Elevating Platinum to Volumetric Capacitance: High Surface Area Electrodes through Reactive Pt Sputtering.

Platinum is the most widespread electrode material used for implantable biomedical and neuroelectronic devices, motivating exploring ways to improve its performance and understand its fundamental properties. Using reactive magnetron sputtering, PtOx is prepared, which upon partial reduction yields a porous thin-film form of platinum with favorable properties, notably record-low impedance values outcompeting other reports for platinum-based electrodes. It is established that its high electrochemical capacitance scales with thickness, in the way of volumetric capacitor materials like IrOx and poly(3,4-ethylenedioxythiophene), PEDOT. Unlike these two well-known analogs, however, it is found that PtOx capacitance is not caused by reversible pseudofaradaic reactions but rather due to high surface area. In contrast to IrOx, PtOx is not a reversible valence-change oxide, but rather a porous form of platinum. The findings show that this oxygen-containing form of Pt can place Pt electrodes on a level competitive with IrOx and PEDOT. Due to its relatively low cost and ease of preparation, PtOx can be a good choice for microfabricated bioelectronic devices.

Time-encoded electrical detection of trace RNA biomarker by integrating programmable molecular amplifier on chip.

One of the serious challenges facing modern point-of-care (PoC) molecular diagnostic platforms relate to reliable detection of low concentration biomarkers such as nucleic acids or proteins in biological samples. Non-specific analyte-receptor interactions due to competitive binding in the presence of abundant molecules, inefficient mass transport and very low number of analyte molecules in sample volume, in general pose critical hurdles for successful implementation of such PoC platforms for clinical use. Focusing on these specific challenges, this work reports a unique PoC biosensor that combines the advantages of nanoscale biologically-sensitive field-effect transistor arrays (BioFET-arrays) realized in a wafer-scale top-down nanofabrication as high sensitivity electrical transducers with that of sophisticated molecular programs (MPs) customized for selective recognition of analyte miRNAs and amplification resulting in an overall augmentation of signal transduction strategy. The MPs realize a programmable universal molecular amplifier (PUMA) in fluidic matrix on chip and provide a biomarker-triggered exponential release of small nucleic acid sequences easily detected by receptor-modified BioFETs. A common miRNA biomarker LET7a was selected for successful demonstration of this novel biosensor, achieving limit of detection (LoD) down to 10 fM and wide dynamic ranges (10 pM-10 nM) in complex physiological solutions. As the determination of biomarker concentration is implemented by following the electrical signal related to analyte-triggered PUMA in time-domain instead of measuring the threshold shifts of BioFETs, and circumvents direct hybridization of biomarkers at transducer surface, this new strategy also allows for multiple usage (>3 times) of the biosensor platform suggesting exceptional cost-effectiveness for practical use.

Lock-in photothermal method for in-plane thermal diffusivity measurements using arrayed temperature sensors on suspended SiNx membranes.

A device consisting of a line- or spiral-shaped temperature sensor array on a two-dimensional (2D) silicon nitride (SiNx) membrane of thickness 50 or 150 nm is developed for use in the lock-in photothermal method to determine the in-plane thermal diffusivity of SiNx membranes in air and in vacuum. The results of 2D heat diffusion are analyzed by the quadrupole method, and the system is approximated to the one-dimensional (1D) fin standing in a surrounding media (the fin approximation). The results show that 2D thermal diffusion on the membrane is affected not only by heat exchange with the surrounding environment but also by parallel thermal diffusion caused by heat conduction in the air along the membrane surface. The measurement using photothermal heating and contact detection of the temperature response enables the phenomenon to be detected consistently at a wide frequency range of temperature waves (50-1000 Hz). The measured thermal diffusivity values of the SiNx membrane are much smaller than those of bulk material, which can be reasonably considered an effect of the confined state of the phonon in the nanoscale geometry of the membrane.

A sigh-performance hydrogen gas sensor based on Ag/Pd nanoparticle-functionalized ZnO nanoplates.

