Biochemical analysis instrument

• US 9,127,313 B2
• Filed: 12/01/2010
• Issued: 09/08/2015
• Est. Priority Date: 12/01/2009
• Status: Active Grant

• Current Assignee: Oxford Nanopore Technologies Limited
• Original Assignee: Oxford Nanopore Technologies Limited
• Inventors: Brown, Clive Gavin, Willcocks, James Peter
• Primary Examiner(s): Sines, Brian J
• Application Number:
  US13/512,937
• Publication Number:
  US 20120322679A1
• Time in Patent Office: 1,742 Days
• Field of Search: 422/50, 422/68.1, 422/81, 422/502, 422/503, 422/504, 422/509, 422/62, 422/63, 422/67, 436/43, 436/180, 436/63, 436/86, 436/89
• US Class Current: 1/1
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 27/44756 Apparatus specially adapted therefor
• CPC Class Codes: G01N 33/48721 Investigating individual macromolecules, e.g. by translocation through nanopores Coulter counters in general G01N15/12; fabrication methods for nanoscale apertures B81B1/00; sequencing of nucleic acids C12Q1/68

Abstract

An analysis instrument comprises plural modules connected together over a data network, each module comprising an analysis apparatus operable to perform biochemical analysis of a sample. Each module comprises a control unit that controls the operation of the analysis apparatus. The control units are addressable to select an arbitrary number of modules to operate as a cluster for performing a common biochemical analysis. The control units communicate over the data network, repeatedly during the performance of the common biochemical analysis, to determine the operation of the analysis apparatus of each module required to meet the global performance targets, on the basis of measures of performance derived from the output data produced by the modules. The arrangement of the instrument as modules interacting in this manner provides a scalable analysis instrument.

Claims

1. An analysis instrument for performing biochemical analysis, the instrument comprising plural modules,

each module comprising an analysis apparatus that is operable to perform biochemical analysis of a sample, the module being arranged to produce output data of at least one channel representing the results of the biochemical analysis, the operation of the module being controllable in a manner that varies its performance,

the analysis instrument further comprising a control system that is arranged to accept input selecting an arbitrary number of modules as a cluster for performing a common biochemical analysis and to accept input representing global performance targets in respect of the common biochemical analysis, the control system being arranged to control the operation of the modules of the cluster to perform the common biochemical analysis,

wherein the control system is arranged to determine, at least once during the performance of the common biochemical analysis, measures of performance of each module from the output data produced by the modules, and the control system is arranged (a) to vary the control of the operation of the modules of the cluster on the basis of the determined measures of performance of all the modules and the global performance targets, and/or arranged (b) to take remedial action in response to the global performance targets not being achievable on the basis of the determined measures of performance of all the modules.

2. An analysis instrument according to claim 1, wherein the modules are capable of connection to a data network to allow connection together over the network.

3. An analysis instrument according to claim 2, wherein the control system comprises a control unit in each module that is operable to control the operation of that module.

4. An analysis instrument according to claim 3, wherein the control units are arranged to present over the data network for a computer connected thereto a user-interface allowing a user to address the control units to provide said input selecting an arbitrary number of modules as a cluster and to provide said input representing global performance targets.

5. An analysis instrument according to claim 3, wherein the control system is arranged to determine local performance targets for each module on the basis of the global performance targets and the control unit in each module is arranged to control the operation of that module on the basis of its local performance target.

6. An analysis instrument according to claim 5, wherein each control unit is arranged to vary the control of the operation of the module on the basis of the measures of performance determined for that module to meet its local performance target.

7. An analysis instrument according to claim 6, wherein the respective control units of the modules of the cluster are arranged to determine said measures of performance in respect of their respective module from the output data produced by their respective module.

8. An analysis instrument according to claim 5, wherein the control system is arranged to vary the local performance targets on the basis of the determined measures of performance and the global performance targets, in order to vary the control of the operation of the modules of the cluster.

