Digitalization of Enzyme-Linked Immunosorbent Assay with Graphene Field-Effect Transistors (G-ELISA) for Portable Ferritin Determination.

Herein, we present a novel approach to quantify ferritin based on the integration of an Enzyme-Linked Immunosorbent Assay (ELISA) protocol on a Graphene Field-Effect Transistor (gFET) for bioelectronic immunosensing. The G-ELISA strategy takes advantage of the gFET inherent capability of detecting pH changes for the amplification of ferritin detection using urease as a reporter enzyme, which catalyzes the hydrolysis of urea generating a local pH increment. A portable field-effect transistor reader and electrolyte-gated gFET arrangement are employed, enabling their operation in aqueous conditions at low potentials, which is crucial for effective biological sample detection. The graphene surface is functionalized with monoclonal anti-ferritin antibodies, along with an antifouling agent, to enhance the assay specificity and sensitivity. Markedly, G-ELISA exhibits outstanding sensing performance, reaching a lower limit of detection (LOD) and higher sensitivity in ferritin quantification than unamplified gFETs. Additionally, they offer rapid detection, capable of measuring ferritin concentrations in approximately 50 min. Because of the capacity of transistor miniaturization, our innovative G-ELISA approach holds promise for the portable bioelectronic detection of multiple biomarkers using a small amount of the sample, which would be a great advancement in point-of-care testing.

Ultrafast and highly sensitive detection of SARS-CoV-2 spike protein by field-effect transistor graphene-based biosensors.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), etiological agent for the coronavirus disease 2019 (COVID-19), has resulted in over 775 million global infections. Early diagnosis remains pivotal for effective epidemiological surveillance despite the availability of vaccines. Antigen-based assays are advantageous for early COVID-19 detection due to their simplicity, cost-effectiveness, and suitability for point-of-care testing (PoCT). This study introduces a graphene field-effect transistor-based biosensor designed for high sensitivity and rapid response to the SARS-CoV-2 spike protein. By functionalizing graphene with monoclonal antibodies and applying short-duration gate voltage pulses, we achieve selective detection of the viral spike protein in human serum within 100 µs and at concentrations as low as 1 fg ml-1, equivalent to 8 antigen molecules perµl of blood. Furthermore, the biosensor estimates spike protein concentrations in serum from COVID-19 patients. Our platform demonstrates potential for next-generation PoCT antigen assays, promising fast and sensitive diagnostics for COVID-19 and other infectious diseases.

Exploring Mixed Ionic-Electronic-Conducting PVA/PEDOT:PSS Hydrogels as Channel Materials for Organic Electrochemical Transistors.

Here, we report the preparation and evaluation of PVA/PEDOT:PSS-conducting hydrogels working as channel materials for OECT applications, focusing on the understanding of their charge transport and transfer properties. Our conducting hydrogels are based on crosslinked PVA with PEDOT:PSS interacting via hydrogen bonding and exhibit an excellent swelling ratio of ~180-200% w/w. Our electrochemical impedance studies indicate that the charge transport and transfer processes at the channel material based on conducting hydrogels are not trivial compared to conducting polymeric films. The most relevant feature is that the ionic transport through the swollen hydrogel is clearly different from the transport through the solution, and the charge transfer and diffusion processes govern the low-frequency regime. In addition, we have performed in operando Raman spectroscopy analyses in the OECT devices supported by first-principle computational simulations corroborating the doping/de-doping processes under different applied gate voltages. The maximum transconductance (gm~1.05 µS) and maximum volumetric capacitance (C*~2.3 F.cm-3) values indicate that these conducting hydrogels can be promising candidates as channel materials for OECT devices.

Independent Dual-Channel Approach to Mesoscopic Graphene Transistors.

Graphene field-effect transistors (GFETs) exhibit unique switch and sensing features. In this article, GFETs are investigated within the tight-binding formalism, including quantum capacitance correction, where the graphene ribbons with reconstructed armchair edges are mapped into a set of independent dual channels through a unitary transformation. A new transfer matrix method is further developed to analyze the electron transport in each dual channel under a back gate voltage, while the electronic density of states of graphene ribbons with transversal dislocations are calculated using the retarded Green's function and a novel real-space renormalization method. The Landauer electrical conductance obtained from these transfer matrices was confirmed by the Kubo-Greenwood formula, and the numerical results for the limiting cases were verified on the basis of analytical results. Finally, the size- and gate-voltage-dependent source-drain currents in GFETs are calculated, whose results are compared with the experimental data.