As a source of clean energy, hydrogen (H2) is a promising alternative to fossil fuels in reducing the carbon footprint. However, due to the highly explosive nature of H2, developing a high-performance sensor for real-time detection of H2 gas at low concentration is essential. Here, we demonstrated the H2 gas sensing performance of Ag/Pd nanoparticle-functionalized ZnO nanoplates. Bimetallic Ag/Pd nanoparticles with an average size of 8 nm were prepared and decorated on the surface of ZnO nanoplates to enhance the H2 gas sensing performance. Compared with pristine ZnO, the sensor based on ZnO nanoplate doped with Ag/Pd (0.025 wt%) exhibited an outstanding response upon exposure to H2 gas (R a/R g = 78 for 500 ppm) with fast response time and speedy recovery. The sensor also showed excellent selectivity for the detection of H2 over the interfering gases (i.e., CO, NH3, H2S, and VOCs). The superior gas sensing of the sensor was dominated by the morphological structure of ZnO, and the synergistic effect of strong adsorption and the optimum catalytic characteristics of the bimetallic Ag/Pd enhances the hydrogen response of the sensors. Thus, bimetallic Ag/Pd-doped ZnO is a promising sensing material for the quantitative determination of H2 concentration towards industrial applications.

Direct measurement of oxygen reduction reactions at neurostimulation electrodes.

Objective. Electric stimulation delivered by implantable electrodes is a key component of neural engineering. While factors affecting long-term stability, safety, and biocompatibility are a topic of continuous investigation, a widely-accepted principle is that charge injection should be reversible, with no net electrochemical products forming. We want to evaluate oxygen reduction reactions (ORR) occurring at different electrode materials when using established materials and stimulation protocols.Approach. As stimulation electrodes, we have tested platinum, gold, tungsten, nichrome, iridium oxide, titanium, titanium nitride, and poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate). We use cyclic voltammetry and voltage-step amperometry in oxygenated versus inert conditions to establish at which potentials ORR occurs, and the magnitudes of diffusion-limited ORR currents. We also benchmark the areal capacitance of each electrode material. We use amperometric probes (Clark-type electrodes) to quantify the O2and H2O2concentrations in the vicinity of the electrode surface. O2and H2O2concentrations are measured while applying DC current, or various biphasic charge-balanced pulses of amplitude in the range 10-30µC cm-2/phase. To corroborate experimental measurements, we employ finite element modelling to recreate 3D gradients of O2and H2O2.Main results. All electrode materials support ORR and can create hypoxic conditions near the electrode surface. We find that electrode materials differ significantly in their onset potentials for ORR, and in the extent to which they produce H2O2as a by-product. A key result is that typical charge-balanced biphasic pulse protocols do lead to irreversible ORR. Some electrodes induce severely hypoxic conditions, others additionally produce an accumulation of hydrogen peroxide into the mM range.Significance. Our findings highlight faradaic ORR as a critical consideration for neural interface devices and show that the established biphasic/charge-balanced approach does not prevent irreversible changes in O2concentrations. Hypoxia and H2O2can result in different (electro)physiological consequences.

Realization of a PEDOT:PSS/Graphene Oxide On-Chip Pseudo-Reference Electrode for Integrated ISFETs.

A stable reference electrode (RE) plays a crucial role in the performance of an ion-sensitive field-effect transistor (ISFET) for bio/chemical sensing applications. There is a strong demand for the miniaturization of the RE for integrated sensor systems such as lab-on-a-chip (LoC) or point-of-care (PoC) applications. Out of several approaches presented so far to integrate an on-chip electrode, there exist critical limitations such as the effect of analyte composition on the electrode potential and drifts during the measurements. In this paper, we present a micro-scale solid-state pseudo-reference electrode (pRE) based on poly(3,4-ethylene dioxythiophene): poly(styrene sulfonic acid) (PEDOT:PSS) coated with graphene oxide (GO) to deploy with an ion-sensitive field-effect transistor (ISFET)-based sensor platform. The PEDOT:PSS was electropolymerized from its monomer on a micro size gold (Au) electrode and, subsequently, a thin GO layer was deposited on top. The stability of the electrical potential and the cross-sensitivity to the ionic strength of the electrolyte were investigated. The presented pRE exhibits a highly stable open circuit potential (OCP) for up to 10 h with a minimal drift of ~0.65 mV/h and low cross-sensitivity to the ionic strength of the electrolyte. pH measurements were performed using silicon nanowire field-effect transistors (SiNW-FETs), using the developed pRE to ensure good gating performance of electrolyte-gated FETs. The impact of ionic strength was investigated by measuring the transfer characteristic of a SiNW-FET in two electrolytes with different ionic strengths (1 mM and 100 mM) but the same pH. The performance of the PEDOT:PSS/GO electrode is similar to a commercial electrochemical Ag/AgCl reference electrode.