9. An analysis instrument according to claim 8, wherein the respective control units of the modules of the cluster are arranged to determine said measures of performance in respect of their respective module from the output data produced by their respective module, and to communicate said measures of performance over the data network.

10. An analysis instrument according to claim 9, wherein the control unit of at least one of the modules of the cluster is arranged to vary the local performance targets on the basis of the determined measures of performance communicated over the data network.

11. An analysis instrument according to claim 10, wherein the control units of all of the modules of the cluster are arranged to co-operate to vary the local performance targets on the basis of the determined measures of performance communicated over the data network.

12. An analysis instrument according to claim 11, wherein the control units of the modules of the cluster are arranged to co-operate on a peer-to-peer basis.

13. An analysis instrument according to claim 11, wherein the control unit of each module of the cluster is arranged to vary the local performance target of the respective module, on the basis of the measures of performance of all the modules communicated over the data network from the other control units of the modules of the cluster.

14. An analysis instrument according to claim 10, wherein the control unit of one or a subset of the modules is arranged to vary the local performance targets of all of the modules of the cluster, on the basis of said measures of performance of all the modules communicated over the data network from the control units of the other modules, said one or said subset of the control units being arranged to communicate the varied local performance targets to the control units of the other modules of the cluster.

15. An analysis instrument according to claim 10, wherein the control system further comprises a federation control unit connected to the network,

the federation control unit being arranged to vary the local performance targets of all of the modules of the cluster, on the basis of said measures of performance of all the modules communicated over the data network from the control units of the modules, the federation control unit being arranged to communicate the varied local performance targets to the respective control units, the respective control units being arranged to vary the control of the operation of the modules of the cluster in response thereto.

16. An analysis instrument according to claim 1, wherein the measures of the performance and global performance targets represent at least one of:

the time within which output data is produced;

the quantity of output data that is produced;

or

the quality of output data that is produced.

17. An analysis instrument according to claim 1, wherein the control system is arranged to determine measures of performance of each module from the output data produced by the modules repeatedly during the common biochemical analysis.

18. An analysis instrument according to claim 1, wherein the control system is both arranged (a) to vary the control of the operation of the modules of the cluster on the basis of the determined measures of performance of all the modules and the global performance targets, and arranged (b) to take remedial action in response to the global performance targets not being achievable on the basis of the determined measures of performance of all the modules.

19. An analysis instrument according to claim 18, wherein said remedial action is to increase the number of modules performing said common biochemical analysis.

20. An analysis instrument according to claim 19, wherein said remedial action includes producing output for indicating to a user that further modules are required to perform said common biochemical analysis.

21. An analysis instrument according to claim 1, wherein the biochemical analysis is analysis of a molecule in the sample.

22. An analysis instrument according to claim 21, wherein the molecule is a polymer.

23. An analysis instrument according to claim 22, wherein the polymer is a polynucleotide.

24. An analysis instrument according to claim 21, wherein the biochemical analysis is sequencing of the polynucleotide, the output data including output sequence data representing a sequence of the polynucleotide.

25. An analysis instrument according to claim 1, wherein the analysis apparatus is capable of supporting plural nanopores and is operable to perform biochemical analysis of a sample using the nanopores.

26. An analysis instrument according to claim 25, wherein the analysis apparatus comprises electrodes arranged to generate an electrical signal across each nanopore, the module comprising a signal processing circuit arranged to generate said output data from the electrical signals generated from said electrodes.

27. An analysis instrument according to claim 26, wherein the control system is arranged to vary the operation of the modules of the cluster by varying at least one of:

the temperature of the analysis apparatus;

electrical parameters of the biochemical analysis;

fluidics parameters of the analysis apparatus;

or

sampling characteristics of the output data.

28. An analysis instrument according to claim 25, wherein the signal processing circuit is arranged to detect events occurring at the nanopores from the electrical signals across each nanopore, and to generate output data representing those events.