Bioreactor and bioprocessing technique

• US 7,041,493 B2
• Filed: 12/12/2003
• Issued: 05/09/2006
• Est. Priority Date: 08/14/2000
• Status: Expired due to Term

• Current Assignee: Hewlett-Packard Development Company, L.P. (HP Inc.)
• Original Assignee: University of Maryland Baltimore County (University of Maryland)
• Inventors: Rao, Govind
• Primary Examiner(s): REDDING, DAVID A
• Application Number:
  US10/733,412
• Publication Number:
  US 20040121453A1
• Time in Patent Office: 879 Days
• Field of Search: 435/288.1, 435/288.4, 435/288.7, 422/82.05
• US Class Current: 435/288.1
• CPC Class Codes: C12M 23/12 Well or multiwell plates C12M25/04 takes precedence
• CPC Class Codes: C12M 41/26 of pH
• CPC Class Codes: C12M 41/32 of substances in solution
• CPC Class Codes: C12M 41/34 of gas
• CPC Class Codes: G01N 2021/6482 Sample cells, cuvettes
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/643 non-biological material
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/76 Chemiluminescence; Bioluminescence
• CPC Class Codes: G01N 21/82 producing a precipitate or turbidity
• CPC Class Codes: G01N 33/52 Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72

Abstract

The inventive bioprocessing system (and technique) relies on non-invasive optical chemical sensing technology wherein an optical excitation source excites an optical chemical sensor. The optical chemical sensor then emits luminescence or absorbs light which is measured by a detector. The luminescence emitted from the chemical sensor or the amount of light absorbed by the chemical sensor is related to the concentration of an analyte, such as oxygen. If the luminescence emitted changes, or if the amount of light absorbed changes, then the concentration of the analyte has changed. Using such a system to measure and adjust multiple parameters at one time allows one to efficiently and cost-effectively determine optimal conditions for a given cell type and/or cell environment, for example. By combining cell cultivation with optical chemical sensing technology, cultivation can be successfully and rapidly performed, controlled and monitored in small volumes in an automated, parallel fashion at less expense than current bioprocess techniques.

Claims

1. A bioprocessing system, comprising:

(a) at least one bioreactor, wherein each bioreactor comprises a well housed in a multiple-well plate;

(b) at least two optical chemical sensors associated with each bioreactor, wherein the optical chemical sensors are located within each bioreactor;

(c) at least one excitation source corresponding to each optical chemical sensor; and

(d) at least one detector.

2. The bioprocessing system of claim 1, wherein the optical chemical sensors are sensor patches positioned at the bottom of the well.

3. The bioprocessing system of claim 1, wherein each bioreactor is a cuvette.

4. The bioprocessing system of claim 3, wherein the optical chemical sensors are sensor patches affixed to at least one wall of the cuvette.

5. The bioprocessing system of claim 1, wherein each bioreactor is a culture vial housed within a receptacle of a multi-receptacle bioreactor platform.

6. The bioprocessing system of claim 5, wherein the optical chemical sensors are sensor patches positioned at the bottom of the culture vial.

7. The bioprocessing system of claim 6, wherein the excitation source is a light emitting diode.

8. The bioprocessing system of claim 7, wherein the detector is an integrated spectrometer and diode array.

9. The bioprocessing system of claim 1, further comprising a bioreactor platform containing at least one receptacle to house each bioreactor.

10. The bioprocessing system of claim 9, further comprising a sub-platform, wherein the bioreactor platform is positioned on top of the sub-platform.

11. The bioprocessing system of claim 10, further comprising an agitator, wherein the sub-platform is positioned on top of the agitator.

12. The bioprocessing system of claim 11, further comprising a positioning table, wherein the positioning table is positioned below the agitator such that the positioning table is capable of moving the bioreactor in an x-y or x-y-z plane to a predetermined position.

13. The bioprocessing system of claim 1 or 12, further comprising a data acquisition and control system connected to components of the bioprocessing system via cabling means.

14. A bioprocessing system, comprising:

at least one bioreactor, wherein each bioreactor comprises a cuvette;

at least two optical chemical sensors associated with each bioreactor, wherein the optical chemical sensors are located within each bioreactor;

at least one excitation source corresponding to each optical chemical sensor; and

at least one detector.

15. A bioprocessing system, comprising:

at least one bioreactor, wherein each bioreactor comprises a culture vial housed within a receptacle of a multi-receptacle bioreactor platform;

at least two optical chemical sensors associated with each bioreactor, wherein the optical chemical sensors are located within each bioreactor;

at least one excitation source corresponding to each optical chemical sensor; and

at least one detector.

16. A bioprocessing system, comprising:

at least one bioreactor;

at least two optical chemical sensors associated with each bioreactor, wherein the optical chemical sensors are located within each bioreactor;

at least one excitation source corresponding to each optical chemical sensor;

at least one detector; and

at least one dispenser positioned to selectively dispense a predetermined substance into the bioreactor.

17. The bioprocessing system of claim 16, wherein the dispenser comprises a liquid dispenser.

18. The bioprocessing system of claim 16, wherein the dispenser comprises a gas dispenser.

19. The bioprocessing system of claim 16, wherein the predetermined substance comprises an acid, a base or a nutrient.