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We present an on-chip optical biosensor for the detection of COVID-19. The subwavelength grating waveguide-based micro-ring resonator with high sensitivity and low limit of detection integrates with microfludic channel, which promises clinical utility in point-of-care diagnostic.

BiFeO3 (BFO) samples with nearly perfect ferroelectric hysteresis loops were synthesized from chemical solution via hydrothermal route at 200 °C. However, for many applications, ceramic samples of reasonable bulk density (>80%) have to be sintered at temperature over 700 °C, which in this case results in a significant reduction in resistivity due to increased amounts of Fe2+. Interestingly, doping of a few percent Sb minimized such a problem and the sintered Sb:BFO ceramics retained a similarly high resistivity as samples cold-pressed from the chemical-solution synthesized powders. However, for cold-pressed samples, Sb:BFO actually had higher conductivity than undoped BFO. Temperature-dependent conductivity showed that cold-pressed samples of both undoped and Sb doped BFO had the similar activation energy of 1.0 eV, typical for electrons trapped in oxygen vacancies. After sintering, the activation energy of Sb:BFO remained almost unchanged, but the activation energy of undoped BFO changed to 0.4 eV, which is associated to electron hopping between Fe2+/Fe3+. X-ray photoelectron spectroscopy (XPS) showed a significant increase in Fe2+/Fe3+ ratio from 6.6/93.4 to 25.7/74.3 in undoped BFO after sintering, while for 1% Sb doped BFO the increase was much milder from 10.9/89.1 to 14.1/85.9. XPS also showed that Sb had single +3 oxidation state before sintering, but after sintering a fairly large portion of Sb5+ occurred. So, charge compensation for oxygen vacancies in undoped BFO was achieved dominantly by reduction of Fe3+ to Fe2+, while in Sb:BFO it was achieved more by cation vacancies.

A microfluidic chip, which can separate and enrich leukocytes from whole blood, is proposed. The chip has 10 switchback curve channels, which are connected by straight channels. The straight channels are designed to permit the inertial migration effect and to concentrate the blood cells, while the curve channels allow the Dean flow to further classify the blood cells based on the cell sizes. Hydrodynamic suction is also utilized to remove smaller blood cells (e.g., red blood cell (RBC)) in the curve channels for higher separation purity. By employing the inertial migration, Dean flow force, and hydrodynamic suction in a continuous flow system, our chip successfully separates large white blood cells (WBCs) from the whole blood with the processing rates as high as 1 &times, 108 cells/sec at a high recovery rate at 93.2% and very few RBCs (~0.1%).

Quantum oscillations have long been regarded as the manifestation of the Fermi surface in metals. However, they were recently observed in Kondo insulators. We examine the Kondo screening due to Landau levels in Kondo insulators. It is shown that even for large Kondo insulating gaps, appreciable amplitudes of quantum oscillations that are consistent with experimental observations are present both in magnetization and resistivity. Specifically, we show that due to the periodic alignment between the Landau levels in the conduction and the f-orbit electrons, the Kondo screening itself undergoes oscillations so that the electronic structure oscillates with the magnetic field. Our results explain main features of quantum oscillations observed in experiments. They indicate that the non-rigidity of the electronic structure results in observable quantum oscillations Kondo insulators. This new effect provides a new way to probe the Fermi surface geometry of insulators., 7 pages, 6 figures, to appear in Phys Rev B

Ciliated muconodular papillary tumor is a rare tumor of the lung with 38 cases reported to date in the English literature. It is typically found incidentally in older adults (average age, 67 years) as a small, peripheral, ground glass opacity or nodule on computed tomography. Microscopically, the tumor is composed of a mixture of ciliated columnar, mucous, and basal cells in a variety of architectural patterns including glandular, papillary, lepidic, and micropapillary growth patterns. Recently, studies have shown the tumor has several associated gene alterations, supporting that the lesion is indeed neoplastic. The tumor seemingly follows an indolent clinical course, as there have been no reported recurrences or metastases. In this article, we review the clinical, radiographic, pathologic, and molecular findings of ciliated muconodular papillary tumors. Diagnostic pitfalls and the diagnostic considerations are discussed.