Wearable electrochemical biosensors to measure biomarkers with complex blood-to-sweat partition such as proteins and hormones.

Smart electronic devices based on micro-controllers, also referred to as fashion electronics, have raised wearable technology. These devices may process physiological information to facilitate the wearer's immediate biofeedback in close contact with the body surface. Standard market wearable devices detect observable features as gestures or skin conductivity. In contrast, the technology based on electrochemical biosensors requires a biomarker in close contact with both a biorecognition element and an electrode surface, where electron transfer phenomena occur. The noninvasiveness is pivotal for wearable technology; thus, one of the most common target tissues for real-time monitoring is the skin. Noninvasive biosensors formats may not be available for all analytes, such as several proteins and hormones, especially when devices are installed cutaneously to measure in the sweat. Processes like cutaneous transcytosis, the paracellular cell-cell unions, or even reuptake highly regulate the solutes content of the sweat. This review discusses recent advances on wearable devices based on electrochemical biosensors for biomarkers with a complex blood-to-sweat partition like proteins and some hormones, considering the commented release regulation mechanisms to the sweat. It highlights the challenges of wearable epidermal biosensors (WEBs) design and the possible solutions. Finally, it charts the path of future developments in the WEBs arena in converging/emerging digital technologies.

An Overview on Bipolar Junction Transistor as a Sensor for X-ray Beams Used in Medical Diagnosis.

Although not manufactured to be used under X-ray photons, the commercial bipolar junction transistor (BJT) is an electronic device that can be used as an ionizing radiation sensor. In this article an overview on the BJT and its principle of operation were made for the purpose of better understanding how such a semiconductor device behaves when under diagnostic X-ray beam. Therefore, it addresses some topics such as the structure of the device, the bias configuration when operating in active mode, and so on. Even knowing that the most complete theory to describe the "transistor effect" is based on quantum theory (the energy band theory of solids), here it is preferable to take a simpler experimental approach to clearly understand the operation of the BJT. In electronics, the BJT is used as a current amplifier, and depending on the bias and point of view it also becomes a voltage amplifier. In the analysis of BJT under an X-ray beam, in addition to its operation as a sensor to measure the dose or some diagnostic X-ray tube parameter, it has also led to technological innovation in the technique of digital data storage based on the effect of radiation.

Ultrahigh-Gain Organic Electrochemical Transistor Chemosensors Based on Self-Curled Nanomembranes.

Organic electrochemical transistors (OECTs) are technologically relevant devices presenting high susceptibility to physical stimulus, chemical functionalization, and shape changes-jointly to versatility and low production costs. The OECT capability of liquid-gating addresses both electrochemical sensing and signal amplification within a single integrated device unit. However, given the organic semiconductor time-consuming doping process and their usual low field-effect mobility, OECTs are frequently considered low-end category devices. Toward high-performance OECTs, microtubular electrochemical devices based on strain-engineering are presented here by taking advantage of the exclusive shape features of self-curled nanomembranes. Such novel OECTs outperform the state-of-the-art organic liquid-gated transistors, reaching lower operating voltage, improved ion doping, and a signal amplification with a >104  intrinsic gain. The multipurpose OECT concept is validated with different electrolytes and distinct nanometer-thick molecular films, namely, phthalocyanine and thiophene derivatives. The OECTs are also applied as transducers to detect a biomarker related to neurological diseases, the neurotransmitter dopamine. The self-curled OECTs update the premises of electrochemical energy conversion in liquid-gated transistors, yielding a substantial performance improvement and new chemical sensing capabilities within picoliter sampling volumes.

Monitoring the hemostasis process through the electrical characteristics of a graphene-based field-effect transistor.

