A Bioinspired Artificial Gustatory Neuron for a Neuromorphic Based Electronic Tongue.

A novel biomimicked neuromorphic sensor for an energy efficient and highly scalable electronic tongue (E-tongue) is demonstrated with a metal-oxide-semiconductor field-effect transistor (MOSFET). By mimicking a biological gustatory neuron, the proposed E-tongue can simultaneously detect ion concentrations of chemicals on an extended gate and encode spike signals on the MOSFET, which acts as an input neuron in a spiking neural network (SNN). Such in-sensor neuromorphic functioning can reduce the energy and area consumption of the conventional E-tongue hardware. pH-sensitive and sodium-sensitive artificial gustatory neurons are implemented by using two different sensing materials: Al2O3 for pH sensing and sodium ionophore X for sodium ion sensing. In addition, a sensitivity control function inspired by the biological sensory neuron is demonstrated. After the unit device characterization of the artificial gustatory neuron, a fully hardware-based E-tongue that can classify two distinct liquids is demonstrated to show a practical application of the artificial gustatory neurons.

Surface Potential-Controlled Oscillation in FET-Based Biosensors.

Field-effect transistor (FET)-based biosensors have garnered significant attention for their label-free electrical detection of charged biomolecules. Whereas conventional output parameters such as threshold voltage and channel current have been widely used for the detection and quantitation of analytes of interest, they require bulky instruments and specialized readout circuits, which often limit point-of-care testing applications. In this study, we demonstrate a simple conversion method that transforms the surface potential into an oscillating signal as an output of the FET-based biosensor. The oscillation frequency is proposed as a parameter for FET-based biosensors owing to its intrinsic advantages of simple and compact implementation of readout circuits as well as high compatibility with neuromorphic applications. An extended-gate biosensor comprising an Al2O3-deposited sensing electrode and a readout transistor is connected to a ring oscillator that generates surface potential-controlled oscillation for pH sensing. Electrical measurement of the oscillation frequency as a function of pH reveals that the oscillation frequency can be used as a sensitive and reliable output parameter in FET-based biosensors for the detection of chemical and biological species. We confirmed that the oscillation frequency is directly correlated with the threshold voltage. For signal amplification, the effects of circuit parameters on pH sensitivity are investigated using different methods, including electrical measurements, analytical calculations, and circuit simulations. An Arduino board to measure the oscillation frequency is integrated with the proposed sensor to enable portable and real-time pH measurement for point-of-care testing applications.

Recent Advances in Aptasensor for Cytokine Detection: A Review.

Cytokines are proteins secreted by immune cells. They promote cell signal transduction and are involved in cell replication, death, and recovery. Cytokines are immune modulators, but their excessive secretion causes uncontrolled inflammation that attacks normal cells. Considering the properties of cytokines, monitoring the secretion of cytokines in vivo is of great value for medical and biological research. In this review, we offer a report on recent studies for cytokine detection, especially studies on aptasensors using aptamers. Aptamers are single strand nucleic acids that form a stable three-dimensional structure and have been receiving attention due to various characteristics such as simple production methods, low molecular weight, and ease of modification while performing a physiological role similar to antibodies.

Aptamer-Based Field-Effect Transistor for Detection of Avian Influenza Virus in Chicken Serum.

Early diagnosis of the highly pathogenic H5N1 avian influenza virus (AIV) is significant for preventing and controlling a global pandemic. However, there is no existing electrical biosensor for detecting biomarkers for AIV in clinically relevant samples such as chicken serum. Herein, we report the first use of an aptamer-functionalized field-effect transistor (FET) as a label-free sensor for AIV detection in chicken serum. A DNA aptamer is employed as a sensitive and selective receptor for hemagglutinin (HA) protein, which is a biomarker for AIVs. This aptamer is immobilized on a gold microelectrode that is connected to the gate of a reusable FET transducer. The specific binding of the target protein results in a change in the surface potential, which generates a signal response of the FET transducer. We hypothesize that a conformational change in the DNA aptamer upon specific binding of HA protein may alter the surface potential. The signal of the aptamer-based FET biosensor increased linearly with the increase in the logarithm of HA protein concentration in a dynamic range of 10 pM to 10 nM with a detection limit of 5.9 pM. The selectivity of the biosensor for HA protein was confirmed by employing relevant interfering proteins. The proposed biosensor was successfully applied to the selective detection of HA protein in a chicken serum sample. Owing to its simple and low-cost architecture, portability, and sensitivity, the aptamer-based FET biosensor has potential as a point-of-care diagnosis of H5N1 AIVs in clinical samples.

pH Sensing Characteristics of Extended-Gate Field-Effect Transistor with Al2O3 Layer.

