Significant progress in the field of solid-state biosensors has occurred over the last decade. Various types of sensing devices with high-density integration and flexible configuration, as well as ...new applications for clinical diagnosis and healthcare, have been developed using blood, serum, and other body fluids such as sweat, tears, and saliva. In this review, we focus on the recent progress of solid-state biosensors in the biomedical field. New concepts, technical achievements, and practical applications of the sensors are described and discussed from the perspective of sensing materials, sensor structures, design of biomolecular recognition, and biomedical applications. Several challenges remain before the solid-state biosensors are realized for point-of-care testing in clinical diagnosis and healthcare. Collaboration among researchers, integration of technologies, and knowledge from different fields are necessary to tackle the remaining challenges.
•This manuscript has surveyed recent progress of solid-state biosensors.•The sensing materials and structures are summarized.•The biomedical applications of solid-state biosensors are described.•The potential applications of solid-state biosensors for liquid biopsy are also discussed.
Functional analyses of the membrane proteins on live cells using ion-sensitive field effect transistors (ISFETs) are described in this review. Expressions of human epidermal growth factor receptor ...(HER2) and epidermal growth factor receptor (EGFR) on live cancer cells have been detected using cell-based field effect transistors (FETs) in combination with enzymatic signal amplification. A good correlation could be obtained between the pH values measured with the cell-based FETs and the fluorescence intensities measured using the fluorescence-activated cell sorting (FACS), with a correlation coefficient of 0.976. The interactions between membrane proteins/transporters and ligands at cell membranes using a cell-based FET with an oocyte were monitored non-invasively. Xenopus laevis oocytes were injected with the capped human organic anion transporting peptide C (hOATP-C) cRNA. Estrone-3-sulfate (E3S) was used as a substrate for hOATP-C during the uptake measurements. The transporting kinetics of the substrate when mediated by the wild-type and the mutant-type transporters could be distinguished using the cell-based FETs. It was found that the signal generation mechanism of the cell-based transistor could be explained by direct or indirect proton transport via the transporters. Measurements of expression levels of membrane proteins is important to analyze their signaling pathways and cellular outcomes. Moreover, membrane proteins and transporters constitute one of the most extensively studied classes of drug targets. Therefore, a system based on cell-based FETs would be suitable for rapid and cost-effective identification of biomarkers and high throughput analysis of drug candidates.
Significant progress has been achieved in the field of solid-state biosensors over the past 50 years. Various sensing devices with high-density integration and flexible configuration, as well as new ...applications for clinical diagnosis and healthcare, have been developed using blood, serum, and other body fluids such as sweat, tears, and saliva. A high-density array of ion-sensitive field effect transistors was developed by exploiting the advantages of advanced semiconductor technologies and commercialized in combination with an enzymatic primer extension reaction as a DNA sequencer in 2011. Different types of materials such as inorganic materials, metals, polymers, and biomolecules are mixed together on the surface of the gate while maintaining their own functions; therefore, compatibility among different materials has to be optimized so that the best detection performance of solid-state biosensors, including stability and reliability, is achieved as designed. Solid-state biosensors are suitable for the rapid, cost-effective, and noninvasive identification of biomarkers at various timepoints over the course of a disease.
We developed a quantitative detection scheme for nucleic acids, combining solid-phase rolling circle amplification and chronocoulometry (RCA-CC). A gold electrode was directly formed on a polystyrene ...substrate as a cost-effective and flexible biosensor for sensitive detection of microRNA (mir-143) in blood samples.
Researchers widely apply enzyme inhibition to chemicals such as pesticides, nerve gases, and anti-Alzheimer’s drugs. However, application of enzyme inhibition to odorant sensors is less common ...because the corresponding reaction mechanisms have not yet been clarified in detail. In this study, we propose a new strategy for highly selective detection of odorant molecules by using an inhibitor-specific enzyme. As an example, we analyzed the selective interactions between acetylcholinesterase (AChE) and limonenethe major odorant of citrus and an AChE inhibitorusing molecular dynamics simulations. In these simulations, limonene was found to be captured at specific binding sites of AChE by modifying the binding site of acetylcholine (ACh), which induced inhibition of the catalytic activity of AChE toward ACh hydrolysis. We confirmed the simulation results by experiments using an ion-sensitive field-effect transistor, and the degree of inhibition of ACh hydrolysis depended on the limonene concentration. Accordingly, we quantitatively detected limonene at a detection limit of 5.7 μM. We furthermore distinguished the response signals to limonene from those to other odorants, such as pinene and perillic acid. Researchers will use our proposed odorant detection method for other odorant–enzyme combinations and applications of miniaturized odorant-sensing systems based on rapid testing.
