Scalable back-gated functionalized graphene field effect transistors for detection of DNA and other target molecules
Inventors
Johnson, Jr., Alan T. • PING, Jinglei • VISHNUBHOTLA, Ramya
Assignees
University of Pennsylvania Penn
Publication Number
US-12379343-B2
Publication Date
2025-08-05
Expiration Date
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Abstract
Provided are devices and methods for detecting a target molecule, based on using a graphene electrode. The devices exhibit high sensitivity to target molecules such as DNA that may be present at comparatively low concentrations.
Core Innovation
Provided are devices and methods for detecting a target molecule, based on using a graphene electrode. The devices exhibit high sensitivity to target molecules such as DNA that may be present at comparatively low concentrations. In meeting the described needs, the present disclosure provides, inter alia, a sensitive sensor platform for drug detection. In some embodiments, the device's monitoring of a voltage signal allows for detection of complementary DNA at, e.g., a concentration of 100 pM, which is a factor of 10,000 improvement over existing alternatives.
The disclosure provides, inter alia, highly-scalable, back-gated arrays of single-strand DNA (ssDNA) decorated field-effect transistors (FETs), based on chemical-vapor-deposited graphene, for detection of complementary DNA. Binding of molecular targets by the DNA chemical recognition element led to a reproducible, concentration-dependent shift in the Dirac voltage on the current-gate voltage characteristic, with a limit of detection less than 100 pM. The technology addresses a need for detection devices having high sensitivity to target molecules, such as ssDNA and other biomolecules, and for a platform sensor technology having a flexible design that can be adapted to detection of a variety of target molecules.
Claims Coverage
This claim coverage identifies 9 inventive features across 4 independent claims.
Array of graphene devices
An array comprising a plurality of sensor devices, each device comprising a portion of graphene.
Polyaromatic molecule attached in electrical communication
A polyaromatic molecule attached to and in electrical communication with the portion of graphene, the polyaromatic molecule comprising a leaving group configured to be displaced by an amine group.
Defined channel dimensions
At least one of the graphene devices comprising a channel having dimensions of about 10 microns by about 100 microns.
Graphene in communication with an electrode
A portion of graphene in communication with at least one electrode.
Detection moiety comprising ssDNA
A detection moiety attached via a linkage to said polyaromatic molecule, said detection moiety comprising a ssDNA.
Attaching selected polyaromatic molecules to graphene
Attaching a polyaromatic molecule selected from the group consisting of: anthracene, phenanthrene, tetracene, chrysene, triphenylene, pentacene, benzo[a] pyrene, corannulene, benzo[ghi] perylene, coronene, or ovalene to a portion of graphene so as to place the polyaromatic molecule into electrical communication with the portion of graphene.
Attaching a ssDNA detection moiety
Attaching a ssDNA detection moiety to the polyaromatic molecule.
Monitoring Dirac voltage
A device featuring a current-gate voltage characteristic with a Dirac voltage, wherein contacting a sample comprising said DNA sequence to the device and monitoring the Dirac voltage yields a concentration-dependent shift in the Dirac voltage.
Polyaromatic molecule selection and attachment
Use of polyaromatic molecules that are attached to the portion of graphene via pi-pi orbital interaction, covalent bonding, ionic bonding, hydrogen bonding, or any combination thereof.
The independent claims cover arrays and individual sensor devices comprising portions of graphene in electrical communication with polyaromatic molecules that include leaving groups displaceable by amines, detection moieties comprising ssDNA attached to those polyaromatic molecules, methods of attaching selected polyaromatic molecules and ssDNA to graphene, and methods of detecting DNA by monitoring a concentration-dependent shift in the Dirac voltage.
Stated Advantages
High sensitivity to target molecules, including detection of complementary DNA at, e.g., 100 pM and lower limits of detection reported for longer probes (e.g., ~100 fM and 1 fM for 40mer and 60mer probe DNA respectively).
Scalable, back-gated arrays enabling multiplexed detection and practical fabrication of multiple devices at once (e.g., arrays with up to 100 graphene FETs).
High specificity, discriminating fully against random ssDNA and by a factor of 10^4 against ssDNA with a single base mismatch.
High fabrication yield enabled by large-area CVD graphene sheets and photolithography (e.g., a yield of over 90% is reported).
Capability to detect small molecule drugs when a ssDNA aptamer is available, demonstrated by selective detection of Tenofovir with negligible response to control drugs.
Documented Applications
Detection of complementary DNA and other ssDNA targets.
Detection of drugs and small molecule drug targets using ssDNA aptamers (demonstrated for Tenofovir).
Monitoring of amplification products and use in a system for quantitative DNA sequencing (detection of amplicons).
Monitoring patients' adherence to a medication regimen.
Detection of drugs or chemicals in urine or blood.
Detection of certain types of cancer via upregulation of a specific DNA strand associated with a malignant tumor.
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