Apparatuses and methods for detecting molecules and binding energy

• US 10,444,179 B2
• Filed: 07/27/2017
• Issued: 10/15/2019
• Est. Priority Date: 08/10/2016
• Status: Active Grant

• Current Assignee: Analog Devices, Inc.
• Original Assignee: Multerra Bio, Inc.
• Inventors: Paik, Kee-Hyun, Milaninia, Kaveh M., Dill, Kilian
• Primary Examiner(s): Brown, Melanie
• Application Number:
  US15/662,168
• Publication Number:
  US 20180045668A1
• Time in Patent Office: 810 Days
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 21/553 and using surface plasmons fluorescence excitation G01N21/648; enhanced Raman G01N21/658
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: G01N 33/487 of liquid biological material
• 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
• CPC Class Codes: G01N 33/54353 with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

The present disclosure provides apparatuses and methods for analyzing the presence of a target analyte. The apparatuses and methods of the present disclosure can be operated in a multiplexed format to perform various assays of clinical significance.

Claims

1. A system for detecting a target analyte, comprising:

a sensor comprising a plurality of electrodes capable of applying an electric field to at least one surface that comprises a capture probe coupled thereto and in proximity to a sensing location, which at least one surface comprises a field confining feature that concentrates the electric field;

a solution chamber in fluid communication with said at least one surface, wherein said solution chamber is configured to retain a solution containing or suspected of containing said target analyte and a non-target analyte, under conditions sufficient to (i) permit said target analyte to couple to said at least one surface through a first non-covalent interaction, which first non-covalent interaction is with said capture probe, and (ii) permit said non-target analyte to couple to said at least one surface through a second non-covalent interaction; and

a controller operatively coupled to said plurality of electrodes, wherein said controller is programmed to;

(i) use electrodes of said plurality of electrodes to apply a first electric field that is sufficient to disrupt said second non-covalent interaction between said non-target analyte and said at least one surface,

(ii) subsequent to applying said first electric field, use electrodes of said plurality of electrodes to apply a second electric field that is sufficient to disrupt said first non-covalent interaction between said target analyte and said capture probe, and

(iii) detect a signal indicative of (1) a presence or absence of said target analyte, or (2) a disruption of said first non-covalent interaction.

2. The system of claim 1, wherein said sensor is part of an array of sensors.

3. The system of claim 2, wherein each sensor of said array of sensors is independently addressable.

4. The system of claim 1, wherein said sensor comprises a bias stabilization unit.

5. The system of claim 1, further comprising a sensing unit operatively coupled to said controller, wherein said controller detects said signal using said sensing unit.

6. The system of claim 5, wherein said sensing unit is an optical sensing unit, and wherein said signal indicative of said presence of said target analyte is an optical signal.

7. The system of claim 1, wherein said field confining feature comprises an orifice.

8. The system of claim 7, wherein said orifice extends through said at least one surface.

9. The system of claim 7, wherein said orifice is a pore.

10. The system of claim 7, wherein said orifice has a diameter of less than about 50 micrometers.

11. The system of claim 7, wherein said orifice has a diameter of less than about 50 nanometers.

12. The system of claim 1, wherein said field confining feature has an aspect ratio of at least about 0.1.

13. The system of claim 1, wherein said capture probe is an antibody, which antibody is coupled to said at least one surface using a linker.

14. The system of claim 13, wherein said linker is an NETS-PEG-maleimide linker.

15. The system of claim 1, wherein said capture probe is coupled to said surface using a linker comprising a dibenzocyclooctyne (DIBO) group and a maleimide moiety.

16. The system of claim 1, wherein said sensing unit comprises a sensing electrode configured to measure an electrical signal associated with a presence or absence of said target analyte.

17. The system of claim 16, wherein said electrical signal is a charge signal.

18. The system of claim 1, wherein said controller is programmed to detect said signal indicative of said presence or absence of said target analyte.

19. The system of claim 1, wherein said controller is programmed to detect said signal indicative of said disruption of said first non-covalent interaction.

20. The system of claim 1, wherein said controller is programmed to detect (1) said signal indicative of said presence or absence of said target analyte, and (2) said signal indicative of said disruption of said first non-covalent interaction.