AUTOMATED MODULAR SYSTEM AND METHOD FOR PRODUCTION OF BIOPOLYMERS

• US 20180311637A1
• Filed: 07/05/2018
• Published: 11/01/2018
• Est. Priority Date: 09/25/2014
• Status: Active Grant

• Current Assignee: Synthego Corp.
• Original Assignee: Synthego Corp.
• Inventors: Dabrowski, Paul, Dabrowski, Michael, Gerlinghaus, Fabian, Pesch, Alex
• Granted Patent: US 10,569,249 B2
• Time in Patent Office: Days
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00691 using robots
• CPC Class Codes: B01J 2219/00693 Means for quality control
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00759 Purification of compounds synthesised
• CPC Class Codes: G05B 19/4182 manipulators and conveyor only
• CPC Class Codes: G05B 19/4189 characterised by the transport system
• CPC Class Codes: G05B 2219/45092 Analysing or chemical synthesis robot, moving samples from station to station
• CPC Class Codes: Y02P 90/02 Total factory control, e.g. smart factories, flexible manufacturing systems [FMS] or integrated manufacturing systems [IMS]
• CPC Class Codes: Y10S 901/02 Arm motion controller

Abstract

The present invention provides an automated modular system and method for production of biopolymers including DNA and RNA. The system and method automates the complete production process for biopolymers. Modular equipment is provided for performing production steps with the individual modules arrange in a linear array. Each module includes a control system and can be rack mounted. One side of the array of modules provides connections for power, gas, vacuum and reagents and is accessible to technicians. On the other side of the array of modules a robotic transport system is provided for transporting materials between module interfaces. The elimination of the requirement for human intervention at multiple steps in the production process significantly decreases the costs of biopolymer production and reduces unnecessary complexity and sources of quality variation.

Claims

1. An automated production system comprising:

a production control system for scheduling and controlling production in an automated production; and

a plurality of equipment modules for synthesizing biopolymers in accordance with pre-determined sequences under control of the production control system.

2. The automated production system of claim 1, wherein the plurality of equipment modules comprise a synthesizer module.

3. The automated production system of claim 1, wherein the plurality of equipment modules are stackable.

4. The automated production system of claim 1, wherein each of the modules can be added or removed from the plurality of equipment modules without interrupting the production process in the remaining modules.

5. The automated production system of claim 1, comprising a plurality of synthesizers operating in parallel with the production control system responsible for distributing and scheduling the synthesis processes.

6. The automated production system of claim 2, wherein the synthesizer module comprises a plurality of independent channels such that a different synthesis can be performed in each independent channel.

7. The automated production system of claim 1, further comprising a quality control software that monitors input and output products.

8. The automated production system of claim 7, wherein the quality control software provides for closed loop control of the automated production system.

9. The automated production system of claim 7, wherein the quality control software provides for closed loop control of the individual modules in the plurality of equipment modules of the system.

10. The automated production system of claim 7, wherein the quality control software provides for closed loop control of individual channels of a synthesizer module of the system.

11. The automated production system of claim 7, wherein the quality control software is a closed loop software that tunes or calibrates the system, the modules, or channels of a synthesizer in response to a collected quality control data to enhance performance.

12. The automated production system of claim 11, wherein the quality control software performs continuous quality control.

13. The automated production system of claim 1, further comprising a customer interface interfacing with the production control system.

14. The automated production system of claim 1, wherein the production control system monitors and tracks materials moving through the automated production system.

15. The automated production system of claim 14, wherein the system does not label intermediate products.

16. The automated production system of claim 1, wherein each module of the plurality of equipment modules has a dedicated control system and a communications interface, wherein the dedicated control system and communications interfaces interact with the production control system.

17. The automated production system of claim 1, further comprising a continuously monitored supply of synthesis reagents and gases that are fed to the synthesizer module.

18. The automated production system of claim 1, wherein the production control system can adjust operation of synthesis to not use a non-functional channel.

19. The automated production system of claim 1, wherein each of the channels is separately controllable.

20. A system comprising a plurality of synthesizers operating in parallel coupled to one another and permitting passage of materials between one another, each synthesizer comprising a plurality of channels, wherein

one or more of the plurality of synthesizers or the plurality of channels, is capable of being inactivated without interrupting the production process.

21. The system of claim 20, wherein the plurality of synthesizers are stacked.

22. The system of claim 20, further comprising a quality control system collecting data relevant to the system, synthesizers or channels.

23. A method for synthesizing a plurality of different biopolymers comprising:

providing a synthesizer comprising;

a plurality of different channels comprising a solid support for performing extension reactions thereon;

independently controlling which reagents are added to each reaction channel, and

continuously analyzing data from the synthesizer for quality control purposes.

24. The method of claim 23, wherein the data is used to determine if tuning or calibration is required.

25. A system for automatically synthesizing a plurality of biopolymers, comprising:

a controller for directing synthesis of said plurality of biopolymers;

a plurality of equipment modules arranged and secured in an array, wherein said plurality of equipment modules comprises a biopolymer synthesis module comprising a first side having a mechanical interface that is configured to receive a plurality of reaction vessels for synthesizing said plurality of biopolymers, and a second side having a fluidics interface for connecting to a plurality of reagents necessary for production of said plurality of biopolymers, wherein said equipment module is configured to;

(i) receive said microplate through said mechanical interface, and

(ii) under automated control of said controller, use said plurality of reagents received through said fluidics interface to synthesize said plurality of biopolymers.

26. The system of claim 25, further comprising a communications interface configured to bring said controller in communication with a customer interface, wherein said controller is configured to direct synthesis of said plurality of biopolymers subsequent to receiving a request based upon information inputted into said customer interface.

27. The system of claim 26, wherein said biopolymer synthesis module is configured to use amidite reagents to synthesize said plurality of biopolymers in accordance with sequences included in said information inputted into said customer interface.

28. The system of claim 25, wherein said plurality of equipment modules further comprises a purification unit, a quantization unit, a transport unit, a quality control unit, or a cleavage unit.

29. The system of claim 25, wherein each reaction vessel in said plurality of reaction vessels comprises a channel or are part of a microplate.

30. (canceled)