A microfluidic device, which performs a primer extension technique onto microbeads, is demonstrated to genotype Single Nucleotide Polymorphism (SNP) on genomic DNA. The device has on-chip heaters and sensors to create a uniform and yet stable temperature gradient between 56 °C and 94 °C across an array of serpentine microchannels, where the microbeads carry allele-specific primers passing through for thermal cycling. As the primers on the beads is designed to be only extended when perfectly matched with the SNP site of the template, the mismatched samples will not be amplified. The SNP discrimination is achieved. In addition that the microfluidic environment promote enhanced mass transport and better hybridization kinetics, the microbeads offer an advantage for faster thermal response and higher signal-to-noise ratio. Three most-frequent variants in one SNP location from genomic DNA of Taiwan country chicken are successfully distinguished in only five thermal cycles, compared to thirty (30) thermal cycles in traditional approaches. Moreover, the SNP genotyping procedures, which typically involves multiple steps in amplification and detection, were integrated onto a single chip.

Floristic study of Marchantia L. in Taiwan has been presented in this paper. Six taxa, namely, M. emarginata subsp. tosana, M. formosana, M. paleacea subsp. paleacea, M. paleacea subsp. diptera, M. pinnata and M. polymorpha are confirmed in Taiwan. Among them, M. formosana is endemic, M. pinnata is shared by Japan and Taiwan, M. paleacea subsp. diptera is distributed in China, Japan and Taiwan, while the remainings are more or less widespreading. Key for taxa in Taiwan is provided for convenience of identification, and descriptions, photos and distribution maps are also provided for each taxon as a basic materials for further studies.

An integrated microchip platform with automated analysis capability for DNA melting curves is developed for Single Nucleotide Polymorphism (SNP) genotyping applications. The microchip contains fluidic channels where genomic DNA samples are encapsulated into a series of droplets and transported through a detection region with a stable temperature gradient. As the temperature is elevated from 60 °C to 85 °C, the DNA strains denature and the associated fluorescence signals decay with this relationship being acquired as the melting curve. The droplets serve as discrete reactors to conduct DNA melting curve analysis in the liquid phase, eliminating the need for immobilization of reagents. They provide the advantage of signal homogeneity, which reduces the signal fluctuations, and thus the signal-to-noise ratio is improved. In addition, a droplet detection and tracking software system which can identify the droplets, records the fluorescence intensities, plots the melting curves, and finds the melting temperatures, is developed making automated SNP genotyping possible. The platform has been verified with genomic DNA from Landrace sows and shown successful SNP discrimination from homozygotes and heterozygotes which demonstrates its potential to conduct on-site SNP genotyping for disease research, medical diagnostics, agriculture, and farm animal reproduction.

Paper-based technologies have been drawing increasing attentions in the biosensor field due to their economical, ecofriendly, and easy-to-fabricate features. In this paper, we present a time-delay valve mechanism to automate a series of procedures for conducting competitive enzyme-linked immunosorbent assay (ELISA) on a paper-based device. The mechanism employs a controllable time-delay valve, which has surfactants to dissolve the hydrophobic barriers, in a fluid pathway. The valves can regulate the liquid and sequentially deliver the sample flow for automating ELISA procedures in microchannels. Competitive ELISA is achieved in a single step once the sample, or small molecule pesticide (e.g., Imidacloprid), is applied onto the paper-based device with a comparable sensitivity to plate-based competitive ELISA. The results further demonstrate the appositeness of using paper-based devices with the valve designs for on-the-go ELISA detection in agriculture and biomedical applications.

Applications in the field of computational lithography require an accurate and extremely fast method to compute light scatterings from a photomask, which is laterally sized on the order of 10 cm in each of two dimensions and consists of dense sub-100 nm geometric patterns. All but every practical solution approaches this challenging problem by integrating scattering effects of knife-edges in association with the mask pattern boundaries. Photomasks in the near future will require integrating effects of curved edges. This paper presents a rigorous mathematical formulation of a geometric theory of diffraction for light scattering from a photomask, as an attempt to not only unify previous edge-based Mask3D models and methods, but also lay the theoretical foundations for continuing technology developments, especially Mask3D modeling of the upcoming curvilinear patterned masks. As a by-product, this paper should be useful for computational electromagnetics practitioners, and computational lithography engineers in particular, to get familiar with some of the powerful mathematical tools in differential forms, tensor analysis, and Riemann surfaces.

