Transistor-based biosensing: Strategies of interface modulation and biomedical applications

The great advancements in precision medicine and personalized healthcare urgent demand for highly sensitive biomolecular detection techniques. Among the diversity of developed detection assays, transistor-based electrical analysis devices have attracted an increasing number of attentions. Transistor-based biosensing is an electrical analytical technique which utilizes field-effect transistors (FETs) as signal amplification and conduction devices along with the recognition function of biological receptors to achieve specific detection of biomolecules or small chemical molecules. With multiple advantages such as fast response, label-free, high sensitivity, easy operation and easy integration, FET biosensors show great potential for applications in biomedical fields including disease diagnosis, pandemic screening, real-time monitoring and being an ideal candidate for serving as point-of-care testing (POCT) tools. In particular, FET-based electronics exhibit superb performance in the determination of trace biomolecules at picomolar and even attomolar levels. However, design of high-performance FET-based electrical biosensors remains a challenge attributed to small intrinsic charges of chemical and biological molecules as well as screening effect of counterions in solution. Given the high sensitivity of sensing channels to the behaviors and characteristics of targets of interest at solid-liquid interfaces, scientists have attempted to design FET-based biosensors that are highly sensitive, selective, and reliably stable by optimizing the interfacial structures, recognition elements and other engineering strategies. In this review, we describe the remarkable achievements during the progression of high-performance FET-based biosensors in the last decade, with an emphasis on strategies of interface modulation and biomedical applications of FET electrical analysis platforms. We highlight the diverse interface engineering approaches for high-performance FET biosensing platforms including development of sensing materials, optimization of biosensing interfaces, and design of recognition elements. These methods get rid of limitations of Debye screening effect, and promote highly sensitive recognition of chemical/biological molecules by FET biosensors. Specifically, the topological structure of semiconductor determines the charge arrangement on solid interface in electrostatic equilibrium and thus contributes to the distribution of ions in solutions, which benefits for modulating the Debye screening effect. The introduction of polymers could change the dielectric constant near the sensing interfaces and increase the Debye length. By reducing the occupied length of recognition elements, the interaction distance of target of interest and sensing channel is able to be effectively decreased, contributing to the enhanced signal response. Besides, a series of recently developed artificial receptors bring a brilliant future to the exploitation of high-performance FET-based assays. On the basis of interface-engineered FET platforms, we provide a comprehensive summary regarding applications of FET electrical analysis for in vitro detection and real-time monitoring of physiological environments, mainly devoted to disease-associated biomarkers identification, pandemic screening as well as wearable electronics. Finally, we discuss the opportunities and key challenges of FET electrical analysis platform towards commercialization, aiming to provide suggestions for optimization of high-performance FETbased biosensing platforms and wearable biosensing devices. We listed the future directions of highly sensitive FET biosensors and electronics, including the structure optimization of sensing interfaces, designof new probes, multi-channel integration, development of manufacturing techniques, calibration of test results as well as exploitation of implantable FET devices. It is expected that this review may offer inspirations and guidance for researchers to design and develop FET-based electronic devices with excellent sensing capability for applications in the fields of bioanalysis, biosensors, nucleic acid chemistry, and bioelectronics.