Cell culture apparatus and cell culture method

Patent metadata

Field	Value
Publication number	US-9845453-B2
Application number	US-201414909277-A
Country	US
Kind code	B2
Filing date	Aug 1, 2014
Priority date	Sep 9, 2013
Publication date	Dec 19, 2017
Grant date	Dec 19, 2017

Abstract

A cell culture apparatus is provided which can continuously and accurately measure turbidity of a cell culture solution and culture a cell, without inserting a turbidity sensor from outside into a sterile bag. The cell culture apparatus includes: a flexible and transparent sterile bag that is installed at a prescribed position in the cell culture apparatus and in which a cell contained in a cell culture solution is cultured; and a turbidity sensor that includes a light emitter which emits light to the cell culture solution in the sterile bag via a portion of the sterile bag, a light receiver which receives the light transmitted through the cell culture solution via another portion of the sterile bag, and that is configured to place the light emitter, the portion of the sterile bag, another portion of the sterile bag, and the light receiver, optically on a same straight line.

First claim

The invention claimed is:

1. A cell culture apparatus comprising:
a recessed portion having a pair of facing surfaces that face each other, the recessed portion being configured to receive between the pair of facing surfaces a portion of a cell culture solution in which cells are cultured, the cell culture solution being contained in a flexible and transparent sterile bag; and
a turbidity sensor that includes:
a light emitter which emits light to the cell culture solution in the sterile bag via a first portion of the sterile bag, and
a light receiver which receives the light that has been transmitted through the cell culture solution in the sterile bag via a second portion of the sterile bag,

wherein:
the light is transmitted along a light path comprising the light emitter, the first portion of the sterile bag, the second portion of the sterile bag, and the light receiver in this order;
a space between the pair of facing surfaces constitutes a part of the light path; and
at least one of the pair of facing surfaces is a stepped surface.

2. The cell culture apparatus according to claim 1 , further comprising a computation unit that is connected to the light receiver and that is configured to calculate a concentration of the cultured cells contained in the cell culture solution, from a measurement value measured by the light receiver, and, based on a result of the calculation, control at least one of a speed of stirring the cell culture solution, a temperature of the cell culture solution, an amount of vented gas, and a medium component of a liquid medium of the cell culture solution.

3. The cell culture apparatus according to claim 1 , further comprising:
a first light path changer, which is configured to change a direction of a path of the light that is emitted from a light source to transmit the light to the cell culture solution via the first portion of the sterile bag, and
a second light path changer, which is configured to change a direction of a path of the light that has been transmitted through the cell culture solution and the second portion of the sterile bag to transmit the light to the light receiver,
wherein the first portion and the second portion of the sterile bag are positioned in between the first light path changer and the second light path changer.

4. The cell culture apparatus according to claim 1 , further comprising a light path change unit comprising a first light path changer and a second light path changer
wherein:
the first light path changer is configured to:
receive light from a light source of the light emitter via the first portion of the sterile bag,
change a direction of a path of the received light to transmit the light to the cell culture solution; and

the second light path changer is configured to:
receive the light whose light path direction has been changed by the first light path changer and has been transmitted through the cell culture solution, and
change a direction of the path of the received light to transmit the light to the light receiver via the second portion of the sterile bag.

5. The cell culture apparatus according to claim 4 , further comprising:
a first magnetic member arranged in the light path change unit, and
a second magnetic member arranged in the turbidity sensor
wherein the first magnetic member and the second magnetic member are configured to perform an alignment of an axis of the light that enters the first light path changer from the light emitter via the first portion of the sterile bag, and an alignment of an axis of the light which enters the light receiver from the second light path changer via the second portion of the sterile bag.

6. The cell culture apparatus according to claim 5 , wherein
the turbidity sensor is separable into a base including the second magnetic member and a main unit including the light emitter and the light receiver, and
the base and the main unit have respective engagement structures for alignment with each other.

7. The cell culture apparatus according to claim 1 , wherein each of the light emitter and the light receiver is arranged in a position where the cell culture solution has a high fluidity.

8. The cell culture apparatus according to claim 1 , wherein the recessed portion is arranged outside of the sterile bag and is configured to receive between the pair of facing surfaces a portion of the sterile bag containing the portion of the cell culture solution.

9. The cell culture apparatus according to claim 4 , wherein
the recessed portion is arranged inside the sterile bag and comprises the light path change unit, and
the turbidity sensor is arranged outside the sterile bag.

10. A cell culture method comprising:
arranging a flexible and transparent sterile bag containing a cell culture solution in a prescribed position in a cell culture apparatus, a portion of the cell culture solution being positioned between a pair of facing surfaces of a recessed portion of the cell culture apparatus, the cell culture solution containing cells to be cultured; and
then culturing the cell culture solution inside the sterile bag; and
measuring turbidity of the cell culture solution by transmitting light from a light emitter of the cell culture apparatus through the portion of the cell culture solution positioned between the pair of facing surfaces of the recessed portion to a light receiver of the cell culture apparatus;
wherein
the light is transmitted along a light path comprising the light emitter, a first portion of the sterile bag, a second portion of the sterile bag, and the light receiver;
a space between the pair of facing surfaces constitutes a part of the light path; and
at least one of the pair of facing surfaces is a stepped surface.

11. The cell culture method according to claim 10 , further comprising:
calculating via a computation unit connected to the light receiver a concentration of the cultured cells contained in the cell culture solution from a measurement value measured by the light receiver, and
controlling at least one of a speed of stirring the cell culture solution, a temperature of the cell culture solution, an amount of vented gas, and a medium component of a liquid medium of the cell culture solution based on the result of the calculation.

12. The cell culture method according to claim 10 , wherein each of the light emitter and the light receiver is arranged in a position where the cell culture solution has a high fluidity.

13. The cell culture method according to claim 10 , further comprising:
a first light path changer, which is configured to change a direction of a path of the light emitted from a light source to transmit the light to the cell culture solution via the first portion of the sterile bag, and
a second light path changer, which is configured to change the direction of a path of the light which has been transmitted through the cell culture solution and the second portion of the sterile bag to transmit the light to the light receiver,
wherein the first portion and the second portion of the sterile bag are in positioned between the first light path changer and the second light path changer.

14. The cell culture method according to claim 10 , further comprising a light path change unit comprising a first light path changer and a second light path,
wherein
the first light path changer is configured to:
receive light from a light source of the light emitter via the first portion of the sterile bag, and
change a direction of a path of the received light to transmit the light to the cell culture solution, and

the second light path changer is configured to:
receiv

Assignees

• Hitachi Ltd

Inventors

• Nanba Masaru
• HAGA Ryouichi
• Murakami Sei
• Suzuki Haruo

Classifications

• C12M23/22

  Transparent or translucent parts (glassware for laboratory use B01L3/00) · CPC title

• C12M23/14

  Bags · CPC title

• C12M41/36

  of biomass, e.g. colony counters or by turbidity measurements (electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404) · CPC title

• C12M41/30 Primary

  of concentration · CPC title

• C12M37/00

  Means for sterilizing, maintaining sterile conditions or avoiding chemical or biological contamination (C12M23/38 takes precedence; filtration in general and filters per se B01D24/00-B01D41/00; autoclaves B01J3/04; treatment of microorganisms with electrical or wave energy C12N13/00) · CPC title