Graphene-based transistors are promising devices in the evaluation of carrier density in biological analytes. We report on the design and fabrication of a graphene-based field-effect transistor for monitoring and assessing the interaction between the coagulation factors based on the charge carrier density in a blood sample. When biochemical reactions occurred during the coagulation cascade process, a dopant effect was noticed on the graphene surface by the change in Dirac point voltage values. Additional experiments were performed using blood samples treated with activators (vitamin K, calcium chloride, and thromboplastin reagent) and inhibitors (heparin drugs) to evaluate the selectivity of the graphene field-effect transistor devices. Since the transfer characteristic curves presented divergent behaviours for different levels of procoagulants and anticoagulants, the measurements showed that the devices can assess changes in the concentrations of factors that inhibit or accelerate the cascade process when using untreated and treated samples. Reproducibility was verified by testing samples from different sources. To the best of our knowledge, this study is the first to demonstrate the potential of graphene in monitoring the hemostasis process through the analysis of the electrical properties of human whole blood.

Field effect in molecule-gated switches and the role of target-to-receptor size ratio in biosensor sensitivity.

We demonstrated here that molecular redox films are electrochemical capacitive devices possessing specific field effect in which molecular moieties within films act as sensitive gates. We confirm that the field effect present in these redox switches is suitable in detecting, in a label-free manner (without needs of redox probe in the biological samples), biomarkers of essential importance for dengue, heart risks and inflammation, Parkinson's disease and tumors. Though the sensitiveness is high, it is governed by Thomas Fermi screening and thus depends on the target-to-receptor size ratio. Thus, we also demonstrated how this target-to-receptor size ratio affects the sensitivity. We concluded that the smaller the biological receptor the greater the sensitivity. Consequently, a larger molecular target associated with a smaller receptor provides a considerable (predictable) improvement of the sensitiveness.

InP Nanowire Biosensor with Tailored Biofunctionalization: Ultrasensitive and Highly Selective Disease Biomarker Detection.

Electrically active field-effect transistors (FET) based biosensors are of paramount importance in life science applications, as they offer direct, fast, and highly sensitive label-free detection capabilities of several biomolecules of specific interest. In this work, we report a detailed investigation on surface functionalization and covalent immobilization of biomarkers using biocompatible ethanolamine and poly(ethylene glycol) derivate coatings, as compared to the conventional approaches using silica monoliths, in order to substantially increase both the sensitivity and molecular selectivity of nanowire-based FET biosensor platforms. Quantitative fluorescence, atomic and Kelvin probe force microscopy allowed detailed investigation of the homogeneity and density of immobilized biomarkers on different biofunctionalized surfaces. Significantly enhanced binding specificity, biomarker density, and target biomolecule capture efficiency were thus achieved for DNA as well as for proteins from pathogens. This optimized functionalization methodology was applied to InP nanowires that due to their low surface recombination rates were used as new active transducers for biosensors. The developed devices provide ultrahigh label-free detection sensitivities ∼1 fM for specific DNA sequences, measured via the net change in device electrical resistance. Similar levels of ultrasensitive detection of ∼6 fM were achieved for a Chagas Disease protein marker (IBMP8-1). The developed InP nanowire biosensor provides thus a qualified tool for detection of the chronic infection stage of this disease, leading to improved diagnosis and control of spread. These methodological developments are expected to substantially enhance the chemical robustness, diagnostic reliability, detection sensitivity, and biomarker selectivity for current and future biosensing devices.

Self-assembled films of dendrimers and metallophthalocyanines as FET-based glucose biosensors.

Separative extended gate field effect transistor (SEGFET) type devices have been used as an ion sensor or biosensor as an alternative to traditional ion sensitive field effect transistors (ISFETs) due to their robustness, ease of fabrication, low cost and possibility of FET isolation from the chemical environment. The layer-by-layer technique allows the combination of different materials with suitable properties for enzyme immobilization on simple platforms such as the extended gate of SEGFET devices enabling the fabrication of biosensors. Here, glucose biosensors based on dendrimers and metallophthalocyanines (MPcs) in the form of layer-by-layer (LbL) films, assembled on indium tin oxide (ITO) as separative extended gate material, has been produced. NH(3)(+) groups in the dendrimer allow electrostatic interactions or covalent bonds with the enzyme (glucose oxidase). Relevant parameters such as optimum pH, buffer concentration and presence of serum bovine albumin (BSA) in the immobilization process were analyzed. The relationship between the output voltage and glucose concentration shows that upon detection of a specific analyte, the sub-products of the enzymatic reaction change the pH locally, affecting the output signal of the FET transducer. In addition, dendritic layers offer a nanoporous environment, which may be permeable to H(+) ions, improving the sensibility as modified electrodes for glucose biosensing.