Ultrasensitive Gas Detection Based on Electrically Enhanced Nanoplasmonic Sensor with Graphene-Encased Gold Nanorod.

Nanoplasmonic sensors are a widely known concept and have been studied with various applications. Among them, gas detection is engaging attention in many fields. However, the analysis performance of nanoplasmonic sensors based on refractive index confined to the metal nanostructure characteristics causes challenges in gas detection. In this study, we develop a graphene-encased gold nanorod (AuNR)-based nanoplasmonic sensor to detect cadaverine gas. The graphene-encased AuNR (Gr@AuNR) presents an ultrasensitive peak wavelength shift even with tiny molecules. In addition, the external potential transmitted through graphene induces an additional shift. A chemical receptor is immobilized on Gr@AuNR (CR@Gr@AuNR) for selectively capturing cadaverine. The CR@Gr@AuNR achieves ultrasensitive detection of cadaverine gas, and the detection limit is increased to 15.99 ppb by applying a voltage to graphene. Furthermore, the experimental results of measuring cadaverine generated from spoiled pork show the practicality of CR@Gr@AuNR. The strategy of external-boosted nanoplasmonics provides new insight into plasmonic sensing and applications.

Low-Power, Multi-Transduction Nanosensor Array for Accurate Sensing of Flammable and Toxic Gases.

Toxic and flammable gases pose a major safety risk in industrial settings; thus, their portable sensing is desired, which requires sensors with fast response, low-power consumption, and accurate detection. Herein, a low-power, multi-transduction array is presented for the accurate sensing of flammable and toxic gases. Specifically, four different sensors are integrated on a micro-electro-mechanical-systems platform consisting of bridge-type microheaters. To produce distinct fingerprints for enhanced selectivity, the four sensors operate based on two different transduction mechanisms: chemiresistive and calorimetric sensing. Local, in situ synthesis routes are used to integrate nanostructured materials (ZnO, CuO, and Pt Black) for the sensors on the microheaters. The transient responses of the four sensors are fed to a convolutional neural network for real-time classification and regression of five different gases (H2 , NO2 , C2 H6 O, CO, and NH3 ). An overall classification accuracy of 97.95%, an average regression error of 14%, and a power consumption of 7 mW per device are obtained. The combination of a versatile low-power platform, local integration of nanomaterials, different transduction mechanisms, and a real-time machine learning strategy presented herein helps advance the constant need to simultaneously achieve fast, low-power, and selective gas sensing of flammable and toxic gases.

ZnO-CuO Core-Hollow Cube Nanostructures for Highly Sensitive Acetone Gas Sensors at the ppb Level.

This paper presents a ZnO-CuO p-n heterojunction chemiresistive sensor that comprises CuO hollow nanocubes attached to ZnO spherical cores as active materials. These ZnO-CuO core-hollow cube nanostructures exhibit a remarkable response of 11.14 at 1 ppm acetone and 200 °C, which is a superior result to those reported by other metal-oxide-based sensors. The response can be measured up to 40 ppb, and the limit of detection is estimated as 9 ppb. ZnO-CuO core-hollow cube nanostructures also present high selectivity toward acetone against other volatile organic compounds and demonstrate excellent stability for up to 40 days. The outstanding gas-sensing performance of the developed nanocubes is attributed to their uniform and unique morphology. Their core-shell-like structures allow the main charge transfer pathways to pass the interparticle p-p junctions, and the p-n junctions in each particle increase the sensitivity of the reactions to gas molecules. The small grain size and high surface area of each domain also enhance the surface gas adsorption.

Barium Titanate Nanoparticles Sensitise Treatment-Resistant Breast Cancer Cells to the Antitumor Action of Tumour-Treating Fields.

Although tumour-treating fields (TTFields) is a promising physical treatment modality based on disruption of dipole alignments and generation of dielectrophoretic forces during cytokinesis, not much is known about TTFields-responsive sensitisers. Here, we report a novel TTFields-responsive sensitiser, barium titanate nanoparticles (BTNPs), which exhibit cytocompatibility, with non-cytotoxic effects on breast cancer cells. BTNPs are characterised by high dielectric constant values and ferroelectric properties. Notably, we found that BTNPs sensitised TTFields-resistant breast cancer cells in response to TTFields. In addition, BTNPs accumulated in the cytoplasm of cancer cells in response to TTFields. Further, we showed that TTFields combined with BTNPs exhibited antitumor activity by modulating several cancer-related pathways in general, and the cell cycle-related apoptosis pathway in particular. Therefore, our data suggest that BTNPs increase the antitumor action of TTFields by an electric field-responsive cytosolic accumulation, establishing BTNP as a TTFields-responsive sensitiser.

Selective protein transport through ultra-thin suspended reduced graphene oxide nanopores.

