We experimentally demonstrate Si-based electrolyte-gated transistors (EGTs) for detecting urea. The top-down-fabricated device exhibited excellent intrinsic characteristics, including a low subthreshold swing (SS) (~80 mV/dec) and a high on/off current ratio (~10⁷). The sensitivity, which varied depending on the operation regime, was analyzed with the urea concentrations ranging from 0.1 to 316 mM. The current-related response could be enhanced by reducing the SS of the devices, whereas the voltage-related response remained relatively constant. The urea sensitivity in the subthreshold regime was as high as 1.9 dec/pUrea, four times higher than the reported value. The extracted power consumption of 0.3 nW was extremely low compared to other FET-type sensors.

The highly sensitive detection of peanut allergens (PAs) using silicon-based electrolyte-gated transistors (Si-EGTs) was demonstrated. The Si-EGT was made using a top-down technique. The fabricated Si-EGT showed excellent intrinsic electrical characteristics, including a low threshold voltage of 0.7 V, low subthreshold swing of <70 mV/dec, and low gate leakage of <10 pA. Surface functionalization and immobilization of antibodies were performed for the selective detection of PAs. The voltage-related sensitivity (S_V) showed a constant behavior from the subthreshold regime to the linear regime. The current-related sensitivity (S_I) was high in the subthreshold regime and then significantly decreased as the drain current increased. The limit of detection (LOD) was calculated to be as low as 25 pg/mL based on S_I characteristics, which is the lowest value reported to date in the literature for various sensor methodologies. The Si-EGT showed selective detection of PA through a non-specific control test. These results confirm that Si-EGT is a high-sensitivity and low-power biosensor for PA detection.

The sensing responses of SARS-CoV-2 spike protein using top-down-fabricated Si-based electrolyte-gated transistors (EGTs) have been investigated. An aptamer was employed as a receptor for the SARS-CoV-2 spike protein. The EGT demonstrated excellent intrinsic characteristics and higher sensitivity in the subthreshold regime compared to the linear regime. The limit of detection (LOD) was achieved as low as 0.94 pg/mL and 20 pg/mL for the current and voltage sensitivity, respectively. To analyze the sensing responses of EGT in detecting the aptamer–SARS-CoV-2 spike protein conjugate, a lumped-capacitive model with the presence of an effective dipole potential and an effective capacitance of the functionalized layer component was employed. The aptamer-functionalized EGT showed high sensitivity even in 10 mM phosphate-buffered saline (PBS) solution. These results suggest that Si-based EGTs are a highly promising method for detecting SARS-CoV-2 spike proteins.

The SARS-CoV-2 pandemic has triggered many studies worldwide in the area of biosensors, leading to innovative approaches for the quantitative assessment of COVID-19. A nanostructured field-effect transistor (FET) is one type of device shown to be ultrasensitive for virus determination. FETs can be used as transducers to analyze changes in electrical current caused by the bonding of viral molecules to the surface of the semiconducting nanomaterial layer of the FETs. Although nano-transistors require simple setups amenable to be miniaturized for point-of-care diagnostic of COVID-19, this type of sensor usually has limited sensitivity in biological fluids. The reason behind this is the shortened screening length in the presence of high ionic strength solutions. In the frame of this study, we propose a methodology consisting of the FET surface modification with a hydrogel based on the star-shaped polyethylene glycol (starPEG), which hosts specific antibodies against SARS-CoV-2 spike protein in its porous structure. The deposition of the hydrogel increases the effective Debye length, preserving the biosensor’s sensitivity. We demonstrate the capability of silicon nanonet-based FETs to detect viral antigens and cultured viral particles in phosphate-buffered saline (PBS) as well as in human-purified saliva. Finally, we discriminated between positive and negative patients’ nasopharyngeal swab samples.

The SARS-CoV-2 pandemic has increased the demand for low-cost, portable and rapid biosensors, driving huge research efforts toward new nanomaterial-based approaches with high sensitivity. Many of them employ antibodies as bioreceptors, which have a costly development process requiring animal facilities. Recently, sybodies emerged as an alternative new class of synthetic binders/receptors with high antigen binding efficiency, improved chemical stability, and lower production costs via animal-free methods. Their smaller size is an important asset to consider in combination with ultrasensitive field-effect transistors (FETs) as transducers, which respond more intensely when the biorecognition occurs in close proximity to their surface. This work demonstrates the immobilization of sybodies against the spike protein of the virus on silicon surfaces, which are often the integral part of the semiconducting channel of FETs. Immobilized sybodies maintain the capability to capture antigens even at low concentrations in the femtomolar range, as observed by fluorescence microscopy. Finally, the first proof-of-concept of sybody-modified FET sensing is provided, using a nanoscopic silicon net as the sensitive area where the sybodies are immobilized. The future development of further sybodies against other biomarkers and their generalization in biosensors could be critical to decrease the cost of biodetection platforms in future pandemics.

The recent COVID-19 outbreak has strongly pushed the field of biosensors, resulting in multiple new approaches for quantitative virus detection. Among them, those using nanostructured field-effect transistors (FETs) as transducers provide an ultrasensitive approach requiring simple setups for their miniaturization toward point-of-care diagnostics of the disease. However, this type of biosensors suffer from limited sensitivity when it comes to analyzing biofluids due to their shortened screening length in presence of complex liquids with high ionic strength. In this work we propose a solution to this problem, which consists on the surface modification of the FETs with a hydrogel based on star-shaped polyethylene glycol and loaded with specific antibodies against SARS-CoV-2 spike protein. The hydrogel increases the effective Debye length, allowing to preserve the sensitivity in high ionic strength solutions. We provide the demonstration employing silicon nanonet-based FETs for the detection of viral antigens in buffer and in saliva, as well as cultured viral particles. We finally discriminate positive and negative patient samples (nasopharyngeal swab), and propose the theoretical frame that discusses the mechanism of the sensitivity preservation based on the presence of the pegylated hydrogel.