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Biologically sensitive field-effect devices (BioFEDs) advantageously combine the electronic field-effect functionality with the (bio)chemical receptor’s recognition ability for (bio)chemical sensing. In this review, basic and widely applied device concepts of silicon-based BioFEDs (ion-sensitive field-effect transistor, silicon nanowire transistor, electrolyte-insulator-semiconductor capacitor, light-addressable potentiometric sensor) are presented and recent progress (from 2019 to early 2021) is discussed. One of the main advantages of BioFEDs is the label-free sensing principle enabling to detect a large variety of biomolecules and bioparticles by their intrinsic charge. The review encompasses applications of BioFEDs for the label-free electrical detection of clinically relevant protein biomarkers, deoxyribonucleic acid molecules and viruses, enzyme-substrate reactions as well as recording of the cell acidification rate (as an indicator of cellular metabolism) and the extracellular potential.
A chip-based amperometric biosensor referring on using the bioelectrocatalytical amplification principle for the detection of low adrenaline concentrations is presented. The adrenaline biosensor has been prepared by modification of a platinum thin-film electrode with an enzyme membrane containing the pyrroloquinoline quinone-dependent glucose dehydrogenase and glutaraldehyde. Measuring conditions such as temperature, pH value, and glucose concentration have been optimized to achieve a high sensitivity and a low detection limit of about 1 nM adrenaline measured in phosphate buffer at neutral pH value. The response of the biosensor to different catecholamines has also been proven. Long-term stability of the adrenaline biosensor has been studied over 10 days. In addition, the biosensor has been successfully applied for adrenaline detection in human blood plasma for future biomedical applications. Furthermore, preliminary experiments have been carried to detect the adrenaline-concentration difference measured in peripheral blood and adrenal venous blood, representing the adrenal vein sampling procedure of a physician.
A field-effect biosensor employing tobacco mosaic virus (TMV) particles as scaffolds for enzyme immobilization is presented. Nanotubular TMV scaffolds allow a dense immobilization of precisely positioned enzymes with retained activity. To demonstrate feasibility of this new strategy, a penicillin sensor has been developed by coupling a penicillinase with virus particles as a model system. The developed field-effect penicillin biosensor consists of an Al-p-Si-SiO₂-Ta₂O₅-TMV structure and has been electrochemically characterized in buffer solutions containing different concentrations of penicillin G. In addition, the morphology of the biosensor surface with virus particles was characterized by scanning electron microscopy and atomic force microscopy methods. The sensors possessed a high penicillin sensitivity of ~ 92 mV/dec in a nearly-linear range from 0.1 mM to 10 mM, and a low detection limit of about 50 µM. The long-term stability of the penicillin biosensor was periodically tested over a time period of about one year without any significant loss of sensitivity. The biosensor has also been successfully applied for penicillin detection in bovine milk samples.
An enzyme-based reversible Controlled NOT (CNOT) logic gate operating on a semiconductor transducer
(2017)
An enzyme-based biocatalytic system mimicking operation of a logically reversible Controlled NOT (CNOT) gate has been interfaced with semiconductor electronic transducers. Electrolyte–insulator–semiconductor (EIS) structures have been used to transduce chemical changes produced by the enzyme system to an electronically readable capacitive output signal using field-effect features of the EIS device. Two enzymes, urease and esterase, were immobilized on the insulating interface of EIS structure producing local pH changes performing XOR logic operation controlled by various combinations of the input signals represented by urea and ethyl butyrate. Another EIS transducer was functionalized with esterase only, thus performing Identity (ID) logic operation for the ethyl butyrate input. Both semiconductor devices assembled in parallel operated as a logically reversible CNOT gate. The present system, despite its simplicity, demonstrated for the first time logically reversible function of the enzyme system transduced electronically with the semiconductor devices. The biomolecular realization of a CNOT gate interfaced with semiconductors is promising for integration into complex biomolecular networks and future biosensor/biomedical applications.
The LAPS (light-addressable potentiometric sensor) platform is one of the most attractive approaches for chemical and biological sensing with many applications ranging from pH and ion/analyte concentration measurements up to cell metabolism detection and chemical imaging. However, although it is generally accepted that LAPS measurements are spatially resolved, the light-addressability feature of LAPS devices has not been discussed in detail so far. In this work, an extended electrical equivalent-circuit model of the LAPS has been presented, which takes into account possible cross-talk effects due to the capacitive coupling of the non-illuminated region. A shunting effect of the non-illuminated area on the measured photocurrent and addressability of LAPS devices has been studied. It has been shown, that the measured photocurrent will be determined not only by the local interfacial potential in the illuminated region but also by possible interfacial potential changes in the non-illuminated region, yielding cross-talk effects. These findings were supported by the experimental investigations of a penicillin-sensitive multi-spot LAPS and a metal-insulator-semiconductor LAPS as model systems.
Label-free Electrostatic Detection of DNA Amplification by PCR Using Capacitive Field-effect Devices
(2016)
A capacitive field-effect EIS (electrolyte-insulator-semiconductor) sensor modified with a positively charged weak polyelectrolyte of poly(allylamine hydrochloride) (PAH)/single-stranded probe DNA (ssDNA) bilayer has been used for a label-free electrostatic detection of pathogen-specific DNA amplification via polymerase chain reaction (PCR). The sensor is able to distinguish between positive and negative PCR solutions, to detect the existence of target DNA amplicons in PCR samples and thus, can be used as tool for a quick verification of DNA amplification and the successful PCR process.
The conjunction of (bio-)chemical recognition elements with nanoscale biological building blocks such as virus particles is considered as a very promising strategy for the creation of biohybrids opening novel opportunities for label-free biosensing. This work presents a new approach for the development of biosensors using tobacco mosaic virus (TMV) nanotubes or coat proteins (CPs) as enzyme nanocarriers. Sensor chips combining an array of Pt electrodes loaded with glucose oxidase (GOD)-modified TMV nanotubes or CP aggregates were used for amperometric detection of glucose as a model system for the first time. The presence of TMV nanotubes or CPs on the sensor surface allows binding of a high amount of precisely positioned enzymes without substantial loss of their activity, and may also ensure accessibility of their active centers for analyte molecules. Specific and efficient immobilization of streptavidin-conjugated GOD ([SA]-GOD) complexes on biotinylated TMV nanotubes or CPs was achieved via bioaffinity binding. These layouts were tested in parallel with glucose sensors with adsorptively immobilized [SA]-GOD, as well as [SA]-GOD crosslinked with glutardialdehyde, and came out to exhibit superior sensor performance. The achieved results underline a great potential of an integration of virus/biomolecule hybrids with electronic transducers for future applications in biosensorics and biochips.