Surface plasmon resonance (SPR) is a key technique in developing sensor platforms for clinical diagnostics, drug discovery, food quality, and environmental monitoring applications. While prism-coupled (Kretschmann) SPR remains a “gold-standard” for laboratory work-flows due to easier fabrication, handling and high through put, other configurations such as grating-coupled SPR (GC-SPR) and wave-guide mode SPR are yet to fulfil their technology potential. This work evaluates the technical aspects influencing the performance of GC-SPR and reviews recent progress in the fabrication of such platforms. In principle, the GC-SPR involves the illumination of the plasmonic metal film with periodic gratings to excite the surface plasmons (SP) via diffraction-based phase matching. The real performance of the GC-SPR is, however, heavily influenced by the topography of the grating structures produced via top-down lithography techniques. This review discusses latest in approaches to achieve consistent plasmonic gratings with uniform features and periodicity over a large scale and explores the choice of plasmon-active and substrate material for enhanced performance. The review also provides insights into the different GC-SPR measurement configurations and highlights on opportunities with their potential applications as biosensors with translational capabilities.

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 biomarkertriggered 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.

A simple equivalent electrical circuit is used to obtain the physical parameters of electrical circuit elements from measured electrochemical impedance spectra. This model consists of four circuit elements with a clear physical meaning for each of the elements. Compared to complex models with multiple constant phase elements or Warburg impedances, our model is suitable for extracting physical values for important electrode parameters with low errors. The feasibility of the model was shown by investigating pure metal or polymer-coated electrodes. Here, gold electrodes were coated either with Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT : PSS), Polypyrrole:poly(styrenesulfonate) (PPy : PSS), or (PEDOT/PPy) : PSS by means of electropolymerization. The model could demonstrate the ionic-electronic differences such as the ion accessibility of the differently coated electrodes. To prove the correctness of the model, the obtained results were compared to the literature.

Realization of generic logic gates and circuits forms the basis of modern computational platforms, which have brought visible changes in everyone’s life. As the miniaturization of solid-state logic systems approach fundamental limits, designing digital logic in fluidics has emerged as a new paradigm to go beyond current architectures and exploit the computational efficiency of soft biological systems. This work reviews emerging fluidic approaches and their implementation as “fluidic logic gates” and circuits. Such platforms are categorized into passive and active fluidic logic based on design-of-integration, operational principles, and application. As the use of such fluidic logic for real computation depends on their large-scale integration, we evaluated miniaturization strategies and associated challenges. Furthermore, we propose integration of such fluidic logics with complementary metal oxide semiconductor-compatible ion-sensitive field-effect transistors, serving as a potential bridge between electronics and fluidics to allow integration of different computational paradigms in the upcoming era of computational convergence.

Silanization is one of the widely explored surface modification strategies for biofunctionalization of oxide interfaces. For biosensor applications, silanes with active terminal groups such as amine, thiol, carboxylic, and aldehyde groups are utilized in routine. In near‐field sensing schemes like biologically sensitive field‐effect transistors, it is crucial to generate a homogeneous layer of silane to confine the biointeractions in close vicinity of the sensor interface. The homogeneity of such biofunctional layer is determined by the surface activation and silanization protocol being applied. Herein, the impact of the surface activation process and silanization on electrical characteristics of field‐effect devices is studied comprehensively using an electrolyte‐oxide‐semiconductor (EOS) capacitor with a high‐quality gate oxide. The thermally grown silicon oxide (SiO 2 ) interface is activated using acidic mixtures and plasma treatment, while the subsequent silanization steps are investigated comparatively using two different silanes (3‐aminopropyl triethoxysilane (APTES) and 3‐glycidyloxypropyl trimethoxysilane (GPTMS) in wet‐chemical and vapor‐phase processes. Furthermore, the optimized silanization process is utilized to immobilize an oligo strand at the EOS capacitor surface, followed by the hybridization of complementary oligo strands. The optimized protocol holds the potential for large‐scale production of functional oxide interfaces for various applications.