A simple and stable pH sensor based on an extended-gate field-effect transistor (EGFET) is demonstrated using electron-beam deposited Al2O3 as a pH sensing layer. The threshold voltage of the EGFET is modulated by different pH values of the buffer solution. A control experiment with a bare Au electrode confirms that the stable pH sensing response with linearity and reproducibility originates from the Al2O3 sensing layer. The minimum area of the pH sensing layer is estimated by considering that the different sizes of the sensing layer are easily modeled with different values of external capacitors connected to the readout transistor. The study verifies that the pH detection accuracy is improved by using the reference electrode with a KCl electrolyte.

Temperature measurement of Joule heated silicon micro/nanowires using selectively decorated quantum dots.

We developed a novel method to measure local temperature at micro/nano-scale regions using selective deposition of quantum dots (QDs) as a sensitive temperature probe and measured the temperature of Joule heated silicon microwires (SiMWs) and silicon nanowires (SiNWs) by this method. The QDs are selectively coated only on the surface of the SiMWs and SiNWs by a sequential process composed of selective opening of a polymethyl methacrylate layer via Joule heating, covalent bonding of QDs, and lift-off process. The temperatures of the Joule-heated SiMWs and SiNWs can be measured by characterizing the temperature-dependent shift of photoluminescence peak of the selectively deposited QDs even with far-field optics. The validity of the extracted temperature has been also confirmed by comparing with numerical simulation results. The proposed method can potentially provide micro/nanoscale measurement of localized temperatures for a wide range of electrical and optical devices.

Cross-Talk Between Ionic and Nanoribbon Current Signals in Graphene Nanoribbon-Nanopore Sensors for Single-Molecule Detection.

Nanopores are now being used not only as an ionic current sensor but also as a means to localize molecules near alternative sensors with higher sensitivity and/or selectivity. One example is a solid-state nanopore embedded in a graphene nanoribbon (GNR) transistor. Such a device possesses the high conductivity needed for higher bandwidth measurements and, because of its single-atomic-layer thickness, can improve the spatial resolution of the measurement. Here measurements of ionic current through the nanopore are shown during double-stranded DNA (dsDNA) translocation, along with the simultaneous response of the neighboring GNR due to changes in the surrounding electric potential. Cross-talk originating from capacitive coupling between the two measurement channels is observed, resulting in a transient response in the GNR during DNA translocation; however, a modulation in device conductivity is not observed via an electric-field-effect response during DNA translocation. A field-effect response would scale with GNR source-drain voltage (Vds), whereas the capacitive coupling does not scale with Vds . In order to take advantage of the high bandwidth potential of such sensors, the field-effect response must be enhanced. Potential field calculations are presented to outline a phase diagram for detection within the device parameter space, charting a roadmap for future optimization of such devices.

Self-heated silicon nanowires for high performance hydrogen gas detection.

Self-heated silicon nanowire sensors for high-performance, ultralow-power hydrogen detection have been developed. A top-down nanofabrication method based on well-established semiconductor manufacturing technology was utilized to fabricate silicon nanowires in wafer scale with high reproducibility and excellent compatibility with electronic readout circuits. Decoration of palladium nanoparticles onto the silicon nanowires enables sensitive and selective detection of hydrogen gas at room temperature. Self-heating of silicon nanowire sensors allows us to enhance response and recovery performances to hydrogen gas, and to reduce the influence of interfering gases such as water vapor and carbon monoxide. A short-pulsed heating during recovery was found to be effective for additional reduction of operation power as well as recovery characteristics. This self-heated silicon nanowire gas sensor will be suitable for ultralow-power applications such as mobile telecommunication devices and wireless sensing nodes.

Electrical biomolecule detection using nanopatterned silicon via block copolymer lithography.

