Method for evaluating ability of cells to grow into sheet

Patent metadata

Field	Value
Publication number	US-11035843-B2
Application number	US-201715717325-A
Country	US
Kind code	B2
Filing date	Sep 27, 2017
Priority date	Mar 30, 2015
Publication date	Jun 15, 2021
Grant date	Jun 15, 2021

Abstract

A method for evaluating the ability of cells to grow into a sheet includes (1) a step of examining cell cultures growing into a sheet to determine their impedance and/or electrical resistance or numerical values relating thereto; (2) a step of comparing the numerical values determined by Step (1) with reference values; and (3) a step of judging, based on the results of comparison obtained in Step (2), the ability of cells to grow into a sheet.

First claim

What is claimed is:

1. A method for evaluating the ability of cells to grow into a sheet, comprising:
examining cell cultures growing into a sheet to determine, using a measuring apparatus, one or more numerical values relating to impedance and/or electrical resistance of the cell cultures growing into a sheet, the numerical values being parameters selected from the group consisting of electrical resistance, capacitance, Rb, α, Rb/α, and Cm and peak values, times to peak, and slopes to peak of the parameters;
comparing one or more of the determined numerical values with one or more reference values;
judging, based on the results of comparing, the ability of cells to grow into a sheet; and
controlling a process for producing the sheet-shaped cell culture based on the result of the judging,
wherein cells are judged to be low in ability to grow into a sheet if
the peak value of the electrical resistance, the peak value of Rb, or the slope to peak of Rb determined is equal to or smaller than the one or more reference values, or
the time to peak of the electrical resistance or the time to peak of Rb determined is equal to or larger than the one or more reference values.

2. The method defined in claim 1 , wherein the determination of impedance and/or electrical resistance is performed periodically.

3. The method defined in claim 1 , wherein the determination of one or more numerical values further includes determination of voltage phase relative to current phase.

4. The method defined in claim 1 , wherein the determining of the one or more numerical values includes determining the one or more numerical values relating to the impedance of the cell cultures growing into a sheet, and the determination of impedance is performed at two or more frequencies.

5. The method defined in claim 1 , wherein the cells are judged to be low in ability to grow into a sheet if the determined electrical resistance is equal to or smaller than the reference value.

6. The method defined in claim 1 , wherein cells are judged to be low in ability to grow into a sheet if the determined values of Rb, α, and Rb/α are equal to or smaller than the reference values.

7. The method defined in claim 1 , wherein cells are judged to be adequate or excessive in ability to grow into a sheet if the determined values of Rb, α, and Rb/α are equal to or larger than the reference values.

8. The method defined in claim 1 , wherein cells are judged to be adequate in ability to grow into a sheet if the numerical values selected from a group consisting of the time to peak of electrical resistance and the time to peak of Rb are equal to or smaller than the reference values and the numerical values selected from a group consisting of the peak value of Rb/α and the slope to peak of Rb/α are equal to or smaller than the reference values, and/or if the numerical values selected from the group consisting of the time to peak of electrical resistance and the time to peak of Rb are equal to or smaller than the reference values and the time to peak of Rb/α is equal to or longer than the reference value.

9. The method defined in claim 1 , wherein cells are judged to have excessive ability to grow into a sheet if the numerical values selected from a group consisting of the peak value of Rb/α and the slope to peak of Rb/α are equal to or larger than the reference values, and/or if the time to peak of Rb/α is equal to or shorter than the reference value.

10. A method for producing a sheet-shaped cell culture, comprising:
performing sheet-forming cultivation to obtain one or more cell cultures growing into a sheet;
examining the one or more cell cultures growing into a sheet to determine one or more numerical values relating to impedance and/or electrical resistance of the cell cultures growing into a sheet, the numerical values being parameters selected from the group consisting of electrical resistance, capacitance, Rb, α, Rb/α, and Cm and peak values, times to peak, and slopes to peak of the parameters;
comparing one or more of the determined numerical values with one or more reference values;
judging, based on the results of the comparing, the ability of cells to grow into a sheet; and
controlling, based on the result of the judging, a process of producing the sheet-shaped cell culture,
wherein cells are judged to be low in ability to grow into a sheet if
the peak value of the electrical resistance, the peak value of Rb, or the slope to peak of Rb determined is equal to or smaller than the one or more reference values, or
the time to peak of the electrical resistance or the time to peak of Rb determined is equal to or larger than the one or more reference values.

11. The method defined in claim 10 , wherein the determination of impedance and/or electrical resistance is performed periodically.

12. The method defined in claim 10 , wherein the determination of the one or more numerical values further includes determination of voltage phase relative to current phase.

13. The method defined in claim 10 , wherein the determining of the one or more numerical values includes determining the one or more numerical values relating to the impedance of the cell cultures growing into a sheet, and the determination of the impedance is performed at two or more frequencies.

14. A method for producing a sheet-shaped cell culture, comprising:
performing sheet-forming cultivation to obtain one or more cell cultures growing into the sheet-shaped cell culture;
determining impedance and/or electrical resistance of the one or more cell cultures growing into the sheet-shaped cell culture to obtain one or more numerical values relating to the determined impedance and/or electrical resistance, the one or more obtained numerical values being parameters selected from the group consisting of electrical resistance, capacitance, Rb, α, Rb/α, and Cm and peak values, times to peak, and slopes to peak of the parameters;
comparing one or more of the obtained numerical values with one or more reference values; and
judging, based on the results of the comparing, the ability of the cell cultures to grow into a sheet, wherein the cells are judged to be low in ability to grow into the sheet if
the peak value of electrical resistance, the peak value of Rb, or the slope to peak of Rb determined is equal to or smaller than the one or more reference values, or
the time to peak of electrical resistance or the time to peak of Rb determined is equal to or larger than the one or more reference values.

15. The method defined in claim 14 , wherein the determination of impedance and/or electrical resistance is performed periodically.

16. The method defined in claim 14 , wherein the determination of the one or more numerical values further includes determination of voltage phase relative to current phase.

17. The method defined in claim 14 , wherein the determining of the one or more numerical values includes determining the one or more numerical values relating to the impedance of the cell cultures growing into a sheet, and the determining of the impedance is performed at two or more frequencies.

18. The method defined in claim 14 , wherein cells are judged to be low in ability to grow into a sheet if the determined electrical resistance is equal to or smaller than the reference value.

19. The method defined in claim 14 , wherein cells are judged to be low in ability to grow into a sheet if the determined values of Rb, α, and Rb/α are equal to or smaller than the reference values.

20. The method defined in claim

Assignees

• Terumo Corp

Inventors

• Takeuchi Ryohei
• Yori Kouichirou

Classifications

• G01N27/026

  Dielectric impedance spectroscopy (electrochemical impedance spectroscopy for measuring corrosion G01N17/02) · CPC title

• G01N33/4833 Primary

  of solid biological material, e.g. tissue samples, cell cultures (tissue in vivo A61B5/00; cell suspensions G01N33/48735) · CPC title

• G01N27/041

  of a solid body · CPC title