Biological culture unit

Patent metadata

Field	Value
Publication number	US-11976262-B2
Application number	US-202017002940-A
Country	US
Kind code	B2
Filing date	Aug 26, 2020
Priority date	Aug 27, 2019
Publication date	May 7, 2024
Grant date	May 7, 2024

Abstract

A biological culture unit comprises a chamber body and a valve plate. The chamber body has defined therein a growth chamber and an aliquot chamber. The valve plate is disposed on the top surface of the chamber body and is movable to define selectable configurations of the biological culture unit for: (1) loading the growth chamber; (3) transferring an aliquot from the growth chamber to the aliquot chamber via a path defined within the biological culture unit in the transfer position; and (4) extracting the aliquot from the aliquot chamber. The selectable positions may further include (2) a growth position, and (5) a termination position for putting a termination agent into the growth and aliquot chambers. The valve plate may further include a neutralizer port that is aligned with the aliquot chamber in the loading position, for loading a neutralizing agent into the aliquot chamber.

First claim

The invention claimed is:

1. A biological culture unit, comprising:
a chamber body having a top surface and a bottom surface, the chamber body having defined therein a growth chamber having an access opening at the top surface and an aliquot chamber having an access opening at the top surface and a first fluid path extending from the growth chamber to the top surface and a second fluid path extending from the aliquot chamber to the top surface;
a valve plate disposed on the top surface of the chamber body and rotatably connected with the chamber body to rotate about a rotation axis relative to the chamber body, the valve plate including a growth chamber access port, an aliquot chamber access port, a transfer actuator, and a third fluid path, the valve plate being rotatable about the rotation axis into a plurality of selectable positions including:
a loading position in which the growth chamber access port is aligned with the access opening of the growth chamber and the third fluid path is not aligned to connect the first and second fluid paths;
a transfer position in which the third fluid path is aligned to connect the first and second fluid paths and the transfer actuator is aligned with one of the access opening of the growth chamber and the access opening of the aliquot chamber; and
an extraction position in which the aliquot chamber access port Is aligned with the access opening of the aliquot chamber and the third fluid path is not aligned to connect the first and second fluid paths.

2. The biological culture unit of claim 1 , wherein the valve plate further includes a neutralizer port which is aligned with the aliquot chamber when the valve plate is rotated into the loading position; or
wherein rotation of the valve plate in a sequence rotary direction cycles through the loading position, the transfer position, and the extraction position in that order; or
wherein the plurality of selectable positions further includes:
a growth position in which the chamber access port is not aligned with the access opening of the growth chamber and the third fluid path is not aligned to connect the first and second fluid paths and the aliquot chamber access port is not aligned with the access opening of the aliquot chamber.

3. The biological culture unit of claim 1 , wherein the valve plate further includes first and second terminator ports and the plurality of selectable positions further includes:
a termination position in which the first terminator port is aligned with the access opening of the growth chamber and the second terminator port is aligned with the access opening of the aliquot chamber.

4. The biological culture unit of claim 1 , wherein, in the transfer position, the transfer actuator is aligned with the access opening of the growth chamber.

5. The biological culture unit of claim 4 , wherein the transfer actuator comprises a plunger that is operable when the valve plate is in the transfer position to increase pressure in the growth chamber; or
wherein the transfer actuator comprises a gas coupling.

6. The biological culture unit of claim 1 , wherein:
the top surface of the chamber body has defined therein an annular gasket seat around the access opening of the growth chamber, an annular gasket seat around the access opening of the aliquot chamber, an annular gasket seat around an opening of the first fluid path at the top surface, and an annular gasket seat around an opening of second fluid path at the top surface; and
gaskets disposed in the respective annular gasket seats.

7. The biological culture unit of claim 1 , wherein the bottom surface of the chamber body has formed therein a growth chamber heater post receptacle aligned with the growth chamber and an aliquot chamber heater post receptacle aligned with the aliquot chamber.

8. The biological culture unit of claim 7 , further comprising:
a heater adapter having a top surface including two heater posts each sized and shaped to mate into either the growth chamber heater post receptacle or the aliquot chamber heater post receptacle, and further having a bottom surface configured to mate with an associated temperature controller.

9. A method of biological culture performed in conjunction with the biological culture unit of claim 1 , the method comprising:
with the valve plate in the loading position, loading a biological sample and a growth medium into the growth chamber via the growth chamber access port aligned with the access opening of the growth chamber;
after the loading, transferring an aliquot into the aliquot chamber by rotating the valve plate to the transfer position and, with the valve plate in the transfer position, operating the transfer actuator to transfer the aliquot from the growth chamber to the aliquot chamber via a transfer route defined by the first fluid path and the second fluid path connected by the third fluid path;
after the transferring, extracting the aliquot by rotating the valve plate to the extraction position and, with the valve plate in the extraction position, removing the aliquot from the aliquot chamber via the aliquot chamber access port aligned with the access opening of the aliquot chamber.

10. The method of claim 9 , further comprising:
after the transferring and before the extracting, heating the aliquot chamber.

11. The method of claim 9 , wherein the valve plate further includes an aliquot chamber preparation port which is aligned with the aliquot chamber when the valve plate is rotated into the loading position, the method further comprising:
with the valve plate in the loading position, loading a base into the aliquot chamber via the aliquot chamber preparation port aligned with the access opening of the aliquot chamber.

12. The method of claim 9 , wherein the extracted aliquot includes the base and the method further comprises:
after the extracting, reducing the pH of the extracted aliquot using an acid.

13. The method of claim 9 , wherein the plurality of selectable positions of the valve plate further includes a growth position in which the chamber access port is not aligned with the access opening of the growth chamber and the third fluid path is not aligned to connect the first and second fluid paths and the aliquot chamber access port is not aligned with the access opening of the aliquot chamber, the method further comprising:
after the loading and before the transferring, growing a culture by rotating the valve plate to the growth position and, with the valve plate in the growth position, applying heat to the growth chamber.

14. The method of claim 9 , wherein the valve plate further includes first and second terminator ports and the plurality of selectable positions of the valve plate further includes a termination position in which the first terminator port is aligned with the access opening of the growth chamber and the second terminator port is aligned with the access opening of the aliquot chamber, the method further comprising:
prior to or concurrently with the loading, disposing a termination agent in the first terminator port and in the second terminator port; and
after the extracting, applying the termination agent disposed in the first terminator port to the growth chamber and the termination agent disposed in the second terminator port to the aliquot chamber by operations including at least rotating the valve plate to the termination position.

15. The method of claim 14 , wherein the termination agent comprises at least calcium hypochlorite.

16. The method of claim 14 , further comprising:
after applying the termination agent disposed in the first

Assignees

• Battelle Memorial Institute

Inventors

• Desanti Charles L
• Daly Ryan W
• Seibert Jr David Charles
• Norris Patrick
• Bartholomew John
• Blight Sherry K

Classifications

• C12M23/16 Primary

  Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093) · CPC title

• C12M23/34

  Internal compartments or partitions · CPC title

• C12M23/40

  Manifolds; Distribution pieces (fluid transfer means B01L3/563) · CPC title

• C12M27/18

  Flow directing inserts · CPC title

• C12M29/10

  Perfusion · CPC title