An electrical biosensor exploiting a nanostructured semiconductor is a promising technology for the highly sensitive, label-free detection of biomolecules via a straightforward electronic signal. The facile and scalable production of a nanopatterned electrical silicon biosensor by block copolymer (BCP) nano-lithography is reported. A cost-effective and large-area nanofabrication, based on BCP self-assembly and single-step dry etching, is developed for the hexagonal nanohole patterning of thin silicon films. The resultant nanopatterned electrical channel modified with biotin molecules successfully detects the two proteins, streptavidin and avidin, down to nanoscale molarities (≈1 nm). The nanoscale pattern comparable to the Debye screening length and the large surface area of the three-dimensional silicon nanochannel enable excellent sensitivity and stability. A device simulation confirms that the nanopatterned structure used in this work is effective for biomolecule detection. This approach relying on the scalable self-assembly principle offers a high-throughput manufacturing process for clinical lab-on-a-chip diagnoses and relevant biomolecular studies.

Core-insulator embedded nanosheet field-effect transistor for suppressing device-to-device variations.

Nanosheet field-effect transistors (NSFETs) have attracted considerable attention for their potential to achieve improved performance and energy efficiency compared to traditional FinFETs. Here, we present a comprehensive investigation of core-insulator-embedded nanosheet field-effect transistors (C-NSFETs), focusing on their improved performance and device-to-device (D2D) variability compared to conventional NSFETs through three-dimensional device simulations. The C-NSFETs exhibit enhanced direct-current (DC) performance, characterized by a steeper subthreshold slope and reduced off-current, indicating better gate electrostatic controllability. Furthermore, the structural design of C-NSFETs enables to demonstrate a notable resilience against D2D variations in nanosheet thickness and doping concentration. In addition, we investigate the effects of interface traps in C-NSFETs, emphasizing the importance of thermal oxidation processes in the formation of core-insulating layers to maintain optimal device performance.

Sensitive and selective electrochemical detection of dopamine using an electrode modified with carboxylated carbonaceous spheres.

A highly sensitive and selective electrochemical sensor of dopamine (DA) has been developed by employing carboxylated carbonaceous spheres to modify glassy carbon electrodes (GCEs). Scanning electron microscopy (SEM) and Fourier transform infrared (FT-IR) spectroscopy were used to characterize as-prepared carbonaceous spheres. The results show that the diameter of carboxylated carbonaceous spheres is uniformly 500 nm and that their surfaces mainly expose carboxyl groups with negative charges. Electrochemical measurements demonstrate that carboxylated carbonaceous spheres greatly improve the accumulation of positively charged dopamine, leading to good sensing performance on a modified GCE. Through applying the differential pulse voltammetric approach, linear calibration curves were obtained in a range of about 0.1 to 40 µM with a detection limit down to 30 nM. Furthermore, depending on the charge-based discrimination, the modified electrode displays good selective detection of DA and reliable anti-interference to UA and glucose besides a weak and negligible response to AA. Therefore, the carboxylated carbonaceous sphere introduced here is a good candidate to develop electrochemical sensors for the sensitive and selective detection of DA.

Self-aligned nanoforest in silicon nanowire for sensitive conductance modulation.

A self-aligned and localized nanoforest structure is constructed in a top-down fabricated silicon nanowire (SiNW). The surface-to-volume ratio (SVR) of the SiNW is enhanced due to the local nanoforest formation. The conductance modulation property of the SiNWs, which is an important characteristic in sensor and charge transfer based applications, can be largely enhanced. For the selective modification of the channel region, localized Joule-heating and subsequent metal-assisted chemical etching (mac-etch) are employed. The nanoforest is formed only in the channel region without misalignment due to the self-aligned process of Joule-heating. The modified SiNW is applied to a porphyrin-silicon hybrid device to verify the enhanced conductance modulation. The charge transfer efficiency between the porphyrin and the SiNW, which is caused by external optical excitation, is clearly increased compared to the initial SiNW. The effect of the local nanoforest formation is enhanced when longer etching times and larger widths are used.

Recent Developments in DNA-Nanotechnology-Powered Biosensors for Zika/Dengue Virus Molecular Diagnostics.

