Dna nanotechnology-based biomarker measurement platform

Patent metadata

Field	Value
Publication number	US-2021403988-A1
Application number	US-202117360008-A
Country	US
Kind code	A1
Filing date	Jun 28, 2021
Priority date	Jun 29, 2020
Publication date	Dec 30, 2021
Grant date	—

Abstract

A biomarker signal amplifier amplifies chemical analyte binding and includes: a surface strand disposed on an analysis substrate and including an exchange region; a particle strand hybridized to the surface strand in an absence of a chemical analyte that preferentially hybridizes to the exchange region as compared with the particle strand, and the particle strand is dissociated from the surface strand when the surface strand is in a presence of the chemical analyte; and a reporter particle attached to the particle strand and disposed proximate to the analysis substrate when the particle strand is hybridized to the surface strand in absence of the chemical analyte and that changes the electrical potential of the analysis substrate depending on whether the particle strand is hybridized to the surface strand.

First claim

What is claimed is:

1 . A biomarker signal amplifier for amplifying chemical analyte binding, the biomarker signal amplifier comprising:
an analysis substrate; a surface strand disposed on the analysis substrate and comprising an exchange region; a particle strand hybridized to the surface strand in an absence of a chemical analyte that preferentially hybridizes to the exchange region as compared with the particle strand, and the particle strand is dissociated from the surface strand when the surface strand is in a presence of the chemical analyte; and a reporter particle attached to the particle strand and disposed proximate to the analysis substrate when the particle strand is hybridized to the surface strand in absence of the chemical analyte and that changes the electrical potential of the analysis substrate depending on whether the particle strand is hybridized to the surface strand.

2 . The biomarker signal amplifier of claim 1 , wherein the reporter particle comprises a nanoparticle, a quantum dot, a charged polymer, or a combination thereof.

3 . The biomarker signal amplifier of claim 2 , wherein the nanoparticle of the reporter particle comprises a gold nanoparticle.

4 . The biomarker signal amplifier of claim 1 , wherein the nanoparticle of the reporter particle comprises a surface charge.

5 . The biomarker signal amplifier of claim 1 , wherein the reporter particle comprises a fluorophore disposed on a nanoparticle.

6 . The biomarker signal amplifier of claim 1 , wherein the chemical analyte comprises a nucleic acid, DNA, RNA, or a combination thereof.

7 . The biomarker signal amplifier of claim 1 , wherein the surface strand comprises a single stranded DNA.

8 . The biomarker signal amplifier of claim 7 , wherein the particle strand comprises a base sequence that is complementary to the single stranded DNA of the surface strand.

9 . The biomarker signal amplifier of claim 1 , wherein the analysis substrate comprises a metal, a glass, a ceramic, or a combination thereof.

10 . The DNA switch of claim 1 , further comprising a signal readout in electrical communication with the analysis substrate and that receives an electrical signal from analysis substrate that changes in response to binding of the chemical analyte to the surface strand.

11 . A DNA switch for amplifying chemical analyte binding, the DNA switch comprising:
an analysis substrate; a DNA nanostructure framework disposed on the analysis substrate comprising a nucleic acid core, a first helix strand protruding from the nucleic acid core and attached to the analysis substrate, and a second helix strand protruding from the nucleic acid core such that the second helix strand is hybridized to the first helix strand in an absence of a chemical analyte that preferentially hybridizes to the first helix strand as compared with the second helix strand, and the second helix strand dissociates from the first helix strand when the first helix strand is in a presence of the chemical analyte; a particle strand hybridized to the second helix strand; and a reporter particle attached to the particle strand and disposed proximate to the analysis substrate when the second helix strand is hybridized to the first helix strand in absence of the chemical analyte and that changes the electrical potential of the analysis substrate depending on whether the second helix strand is hybridized to the first helix strand.

12 . The DNA switch of claim 11 , wherein when the chemical analyte is hybridized to the first helix strand: the reporter particle remains attached to the nucleic acid core, and is sterically or thermodynamically precluded from interacting with first helix strand.

13 . The DNA switch of claim 11 , wherein the DNA nanostructure framework comprises a 2D nanostructure.

14 . The DNA switch of claim 11 , wherein the DNA nanostructure framework comprises a 3D nanostructure.

15 . The DNA switch of claim 11 , wherein the DNA nanostructure framework comprises a DNA backbone helix.

16 . The DNA switch of claim 11 , wherein the reporter particle comprises a nanoparticle, a quantum dot, a charged polymer, or a combination thereof.

17 . The DNA switch of claim 16 , wherein the nanoparticle of the reporter particle comprises a gold nanoparticle.

18 . The DNA switch of claim 16 , wherein the nanoparticle of the reporter particle comprises a surface charge.

19 . The DNA switch of claim 11 , wherein the reporter particle comprises a fluorophore disposed on a nanoparticle.

20 . The DNA switch of claim 11 , wherein the chemical analyte comprises a nucleic acid, DNA, RNA, or a combination thereof.

21 . The DNA switch of claim 20 , wherein the chemical analyte further comprises an aptamer and an analyte.

22 . The DNA switch of claim 11 , further comprising a signal readout in electrical communication with the analysis substrate and that receives an electrical signal from analysis substrate that changes in response to binding of the chemical analyte to the first helix strand.

23 . The DNA switch of claim 11 , wherein a plurality of first helix strands and second helix strands protrude from the nucleic acid core with each second helix strand hybridized to a separate first helix strand in absence of the chemical analyte; and each second helix strand is hybridized to a separate particle strand such that each particle strand is independently attached to a separate reporter particle.

24 . The DNA switch of claim 23 , wherein at least one of the first helix strands has a different nucleic acid base sequence so that the DNA nanostructure framework simultaneously detects multiple different chemical analyte.

25 . The DNA switch of claim 24 , wherein the DNA nanostructure framework is configured to barcode chemical signatures from the multiple different chemical analyte.

26 . The DNA switch of claim 23 , wherein the DNA nanostructure framework is configured to measure concentration of the chemical analyte.

27 . A sensor array for performing spatially resolved biomarker measurements, the sensor array comprising a plurality of the DNA switches of claim 11 arranged in an array, wherein the plurality of first helix strands independently hybridize separate chemical analytes and produce individual electrical signals indicative of presence and absence of the chemical analyte at individual first helix strands.

Assignees

• Government Of The Us Secretary Of Commerce

Inventors

• Balijepalli Arvind Kumar
• Majikes Jacob Michael

Classifications

• C12Q1/6816 Primary

  characterised by the detection means (C12Q1/6804 takes precedence) · CPC title

• G01N33/5308

  for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites · CPC title

• C12Q1/6823 Primary

  Release of bound markers · CPC title