DNA nanotechnology-based biomarker measurement platform
Inventors
Balijepalli, Arvind Kumar • Majikes, Jacob Michael
Assignees
United States Department of Commerce
Publication Number
US-12195787-B2
Publication Date
2025-01-14
Expiration Date
2041-06-28
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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.
Core Innovation
The invention discloses a DNA nanotechnology-based biomarker measurement platform that uses engineered DNA nanostructures to amplify chemical analyte binding signals. The platform includes a biomarker signal amplifier comprising an analysis substrate, a surface strand with an exchange region disposed on the substrate, a particle strand hybridized to the surface strand in the absence of a chemical analyte and dissociated upon analyte presence, and a reporter particle attached to the particle strand that changes the electrical potential of the substrate depending on hybridization status. This configuration enables sensitive and specific detection of biomolecules using signal amplification via strand displacement.
The problem addressed relates to challenges in achieving specificity, sensitivity, and stability in current aptamer-based sensors and broader DNA-based sensor technologies for diverse chemical analytes. Existing methods often suffer from measurement specificity issues that limit clinical diagnostics and healthcare applications. The platform solves these issues by leveraging precise addressability and tunable DNA nanostructures that provide in situ calibration, robust statistical sampling, and multiplexed measurements with high accuracy beyond conventional approaches.
Further, the invention provides a DNA switch comprising a DNA nanostructure framework with first and second helix strands and particle strands hybridized thereto. The DNA switch changes configuration based on the presence of a chemical analyte, releasing the reporter particle and altering the electrical potential. The design restricts non-specific interactions by steric and thermodynamic preclusion of reporter particle binding when analytes are present, and tunable sensitivity is enabled by adjusting strand affinities. The platform supports multiple readout methods including electrical and optical detection, and can be arranged into sensor arrays for spatially resolved, multiplexed biomarker measurements.
Claims Coverage
The patent includes three independent claims covering a biomarker signal amplifier, a DNA switch, and a sensor array. The main inventive features pertain to components and operation of these devices for amplified chemical analyte detection with specificity and multiplexing capability.
Biomarker signal amplifier with strand displacement and reporter particle
Comprises an analysis substrate with a surface strand having an exchange region, a particle strand hybridized thereto absent analyte and displaced upon analyte presence, and a reporter particle attached to the particle strand that changes electrical potential of the substrate based on strand hybridization state.
DNA switch with a DNA nanostructure framework enabling analyte-induced strand displacement
Includes an analysis substrate with a DNA nanostructure framework comprising a nucleic acid core, first and second helix strands hybridized absent analyte with dissociation upon analyte binding, a particle strand hybridized to the second helix strand, and a reporter particle attached to the particle strand that modulates the electrical potential contingent on hybridization.
Sensor array of DNA switches for spatially resolved biomarker detection
A plurality of DNA switches arranged in an array where first helix strands independently hybridize distinct chemical analytes and produce electrical signals indicating analyte presence or absence at individual sites.
The inventive features collectively cover a platform that uses DNA strand displacement mediated reporter particle positioning to amplify biomarker signals with electrical readout, provide high specificity via DNA nanostructure frameworks, and enable multiplexed, spatially resolved analyte measurements using sensor arrays.
Stated Advantages
Provides high sensitivity and specificity by selectively amplifying chemical analyte binding through DNA strand displacement.
Enables multiplexed and spatially resolved measurements on chip for improved accuracy and statistical sampling.
Allows tunable gain and affinity for engineered dynamic range, enhancing measurement resolution and robustness.
Compatible with multiple readout approaches including label-free electronic detection and optical methods.
Minimizes non-specific interactions and measurement error rates by steric and thermodynamic control of reporter particle binding.
Facilitates modular adaptation for diverse chemical analytes using molecular adapters such as aptamers.
Supports rapid, miniaturized testing applicable to clinical diagnostics, therapeutic development, bionanotechnology, and other fields.
Documented Applications
Clinical diagnostics, including detection and quantification of microRNAs linked to physiological states such as ionizing radiation exposure.
Therapeutic development through precise biomarker measurements.
Bionanotechnology applications requiring nanoscale biomolecule sensing.
Multiplexed, chip-scale chemical analyte detection with spatial resolution for complex samples and chemical dynamics monitoring.
Measurement platforms that incorporate molecular adapters like aptamers for targeting specific analytes.
Embedded chemical measurements within cell and tissue cultures, e.g., in body-on-a-chip systems.
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