Process Variability in Top-Down Fabrication of Silicon Nanowire-Based Biosensor Arrays.

Silicon nanowire field-effect transistors (SiNW-FET) have been studied as ultra-high sensitive sensors for the detection of biomolecules, metal ions, gas molecules and as an interface for biological systems due to their remarkable electronic properties. "Bottom-up" or "top-down" approaches that are used for the fabrication of SiNW-FET sensors have their respective limitations in terms of technology development. The "bottom-up" approach allows the synthesis of silicon nanowires (SiNW) in the range from a few nm to hundreds of nm in diameter. However, it is technologically challenging to realize reproducible bottom-up devices on a large scale for clinical biosensing applications. The top-down approach involves state-of-the-art lithography and nanofabrication techniques to cast SiNW down to a few 10s of nanometers in diameter out of high-quality Silicon-on-Insulator (SOI) wafers in a controlled environment, enabling the large-scale fabrication of sensors for a myriad of applications. The possibility of their wafer-scale integration in standard semiconductor processes makes SiNW-FETs one of the most promising candidates for the next generation of biosensor platforms for applications in healthcare and medicine. Although advanced fabrication techniques are employed for fabricating SiNW, the sensor-to-sensor variation in the fabrication processes is one of the limiting factors for a large-scale production towards commercial applications. To provide a detailed overview of the technical aspects responsible for this sensor-to-sensor variation, we critically review and discuss the fundamental aspects that could lead to such a sensor-to-sensor variation, focusing on fabrication parameters and processes described in the state-of-the-art literature. Furthermore, we discuss the impact of functionalization aspects, surface modification, and system integration of the SiNW-FET biosensors on post-fabrication-induced sensor-to-sensor variations for biosensing experiments.

PEDOT:PSS organic electrochemical transistors for electrical cell-substrate impedance sensing down to single cells.

The adhesion of cells on organic electrochemical transistors (OECT) is investigated down to a single cell resolution using an impedimetric readout method of the transistors. For this purpose a fabrication protocol for micro-sized OECTs based on Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonic acid) (PEDOT:PSS) was developed. OECTs with gate dimensions of 20 µm × 20 µm with cut-off frequencies up to 10 kHz at -3 dB were fabricated. Impedance spectra of the OECTs changed drastically when HEK 293 cells were adhered to the OECT gates. To confirm the single-cell sensitivity, individual cells were removed from the device surface with patch-clamp pipettes while impedance measurements were performed. In addition, the calcium chelator EGTA was used to demonstrate the reproducible activation and deactivation of tight gap junctions in Madin Darby Canine Kidney cells adhered on the OECT gates. We applied an analytical mathematical model combined with an electrically equivalent circuit model to describe the measured impedance spectra and to calculate the cell-related parameters of the adherent cells. The novel technique of impedimetric readout of OECTs for the detection of single cell adhesion offers various future applications.

Point-of-care-ready nanoscale ISFET arrays for sub-picomolar detection of cytokines in cell cultures.

