and

on the basis of the baseline intensity, the auxiliary baseline intensity, the measurement intensity, and the auxiliary measurement intensity, calculating an absorbance of the pH indicator at at least one wavelength included in emitted light from the light source.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 7, 2022
From: OLYMPUS CORPORATION
To: EVIDENT CORPORATION
Reel/Frame 061396/0129 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 3, 2021
From: HIRATA, TADASHI
To: OLYMPUS CORPORATION
Reel/Frame 058281/0286 →
Continuity (2)
Continuation PCTJP2019026841 · Jul 5, 2019
Related Publication 20220091046A1 · Mar 24, 2022