Thickness evaluation method of cell sheet

Patent metadata

Field	Value
Publication number	US-11906301-B2
Application number	US-202117469119-A
Country	US
Kind code	B2
Filing date	Sep 8, 2021
Priority date	Sep 23, 2020
Publication date	Feb 20, 2024
Grant date	Feb 20, 2024

Abstract

A thickness evaluation method of the cell sheet according to the invention includes tomographically imaging a cell sheet by optical coherence tomography and obtaining a thickness distribution of the cell sheet based on a result of the tomography imaging. A tomographic image corresponding to one cross section of the cell sheet is obtained by tomography imaging while scanning the light in a main scanning direction. The tomography imaging is performed in every time while moving an incident position of the light at a predetermined feed pitch in a sub-scanning direction, thereby a plurality of the tomographic images corresponding to a plurality of cross-sections are obtained. One-dimensional thickness distributions of the cell sheet in the corresponding cross-sections are obtained based on each of the plurality of tomographic images, and a two-dimensional thickness distribution of the cell sheet is obtained by interpolating the one-dimensional thickness distributions.

First claim

What is claimed is:

1. A thickness evaluation method of a cell sheet, comprising:
capturing a plurality of tomographic images of the cell sheet using optical coherence tomography by causing light to be incident on the cell sheet in a in a direction intersecting a principal surface of the cell sheet; and
obtaining a thickness distribution of the cell sheet based on a result of the tomography imaging,
wherein the imaging step includes:
scanning repeatedly the light in a main scanning direction while moving an incident position of the light in a sub-scanning direction intersecting the main scanning direction at a feed pitch larger than a size corresponding to one pixel in the tomographic images; and
capturing a tomographic image of the cell sheet at each scan in the main scanning direction, thereby generating the plurality of the tomographic images corresponding to cross-sections at positions different from each other in the sub-scanning direction,

wherein the obtaining step includes:
obtaining one-dimensional thickness distributions of the cell sheet in the corresponding cross-sections based on each of the plurality of tomographic images; and
obtaining a two-dimensional thickness distribution of the cell sheet by interpolating the one-dimensional thickness distributions, and

wherein the method further comprises:
capturing a plurality of partial tomographic images corresponding to a partial region of the cell sheet while moving the light incident position in the sub-scanning direction at a standard interval determined in advance,
obtaining the one-dimensional thickness distributions of the partial region in cross-sections corresponding to the partial tomographic images, and
setting the feed pitch larger than the standard pitch based on the obtained one-dimensional thickness distributions.

2. The thickness evaluation method of the cell sheet according to claim 1 , further comprising:
thinning of the partial tomographic images at a certain rate;
interpolating the one-dimensional thickness distributions of the cell sheet in the sub-scanning direction based on the partial tomographic images remained after thinning; and
setting the feed pitch so that errors between the thicknesses obtained by interpolation and actually measured thicknesses in the thinned partial tomographic images do not exceed an allowable error in advance.

3. The thickness evaluation method of the cell sheet according to claim 2 , wherein
an approximation curve representing a change of the error is obtained by polynomial approximation using a thinning interval as a variable, the thinning interval being an interval between the partial tomographic images after thinning, and
a value of the thinning interval when a derivative value of the approximation curve becomes minimum is set as the feed pitch.

4. The thickness evaluation method of the cell sheet according to claim 2 , wherein
a change of the error by two regression lines corresponding to mutually different ranges of a thinning interval is performed using the thinning interval as a variable, the thinning interval being an interval between the partial tomographic images after thinning, and
a value of the thinning interval corresponding to an intersection of the two regression lines is set as the feed pitch.

5. The thickness evaluation method of the cell sheet according to claim 1 , wherein
the main scanning direction and the sub-scanning direction are switched and the partial tomographic images are imaged before and after that switch, and
the feed pitch is set based on the one-dimensional thickness in two directions.

6. A thickness evaluation method of the cell sheet comprising:
capturing a plurality of tomographic images of the cell sheet using optical coherence tomography by causing light to be incident on the cell sheet in a direction intersecting a principal surface of the cell sheet; and
obtaining a thickness distribution of the cell sheet based on a result of the tomography imaging,
wherein the imaging step includes:
scanning repeatedly the light in a main scanning direction while moving an incident position of the light in a sub-scanning direction intersecting the main scanning direction at a feed pitch larger than a size corresponding to one pixel in the tomographic images; and
capturing a tomographic image of the cell sheet at each scan in the main scanning direction, thereby generating the plurality of the tomographic images corresponding to cross-sections at positions different from each other in the sub-scanning direction,

wherein the obtaining step includes:
obtaining one-dimensional thickness distributions of the cell sheet in the corresponding cross-sections based on each of the plurality of tomographic images; and
obtaining a two-dimensional thickness distribution of the cell sheet by interpolating the one-dimensional thickness distributions,

wherein tomographic images in which the main scanning direction and the sub-scanning direction are switched are further imaged, and
wherein the two-dimensional thickness distribution is obtained by two-dimensional interpolation using one-dimensional thickness distributions obtained for the respective tomographic images imaged before and after that switch.

Assignees

• Screen Holdings Co Ltd

Inventors

• HASEBE Ryo

Classifications

• G01B9/02063 Primary

  by particular alignment of focus position, e.g. dynamic focussing in optical coherence tomography · CPC title

• G01B9/02002

  using two or more frequencies · CPC title

• G01B9/02012

  using temporal intensity variation · CPC title

• G01B9/02071

  by measuring path difference independently from interferometer · CPC title

• G01B9/02072

  by calibration or testing of interferometer · CPC title