Silicon nanowire field‐effect transistors (SiNW‐FETs) are offering a label‐free sensing of DNA molecules based on the detection of the biomolecules’ charges. Typically, the charge accumulation at the solid–liquid interface is leading to a change in surface potential of the device. In other works, this effect is usually displayed as change in conductance of the nanowires. In this paper, we show that our topdown processed SiNW‐FET devices can be regarded as long‐channel, ion‐sensitive field‐effect transistor devices (ISFETs) and that their electronic characteristics can be fitted by an advanced MOSFET model taking narrow channel effects into account. In DNA experiments, changes in threshold voltage upon immobilization of capture DNA and hybridization with complementary target DNA were recorded as reported before. The signal amplitudes were scaling with different concentrations of electrolyte buffer as known from the commonly used Poisson–Boltzmann theory. In reports from other groups, the sensitivity of SiNW‐FETs was reported to be superior compared to ISFETs and scaling effects were observed with smaller wires having higher sensitivities. From our experiments, it seems that the immobilization of the DNA to the wire structure is leading to two effects: firstly, the threshold voltage is changing, leading to a shift in the transistors’ transfer characteristics similar to what was described for ISFET devices. In addition, upon DNA binding, a general increase in charge carrier density inside the nanowire is leading to an enhanced conductance. We assume that the latter effect is scaling with nanowire dimensions, while the surface effect is typically constant for all sensor structures.
In this work, we present a reduced graphene oxide‐based impedimetric histamine biosensor. Histamine as a bioamine mediates immune‐modulatory effects in acute inflammatory and allergic reactions. In a proof‐of‐principle approach, the low‐cost sensor platform determines low concentrations of histamine in buffer solution with an impedimetric readout technique. As a sensor platform we used ultra‐thin graphene oxide lines fabricated by a simple soft‐lithographic approach. The lines of about 20 μm width were characterised by atomic force microscopy and scanning electron microscopy. Reduction of graphene oxide to a conductive transducer material was performed by a rapid thermal protocol in inert atmosphere. The reduction process was monitored by impedance spectroscopy and X‐ray photoelectron spectroscopy. For our biosensor experiments we adopted a commonly‐used protocol for surface plasmon resonance (SPR) detection of histamine. With our reduced graphene oxide platform we detected antigen‐antibody binding events of histamine with concentrations of 0.1–1 μM via impedance changes in a low frequency range. The results from the rGO sensors were comparable to the SPR detection.
The semiconductor field-effect platform represents a powerful tool for detecting the adsorption and binding of charged macromolecules with direct electrical readout. In this work, a capacitive electrolyte-insulator-semiconductor (EIS) field-effect sensor consisting of an Al-p-Si-SiO2 structure has been applied for real-time in situ electrical monitoring of the layer-by-layer formation of polyelectrolyte (PE) multilayers (PEM). The PEMs were deposited directly onto the SiO2 surface without any precursor layer or drying procedures. Anionic poly(sodium 4-styrene sulfonate) and cationic weak polyelectrolyte poly(allylamine hydrochloride) have been chosen as a model system. The effect of the ionic strength of the solution, polyelectrolyte concentration, number and polarity of the PE layers on the characteristics of the PEM-modified EIS sensors have been studied by means of capacitance-voltage and constant-capacitance methods. In addition, the thickness, surface morphology, roughness and wettabilityof the PE mono- and multilayers have been characterised by ellipsometry, atomic force microscopy and water contact-angle methods, respectively. To explain potential oscillations on the gate surface and signal behaviour of the capacitive field-effect EIS sensor modified with a PEM, a simplified electrostatic model that takes into account the reduced electrostatic screening of PE charges by mobile ions within the PEM has been proposed and discussed.
An array of electrically isolated nanoplate field-effect silicon-on-insulator (SOI) capacitors as a new transducer structure for multi-parameter (bio-) chemical sensing is presented. The proposed approach allows addressable biasing and electrical readout of multiple nanoplate field-effect capacitive (bio-) chemical sensors on the same SOI chip, as well as differential-mode measurements. The realized sensor chip has been applied for pH and penicillin concentration measurements, electrical monitoring of polyelectrolyte multilayer formation, and the label-free electrical detection of consecutive deoxyribonucleic acid (DNA) hybridization and denaturation events.