Integration of biochemical reaction networks (BRNs) with biosensor platforms has emerged as a technological niche overcoming challenges related to the loss of sensitivity and selectivity in biological media. Optimal operation of BRNs in microfluidics requires control over reaction-diffusion dominated mass transport, heavily influenced by fluidic parameters. In this work, we study and design an on-chip platform combining a programable unique molecular amplification as BRNs with nanoscale biologically sensitive field-effect transistor (BioFET) arrays, which employs a physical diffusion barrier to gain spatial and temporal control over mass transport. Computational and numerical approaches, such as finite element and finite volume methods, were implemented to solve partial differential equations numerically after domain approximation by numerous finite elements. The focus on geometrical optimizations of fluidics is aimed at mass transport to occur with precise spatial and temporal control toward BioFET-arrays. Adopting a 0.5 pM limit-of-detection (LoD) for biochemical monitoring of BRNs via a single-stranded deoxyribonucleic acid (ssDNA) output, we show that it was possible to compartmentalize the mass transport spatiotemporally without crosstalk, which can be of critical advantage for using biosensor arrays in order to realize simplified multiplexed point-of-care biosensors.

The lack of long-term stability of polymeric neural interfaces remains one of the most important and less tackled issues in this research field. To address this issue, we fabricated two test structures based on interdigitated electrodes (IDEs) encapsulated with polyimide (PI). One of the test samples was pretreated with barrel oxygen plasma prior to spin coating of the second PI layer. The second test structure was pretreated using a reactive ion etching (RIE) process. The test samples were immersed in an electrolyte solution at elevated temperatures to mimic the conditions inside the human brain. The samples were then electrically and mechanically stressed to accelerate their degradation. Real-time monitoring of the electrical insulation stability was used to compare the impact of the pretreatment on the long-term stability. Barrel-plasma-activated test samples showed a mean lifetime of 1.5 days, whereas RIE pretreatment increased the mean lifetime to 24 days. Therefore, RIE-pretreated test samples exhibited 16 times longer mean stability compared to purely chemically activated test samples. Furthermore, the electrical measurements were correlated with mechanical adhesion tests. Chemically activated test samples showed significant delamination, whereas RIE pretreatment enhanced the adhesion, and no delamination could be observed. The correlation of these investigations suggests that the adhesion between different layers is higher following RIE pretreatment compared to pretreatment with chemical barrel plasma. In conclusion, the adhesion between the two PI foils seems to play a key role in the long-term stability of such devices.

Despite significant eradication efforts, malaria remains a persistent infectious disease with high mortality due to the lack of efficient point-of-care (PoC) screening solutions required to manage low-density asymptomatic parasitemia. In response, we demonstrate a quantitative electrical biosensor based on system-integrated twodimensional field-effect transistors (2DBioFETs) of reduced graphene oxide (rGO) as transducer for high sensitivity screening of the main malaria biomarker, Plasmodium falciparum lactate dehydrogenase (PfLDH). The 2DBioFETs were biofunctionalized with pyrene-modified 2008s aptamers as specific PfLDH receptors. While we systematically optimize biosensor interface for optimal performance, aptamer-protein transduction at 2DBioFETs is elucidated based on delineation of charge and capacitance in an updated analytical model for two-dimensional rGO/biofunctional layer/electrolyte (2DiBLE) interfaces. Our 2DBioFET-aptasensors display a limit-of-detection down to 0.78 fM (0.11 pg/mL), dynamic ranges over 9 orders of magnitude (subfemto to submicromolar), high sensitivity, and selectivity in human serum validating their diagnostic potential as rapid PoC tests for malarial management.

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.

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.

Fully screen-printed resistive pressure sensors have attracted rising attention in recent years. The possibility to fabricate them on any substrate as well as their low thickness and overall flexibility allow their application on curved surfaces or for material integrated sensing. However, these applications often apply additional loads other than only pressure to the sensors. A major concern is the cross-sensitivity of the sensors to strain. Thus, this work investigates the influence of the electrode geometry used for screen-printed pressure sensors on the device performance and on the cross-sensitivity to strain. It is shown, that the performance as well as the cross-sensitivity to strain are affected by electrode setup and orientation. The pressure sensitivity increases with the number of interdigital electrodes. The cross-sensitivity to temperature is not affected by the electrode setup.