Zika virus (ZIKV) and dengue virus (DENV) are highly contagious and lethal mosquito-borne viruses. Global warming is steadily increasing the probability of ZIKV and DENV infection, and accurate diagnosis is required to control viral infections worldwide. Recently, research on biosensors for the accurate diagnosis of ZIKV and DENV has been actively conducted. Moreover, biosensor research using DNA nanotechnology is also increasing, and has many advantages compared to the existing diagnostic methods, such as polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). As a bioreceptor, DNA can easily introduce a functional group at the 5' or 3' end, and can also be used as a folded structure, such as a DNA aptamer and DNAzyme. Instead of using ZIKV and DENV antibodies, a bioreceptor that specifically binds to viral proteins or nucleic acids has been fabricated and introduced using DNA nanotechnology. Technologies for detecting ZIKV and DENV can be broadly divided into electrochemical, electrical, and optical. In this review, advances in DNA-nanotechnology-based ZIKV and DENV detection biosensors are discussed.

A nanoforest structure for practical surface-enhanced Raman scattering substrates.

A nanoforest structure for surface-enhanced Raman scattering (SERS) active substrates is fabricated and analyzed. The detailed morphology of the resulting structure can be easily controlled by modifying the process parameters such as initial gold layer thickness and etching time. The applicability of the nanoforest substrate as a label-free SERS immunosensor is demonstrated using influenza A virus subtype H1N1. Selective binding of the H1N1 surface antigen and the anti-H1 antibody is directly detected by the SERS signal differences. Simple fabrication and high throughput with strong in-plane hot-spots imply that the nanoforest structure can be a practical sensing component of a chip-based SERS sensing system.

Transformable functional nanoscale building blocks with wafer-scale silicon nanowires.

Through the fusion of electrostatics and mechanical dynamics, we demonstrate a transformable silicon nanowire (SiNW) field effect transistor (FET) through a wafer-scale top-down approach. By felicitously taking advantage of the proposed electrostatic SiNW-FET with mechanically movable SiNWs, all essential logic gates, including address decoders, can be monolithically integrated into a single device. The unification of various functional devices, such as pn-diodes, FETs, logic gates, and address decoders, can therefore eliminate the complex fabrication issues associated with nanoscale integration. These results represent a step toward the creation of multifunctional and flexible nanoelectronics.

A pretreatment-free electrical capacitance biosensor for exosome detection in undiluted serum.

The exosome is considered a useful biomarker for the early diagnosis of cancer. However, pretreatment of samples used in diagnosis is time-consuming. Herein, we fabricated a capacitance-based electrical biosensor that requires no pretreatment of the sample; it is composed of a DNA aptamer/molybdenum disulfide (MoS2) heterolayer on an interdigitated micro-gap electrode (IDMGE)/printed circuit board (PCB) system for detecting exosomes in an undiluted serum sample. The DNA aptamer detects the CD63 protein on the exosome as the biomarker, while the MoS2 nanoparticle enhances electrical sensitivity. In this study, for the first time, the IDMGE system was used to amplify the electrical signal efficiently for exosome detection. The IDMGE amplifies the capacitance signal as the gap between electrodes decreases, making it easy to detect the target by utilizing the heightened sensitivity. Moreover, it is possible to immobilize a bio-probe more efficiently than with an electrical sensitivity-enhancing electrode with the same area. The thiol-modified (SH-) CD63 DNA aptamer was introduced as the bio-probe that selectively binds to the CD63 protein on the exosome surface. The capacitance signal from the IDMGE electrical sensor increased linearly with the increase in the concentration of exosomes in human serum expressed on a logarithmic scale, the detection limit being 2192.6 exosomes/mL. The proposed biosensor can detect exosomes in undiluted human serum with high selectivity and sensitivity. A blind test was also carried out to test the reliability of the biosensor. The capacitance-based electrical biosensor thus offers a new platform for cancer diagnosis in the future.

Double-gate nanowire field effect transistor for a biosensor.

A silicon nanowire field effect transistor (FET) straddled by the double-gate was demonstrated for biosensor application. The separated double-gates, G1 (primary) and G2 (secondary), allow independent voltage control to modulate channel potential. Therefore, the detection sensitivity was enhanced by the use of G2. By applying weakly positive bias to G2, the sensing window was significantly broadened compared to the case of employing G1 only, which is nominally used in conventional nanowire FET-based biosensors. The charge effect arising from biomolecules was also analyzed. Double-gate nanowire FET can pave the way for an electrically working biosensor without a labeling process.