The nanoporous free-standing graphene membrane is of great interest in high performance separation technology. In particular, the separation of biological molecules with similar sizes is one of the key challenges in the purification of biomaterials. Here, we report a reliable, cost-effective, and facile method for the fabrication of a graphene-based nanosieve and its application in the separation of similar-size proteins. A suspended reduced graphene oxide (rGO) nanosieve with ultra-thin, large-area, well-ordered, and dense 15 nm-sized pores was fabricated using block copolymer (BCP) lithography. The fabricated 5 nm-ultrathin nanosieve with an area of 200 µm × 200 µm (an ultra-high aspect ratio of ∼40 000) endured pressure up to 1 atm, and effectively separated hemoglobin (Hb) from a mixture of hemoglobin and immunoglobulin G (IgG), the common proteins in human blood, in a highly selective and rapid manner. The use of the suspended rGO nanosieve is expected to provide a simple and manufacturable platform for practical biomolecule separation offering high selectivity and a large throughput.

Nonstoichiometric Co-rich ZnCo2O4 Hollow Nanospheres for High Performance Formaldehyde Detection at ppb Levels.

Since metal oxide semiconductors were investigated as chemiresistors, rapid advances have been reported in this field. However, better performance metrics are still required, such as higher sensitivity and selectivity levels for practical applications. To improve the sensing performance, we discuss an optimal composition of the active sensing material, nonstoichiometric Co-rich ZnCo2O4, prepared by the partial substitution of Co(2+) into Zn(2+) in Co3O4 without altering a hollow sphere morphology. Remarkably, this Co-rich ZnCo2O4 phase achieved detection limits for formaldehyde as low as 13 ppb in experimental measurements and 2 ppb in theory, which were the lowest values ever reported from actual measurements at a working temperature of 225 °C. It was also unprecedented that the selectivity for formaldehyde was greatly enhanced with respect to the selectivity levels against other volatile organic compounds (VOCs). These excellent sensing performances are due to the optimal composition of the Co-rich ZnCo2O4 material with a proper hole concentration and well-organized conductive network.

Pore-size reduction protocol for SiN membrane nanopore using the thermal reflow in nanoimprinting for nanobio-based sensing.

Micro- and nano-fabrication methods facilitate the use of nanostructures for the separation of collections of particles and nanobio-based optical and electrochemical sensing. We have presented an easy and simple nanopore size reduction method of a low-stressed silicon nitride (SiN) membrane nanosieve (100×100 µm2) using a nanoimprinting method based on a natural thermal reflow of the contact imprinting polymer, possibly maintaining compatibility with complementary metal-oxide semiconductor integrated circuit processes. The nanopore pattern size of this nanosieve membrane was precisely patterned by a nanoimprinting process using an electron beam patterned silicon master, to about 30-nm diameter. By employing mainly an electron beam resist reflow phenomena after a nanoimprinting process and anisotropic reactive ion etch, the etch holes' size was fabricated to be the same with nanopatterns on the polymer. The contact imprinting master can be used continually for the generation of nanopore patterns simply and easily. It can endure harsh conditions like high temperature up to 800°C, and it is inert to many aggressive and strong chemicals. Also, this would be a low-cost, simple, and easy fabrication method for the precise and reliable size-reduction control of nanopores for mass production of nanobio sensors or chips.

Use of a columnar metal thin film as a nanosieve with sub-10 nm pores.

A columnar-structured nanosieve is unique in the sense that it is a general thin film formed by physical vapor deposition (PVD). Instead of additional processes to make nanopores, the numerous voids naturally formed among columnar grains during PVD are used as nanopores. Since the thin film formed by PVD has vertically grown columnar grains, the fabricated nanosieve has numerous straight-opened nanopores, which is an ideal structure for a nanosieve.

Microfabrication of SiN membrane nanosieve using anisotropic reactive ion etching (ARIE) with an Ar/CF4 gas flow.

We have designed, fabricated, and characterized a low-stressed silicon nitride (SiN) membrane nanosieve (100 microm x 100 microm) using an anisotropic reactive ion etching (ARIE) combining with gas mixture, thus maintaining compatibility with the complementary metal-oxide semiconductor integrated circuit (CMOS IC) processes. The holes pattern of this nanosieve membrane was precisely controlled under 30 nm diameter by the electron beam writing. By employing mainly anisotropic reactive ion etching plus diffusion to the depth direction, the etch holes size was controlled to be the same with patterns on the e-beam resist (ER). This nanosieve membrane has proper mechanical strength withstanding up to one bar of transmembrane pressure. And it can endure harsh treatments such as high temperature up to 800 degrees C. In addition, it is inert to a number of strong chemicals including the piranha (H2SO4 + H2O2) solution, highly-concentrated potassium hydroxide (KOH), hydrogen fluoride (HF), hydrogen chloride (HCI), and nitric acid (HNO3).

