“…Instead, it is the overall concavity of the structure, and the binding of biomolecules in concave areas, which results in higher sensitivity. This finding has important implications for the future of biosensors: efforts are underway to increase the limit of detection of biosensors by ensuring that biomolecules bind only to the NW directly (16,21). However, the conventional wisdom-that nanoscale structures are more sensitive-fails in this regime.…”
Electrostatic counter ion screening is a phenomenon that is detrimental to the sensitivity of charge detection in electrolytic environments, such as in field-effect transistor-based biosensors. Using simple analytical arguments, we show that electrostatic screening is weaker in the vicinity of concave curved surfaces, and stronger in the vicinity of convex surfaces. We use this insight to show, using numerical simulations, that the enhanced sensitivity observed in nanoscale biosensors is due to binding of biomolecules in concave corners where screening is reduced. We show that the traditional argument, that increased surface area-to-volume ratio for nanoscale sensors is responsible for their increased sensitivity, is incorrect.I n recent years, there has been a major drive to use field-effect transistor (FET)-based devices to detect biological molecules in electrolytic environments (1). These biosensors use the charge of biomolecules to gate the current through a transistor (2). Frequently, the transistor is based on a quasi-1D nanostructure, such as a nanowire (NW) or nanotube, and the biomolecules bind directly to the surface of the nanoscale structure (1, 3). The use of such nanostructures is justified by the belief that nanoscale biosensors are more sensitive, with sensitivity defined as the relative change in drain current or a shift in threshold voltage in response to a change in bound biomolecule density. A few experiments specifically studied the effect of shrinking nanowire radii on sensitivity, albeit with varying structures, analytes, and sensing circumstances, and found that shrinking a sensor's dimensions indeed improves its sensitivity (4-6). The enhanced sensitivity has been loosely attributed to the increase in the sensor's surface area-to-volume ratio, which is a direct result of shrinking its dimensions. This argument has been analytically justified in the context of gas sensors (7). However, there is a fundamental difference between gas and biomolecule sensing: biomolecule sensing is performed in an electrolyte, and the ions therein will screen the charge of bound biomolecules in a phenomenon known as Debye screening (8, 9). The direct application of the gas sensing result to the biosensing environment implicitly assumes that the screening effect does not change with shrinking dimensions, an assumption we believe to be false. There have been studies that included a rigorous treatment of screening in biosensors, but they studied neither the specific cause of increased sensitivity at the nanoscale, nor the effect of varying size on screening behavior (10). We believe the phenomenon responsible for the increased sensitivity of nanowires in particular, and nanostructured biosensors in general, have not yet been uncovered by the research community.We have previously dissected the operation of biosensors into two independent parts to better understand the underlying physics (11): first, biomolecule charges cause a change in the local electrostatic potential at the outer surface of the gate dielectri...
“…Instead, it is the overall concavity of the structure, and the binding of biomolecules in concave areas, which results in higher sensitivity. This finding has important implications for the future of biosensors: efforts are underway to increase the limit of detection of biosensors by ensuring that biomolecules bind only to the NW directly (16,21). However, the conventional wisdom-that nanoscale structures are more sensitive-fails in this regime.…”
Electrostatic counter ion screening is a phenomenon that is detrimental to the sensitivity of charge detection in electrolytic environments, such as in field-effect transistor-based biosensors. Using simple analytical arguments, we show that electrostatic screening is weaker in the vicinity of concave curved surfaces, and stronger in the vicinity of convex surfaces. We use this insight to show, using numerical simulations, that the enhanced sensitivity observed in nanoscale biosensors is due to binding of biomolecules in concave corners where screening is reduced. We show that the traditional argument, that increased surface area-to-volume ratio for nanoscale sensors is responsible for their increased sensitivity, is incorrect.I n recent years, there has been a major drive to use field-effect transistor (FET)-based devices to detect biological molecules in electrolytic environments (1). These biosensors use the charge of biomolecules to gate the current through a transistor (2). Frequently, the transistor is based on a quasi-1D nanostructure, such as a nanowire (NW) or nanotube, and the