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.
Conferring antifouling properties can extend the use of conducting polymers in biosensors and bioelectronics under complex biological conditions. On the basis of the antifouling properties of a ...series of zwitterionic polymers, we synthesized new thiophene-based compounds bearing a phosphorylcholine, carboxybetaine, or sulfobetaine pendant group. The monomers were synthesized by a facile reaction of thiol-functionalized 3,4-ethylenedioxythiophene with zwitterionic methacrylates. Electrochemical copolymerization was performed to deposit zwitterionic poly(3,4-ethylenedioxythiophene) (PEDOT) films with tunable conducting and antifouling properties on a conducting substrate. Electrochemical impedance spectroscopy showed that the conductivity and capacitance decreased with increasing zwitterionic content in the films. Protein adsorption and cell adhesion studies showed the effects of the type and content of zwitterions on the antifouling characteristics. Optimization of the electrodeposition conditions enabled development of both conducting and antifouling polymer films. These antifouling conjugated functional polymers have promising applications in biological environments.
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.
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•An organic electrochemical transistor with trisaccharide-functionalized PEDOT:PSS was developed for human influenza virus sensing.•The interaction of sialyllactose with hemagglutinin ...on the viral surface mimicked the host infection mechanism.•Influenza virus recognition was continuously monitored by drain current changes at no gate bias.•The limit of detection for human influenza A virus was 0.025 HAU.
An organic electrochemical transistor (OECT) with a trisaccharide-grafted conductive polymer channel was developed for human influenza A virus detection under aqueous conditions. A target recognition element was introduced into the electrochemical amplifier of the OECT for highly sensitive, selective, and label-free virus sensing. 3,4-Ethylenedioxythiophene (EDOT) and its derivative bearing an oxylamine moiety (EDOTOA) were electrochemically copolymerized on the channel region composed of a PEDOT:PSS thin film. The trisaccharides composed of Sia-α2,6′-Gal-Glu (2,6-sialyllactose), a specific receptor for the hemagglutinin used as a spike protein on the surface of human influenza A virus, were covalently introduced into the EDOTOA unit. Changes in the drain current of the OECT were observed following virus adsorption onto the 2,6-sialyllactose-functionalized channel. A signal transduction mechanism involving a doping effect due to the adsorption of negatively-charged virus nanoparticles is proposed. The limit of detection was more than two orders of magnitude lower than commercial immunochromatographic influenza virus assays over the same detection time. Because of its processability with printing technologies and low power consumption, the OECT device developed here may be suitable for the wearable monitoring of influenza virus infection.
PIC‐ing a winner: siRNA encapsulated by a phenylboronate‐functionalized polyion complex (PIC) micelle shows binding between the phenylboronate and the 3′ ribose of the siRNA (see scheme), stabilizing ...the complex under conditions equivalent to the extracellular environment. This complex is disrupted in response to addition of ATP, at a concentration comparable to that inside cells.
Protein‐free: A hydrogel containing phenylboronate was optimized so as to undergo rapid glucose‐dependent changes in the state of hydration under physiological aqueous conditions. A localized ...dehydration of the gel surface to form a “skin layer” enabled control of the release of insulin from the gel. This dehydration is induced by fluctuations in the glucose concentration in the range between normo‐ and hyperglycemia.
Conducting polymers possessing biorecognition elements are essential for developing electrical biosensors sensitive and specific to clinically relevant biomolecules. We developed a new ...3,4-ethylenedioxythiophene (EDOT) derivative bearing a zwitterionic phosphorylcholine group via a facile synthesis through the Michael-type addition thiol–ene “click” reaction for the detection of an acute-phase biomarker human C-reactive protein (CRP). The phosphorylcholine group, a major headgroup in phospholipid, which is the main constituent of plasma membrane, was also expected to resist nonspecific adsorption of other proteins at the electrode/solution interface. The biomimetic EDOT derivative was randomly copolymerized with EDOT, via an electropolymerization technique with a dopant sodium perchlorate, onto a glassy carbon electrode to make the synthesized polymer film both conductive and target-responsive. The conducting copolymer films were characterized by cyclic voltammetry, scanning electron microscopy, attenuated total reflection Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. The specific interaction of CRP with phosphorylcholine in a calcium-containing buffer solution was determined by differential pulse voltammetry, which measures the altered redox reaction between the indicators ferricyanide/ferrocyanide as a result of the binding event. The conducting polymer-based protein sensor achieved a limit of detection of 37 nM with a dynamic range of 10–160 nM, covering the dynamically changing CRP levels in circulation during the acute phase. The results will enable the development of metal-free, antibody-free, and low-impedance electrochemical biosensors for the screening of nonspecific biomarkers of inflammation and infection.
Alternations of sialic acid (SA) content on cell surface glycan chains have been implicated in numerous normal and pathological processes including developments, differentiations, and tumor ...metastasis. Overexpressions of SA have been implicated in the malignant and metastatic phenotypes for many different types of cancers, while decreased SA expression has also been identified in erythrocytes of diabetic mellitus. Techniques to conveniently monitor cell surface SA would therefore have great relevance to cytology. Preexisting methodologies to quantify SA, however, involve multiple enzymatic, dye-labeling, and lethal procedures, which are costly and time-consuming. Here we developed a potentiometric SA detection using a phenylboronic acid (PBA) compound integrated into the form of a self-assembled monolayer (SAM) onto a field effect transistor (FET) extended gold gate electrode. Due to selective binding between undisassociated PBA and SA at pH 7.4 among other glycan chain constituent monosaccharides, we found that carboxyl anions of SA were exclusively detectable as the change in threshold voltage (V T) of the PBA-modified FET. The technique was applied to analyses of altered SA expressions on rabbit erythrocyte as a model for diabetes. Comparative SA expression analyses for each healthy and diseased model revealed that the disease could be feasibly diagnosed simply by placing the known-count cell suspensions onto the device without any labeling and enzymatic procedures. Such a technique may also provide a quantitative adjunct to histological evaluation of tumor malignancy and metastatic potential during intra- and postoperative diagnoses. Also advantageously, a technique herein described is all within a CMOS (Complementary Metal Oxide Semiconductor) compatible format thus promising for highly efficient and low cost manufacturing with readiness of downsizing and integration by virtue of advanced semiconductor processing technologies.
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