Graphene-enabled DNA biosensors with enhanced sensitivity and specificity
Inventors
Johnson, Jr., Alan T. • GAO, Zhaoli • Xia, Han
Assignees
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Publication Number
US-12674778-B2
Publication Date
2026-07-07
Expiration Date
Abstract
Provided are electronic biosensors based on graphene field effect transistors that utilize engineered hairpin probe DNA that allows for target recycling and hybridization chain reactions.
Core Innovation
The document provides a detector that includes a first portion of functionalized graphene and a first hairpin probe (H1) linked through a graphene field effect transistor (GFET). The first hairpin probe (H1) is in a hairpin configuration with a bottom portion linked to the graphene and a paired portion, and opens upon binding by a target molecule (T), giving rise to an H1–T complex having a paired region formed between the first hairpin probe (H1) and the target (T) and a protruding segment.
The H1–T complex with the protruding segment enables a triggered self-assembly pathway in which helper DNA binds to form larger complexes and produces target recycling. In this pathway, a first hairpin helper (H2) binds the protruding segment and paired region to displace the target and form an H1–H2 complex with a protruding segment, and additional helper hairpins including a second hairpin helper (H3) with a toehold portion can open to form an H1–H2–H3 complex with a protruding segment.
This forms a hybridization chain reaction (HCR)-based signal amplification using helper hairpins that progressively build higher-order complexes. Electrical readout is provided using the GFET response, including a signal based on Dirac voltage shifts, and the document reports multiplexed detection using GFET arrays with site-specific functionalization of different hairpin probes (H1 and H1′).
Claims Coverage
The independent claims define three inventive features: a GFET-based detector using target-triggered hairpin opening, a method of detecting a target by contacting H1 under conditions that form an H1–T complex, and a method using multiple hairpin probes with different nucleotides to detect multiple targets.
GFET-linked hairpin probe opening to form H1–T complex with protruding segment
A detector comprising a first portion of functionalized graphene and a first hairpin probe (H1) linked through a graphene field effect transistor (GFET) to the first portion of functionalized graphene, where the hairpin probe opens upon binding by a target molecule (T) and gives rise to an H1–T complex having a paired region and a protruding segment.
Contacting H1 with target to open H1 and form H1–T complex
A method of detecting a target comprising contacting the first hairpin probe (H1) linked through a GFET to a first portion of graphene under conditions that cause target binding, opening of H1, and formation of an H1–T complex having a paired region and a protruding segment.
Multiple GFET-linked hairpin probes for detecting multiple targets via opened H1i–Tj complex
A method of detecting a target comprising one or more first hairpin probes (H1i=1 to n) each comprising a different plurality of nucleotides and linked through a GFET to a first portion of graphene, where one or more target molecules bind and open one or more hairpin probes to form an H1i–Tj complex having a paired region and a protruding segment.
Across the independent claims, the document centers on GFET-linked hairpin probes that open upon target binding to form an H1–T or H1i–Tj complex with a paired region and a protruding segment, including multiplexed use of multiple hairpin probes with different pluralities of nucleotides.
Stated Advantages
Enhanced performance metrics, including limit of detection down to about 5 fM (21-mer) and potential <1 fM with longer incubation.
Improved specificity against single-base mismatches.
Demonstrated multiplexed detection using GFET arrays with site-specific functionalization of different hairpin probes (H1 and H1′).
Documented Applications
Detecting a target molecule using GFET electronic biosensors functionalized with engineered hairpin probe DNA that opens upon target binding and enables signal amplification with hybridization chain reaction using helper hairpins.
Multiplexed detection using GFET sensor arrays with site-specific functionalization of different hairpin probes (H1 and H1′).
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