SYSTEM FOR DETECTING ELECTRICAL PROPERTIES OF A MOLECULAR COMPLEX

• US 20120187963A1
• Filed: 10/12/2011
• Published: 07/26/2012
• Est. Priority Date: 01/24/2011
• Status: Active Grant

• Current Assignee: Roche Sequencing Solutions, Inc. (Roche Holding AG)
• Original Assignee: Genia Technologies, Inc. (Roche Holding AG)
• Inventors: Chen, Roger
• Granted Patent: US 8,962,242 B2
• Time in Patent Office: Days
• US Class Current: 324/663
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G01N 27/3278 involving nanosized elements, e.g. nanogaps or nanoparticles nanopores G01N33/48721; magnetic beads G01N27/745
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• 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

A system for detecting electrical properties of a molecular complex is disclosed. The system includes an electrode electrically coupled to a molecular complex that outputs an electrical signal affected by an electrical property of the molecular complex, wherein the effect of the electrical property of the molecular complex on the electrical signal is characterized by an expected bandwidth. The system further includes an integrating amplifier circuit configured to receive the electrical signal from the electrode. The integrating amplifier circuit is further configured to selectively amplify and integrate a portion of the electrical signal over time within a predetermined bandwidth, wherein the predetermined bandwidth is selected at least in part based on the expected bandwidth.

Claims

1. A system for detecting electrical properties of a molecular complex, comprising:

an electrode electrically coupled to a molecular complex that outputs an electrical signal affected by an electrical property of the molecular complex, wherein the effect of the electrical property of the molecular complex on the electrical signal is characterized by an expected bandwidth; and

an integrating amplifier circuit configured to;

receive the electrical signal from the electrode; and

selectively amplify and integrate a portion of the electrical signal over time within

a predetermined bandwidth, wherein the predetermined bandwidth is selected at least in

part based on the expected bandwidth.

2. The system of claim 1, wherein the expected bandwidth comprises a bandwidth of events of interest of the molecular complex.

3. The system of claim 1, wherein the events of interest include additions or subtractions to the molecular complex.

4. The system of claim 1, wherein the events of interest include conformation changes of the molecular complex.

5. The system of claim 1, wherein the molecular complex is composed of monomers that make up an oligomeric nanopore and a single strand of DNA and anything bound to that single strand of DNA.

6. The system of claim 1, wherein the electrical property comprises one of the following:

a current, voltage, charge, or capacitance.

7. The system of claim 1, wherein the integrating amplifier circuit is further configured to:

compare the selectively amplified and integrated electrical signal to a threshold; and

output an indication that the selectively amplified and integrated electrical signal has reached the threshold.

8. The system of claim 7, wherein the predetermined bandwidth is adjusted based at least in part on adjusting the threshold.

9. The system of claim 7, wherein the indication corresponds to a mean value of the electrical property.

10. The system of claim 7, wherein the indication comprises a 1-bit flag.

11. The system of claim 7, wherein the integrating amplifier circuit is configured to:

initiate the integration based on an initiation flag; and

terminate the integration based on the indication.

12. The system of claim 11, wherein a time period between the initiating and the terminating of the integration corresponds to a mean value of the electrical property.

13. The system of claim 11, wherein the integration over time is repeated by deriving the initiation flag based at least in part on the indication.

14. The system of claim 13, wherein the initiation flag is re-asserted in response to the indication.

15. The system of claim 1, wherein the predetermined bandwidth is adjusted based at least in part on adjusting a capacitance value associated with the integrating amplifier circuit.

16. The system of claim 1, wherein the predetermined bandwidth is adjusted based at least in part on adjusting a bias voltage applied across a nanopore associated with the molecular complex.

17. The system of claim 1, wherein the integrating amplifier circuit further comprises a noise filter filtering the electrical signal.

18. A method for detecting electrical properties of a molecular complex, comprising:

electrically coupling an electrode to a molecular complex that outputs an electrical signal affected by an electrical property of a molecular complex, wherein the effect of the electrical property of the molecular complex on the electrical signal is characterized by an expected bandwidth;

receiving the electrical signal from the electrode; and

selectively amplifying and integrating a portion of the electrical signal over time within a predetermined bandwidth, wherein the predetermined bandwidth is selected at least in part based on the expected bandwidth.

19. The method of claim 18, wherein the expected bandwidth comprises a bandwidth of events of interest of the molecular complex.

20. The method of claim 18, wherein the electrical property comprises one of the following:

a current, voltage, charge, or capacitance.

21. The method of claim 18, further comprising:

comparing the selectively amplified and integrated electrical signal to a threshold; and

outputting an indication that the selectively amplified and integrated electrical signal has reached the threshold.

22. The method of claim 21, further comprising adjusting the predetermined bandwidth based at least in part on adjusting the threshold.

23. The method of claim 21, wherein the indication corresponds to a mean value of the electrical property.

24. The method of claim 21, wherein the indication comprises a 1-bit flag.

25. The method of claim 21, further comprising:

initiating the integration based on an initiation flag; and

terminating the integration based on the indication.

26. The method of claim 25, wherein a time period between the initiating and the terminating of the integration corresponds to a mean value of the electrical property.

27. The method of claim 25, wherein the integration over time is repeated by deriving the initiation flag based at least in part on the indication.

28. The method of claim 27, wherein the initiation flag is re-asserted in response to the indication.

29. The method of claim 18, wherein the predetermined bandwidth is adjusted based at least in part on adjusting a capacitance value associated with the integrating amplifier circuit.

30. The method of claim 18, wherein the predetermined bandwidth is adjusted based at least in part on adjusting a bias applied across a nanopore associated with the molecular complex.

31. The method of claim 18, further comprising noise filtering the electrical signal.