Granted Patent B2

US 12,614,610 · App. 17/845,682 · Granted Apr 28, 2026

Inventors: Arvind Kumar Balijepalli (Washington, DC); Jacob Michael Majikes (Gaithersburg, MD); Alokik Kanwal (Gaithersburg, MD); Peter Michael Vallone (Potomac, MD); Kevin Michael Kiesler (Rockville, MD); Erica Lee Romsos (Ijamsville, MD); Anthony José Kearsley (Hanover, MD)

Assignee: GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF COMMERCE

G16B25/30B01L3/502715G16B25/00C12Q1/6825

Abstract

Claims (28)

1 . A process for measuring a biomarker with an agile nucleic acid sensor array, the process comprising:

operating the agile nucleic acid sensor array that comprises:

a plurality of agile nucleic acid sensors arranged in array and that individually comprise:

a DNA switch comprising a DNA nanostructure framework disposed on an analysis substrate and comprising a nucleic acid core, a first helix strand protruding from the nucleic acid core and attached to the analysis substrate, a second helix strand protruding from the nucleic acid core, a particle strand hybridized to the second helix strand, and a reporter particle attached to the particle strand;

the analysis substrate in electrostatic communication with the DNA switch that is disposed on the analysis substrate, wherein the second helix strand is hybridized to the first helix strand in an absence of a chemical analyte such that the reporter particle is disposed proximate to the analysis substrate;

a transduction member in electrical communication with the analysis substrate;

a sensor counter electrode in electrical communication with and capacitively coupled to the analysis substrate;

a sensor reference electrode in electrical communication and capacitively coupled to the analysis substrate; and

a voltage follower in electrical communication with the sensor counter electrode and the sensor reference electrode;

for individual agile nucleic acid sensor in the agile nucleic acid sensor array:

producing a counter electrode voltage by the voltage follower;

subjecting the sensor counter electrode to the counter electrode voltage from the voltage follower;

contacting the DNA switch with the chemical analyte comprising the biomarker to dissociate the second helix strand from the first helix strand and displace the reporter particle relative to the analysis substrate;

producing, by the analysis substrate, a biomarker electrical signal in response to the chemical analyte contacting the DNA switch;

receiving, by the transduction member, the biomarker electrical signal from the analysis substrate and producing a transduction signal from the biomarker electrical signal;

determining the impedance of the analysis substrate from the transduction signal;

estimating kinetic rate constants for each contact between the chemical analyte and the DNA switch; and

combining the kinetic rate constants and producing a mean kinetic rate constant with uncertainty quantification for the kinetic rate constants;

aggregating the mean kinetic rate constants for the plurality of agile nucleic acid sensor in the agile nucleic acid sensor array; and

producing a kinetic fingerprint for the chemical analyte from the mean kinetic rate constants.

2 . The process of claim 1 , further comprising:

reading the kinetic fingerprint from the agile nucleic acid sensor array;

providing the kinetic fingerprint as input to a machine learning model for classification;

providing the kinetic fingerprint as input to an AI-enhanced simulator;

updating training data for the AI-enhanced simulator machine learning models;

providing a physical model of the agile nucleic acid sensor and kinetic fingerprint measurement to the AI-enhanced simulator machine learning models;

combining the kinetic fingerprint, physical models, and parameter uncertainties using machine learning model to generate physics enhanced training data with uncertainty quantification; and

combining AI-enhanced simulator training data with the sensor array kinetic fingerprint by analyte classification machine learning to produce analyte classification with uncertainty quantification.

Assignments (1)

Continuity (4)

References Cited (37)