A method for the routine fabrication of graphene (reduced graphene oxide (r-GO)) based devices is reported. We describe a solution-based technique for the fabrication of the devices on alternative substrates and subsequent on-substrate processing of graphene oxide into reduced graphene oxide. As sensor platform we mainly used interdigitated gold electrodes forming microarray structures on glass substrates. Graphene oxide was site-specifically deposited onto microelectrode arrays by dielectrophoresis followed by a solution-based reduction of graphene oxide with L-ascorbic acid. In order to test the r-GO sensor stability and performance, impedance spectroscopy was used. The optimized all solution processed fabrication provides an attractive fabrication route for robust r-GO microarray devices in a flexible, scalable and cost-effective approach. Schematics for a microarray chip based on reduced graphene oxide.
In the present study, reduced graphene oxide (rGO) is used as a biointerface for the investigation of cell adhesion of human embryonic kidney (HEK 293) cells. A fast, straightforward, and substrate-independent soft lithography approach known as Micromolding In Capillaries (MIMIC) was utilized to pattern graphene oxide (GO) arrays. Large-scale GO patterns with widths and distances in the micrometer range were obtained and were subsequently reduced to rGO via an environmentally-friendly procedure using L-ascorbic acid. Physical characterization of rGO patterns and cells was performed by optical microscopy, atomic force microscopy, and scanning electron microscopy. Impedance spectroscopy was used for the electrochemical characterization of GO before and after reduction. Cell adhesion and alignment was strong on the rGO micropatterns. In future assays, the rGO could combine two functions: cellular patterning and electrical interfacing of cells. HEK 293 cells aligning on rGO micro patterns (SEM image)
Field-effect-based semiconductor devices for the label-free detection of molecular interactions represent a promising platform for biosensor applications. However, a quantitative physical understanding of experimental observations is still not complete in many situations. Therefore, it is important to elucidate the possibilities and limitations of field-effect sensors for the detection of charged macromolecules. In this work, a capacitive electrolyte-insulator-semiconductor field-effect sensor has been applied for real-time in-situ electrical monitoring of a layer-by-layer build-up of polyelectrolyte multilayers. The thickness of polyelectrolyte layers and changes in the surface morphology after the adsorption of each polyelectrolyte layer has been studied by ellipsometry and scanning-electron microscopy. Reproducible oscillations of the sensor signal have been observed upon repetitive alternating adsorption of positively and negatively charged polyelectrolyte layers. To explain signal behaviour of a capacitive field-effect sensor modified with polyelectrolyte multilayers, potential oscillations on the gate surface were simulated using a simplified electrostatic model that accounts for the screening of polyelectrolyte charges by mobile ions within the PEM film.
In this study, impedance spectroscopy measurements of silicon-based open-gate field-effect transistor (FET) devices were utilized to study the adhesion status of cancer cells at a single cell level. We developed a trans-impedance amplifier circuit for the FETs with a higher bandwidth compared to a previously described system. The new system was characterized with a fast lock-in amplifier, which enabled measuring of impedance spectra up to 50 MHz. We studied cellular activities, including cell adhesion and anti-cancer drug induced apoptosis of human embryonic kidney (HEK293) and human lung adenocarcinoma epithelial (H441) cells. A well-known chemotherapeutic drug, topotecan hydrochloride, was used to investigate the effect of this drug to tumor cells cultured on the FET devices. The presence of the drug resulted in a 20% change in the amplitude of the impedance spectra at 200 kHz as a result of the induced apoptosis process. Real-time impedance measurements were performed inside an incubator at a constant frequency. The experimental results can be interpreted with an equivalent electronic circuit to resolve the influence of the system parameters. The developed method could be applied for the analysis of the specificity and efficacy of novel anti-cancer drugs in cancer therapy research on a single cell level in parallelized measurements.
Field-effect capacitive electrolyte-insulator-semiconductor (EIS) sensors functionalised with citrate-capped gold nanoparticles (AuNP) have been used for the electrostatic detection of macromolecules by their intrinsic molecular charge. The EIS sensor detects the charge changes in the AuNP/macromolecule hybrids induced by the adsorption or binding events. A feasibility of the proposed detection scheme has been exemplary demonstrated by realising EIS sensors for the detection of poly-D-lysine molecules.