Multienzyme-modified biosensing surface for the electrochemical analysis of aspartate transaminase and alanine transaminase in human plasma.

We investigated the electrochemical detection of aspartate transaminase (AST) and alanine transaminase (ALT) by using a multienzyme-modified electrode surface. Determination of the activities of transaminases in human serum is clinically significant because their concentrations and ratios indicate the presence of hepatic diseases or myocardial dysfunction. For electrochemical detection of AST and ALT, enzymes that participate in the reaction mechanism of AST and ALT, such as pyruvate oxidase (POX) and oxaloacetate decarboxylase, were immobilized on an electrode surface by using an amine-reactive self-assembled monolayer and a homobifunctional cross-linker. In the presence of suitable substrates such as L-aspartate (L-alanine) and α-ketoglutarate, AST and ALT generate pyruvate as an enzymatic end product. To determine the activities of AST and ALT, electroanalyses of pyruvate were conducted using a POX and ferrocenemethanol electron shuttle. Anodically generated oxidative currents from multienzyme-mediated reactions were correlated to AST and ALT levels in human plasma. On the basis of the electrochemical analysis, we obtained calibration results for AST and ALT concentrations from 7.5 to 720 units/L in human plasma-based samples, covering the required clinical detection range.

A simple and smart telemedicine device for developing regions: a pocket-sized colorimetric reader.

We have proposed a novel mobile healthcare platform, combining a pocket-sized colorimetric reader (13.5 × 6.5 × 2.5 cm(3)) and commercially available 10-parameter urinalysis paper strips (glucose, protein, glucose, bilirubin, urobilinogen, ketones, nitrite, pH, specific gravity, erythrocytes, and leukocytes), capable of sending data with a smart phone. The reader includes a novel colorimetric multi-detection module, which consists of three-chromatic light-emitting diodes, silicon photodiodes and a novel poly(methylmethacrylate) (PMMA) optical splitter. We employed data reading methods using conversions of the signal data (red, blue, and green) to the hue (H) color map or the Y model data, and used a curve-fitting method for the quantification. The reader is battery-powered, inexpensive, light-weight, and very speedy in analysis. And, it was applied to detection of a thousand of human urine samples and demonstrated reliable quantification of urinary glucose and protein. The features can be used by unskilled people on-site to transfer the analyzed data to experts off-site.

A surface acoustic wave-based immunosensing device using a nanocrystalline ZnO film on Si.

The novelty of this study resides in the fabrication of a bio-sensing device, based on the surface acoustic wave (SAW) on a nanocrystalline ZnO film. The ZnO film was deposited using an rf magnetron sputtering at room temperature on silicon. The deposited films showed the c-axis-oriented crystallite with grain size of approximately 40 nm. The immunosensing device was fabricated using photolithographic protocols on the film. As a model biomolecular recognition and immunosensing, biospecific interaction between a 6-(2,4-dinitrophenyl)aminohexanoic acid (DNP) antigen and its antibody was employed, demonstrating the shifts of resonant frequencies on SAW immunosensing device. The device exhibited a linearity as a function of the antibody concentration in the range of 20-20,000 ng/ml.

Nanocrystalline ZnO film layer on silicon and its application to surface acoustic wave-based streaming.

A surface acoustic wave (SAW) device consisting of 1-6 microm-thick ZnO thin films deposited on Si wafer was designed, fabricated, and characterized in this study. Photolithographic protocols for interdigitated transducers (IDTs) and surface modification using fluoroalkylsilane are employed with the aim of droplet-based microfluidic actuations in bio-microsystems. A ZnO thin film was grown on a 4' silicon wafer with c-axis orientation, an average roughness of 11.6 nm, and a small grain size of 20 nm. It was found that the resonant frequencies (Rayleigh and Sezawa modes) of SAW devices move to a lower frequency range as the thickness of the ZnO thin films increases. Through the silane surface modification, a hydrophobic surface with a contact angle of 114 degrees was obtained. Finally, liquid streaming by acoustic wave was demonstrated by observing the actuation of SiO2 microparticles in a microfluidic drop.

Microfluidic chip accomplishing self-fluid replacement using only capillary force and its bioanalytical application.

A polymer microfluidic chip accomplishing automated sample flow and replacement without external controls and an application of the chip for bioanalytical reaction were described. All the fluidic operations in the chip were achieved by only natural capillary flow in a time-planned sequence. For the control of the capillary flow, the geometry of the channels and chambers in the chip was designed based on theoretical considerations and numerical simulations. The microfluidic chip was made by using polymer replication techniques, which were suitable for fast and cheap fabrication. The test for a biochemical analysis, employing an enzyme (HRP)-catalyzed precipitation reaction, exhibited a good performance using the developed chip. The presented microfluidic method would be applicable to biochemical lab-on-a-chips with integrated fluid replacement steps, such as affinity elution and solution exchange during biosensor signaling.

