Automated modular system and method for production of biopolymers

• US 10,040,048 B1
• Filed: 09/25/2015
• Issued: 08/07/2018
• 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
• Primary Examiner(s): Wilson, Allan R
• Application Number:
  US14/866,091
• Time in Patent Office: 1,047 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 which controls production in an automated oligonucleotide production process;

a plurality of equipment modules for processing materials under control of the production control system, wherein each equipment module comprises on a front side a mechanical interface for receiving materials and transmitting processed materials, and, on a rear side, an interface for connecting power, network, and any required reagents;

wherein the plurality of equipment modules includes;

an oligonucleotide synthesis system and one or more of,

an oligonucleotide purification system,

an oligonucleotide quantization system,

an oligonucleotide quality control system, and

a packaging/labeling system;

a linear array in which the plurality of equipment modules is secured such that the mechanical interfaces are accessible from a front side of the linear array and all the interfaces are accessible from a rear side of the linear array; and

a robotic transport system positioned adjacent to the front side of the linear array, wherein the robotic transport system includes a plurality of robot arms adapted to move processed materials between the mechanical interfaces of the plurality of equipment modules under the control of the production control system;

whereby oligonucleotides can be automatically synthesized and processed by the plurality of equipment modules under control of the production control system.

2. The automated production system of claim 1, wherein;

the robotic transport system and the front side of the linear array is secured as a human-free zone; and

technician access to the linear array is limited, during operation of the automated production system, to the rear side of the linear array.

3. The automated production system of claim 1, wherein the plurality of equipment modules are hot-swappable under control of the production control system such that individual equipment modules may be deactivated and removed from the linear array for servicing without interruption to the automated production process.

4. The automated production system of claim 1, wherein the robotic transport system comprises a gantry system for moving the robot arms in a direction parallel to the linear array of equipment modules such that the robot arms can access the mechanical interfaces of the plurality of equipment modules.

5. The automated production system of claim 1, wherein the oligonucleotide production process is one of a DNA synthesis and an RNA synthesis process.

6. The automated production system of claim 1, further comprising:

a customer interface for receiving production orders from customers and providing production orders to the production control system whereby the production control system can control production of oligonucleotides in the automated oligonucleotide production process in response to said production orders received from customers via the customer interface.

7. An automated production system comprising:

a production control system which controls an automated oligonucleotide production process;

a plurality of equipment modules which process materials under control of the production control system, wherein each equipment module comprises a mechanical interface for receiving materials and transmitting processed materials, a system interface for connecting power, network, and any required fluids, and reagents;

wherein the plurality of equipment modules includes;

an oligonucleotide synthesis system and one or more of,

an oligonucleotide purification system,

an oligonucleotide quantization system,

an oligonucleotide quality control system, and

a packaging/labeling system;

an array in which the plurality of equipment modules is arranged and secured such that the mechanical interfaces are accessible from a front side of the array; and

a robotic transport system positioned adjacent to the front side of the array, wherein the robotic transport system includes one or more robot arms adapted to move materials and processed materials between the mechanical interfaces of the plurality of equipment modules under the control of the production control system;

whereby oligonucleotides can be automatically synthesized and processed by the plurality of equipment modules under control of the production control system.

8. The automated production system of claim 7, wherein the robotic transport system and the front side of the array is secured as a human-free zone.

9. The automated production system of claim 7, wherein the plurality of equipment modules are hot-swappable under control of the production control system such that individual equipment modules may be deactivated and removed from the array for servicing without interruption to the automated production process.

10. The automated production system of claim 7, wherein the oligonucleotide production process is one of a DNA synthesis process and an RNA synthesis process.

11. The automated production system of claim 7, further comprising:

a customer interface connected to the production control system wherein the customer interface receives oligonucleotide production orders including sequence information from customers and provides oligonucleotide production information to the production control system whereby oligonucleotides having sequences specified by the oligonucleotide sequence information in the oligonucleotide production orders can be automatically synthesized and processed by the plurality of equipment modules under control of the production control system.

12. The automated production system of claim 7, wherein the plurality of equipment modules includes an oligonucleotide synthesis system, an oligonucleotide purification system, an oligonucleotide quality control system, an oligonucleotide re-plating system, and a centrifuge system for oligonucleotide dry down, whereby oligonucleotides can be automatically synthesized and processed by the plurality of equipment modules under control of the production control system.

13. The automated production system of claim 12, wherein the automated production system is configured for production of DNA oligonucleotides.

14. The automated production system of claim 12, wherein the automated production system is configured for production of RNA oligonucleotides.

15. An automated production system comprising:

a production control system which controls production in an automated oligonucleotide production process;

a plurality of equipment modules which process materials under control of the production control system wherein the plurality of equipment modules includes;

an oligonucleotide synthesis system and one or more of,

an oligonucleotide cleavage system

an oligonucleotide purification system,

an oligonucleotide quantization system,

an oligonucleotide quality control system,

an oligonucleotide re-plating system,

a centrifuge system for oligonucleotide dry down, and

a packaging/labeling system;

wherein each equipment module comprises a mechanical interface for receiving materials and transmitting processed materials, and, a system interface which provides power, communication with the production control system, and any required reagents;

a robotic transport system including one or more robotic arms adapted to move processed materials between the mechanical interfaces of the plurality of equipment modules under the control of the production control system; and

an array in which the plurality of equipment modules is arranged adjacent to the robotic transport system such that the mechanical interfaces are accessible by the one or more robotic arms;

whereby oligonucleotides can be automatically synthesized and processed by the plurality of equipment modules under control of the production control system.

16. The automated production system of claim 15, wherein the robotic transport system is secured as a human-free zone.

17. The automated production system of claim 15, wherein the plurality of equipment modules are hot-swappable under control of the production control system such that individual equipment modules may be deactivated and removed from the array for servicing without interruption to the automated production process.

18. The automated production system of claim 15, further comprising:

a customer interface connected to the production control system wherein the customer interface receives oligonucleotide production orders including oligonucleotide sequence information from customers and provides oligonucleotide production information to the production control system whereby oligonucleotide having sequences specified by the oligonucleotide sequence information in the oligonucleotide production orders can be automatically synthesized and processed by the plurality of equipment modules under control of the production control system.

19. The automated production system of claim 16, wherein the oligonucleotide production process is a DNA oligonucleotide synthesis process and the plurality of equipment modules includes a DNA oligonucleotide synthesis system, a DNA oligonucleotide purification system, and one or more of a DNA oligonucleotide cleavage system, a DNA oligonucleotide quality control system, a DNA oligonucleotide re-plating system, a centrifuge system for DNA oligonucleotide dry down, and a packaging and labeling system.

20. The automated production system of claim 16, wherein the oligonucleotide production process is an RNA oligonucleotide synthesis process and the plurality of equipment modules includes an RNA oligonucleotide synthesis system, an RNA oligonucleotide purification system, and one or more of an RNA oligonucleotide cleavage system, an RNA oligonucleotide quality control system, an RNA oligonucleotide re-plating system, a centrifuge system for RNA oligonucleotide dry down, and a packaging and labeling system.