Apparatus and methods for bioprocesses and other processes

Patent metadata

Field	Value
Publication number	US-10711237-B2
Application number	US-201715683235-A
Country	US
Kind code	B2
Filing date	Aug 22, 2017
Priority date	Aug 22, 2017
Publication date	Jul 14, 2020
Grant date	Jul 14, 2020

Abstract

Apparatus and methods for providing a single-use, disposable module or manifold for testing and analysis of bioprocesses. A module comprising a valve, a filter or guard column, an affinity column, and a flow cell is provided with several ports for receiving tubing connections for a sample and one or more solvents, as well as one or more outlet ports for connections to one or more waste reservoirs. The flow cell may use UV light to determine a protein concentration of a sample in one particular example. The module can be connected directly or indirectly to a bioreactor containing the bioprocess and material to be sampled, and can be disposed of once a production run has been completed. In addition, manifolds are provided which can be embodied as a valve assembly, and which can comprise the same components and features as the disposable module. The manifolds and modules are compact and easy to use. A portable device for use with a module is also provided.

First claim

We claim:

1. A single use module for analysis of a bioprocess, comprising:
a housing having a plurality of inlet ports and a plurality of outlet ports, wherein said housing has a flow cell therein or extending at least partially from one side thereof, a valve located at least partially in said housing, a guard column and a column located in said housing, wherein said housing is adapted to receive a biological sample through a sample inlet port in one side thereof, and, when a solvent is pumped under pressure into said housing, move through the valve, the guard column, the column, and then the flow cell, and wherein the flow cell is adapted to determine a characteristic of the sample, wherein the characteristic of the sample comprises:
protein concentration, spectral information, fluorescence, or a combination thereof.

2. The module according to claim 1 wherein the column comprises any one of the following: affinity column, or chromatographic media.

3. The module according to claim 1 wherein said module comprises at least one removable side.

4. The module according to claim 1 wherein said module is tamper-resistant.

5. The module according to claim 1 wherein said housing further comprises at least one sample inlet port, at least two solvent inlet ports, and at least one waste outlet port.

6. The module according to claim 1 further comprising a frit.

7. The module according to claim 1 wherein the sample inlet port, the column, the flow cell, and the valve define a fluid pathway through said module, and wherein the materials which define the fluid pathway all comprise biocompatible materials.

8. The module according to claim 1 wherein the flow cell comprises an ultraviolet source and an ultraviolet detector.

9. The module according to claim 1 wherein said module is adapted to operate with fluid pressures up to at least 500 psi.

10. The module according to claim 1 wherein said module is adapted to operate with fluid pressures up to at least 6,000 psi.

11. The module according to claim 1 wherein said module is adapted to operate with fluid pressures up to at least 9,000 psi.

12. The module according to claim 1 wherein said module is adapted to operate with fluid pressures up to at least 15,000 psi.

13. The module according to claim 1 wherein said module is adapted to operate with fluid pressures up to at least 20,000 psi.

14. A device for a bioprocess comprising:
a device adapted to be removably connected to an outlet from a bioreactor vessel containing a biological process, wherein said device is further adapted to removably hold a module adapted for single use with a bioprocess, the module having an inlet in fluid communication with the outlet from said vessel, wherein said module comprises a housing having at least one inlet port and at least one outlet port, wherein said housing has a flow cell therein or extending at least partially from one side thereof, a valve located at least partially in said housing, a guard column or frit located in said housing, and a column located in said housing, wherein said housing is adapted to receive a biological sample through a sample inlet port in one side thereof, and, when a solvent is pumped under pressure into said housing, move through the valve, the guard column or fit, the column, and then the flow cell, and wherein the flow cell is adapted to be connected to at least one or more instruments for determining a characteristic of the sample, wherein said module is adapted to be removably held in a portion of said device, and wherein the characteristic of the sample comprises: protein concentration, spectral information, fluorescence, or a combination thereof.

15. The device according to claim 14 wherein the portion of said device comprises an extendable drawer of said device.

16. The device according to claim 14 wherein the inlet port, flow cell, column, and sample inlet port are connected by tubing within said module, and comprise one or more biocompatible materials.

17. A method for monitoring a biological process comprising:
(a) connecting an outlet from at least one bioreactor containing a biological process, directly or indirectly, to a sample inlet of a first module, wherein the first module comprises a valve, a flow cell, a guard column or frit, and a column therein, and the first module is adapted for use with a single production batch of the at least one bioreactor;
(b) providing a sample from the at least one production batch to the sample inlet of the first module;
(c) providing a solvent under pressure to the valve and moving the sample through the guard column or frit, through the column, and then through the flow cell;
(d) analyzing the sample with the first module;
(e) repeating steps (b) through (d) as desired;
(f) disconnecting the first module from the at least one bioreactor when the biological process is deemed complete, or when one or more characteristics of the biological process in the at least one bioreactor have been determined.

18. The method according to claim 17 further comprising the step of:
connecting a second module to the bioreactor when the at least one bioreactor is to be used for a second production batch of a biological process, wherein the second module comprises a valve, a flow cell, a guard column or frit, and a column substantially the same as that of the first module.

19. The method according to claim 17 further comprising the step of:
(g) connecting an outlet from a second bioreactor used for a second production batch, directly or indirectly, to an inlet of the first module;
(h) providing a second sample from the second production batch to the first module;
(i) providing a solvent under pressure to the valve and moving the sample through the guard column or frit, through the column, and then through the flow cell;
(j) analyzing the second sample with the first module;
(k) repeating steps (h) through (k) as desired;
(l) disconnecting the first module from the second bioreactor when the biological process is deemed complete, or when one or more characteristics of the biological process in the second bioreactor have been determined.

20. The method according to claim 17 further comprising the step of:
connecting a second module to the bioreactor when the at least one bioreactor is to be used for a second production batch of a biological process, wherein the second module comprises a flow cell and a column, at least one of which is of a different kind than the flow cell or column of the first module.

21. The module according to claim 1 , wherein at least one of the valve, column, and flow cell are adapted to test samples for protein concentration in a range of 0.15 mg/ml to 10.0 mg/ml.

22. The device according to claim 14 , wherein at least one of the valve, column, and flow cell are adapted to test samples for protein concentration in a range of 0.15 mg/ml to 10.0 mg/ml.

23. The method according to claim 17 , wherein the module is adapted to test samples for protein concentration in a range of 0.15 mg/ml to 10.0 mg/ml.

Assignees

• Idex Health And Science Llc
• Idex Health & Science Llc

Inventors

• Simonyi Victor
• Pickle Darrin Kurt
• Smyth James
• Love Craig

Classifications

• G01N2030/8881

  Modular construction, specially adapted therefor · CPC title

• G01N2030/8831

  involving peptides or proteins · CPC title

• G01N2015/0687

  in solutions, e.g. non volatile residue · CPC title

• G01N21/6489

  Photoluminescence of semiconductors · CPC title

• G01N21/33

  using ultraviolet light (G01N21/39 takes precedence) · CPC title