Passive microfluidic control of two merging streams by capillarity and relative flow resistance.

In the progress of microfluidic devices, a simple and precise control of multiple streams has been essential for complex microfluidic networks. Consequently, microfluidic devices, which have a simple structure, typically use external energy sources to control the multiple streams. Here, we propose a pure passive scheme that uses capillarity without using external force or external regulation to control the merging of two streams and even to regulate their volumetric flow rate (VFR). We accomplish this process by controlling the geometry of two inlets and a junction, and by regulating the hydrophilicity of a substrate. Additionally, we use the relative flow resistance to control the VFR ratio of the merged two streams. Our results will significantly simplify the control of multiple streams without sacrificing precision.

Wafer-scale fabrication of polymer-based microdevices via injection molding and photolithographic micropatterning protocols.

Because of their broad applications in biomedical analysis, integrated, polymer-based microdevices incorporating micropatterned metallic and insulating layers are significant in contemporary research. In this study, micropatterns for temperature sensing and microelectrode sets for electroanalysis have been implemented on an injection-molded thin polymer membrane by employing conventional semiconductor processing techniques (i.e., standard photolithographic methods). Cyclic olefin copolymer (COC) is chosen as the polymer substrate because of its high chemical and thermal stability. A COC 5-in. wafer (1-mm thickness) is manufactured using an injection molding method, in which polymer membranes (approximately 130 microm thick and 3 mm x 6 mm in area) are implemented simultaneously in order to reduce local thermal mass around micropatterned heaters and temperature sensors. The highly polished surface (approximately 4 nm within 40 microm x 40 microm area) of the fabricated COC wafer as well as its good resistance to typical process chemicals makes it possible to use the standard photolithographic and etching protocols on the COC wafer. Gold micropatterns with a minimum 5-microm line width are fabricated for making microheaters, temperature sensors, and microelectrodes. An insulating layer of aluminum oxide (Al2O3) is prepared at a COC-endurable low temperature (approximately 120 degrees C) by using atomic layer deposition and micropatterning for the electrode contacts. The fabricated microdevice for heating and temperature sensing shows improved performance of thermal isolation, and microelectrodes display good electrochemical performances for electrochemical sensors. Thus, this novel 5-in. wafer-level microfabrication method is a simple and cost-effective protocol to prepare polymer substrate and demonstrates good potential for application to highly integrated and miniaturized biomedical devices.

Bulk-micromachined submicroliter-volume PCR chip with very rapid thermal response and low power consumption.

The current paper describes the design, fabrication, and testing of a micromachined submicroliter-volume polymerase chain reaction (PCR) chip with a fast thermal response and very low power consumption. The chip consists of a bulk-micromachined Si component and hot-embossed poly(methyl methacrylate)(PMMA) component. The Si component contains an integral microheater and temperature sensor on a thermally well-isolated membrane, while the PMMA component contains a submicroliter-volume PCR chamber, valves, and channels. The micro hot membrane under the submicroliter-volume chamber is a silicon oxide/silicon nitride/silicon oxide (O/N/O) diaphragm with a thickness of 1.9 microm, resulting in a very low thermal mass. In experiments, the proposed chip only required 45 mW to heat the reaction chamber to 92 degrees C, the denaturation temperature of DNA, plus the heating and cooling rates are about 80 degrees C s(-1) and 60 degrees C s(-1), respectively. We validated, from the fluorescence results from DNA stained with SYBR Green I, that the proposed chip amplified the DNA from vector clone, containing tumor suppressor gene BRCA 1 (127 base pairs at 11th exon), after 30 thermal cycles of 3 s, 5 s, and 5 s at 92 degrees C, 55 degrees C, and 72 degrees C, respectively, in a 200 nL-volume chamber. As for specificity of DNA products, owing to difficulty in analyzing the very small volume PCR results from the micro chip, we vicariously employed the larger volume PCR products after cycling with the same sustaining temperatures as with the micro chip but with much slower ramping rates (3.3 degrees C s(-1) when rising, 2.5 degrees C s(-1) when cooling) within circa 20 minutes on a commercial PCR machine and confirmed the specificity to BRCA 1 (127 base pairs) with agarose gel electrophoresis. Accordingly, the fabricated micro chip demonstrated a very low power consumption and rapid thermal response, both of which are crucial to the development of a fully integrated and battery-powered instrument for a lab-on-a-chip DNA analysis.

Washing-free electrochemical DNA detection using double-stranded probes and competitive hybridization reaction.

A new electrochemical DNA detection method using double-stranded probes and competitive hybridization reaction offers highly selective discrimination of single base mismatch without post-hybridization washing.