Recent Advances in Biomolecule-Nanomaterial Heterolayer-Based Charge Storage Devices for Bioelectronic Applications.

With the acceleration of the Fourth Industrial Revolution, the development of information and communications technology requires innovative information storage devices and processing devices with low power and ultrahigh stability. Accordingly, bioelectronic devices have gained considerable attention as a promising alternative to silicon-based devices because of their various applications, including human-body-attached devices, biomaterial-based computation systems, and biomaterial-nanomaterial hybrid-based charge storage devices. Nanomaterial-based charge storage devices have witnessed considerable development owing to their similarity to conventional charge storage devices and their ease of applicability. The introduction of a biomaterial-to-nanomaterial-based system using a combination of biomolecules and nanostructures provides outstanding electrochemical, electrical, and optical properties that can be applied to the fabrication of charge storage devices. Here, we describe the recent advances in charge storage devices containing a biomolecule and nanoparticle heterolayer including (1) electrical resistive charge storage devices, (2) electrochemical biomemory devices, (3) field-effect transistors, and (4) biomemristors. Progress in biomolecule-nanomaterial heterolayer-based charge storage devices will lead to unprecedented opportunities for the integration of information and communications technology, biotechnology, and nanotechnology for the Fourth Industrial Revolution.

Joule-Heated and Suspended Silicon Nanowire Based Sensor for Low-Power and Stable Hydrogen Detection.

We developed self-heated, suspended, and palladium-decorated silicon nanowires (Pd-SiNWs) for high-performance hydrogen (H2) gas sensing with low power consumption and high stability against diverse environmental noises. To prepare the Pd-SiNWs, SiNWs were fabricated by conventional complementary metal-oxide-semiconductor (CMOS) processes, and Pd nanoparticles were coated on the SiNWs by a physical vapor deposition method. Suspended Pd-SiNWs were simply obtained by etching buried oxide layer and Pd deposition. Joule heating of Pd-SiNW (<1 mW) enables the detection of H2 gas with a faster response and without the reduction of sensitivity unlike other Pd-based H2 gas sensors. We proposed a H2 sensing model using oxygen adsorption on the Pd nanoparticle-coated silicon oxide surface to understand the H2 response of Joule-heated Pd-SiNWs. A suspended Pd-SiNW showed a similar transient sensing response with around four times lower Joule heating power (147 µW) than the substrate-bound Pd-SiNW (613 µW). The effect of interfering gas on the Pd-SiNW was investigated, and it was found that the Joule heating of Pd-SiNW helps to maintain the H2 sensing performance in humid or carbon monoxide environments.

Nanoscale FET-Based Transduction toward Sensitive Extended-Gate Biosensors.

Owing to their simple and low-cost architecture, extended-gate biosensors based on the combination of a disposable sensing part and a reusable transducer have been widely utilized for the label-free electrical detection of chemical and biological species. Previous studies have demonstrated that sensitive and selective detection of ions and biomolecules can be achieved by controlled modification of the sensing part with an ion-selective membrane and receptors of interest. However, no systematic studies have been performed on the impact of the transducer on sensing performance. In this paper, we introduce the concept of a nanoscale field-effect transistor (FET) as a reusable and sensitive transducer for extended-gate biosensors. The capacitive effect from the external sensing part can degrade the sensing performance, but the nanoscale FET can reduce this effect. The nanoscale FET with a gate-all-around (GAA) structure exhibits a higher pH sensitivity than a commercially available FET, which is widely used in conventional extended-gate biosensors. A sensitivity reduction is observed for the commercial FET, whereas the pH sensitivity is insensitive to the area of the sensing region in the nanoscale FET, thus allowing the scaling of the detection area. Our analysis based on a capacitive model suggests that the high pH sensitivity in the compact sensing area originates from the small input capacitance of the nanoscale FET transducer. Moreover, a decrease in the nanowire width of the GAA FET leads to an improvement in the pH sensitivity. The extended-gate approach with the nanoscale FET-based transduction can pave the way for a highly sensitive analysis of chemical and biological species with a small sample volume.