Advanced Detection of SARS-CoV-2 and Omicron Variants via MXene-Graphene Hybrid Biosensors Utilizing Nucleic Acid Probes

Low-cost biosensors that can rapidly and widely detect viruses are critical for faster diagnosis and treatment decision-making, especially for infections. The commonly used field-effect transistor is sensitive to the biomarker’s detection but struggles with precise detection, particularly of nontargets such as ions and proteins. To overcome this limitation, we developed a field-effect transistor biosensor design based on MXene-graphene materials to increase the accuracy and sensitivity of virus detection. Based on the hybridization process between two complementary DNA strands, single-stranded nucleic acids were immobilized on the sensing surface via 3-aminopropyltriethoxysilane and glutaraldehyde to capture the nucleic acids of the target virus. The addition of the MXene layer provides a reduced system capacitance and tuned bandgap compared to that of stand-alone graphene. This tuning can significantly enhance the sensitivity of the developed platform. The SARS-CoV-2 and its Omicron variant were used to validate the developed biosensor. The results showed high accuracy with detection limits as low as 1 × 10–21 and 1 × 10–22 mol/L (60.2 and 6.02 copies/L equivalently), for SARS-CoV-2 and its Omicron variant, respectively. Twenty-four clinical tests were also conducted using the developed ssDNA-MXene-graphene biosensors with patients’ nasopharyngeal swab samples. The biosensor’s results closely matched those of the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) detection but with a significantly shorter detection time, demonstrating the sensors’ real-time, in situ, practical application. This result also demonstrates the promising future of MXene-based biosensors for virus detection using nucleic acid probes.