We have developed a DNA aptamer-conjugated graphene field-effect transistor (GFET) biosensor platform to detect receptor-binding domain (RBD), nucleocapsid (N), and spike (S) proteins, as well as viral particles of original Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus and its variants in saliva samples. The GFET biosensor is a label-free, rapid (≤20 min), ultrasensitive handheld wireless readout device. The limit of detection (LoD) and the limit of quantitation (LoQ) of the sensor are 1.28 and 3.89 plaque-forming units (PFU)/mL for S protein and 1.45 and 4.39 PFU/mL for N protein, respectively. Cognate spike proteins of major variants of concern (N501Y, D614G, Y453F, Omicron-B1.1.529) showed sensor response ≥40 mV from the control (aptamer alone) for fM to nM concentration range. The sensor response was significantly lower for viral particles and cognate proteins of Middle East Respiratory Syndrome (MERS) compared to SARS-CoV-2, indicating the specificity of the diagnostic platform for SARS-CoV-2 vs. MERS viral proteins. During the early phase of the pandemic, the GFET sensor response agreed with RT-PCR data for oral human samples, as determined by the negative percent agreement (NPA) and positive percent agreement (PPA). During the recent Delta/Omicron wave, the GFET sensor also reliably distinguished positive and negative clinical saliva samples. Although the sensitivity is lower during the later pandemic phase, the GFET-defined positivity rate is in statistically close alignment with the epidemiological population-scale data. Thus, the aptamer-based GFET biosensor has a high level of precision in clinically and epidemiologically significant SARS-CoV-2 variant detection. This universal pathogen-sensing platform is amenable for a broad range of public health applications and real-time environmental monitoring.

The detection of lead ion (Pb2+) contamination in aqueous media is relevant for preventing endemic health issues as well as damage to cognitive and physical health. Existing home kit tests are unable to achieve clinically relevant sensitivity and specificity. Here, a label-free graphene field-effect transistor sensor for detecting Pb2+ at the femtomolar (fM) level, discriminating between confounding ions, is reported. The sensing principle is based on electrically monitoring Pb2+-binding-mediated conformational changes of a specific aptamer tethered to graphene, modeled through the Hills–Langmuir mechanism. A record sensitivitythrough a limit of detection of ∼61 fM, for Pb2+ was demonstrated. For model verification, specific discrimination of Pb2+ from other ions at the 1 picomolar (pM) level was shown. The reported work provides motivation for development of portable, label-free, point-of-care devices with both high specificity and sensitivity.

The interaction of specific surface plasmon modes in metal-dielectric-metal arrangements is investigated, motivated by their relevance to device-based configurations. The absorption spectra of the relevant nanostructures considering geometrical variation, such as the width and height of the metal or dielectric, are probed considering such interactions. Frequency domain simulations are used to study related multiple surface plasmon polariton resonance modes. It is indicated that the resonant energy level interaction due to the coupling between modes in a horizontal dielectric layer and those in a vertical groove can be engineered and understood in terms of energy level hybridization.

Background: Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been found to act as miRNA sponges that competitively inhibit the binding of miRNA to target mRNA. However, studies on circRNA in pancreatic ductal adenocarcinoma are still lacking and need to be further explored. Methods: The expression level of SOX4 in pancreatic cancer cells and tissues was detected by qRT-PCR and immunohistochemistry, and the correlation between the expression level of SOX4 in pancreatic cancer tissues and clinicopathological features was analyzed by Pearson Chi-square test. Kaplan-meier method was used to analyze the survival curve of pancreatic cancer patients. The circRNA regulating SOX4 was predicted by bioinformatics and verified in pancreatic cancer cells and tissues. The miRNA and target genes were predicted by bioinformatics, and the circRNA-miRNA-mRNA regulatory network was constructed. Then, the expression of SFRP2 in pancreatic cancer cells and tissues was detected by qRT-PCR and immunohistochemistry, and the correlation between clinicopathological features and prognosis was analyzed. Finally, the biological function of SFRP2 was analyzed by bioinformatics to construct a prognostic model for pancreatic cancer. Result: The expression level of SOX4 was significantly up-regulated in various tumor tissues including pancreatic ductal adenocarcinoma. Further analysis showed that up-regulated SOX4 expression was correlated with tumor size and T stage of patients and resulted in poor prognosis of patients. Bioinformatics analysis revealed that SOX4 was a key protein in the Wnt/β-catenin pathway. QRT-PCR was used to detect tissue samples and cells of 9 pancreatic cancer patients, and the expression of 4 circRNA was down-regulated, among which hsa_circ_0131457 was the most significant. A total of 10 miRNA were selected for the prediction of miRNA that bind to hsa_circ_0131457, and the optimal matching value was miR-636. The mRNA targeted to miR-636 was predicted, SFRP2 with the most obvious differential expression was screened out, and the hsa_circ_0131457-miR-636-SFRP2 network regulation map was constructed. Analysis and verification of the target gene SFRP2 showed that the expression of SFRP2 was significantly down-regulated in pancreatic cancer tissues and cells, which was related to preoperative direct bilirubin, tumor size, T stage and tumor differentiation degree. In addition, downregulation of SFRP2 expression in cancer tissues predicted poor prognostic survival in pancreatic cancer patients. Functional analysis of SFRP2 revealed that SFRP2 is a key protein in the Wnt/β-catenin pathway and may be involved in epithelial-mesenchymal transition (EMT). Conclusion: hsa_circ_0131457 and target gene SFRP2 were found to be low expressed in pancreatic cancer, and SFRP2 had an inhibitory effect on the progression of pancreatic cancer. Therefore, the potential regulatory mechanism of hsa_circ_0131457/miR-636/SFRP2 inhibiting the invasion and metastasis of pancreatic cancer was inferred.

A methodology for enhancing the surface plasmon polariton (SPP) resonance associated with graphene, through nanoscale metal-dielectric-metal (MDM) gaps, is proposed. The modulation of the resonances, in the range of 0.7 µm to 1 µm was done through tuning the carrier density in graphene and has been shown to be of potential utility for surface analyte sensing. It was shown, from finite element simulations in the frequency domain, that the related hybrid SPP modes could be clearly delineated in far field spectroscopy.