System for detecting electrical properties of a molecular complex

• US 10,156,541 B2
• Filed: 11/21/2017
• Issued: 12/18/2018
• 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 J. A.
• Primary Examiner(s): CROW, ROBERT THOMAS
• Application Number:
  US15/819,994
• Publication Number:
  US 20180100827A1
• Time in Patent Office: 392 Days
• Field of Search: None
• 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;

selectively integrate the electrical signal within a predetermined bandwidth, wherein the predetermined bandwidth is selected at least in part based on the expected bandwidth;

compare the selectively integrated electrical signal to a threshold;

output an indication that the selectively integrated electrical signal has reached the threshold;

initiate the integrating based on an initiation flag; and

terminate the integrating based on the indication.

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 electrical property comprises one of the following:

a current, voltage, charge, or capacitance.

4. The system of claim 1, wherein the integrating amplifier circuit is further configured to adjust the predetermined bandwidth based at least in part on adjusting the threshold.

5. The system of claim 1, wherein the indication corresponds to a mean value of the electrical property.

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

7. The system of claim 1, wherein a time period between the initiating and the terminating of the integrating corresponds to a mean value of the electrical property.

8. The system of claim 1, wherein the integrating is repeated by deriving the initiation flag based at least in part on the indication.

9. The system of claim 8, wherein the initiation flag is re-asserted in response to the indication.

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

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

12. The system of claim 1, wherein the integrating amplifier circuit is further configured to filter noise associated with the electrical signal.