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The prevalence of mutated species of COVID-19 antigens has provided a strong impetus for identifying a cost-effective, rapid and facile strategy for identifying the viral loads in public places. The ever-changing genetic make-up of SARS-CoV-2 posts a significant challenfge for the research community to identify a robust mechanism to target, bind and confirm the presence of a viral load before it spreads. Synthetic DNA constructs are a novel strategy to design complementary DNA sequences specific for antigens of interest as in this review's case SARS-CoV-2 antigens. Small molecules, complementary DNA and protein-DNA complexes have been known to target analytes in minimal concentrations. This phenomenon can be exploited by nanomaterials which have unique electronic properties such as ballistic conduction. Graphene is one such candidate for designing a device with a very low LOD in the order of zeptomolar and attomolar concentrations. Surface modification will be the significant aspect of the device which needs to have a high degree of sensitivity at the same time as providing a rapid signaling mechanism.

We propose a novel, to the best of our knowledge, plasmonic-based methodology for the purpose of fast DNA sequencing. The interband surface plasmon resonance and field-enhancement properties of graphene nanopore in the presence of the DNA nucleobases are investigated using a hybrid quantum/classical method (HQCM), which employs time-dependent density functional theory and a quasistatic finite difference time domain approach. In the strong plasmonic-molecular coupling regime where the plasmon and DNA absorption frequencies are degenerated, the optical response of DNA molecule in the vicinity of the nanopore is enhanced. In contrast, when the plasmon and nucleobases resonances are detuned the distinct peaks and broadening of the molecular resonances represent the inherent properties of the nucleobase. Due to the different optical properties of DNA nucleobases in the ultraviolet (UV) region of light, the signal corresponding to the replacement of nucleobases in a DNA block can be determined by considering the differential absorbance. Results show the promising capability of the present mechanism for practical DNA sequencing.

The rapid and unexpected spread of SARS-CoV-2 worldwide has caused unprecedented disruption to daily life and has brought forward critical challenges for public health. The disease was the largest cause of death in the United States in early 2021. Likewise, the COVID-19 pandemic has highlighted the need for rapid and accurate diagnoses at scales larger than ever before. To improve the availability of current gold standard diagnostic testing methods, the development of point-of-care devices that can maintain gold standard sensitivity while reducing the cost and providing portability is much needed. In this work, we combine the amplification capabilities of reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) techniques with high-sensitivity end-point detection of crumpled graphene field-effect transistors (cgFETs) to develop a portable detection cell. This electrical detection method takes advantage of the ability of graphene to adsorb single-stranded DNA due to noncovalent π-π bonds but not double-stranded DNA. These devices have demonstrated the ability to detect the presence of the SARS-CoV-2 virus in a range from 10 to 10 4 copies/μL in 20 viral transport medium (VTM) clinical samples. As a result, we achieved 100% PPV, NPV, sensitivity, and specificity with 10 positive and 10 negative VTM clinical samples. Further, the cgFET devices can differentiate between positive and negative VTM clinical samples in 35 min based on the Dirac point shift. Likewise, the improved sensing capabilities of the crumpled gFET were compared with those of the traditional flat gFET devices.

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.

Single-nucleotide polymorphisms (SNPs) in a gene sequence are markers for a variety of human diseases. Detection of SNPs with high specificity and sensitivity is essential for effective practical implementation of personalized medicine. Current DNA sequencing, including SNP detection, primarily uses enzyme-based methods or fluorophore-labeled assays that are time-consuming, need laboratory-scale settings, and are expensive. Previously reported electrical charge-based SNP detectors have insufficient specificity and accuracy, limiting their effectiveness. Here, we demonstrate the use of a DNA strand displacement-based probe on a graphene field effect transistor (FET) for high-specificity, single-nucleotide mismatch detection. The single mismatch was detected by measuring strand displacement-induced resistance (and hence current) change and Dirac point shift in a graphene FET. SNP detection in large double-helix DNA strands (e.g., 47 nt) minimize false-positive results. Our electrical sensor-based SNP detection technology, without labeling and without apparent cross-hybridization artifacts, would allow fast, sensitive, and portable SNP detection with single-nucleotide resolution. The technology will have a wide range of applications in digital and implantable biosensors and high-throughput DNA genotyping, with transformative implications for personalized medicine.