Cell observation system and cell observation method

Patent metadata

Field	Value
Publication number	US-12019005-B2
Application number	US-202017310813-A
Country	US
Kind code	B2
Filing date	Feb 14, 2020
Priority date	Feb 27, 2019
Publication date	Jun 25, 2024
Grant date	Jun 25, 2024

Abstract

A cell observation system observes a cell moving in a flow path with a fluid, and includes a first imaging apparatus, a second imaging apparatus, and a control device. The first imaging apparatus includes a first optical system and a first imaging element, and captures an image of the cell at a first position in a moving direction. The second imaging apparatus includes a second optical system, in which a focus is adjusted based on a focus adjustment signal, and a second imaging element, and captures an image of the cell at a second position downstream of the first position. The control device obtains a passing position of the cell in a cross section of the flow path based on the image obtained by the first imaging element, generates the focus adjustment signal, and provides the signal to the second optical system.

First claim

The invention claimed is:

1. A cell observation system for observing a cell moving in a flow path with a fluid, the system comprising:
a first imaging apparatus including a first optical system and a first imaging element, and configured to capture an image of the cell by receiving, by the first imaging element, light reaching the first imaging element from the cell at a first position in a moving direction of the cell in the flow path through the first optical system;
a second imaging apparatus including a second optical system, in which a focus is adjusted based on a focus adjustment signal, and a second imaging element, and configured to capture an image of the cell by receiving, by the second imaging element, light reaching the second imaging element from the cell at a second position downstream of the first position in the moving direction of the cell in the flow path through the second optical system; and
a controller configured to obtain a passing position of the cell in a cross section of the flow path based on the image obtained by imaging by the first imaging element of the first imaging apparatus, and generate the focus adjustment signal based on the obtained passing position to provide the signal to the second optical system of the second imaging apparatus.

2. The cell observation system according to claim 1 , wherein the controller is configured to determine whether to adjust the focus of the second optical system based on the passing position, and provide the focus adjustment signal to the second imaging apparatus when it is determined to adjust the focus of the second optical system.

3. The cell observation system according to claim 1 , wherein the first imaging apparatus is a quantitative phase microscope.

4. The cell observation system according to claim 1 , wherein the second imaging apparatus is a quantitative phase microscope or a phase tomographic microscope.

5. The cell observation system according to claim 1 , wherein the first imaging apparatus is a quantitative phase microscope, and the second imaging apparatus is a phase tomographic microscope.

6. The cell observation system according to claim 1 , wherein the controller is configured to obtain the passing position based on the image by a phase difference autofocus technique, an image plane phase difference focus technique, or an autofocus technique using digital holography.

7. The cell observation system according to claim 1 , wherein the fluid is caused to flow as a laminar flow in the flow path by using a hydrodynamic focusing effect.

8. A cell observation method for observing a cell moving in a flow path with a fluid, the method comprising:
performing a first imaging of, using a first imaging apparatus including a first optical system and a first imaging element, capturing an image of the cell by receiving, by the first imaging element, light reaching the first imaging element from the cell at a first position in a moving direction of the cell in the flow path through the first optical system;
performing a second imaging of, using a second imaging apparatus including a second optical system, in which a focus is adjusted based on a focus adjustment signal, and a second imaging element, capturing an image of the cell by receiving, by the second imaging element, light reaching the second imaging element from the cell at a second position downstream of the first position in the moving direction of the cell in the flow path through the second optical system; and
performing a focus adjustment instruction of, after the first imaging and before the second imaging, obtaining a passing position of the cell in a cross section of the flow path based on the image obtained by imaging by the first imaging element of the first imaging apparatus, and generating the focus adjustment signal based on the obtained passing position to provide the signal to the second optical system of the second imaging apparatus.

9. The cell observation method according to claim 8 , wherein, in the focus adjustment instruction, whether to adjust the focus of the second optical system is determined based on the passing position, and the focus adjustment signal is provided to the second imaging apparatus when it is determined to adjust the focus of the second optical system.

10. The cell observation method according to claim 8 , wherein a quantitative phase microscope is used as the first imaging apparatus.

11. The cell observation method according to claim 8 , wherein a quantitative phase microscope or a phase tomographic microscope is used as the second imaging apparatus.

12. The cell observation method according to claim 8 , wherein a quantitative phase microscope is used as the first imaging apparatus, and a phase tomographic microscope is used as the second imaging apparatus.

13. The cell observation method according to claim 8 , wherein, in the focus adjustment instruction step, the passing position is obtained based on the image by a phase difference autofocus technique, an image plane phase difference focus technique, or an autofocus technique using digital holography.

14. The cell observation method according to claim 8 , wherein the fluid is caused to flow as a laminar flow in the flow path by using a hydrodynamic focusing effect.

Assignees

• National Univ Corporation Hamamatsu Univ School Of Medicine
• Hamamatsu Photonics Kk

Inventors

• Kikuchi Hirotoshi
• Yamada Hidenao
• Hirotsu Amane
• Yamashita Daisuke
• Okazaki Shigetoshi

Classifications

• G01N2015/016

  White blood cells · CPC title

• G01N2015/012

  Red blood cells · CPC title

• G01N15/1433

  using image recognition · CPC title

• G02B21/361

  Optical details, e.g. image relay to the camera or image sensor (G02B21/364 takes precedence; illumination details G02B21/06 and subgroups) · CPC title

• G01N2015/144

  Imaging characterised by its optical setup · CPC title