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Abstract Cancer is a significant healthcare issue, and early screening methods based on biomarker analysis in liquid biopsies are promising avenues to reduce mortality rates. Electrical detection of nucleic acids at the single molecule level could enable these applications. We examine the electrical detection of RNA cancer biomarkers (KRAS mutants G12C and G12V) as a single-molecule proof-of-concept electrical biosensor for cancer screening applications. We show that the electrical conductance is highly sensitive to the sequence, allowing discrimination of the mutants from a wild-type KRAS sequence differing in just one base. In addition to this high specificity, our results also show that these biosensors are sensitive down to an individual molecule with a high signal-to-noise ratio. These results pave the way for future miniaturized single-molecule electrical biosensors that could be groundbreaking for cancer screening and other applications.
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Ultrasensitive detection of nucleic acids using deformed graphene channel field effect biosensors
Abstract Field-effect transistor (FET)-based biosensors allow label-free detection of biomolecules by measuring their intrinsic charges. The detection limit of these sensors is determined by the Debye screening of the charges from counter ions in solutions. Here, we use FETs with a deformed monolayer graphene channel for the detection of nucleic acids. These devices with even millimeter scale channels show an ultra-high sensitivity detection in buffer and human serum sample down to 600 zM and 20 aM, respectively, which are ∼18 and ∼600 nucleic acid molecules. Computational simulations reveal that the nanoscale deformations can form ‘electrical hot spots’ in the sensing channel which reduce the charge screening at the concave regions. Moreover, the deformed graphene could exhibit a band-gap, allowing an exponential change in the source-drain current from small numbers of charges. Collectively, these phenomena allow for ultrasensitive electronic biomolecular detection in millimeter scale structures.
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- Award ID(s):
- 1720633
- PAR ID:
- 10153554
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 11
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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