In recent years, isothermal nucleic acid amplification techniques have been developed as alternatives to polymerase chain reaction (PCR) requiring thermal cycles. The integration of isothermal ...amplification into electrical or electrochemical devices realizes high throughput nucleic acid-based assays and confers high sensitivity. In this research, we tried to develop electrical/electrochemical biosensors detecting nucleic acids aiming at application to future liquid biopsy. For detection of small DNAs or microRNAs (miRNAs), isothermal amplification methods were employed, and the signal changes based on the extension reaction by polymerases were detected using electrical/electrochemical devices, namely, a chronocoulometric sensor and a micro pH sensor. These small sensors based on electrochemical technique might be a promising tool in on-site detection of nucleic acids related to cancer diagnosis.
A chairside tool for quantitative analysis of dental caries would improve clinical dental inspections. The wireless caries sensing tool with dental-explorer size has been developed comparing two ...sensing methods, Raman reading and pH reading for evaluating dental caries. The Raman spectra at 575 cm−1 and 960 cm−1 for in inorganic compounds, as well as 1450 cm−1 and 2940 cm−1 for organic compounds reinforced and supported the pH results. An Iridium/Iridium oxide (Ir/IrOx) pH sensing probe and wireless pH sensor (comprising an ESP8266 ESP-01 wireless module and ADS1115 analog digital converter) has been developed to quantitatively evaluate dental caries. All the operations of the wireless pH sensor were performed with a developed LabVIEW-based real-time data monitoring program. The slope and the linear fitting regression value (R2) of the wireless pH sensor using seven standards were −54.9 mV/pH and 0.999, respectively, showing high accuracy and stability for the pH measurements. The pH on the dental caries surface was measured with the wireless pH sensor, and the pH mapping results in the non-caries and caries areas were 6.9 and 5.7, respectively. The developed wireless pH sensor would be useful to understand the condition of dental caries and support dentists’ inspection to remove only the caries part while keeping the non-caries structure.
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•The surface pH of the dental caries in relation to the molecular composition of the caries areas have been evaluated.•The wireless pH sensor is developed combining with a wireless module, a pH electrode and data acquisition system.•The pH value of the non-caries and caries area were 6.9 and 5.8, which was comparable to the wired pH sensor results.
We developed a new building block for a protein- and cell-repellant self-assembled monolayer (SAM) from 2-methacryloyloxyethyl phosphorylcholine (MPC) via a simple Michael-type addition to one ...mercapto group in alkanedithiol. The thiolated MPC can enable functionalization of a noble metal electrode to minimize noise signal in biosensing.
A quantitative diagnostic method for dental caries would improve oral health, which directly affects the quality of life. Here we describe the preparation and application of Ir/IrOx pH sensors, which ...are used to measure the surface pH of dental caries. The pH level is used as an indicator to distinguish between active and arrested caries. After a dentist visually inspected and defined 18 extracted dentinal caries at various positions as active or arrested caries, the surface pH values of sound and caries areas were directly measured with an Ir/IrOx pH sensor with a diameter of 300 μm as a dental explorer. The average pH values of the sound root, the arrested caries, and active caries were 6.85, 6.07, and 5.30, respectively. The pH obtained with an Ir/IrOx sensor was highly correlated with the inspection results by the dentist, indicating that the types of caries were successfully categorized. This caries testing technique using a micro Ir/IrOx pH sensor provides an accurate quantitative caries evaluation and has potential in clinical diagnosis.
Significant progress has been achieved in the field of solid-state biosensors over the past 50 years. Various sensing devices with high-density integration and flexible configuration, as well as new ...applications for clinical diagnosis and healthcare, have been developed using blood, serum, and other body fluids such as sweat, tears, and saliva. A high-density array of ion-sensitive field effect transistors was developed by exploiting the advantages of advanced semiconductor technologies and commercialized in combination with an enzymatic primer extension reaction as a DNA sequencer in 2011. Different types of materials such as inorganic materials, metals, polymers, and biomolecules are mixed together on the surface of the gate while maintaining their own functions; therefore, compatibility among different materials has to be optimized so that the best detection performance of solid-state biosensors, including stability and reliability, is achieved as designed. Solid-state biosensors are suitable for the rapid, cost-effective, and noninvasive identification of biomarkers at various timepoints over the course of a disease.
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