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.

Detection of COVID-19: A review of the current literature and future perspectives

“…However, it was found that the solution commonly used to store respiratory virus samples, the universal transport medium (UTM), can produce a high noise signal and thus, the LOD in UTM decreased to 242 copies/mL ( Seo et al, 2020 ). Novel materials or engineering methods must be developed to reduce noise signals in FET biosensors, and thereby improving the signal-to-noise ratio to allow high sensitivity screening of low virus load COVID-19 patients ( Hwang et al, 2020 ). Moreover, coupling FET sensors with magnetic particle pre-concentration before detection can minimise the effect of interferents on sample matrix by attracting immunocomplex onto the surface of the sensor via an external magnetic field, thereby increasing detection sensitivity and producing a high signal-noise ratio ( Farka et al, 2017 ).…”

“…By virtue of this modified sensor, as few as 60 chondroitin sulfate proteoglycan 4 (0.01 fM) molecules could be detected in undiluted serum ( Yeh et al, 2016 ). A recent study adopted crumpled graphene to increase the Debye length (e.g., shielding of the molecule charge by the counter ions in the solution); thereby enhancing the detection sensitivity of the graphene FET ( Hwang et al, 2020 ). The further combination of the high DNA binding capacity of PNAs and the crumpled graphene FET showed ultra-high sensitivity nucleic acid detection in buffer and human serum samples, with LOD down to 600 zM and 20 aM, respectively, in a 1-h incubation time; these LODs are significantly lower than those of the flat, reduced graphene oxide FET biosensors ( Cai et al, 2014 ; Hwang et al, 2020 ).…”

“…A recent study adopted crumpled graphene to increase the Debye length (e.g., shielding of the molecule charge by the counter ions in the solution); thereby enhancing the detection sensitivity of the graphene FET ( Hwang et al, 2020 ). The further combination of the high DNA binding capacity of PNAs and the crumpled graphene FET showed ultra-high sensitivity nucleic acid detection in buffer and human serum samples, with LOD down to 600 zM and 20 aM, respectively, in a 1-h incubation time; these LODs are significantly lower than those of the flat, reduced graphene oxide FET biosensors ( Cai et al, 2014 ; Hwang et al, 2020 ). This G-FET has been applied to highly sensitive virus antigen detection, such as detection of the ZIKA virus antigen NS1 and Ebola virus antigen glycoprotein ( Afsahi et al, 2018 ; Maity et al, 2018 ).…”

Recent developments in carbon-based two-dimensional materials: synthesis and modification aspects for electrochemical sensors

“…The films are prone to the introduction of cracks and wrinkles, which lead to a deterioration of the physical properties [55]. In contrast, a systematic introduction of defects by transferring cvdG, specifically to form a wrinkled layer, was found to induce a bandgap [56]. Besides the transfer, also a modification might induce defects within the CVD grown layer.…”

Review of fabrication methods of large-area transparent graphene electrodes for industry

“…Potentially every single atom of the structure can be affected by an adsorbate, making graphene's inherent sensitivity high. Graphene based field-effect-transistor (GFET) sensor is a common and reliable sensor [204], and has been used recently e.g., for early detection of the Zika-virus [205], RNA and DNA detection down to 10 -17 mol/L concentrations [206,207], in operando TEM measurements of neuropeptide capture and release [208] as well as detection of SARS-CoV-2 virus [209], the cause of the global COVID-19 pandemic of 2020. Other measurement schemes can be used as well, such as, Hall effect in standard [210], gated [211] and photonic spin [212,213] Table 2 Summary of different graphene based transparent electrodes, where R s , T, DC / OP and R change refer to sheet resistance, transmittance (at nm unless otherwise specified), figure of merit and decrease of sheet resistance due to doping, respectively.…”