Granted Patent B2

US 12,607,593 · App. 16/070,133 · Granted Apr 21, 2026

Inventors: Barry L. Merriman (San Diego, CA); Paul W. Mola (San Diego, CA); Chulmin Choi (San Diego, CA)

Assignee: SemiconBio Inc.

G01N27/4145B82Y15/00C12Q1/6825G01N33/48721C12Q1/6869

Abstract

Claims (32)

1 . A sensor comprising:

a source electrode comprising a metal contact;

a drain electrode comprising a metal contact and spaced apart from the source electrode by a sensor gap, wherein the source and drain electrodes cooperate to form an electrode circuit;

a bridge molecule comprising a protein alpha helix or a nucleic acid duplex bridging across said sensor gap, coupling the source and drain electrodes, wherein the bridge molecule comprises two thiol containing groups coupled to the metal contacts of the source and drain electrodes by a thiol-metal bond; and

a probe coupled to the bridge molecule by a linker comprising a molecular complex configured to connect the probe to the bridge molecule, the probe configured to receive and interact with a nucleic acid;

wherein interaction of the probe with the nucleic acid is detectable by monitoring at least one parameter of the electrode circuit, and

wherein a molecular complex formed by the probe and the linker is interposed between the bridge molecule and the nucleic acid.

2 . The sensor of claim 1 , wherein the nucleic acid that interacts with the probe comprises DNA or RNA, or variants thereof.

3 . The sensor of claim 1 , wherein the probe comprises an enzyme.

4 . The sensor of claim 3 , wherein the enzyme comprises a DNA polymerase, a reverse transcriptase, an exonuclease, or a helicase.

5 . The sensor of claim 4 , wherein the enzyme comprises a DNA polymerase.

6 . The sensor of claim 5 , wherein the DNA polymerase is Phi29, PolI, or a mutant thereof.

7 . The sensor of claim 1 , wherein the bridge molecule comprises a double-stranded DNA having a thiol-modified nucleotide configured for self-assembling to one of the source or the drain electrodes.

8 . The sensor of claim 7 , wherein the bridge molecule comprises one of a DNA duplex, a DNA-RNA hybrid duplex, a DNA-PNA hybrid duplex, a PNA-PNA duplex, and a DNA-LNA hybrid duplex.

9 . The sensor of claim 1 , wherein the bridge molecule comprises a peptide or protein alpha-helix.

10 . The sensor of claim 1 , wherein the metal contacts on the source and drain electrodes comprise gold.

11 . The sensor of claim 1 , wherein the probe is configured to attach to the bridge molecule via a self-assembling linker.

12 . The sensor of claim 1 , wherein the at least one detected parameter of the electrode circuit correlates to a specific and identifiable nucleotide incorporation.

13 . A sensor comprising:

a first electrode overlying a substrate surface, the first electrode comprising a metal contact;

a second electrode overlying the substrate surface, the second electrode comprising a metal contact;

a sensor gap defined between the first electrode and the second electrode;

a biopolymer bridge molecule comprising an sDNA or dsDNA and having a first end and a second end; and

a probe molecule coupled to the biopolymer bridge molecule through a linker;

wherein one or both of the first end and second end of the biopolymer bridge molecule comprises a thiolated nucleotide at a respective end in which a thiol group is coupled to the metal contact of the first and second electrodes by a thiol-metal bond; and

wherein the probe molecule interacts with a nucleic acid to generate a signal, and wherein a molecular complex formed by the probe and the linker is interposed between the bridge molecule and the nucleic acid.

14 . The sensor of claim 13 , wherein the biopolymer bridge molecule comprises a nucleic acid complex.

15 . The sensor of claim 14 , wherein the nucleic acid duplex comprises one of a DNA duplex, a DNA-RNA hybrid duplex, a DNA-PNA hybrid duplex, a PNA-PNA duplex, and a DNA-LNA hybrid duplex.

16 . The sensor of claim 13 , wherein the biopolymer bridge comprises a peptide alpha-helix.

17 . The sensor of claim 13 , wherein the biopolymer bridge comprises a synthetic molecule.

18 . The sensor of claim 13 , wherein the biopolymer bridge comprises an antibody.

19 . The sensor of claim 13 , wherein the metal contacts on the source and drain electrodes comprise gold.

Assignments (5)

Continuity (4)

References Cited (400)