biomolecules bind directly to the surface of the nanoscale structure (1, 3). The use of such nanostructures is justified by the belief that nanoscale biosensors are more sensitive, with sensitivity defined as the relative change in drain current or a shift in threshold voltage in response to a change in bound biomolecule density. A few experiments specifically studied the effect of shrinking nanowire radii on sensitivity, albeit with varying structures, analytes, and sensing circumstances, and found that shrinking a sensor's dimensions indeed improves its sensitivity (4-6). The enhanced sensitivity has been loosely attributed to the increase in the sensor's surface area-to-volume ratio, which is a direct result of shrinking its dimensions. This argument has been analytically justified in the context of gas sensors (7). However, there is a fundamental difference between gas and biomolecule sensing: biomolecule sensing is performed in an electrolyte, and the ions therein will screen the charge of bound biomolecules in a phenomenon known as Debye screening (8, 9). The direct application of the gas sensing result to the biosensing environment implicitly assumes that the screening effect does not change with shrinking dimensions, an assumption we believe to be false. There have been studies that included a rigorous treatment of screening in biosensors, but they studied neither the specific cause of increased sensitivity at the nanoscale, nor the effect of varying size on screening behavior (10). We believe the phenomenon responsible for the increased sensitivity of nanowires in particular, and nanostructured biosensors in general, have not yet been uncovered by the research community.We have previously dissected the operation of biosensors into two independent parts to better understand the underlying physics (11): first, biomolecule charges cause a change in the local electrostatic potential at the outer surface of the gate dielectri...
The use of field-Effect-Transistor (FET) type biosensing arrangements has been highlighted by researchers in the field of early biomarker detection and drug screening. Their non-metalized gate dielectrics that are exposed to an electrolyte solution cover the semiconductor material and actively transduce the biological changes on the surface. The efficiency of these novel devices in detecting different biomolecular analytes in a real-time, highly precise, specific, and label-free manner has been validated by numerous research studies. Considerable progress has been attained in designing FET devices, especially for biomedical diagnosis and cell-based assays in the past few decades. The exceptional electronic properties, compactness, and scalability of these novel tools are very desirable for designing rapid, label-free, and mass detection of biomolecules. With the incorporation of nanotechnology, the performance of biosensors based on FET boosts significantly, particularly, employment of nanomaterials such as graphene, metal nanoparticles, single and multi-walled carbon nanotubes, nanorods, and nanowires. Besides, their commercial availability, and high-quality production on a large-scale, turn them to be one of the most preferred sensing and screening platforms. This review presents the basic structural setup and working principle of different types of FET devices. We also focused on the latest progression regarding the use of FET biosensors for the recognition of viruses such as, recently emerged COVID-19, Influenza, Hepatitis B Virus, protein biomarkers, nucleic acids, bacteria, cells, and various ions. Additionally, an outline of the development of FET sensors for investigations related to drug development and the cellular investigation is also presented. Some technical strategies for enhancing the sensitivity and selectivity of detection in these devices are addressed as well. However, there are still certain challenges which are remained unaddressed concerning the performance and clinical use of transistor-based point-of-care (POC) instruments; accordingly, expectations about their future improvement for biosensing and cellular studies are argued at the end of this review.
“…The risk groups have been defined by American Heart Association and U.S. Disease Control and Prevention and separated to three levels that are low risk: less than 1 μg/ml, average risk: 1-3 μg/ml, and high risk: above 3 μg/ml. Recently, several miniaturized devices for CRP detection were reported, e.g., a piezoresistive micro-cantilever beam (Wee et al 2005), an antibody-coated magnetic particle immunoassay (Tsai et al 2007), a quartz crystal microbalance (QCM) immunosensor (Kurosawa et al 2004), a surface plasmon resonance (SPR) immunosensor (Hu et al 2006;Meyer et al 2006), a CMOS image sensor (Devadhasan et al 2012), an enzyme-linked immunosorbent assay (Pultar et al 2009;Wu et al 2002), and an electric current using a field-effect transistor (Kim et al 2013). Such applications give CRP detection time typically in the range of 10-40 min.…”
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