For chronic applications of flexible neural implants, e.g., intracortical probes, the flexible substrate material has to encapsulate the electrical conductors with a long-term stability against the saline environment of the neural tissue. The biocompatible polymer polyimide is often used for this purpose. Due to its chemical inertness, the adhesion between two polyimide layers is, however, a challenge, which can lead to delamination and, finally, to short circuits. The state-of-the-art method to improve the adhesion strength is activating the polyimide surface using oxygen reactive ion etching (O2 RIE). However, the influence of the process variations (etching time, bias power) on the long-term stability is still unclear. Therefore, we establish a test method, where the aging of a gold interdigital structure embedded in two polyimide layers and immersed in saline solution is accelerated using an elevated temperature, mechanical stress and an electrical field. A continuous measurement of a leakage current is used to define the failure state. The results show that the variation of the O2 RIE plasma process has a significant effect on the long-term stability of the test samples. Comparing the two different plasma treatments 0.5 min at 25 W and 1 min at 50 W, the long-term stability could be increased from 20.9 ± 19.1 days to 44.9 ± 18.9 days. This corresponds to more than a doubled lifetime. An ideal solution for the delamination problem is still not available; however, the study shows that the fine-tuning of the fabrication processes can improve the long-term stability of chronically implanted neural electrodes.

This work presents the realization of a lab-on-a-chip (LoC) platform based on a SiNW-FET sensor array, a temperature control unit, on-chip temperature sensors, and an on-chip pseudo-reference electrode (pRE) for bio/chemical sensor applications. The SiNW sensors were fabricated based on a mix-and-match "top-down" approach combining electron beam lithography (EBL) and optical lithography on a 4-inch silicon-on-insulator (SOI) wafer (SOITEC, France). The fabrication processes of SiNW-arrays were carried out in a fully CMOS-compatible process. After that, micro-sized temperature sensors based on Pt were fabricated on the wafer close to the SiNW-FET sensors. Up to three on-chip pREs were integrated on the chip surface. Post-CMOS passivation for the temperature sensors based on low-temperature oxidation of titanium was developed to allow the operation of the sensor in liquids and to suppress the interference between the supplied power for the temperature sensor and the liquid-gated SiNW-FETs. For this purpose, a 20 nm thick titanium layer was oxidized at 300deg C in an RTP oven for 90 minutes in pure oxygen. The LoC platform was thoroughly characterized and proofs-of-concept were carried out for the detection of poly-D-lysine (PDL) molecules and a chemical reaction-diffusion network.

: An electrochemical impedance spectroscopy (EIS) sensor design is proposed based on a standard interdigitated electrode layout in which the smaller working electrode consists of gold (Au) whereas the larger combined counter and reference electrode is coated with a porous layer of polypyrrole (PPy) doped with polysty-rene sulfonate (PSS) (PPy:PSS). Each electrode material was first characterized by EIS in a standard 3-electrode setup with subsequent spectra fitting by a modified Randles equivalent circuit. The differences in the spectra obtained by the PPy:PSS coated electrodes can be explained by an increased electroactive surface area due to the porous polymer film. The changes in morphology of the film are discussed with respect to the evolution of the elements of the electric equivalent circuit. When applying the Au/PPy:PSS electrode combination to a standard 2-electrode arrangement, the enlarged highly electroactive surface area of the PPy:PSS coating lowers the interfacial impedance in a way that mainly the gold working electrode contributes to the overall system impedance. Therefore, obtaining reproducible EIS signals depends only on the electrode’s open-circuit potential (OCP) and on additional adsorption events at the gold electrode/electrolyte interface. We present a protocol for microelectrode coating with PPy:PSS, which enables highly stable 2-electrode EIS experiments without the need of a reference electrode. This combination is believed to be very useful if an integration of sensing electrodes inside Micro Total Analysis Systems is aspired.

Commercial pressure sensors are often fabricated using well-established silicon micromachining technologies. The thickness and stiffness of silicon-based sensors make them in most cases unsuitable for the integration into materials and surfaces. We present a flexible pressure sensor fabricated by printing technology. Therefore, an intrinsically pressure sensitive ink is screen printed on interdigital electrodes on a thin and flexible foil substrate. The sensor shows sufficient sensitivity and is applicable in a wide pressure range from 0 to 2 MPa. The sensor can completely be fabricated using a low-cost screen printing process. It is very thin and flexible, making it possible to be applied on curved surfaces or to be integrated into materials in a minimal invasive way.