Rapid and frequent screening of cytokines as immunomodulation agents is necessary for precise interventions in severe pathophysiological conditions. In addition to high-sensitivity detection of such analytes in complex biological fluids such as blood, saliva, and cell culture medium samples, it is also crucial to work out miniaturized bioanalytical platforms with potential for high-density integration enabling screening of multiple analytes. In this work, we show a compact, point-of-care-ready bioanalytical platform for screening of cytokines such as interleukin-4 (IL-4) and interleukin-2 (IL-2) based on one-dimensional ion-sensitive field-effect transistors arrays (nanoISFETs) of silicon fabricated at wafer-scale via nanoimprint lithography. The nanoISFETs biofunctionalized with receptor proteins alpha IL-4 and alpha IL-2 were deployed for screening cytokine secretion in mouse T helper cell differentiation culture media, respectively. Our nanoISFETs showed robust sensor signals for specific molecular binding and can be readily deployed for real-time screening of cytokines. Quantitative analyses of the nanoISFET-based bioanalytical platform was carried out for IL-4 concentrations ranging from 25 fg/mL (1.92 fM) to 2.5 µg/mL (192 nM), showing a limit of detection down to 3-5 fM, which was found to be in agreement with ELISA results in determining IL-4 concentrations directly in complex cell culture media. Graphical abstract.

Comprehensive Understanding of Silicon-Nanowire Field-Effect Transistor Impedimetric Readout for Biomolecular Sensing.

Impedance sensing with silicon nanowire field-effect transistors (SiNW-FETs) shows considerable potential for label-free detection of biomolecules. With this technique, it might be possible to overcome the Debye-screening limitation, a major problem of the classical potentiometric readout. We employed an electronic circuit model in Simulation Program with Integrated Circuit Emphasis (SPICE) for SiNW-FETs to perform impedimetric measurements through SPICE simulations and quantitatively evaluate influences of various device parameters to the transfer function of the devices. Furthermore, we investigated how biomolecule binding to the surface of SiNW-FETs is influencing the impedance spectra. Based on mathematical analysis and simulation results, we proposed methods that could improve the impedimetric readout of SiNW-FET biosensors and make it more explicable.

Monatomic phase change memory.

Phase change memory has been developed into a mature technology capable of storing information in a fast and non-volatile way1-3, with potential for neuromorphic computing applications4-6. However, its future impact in electronics depends crucially on how the materials at the core of this technology adapt to the requirements arising from continued scaling towards higher device densities. A common strategy to fine-tune the properties of phase change memory materials, reaching reasonable thermal stability in optical data storage, relies on mixing precise amounts of different dopants, resulting often in quaternary or even more complicated compounds6-8. Here we show how the simplest material imaginable, a single element (in this case, antimony), can become a valid alternative when confined in extremely small volumes. This compositional simplification eliminates problems related to unwanted deviations from the optimized stoichiometry in the switching volume, which become increasingly pressing when devices are aggressively miniaturized9,10. Removing compositional optimization issues may allow one to capitalize on nanosize effects in information storage.

Top-Down Fabricated Silicon Nanowire Arrays for Field-Effect Detection of Prostate-Specific Antigen.

Highly sensitive electrical detection of biomarkers for the early stage screening of cancer is desired for future, ultrafast diagnostic platforms. In the case of prostate cancer (PCa), the prostate-specific antigen (PSA) is of prime interest and its detection in combination with other PCa-relevant biomarkers in a multiplex approach is advised. Toward this goal, we demonstrate the label-free, potentiometric detection of PSA with silicon nanowire ion-sensitive field-effect transistor (Si NW-ISFET) arrays. To realize the field-effect detection, we utilized the DNA aptamer-receptors specific for PSA, which were covalently and site-specifically immobilized on Si NW-ISFETs. The platform was used for quantitative detection of PSA and the change in threshold voltage of the Si NW-ISEFTs was correlated with the concentration of PSA. Concentration-dependent measurements were done in a wide range of 1 pg/mL to 1 µg/mL, which covers the clinical range of interest. To confirm the PSA-DNA aptamer binding on the Si NW surfaces, a sandwich-immunoassay based on chemiluminescence was implemented. The electrical approach using the Si NW-ISFET platform shows a lower limit of detection and a wide dynamic range of the assay. In future, our platform should be utilized to detect multiple biomarkers in one assay to obtain more reliable information about cancer-related diseases.

PEDOT:PSS organic electrochemical transistor arrays for extracellular electrophysiological sensing of cardiac cells.

Electrophysiological biosensors embedded in planar devices represent a state of the art approach to measure and evaluate the electrical activity of biological systems. This measurement method allows for the testing of drugs and their influences on cells or tissues, cytotoxicity, as well as the direct implementation into biological systems in vivo for signal transduction. Multi-electrode arrays (MEAs) with metal or metal-like electrodes on glass substrates are one of the most common, well-established platforms for this purpose. In recent years organic electrochemical transistors (OECTs) made of poly(2,3-dihydrothieno-1,4-dioxin)-poly(styrenesulfonate) (PEDOT:PSS) have as well shown their value in transducing and amplifying the ionic signals in biological systems. We developed OECT devices in a wafer-scale process and used them as electrophysiological biosensors measuring electrophysiological activity of the cardiac cell line HL-1. Our optimized devices show very promising properties such as good signal-to-noise ratio as well as the ability to record fast components of extracellular signals. Combined with an easy, cost effective fabrication and the transparency of the polymer, this platform offers a valuable alternative to traditional MEA systems for future cell sensing applications.

On the Use of Scalable NanoISFET Arrays of Silicon with Highly Reproducible Sensor Performance for Biosensor Applications.

As a prerequisite to the development of real label-free bioassay applications, a high-throughput top-down nanofabrication process is carried out with a combination of nanoimprint lithography, anisotropic wet-etching, and photolithography methods realizing nanoISFET arrays that are then analyzed for identical sensor characteristics. Here, a newly designed array-based sensor chip exhibits 32 high aspect ratio silicon nanowires (SiNWs) laid out in parallel with 8 unit groups that are connected to a very highly doped, Π-shaped common source and individual drain contacts. Intricately designed contact lines exert equal feed-line resistances and capacitances to homogenize the sensor response as well as to minimize parasitic transport effects and to render easy integration of a fluidic layer on top. The scalable nanofabrication process as outlined in this article casts out a total of 2496 nanowires (NWs) on a 4 inch p-type silicon-on-insulator (SOI) wafer, yielding 78 sensor chips based on nanoISFET arrays. The sensor platform exhibiting high-performance transistor characteristics in buffer solutions is thoroughly characterized using state-of-the-art surface and electrical measurement techniques. Deploying a pH sensor in liquid buffers after high-quality gas-phase silanization, nanoISEFT arrays demonstrate typical pH sensor behavior with sensitivity as high as 43 ± 3 mV·pH-1 and a device-to-device variation of 7% at the wafer scale. Demonstration of a high-density sensor platform with uniform characteristics such as nanoISFET arrays of silicon (Si) in a routine and refined nanofabrication process may serve as an ideal solution deployable for real assay-based applications.

Human T cells monitored by impedance spectrometry using field-effect transistor arrays: a novel tool for single-cell adhesion and migration studies.

Cytotoxic T lymphocytes (CTLs) play an important role in the immune system by recognizing and eliminating pathogen-infected and tumorigenic cells. In order to achieve their function, T cells have to migrate throughout the whole body and identify the respective targets. In conventional immunology studies, interactions between CTLs and targets are usually investigated using tedious and time-consuming immunofluorescence imaging. However, there is currently no straightforward measurement tool available to examine the interaction strengths. In the present study, adhesion strengths and migration of single human CD8(+) T cells on pre-coated field-effect transistor (FET) devices (i.e. fibronectin, anti-CD3 antibody, and anti-LFA-1 antibody) were measured using impedance spectroscopy. Adhesion strengths to different protein and antibody coatings were compared. By fitting the data to an electronically equivalent circuit model, cell-related parameters (cell membrane capacitance referring to cell morphology and seal resistance referring to adhesion strength) were obtained. This electronically-assessed adhesion strength provides a novel, fast, and important index describing the interaction efficiency. Furthermore, the size of our detection transistor gates as well as their sensitivity reaches down to single cell resolution. Real-time motions of individually migrating T cells can be traced using our FET devices. The in-house fabricated FETs used in the present study are providing a novel and very efficient insight to individual cell interactions.