We presents a microinjection system for gene delivery to planarian. The system consists of two parts: a planarian-fixing platform, which provides a low-temperature environment to make planarian become motionless for injection, and a nanoliter injector (nanoliter-scale microinjector). The system is tested by injecting fluorescent microbeads and gene (e.g. dsRNA) respectively into planarian. In particular, successful delivery of DjAg02 dsRNA leads to a reduction of DjAg02 expression, which results in a degenerated phenotype of planarian. The results show our system as an alternative to traditional gene delivery (i.e. ingestion, which performs delivery by feeding planarian genetic substances mixed food). Our system is applicable to studying the function of genes related to starvation condition. Additionally, the dosage of genetic substances is consistent, which is required for the following analyses.

DNA methylation is an epigenetic regulation of gene expression, which has drawn great attention in biomedical research due to its association with various diseases. A robust, inexpensive platform to detect and quantify the methylation status in a specific genomic region is necessary. In this study, an on-chip analytical technique of cytosine methylation with droplets in a microchannel is proposed. Genomic DNA samples are encapsulated into a series of droplets and transported through a detection region, where a stable temperature gradient is created. As the temperature is elevated from 60 °C to 85 °C, the DNA samples denature and the associated fluorescence signals decay, with the relationship being acquired as the melting curve. The droplets serve as discrete reactors for conducting DNA melting curve analysis in the liquid phase, thereby eliminating the need for immobilization of reagents. Due to a high heating rate and greater enhanced thermal stability, this microchip allows larger melting temperature differences for the samples at different percentages of methylated DNA. It has an enhanced discrimination ability and lower volume consumption, compared to the commercial qPCR machine. This chip enables quantification of the methylation levels of the pluripotent stem cell factor Oct-4 in its distal enhancer (DE) region, with a designed probe after bisulfite treatment and asymmetric PCR.

The genetic markers associated with economic traits have been widely explored for animal breeding. Among these markers, single-nucleotide polymorphism (SNPs) are gradually becoming a prevalent and effective evaluation tool. Since SNPs only focus on the genetic sequences of interest, it thereby reduces the evaluation time and cost. Compared to traditional approaches, SNP genotyping techniques incorporate informative genetic background, improve the breeding prediction accuracy and acquiesce breeding quality on the farm. This article therefore reviews the typical procedures of animal breeding using SNPs and the current status of related techniques. The associated SNP information and genotyping techniques, including microarray and Lab-on-a-Chip based platforms, along with their potential are highlighted. Examples in pig and poultry with different SNP loci linked to high economic trait values are given. The recommendations for utilizing SNP genotyping in nimal breeding are summarized.

DNA extraction is one of the most essential steps in nucleic acid testing, which usually requires a series of reagent mixing, centrifugal separations, and manual operations. While microfluidic devices have shown their capability in point-of-care applications, some of them face the challenge in on-chip sample preparation, such as DNA extraction from blood samples, prior to the diagnosis. Although digital microfluidic (DMF) eliminates the need of complicated fluidic actuation components and draws great attentions as a promising Lab-on-a-Chip platform, its capability in DNA extraction has been limitedly shown. Herein, we develop a protocol on a DMF platform for DNA extraction. As the protocol contains blood, magnetic beads, a variety of liquids, and complicated steps, it was implemented in a sequence of droplet operations with our proposed washing/droplet-separation strategy. Our on-chip extraction protocol was conducted with room-temperature incubations and much less washing cycles. The results were confirmed by using SYBR-Green dye staining and gel electrophoresis. Therefore, the DMF device was shown to permit on-chip DNA extraction with fewer sample/reagent consumption and shorter operation time.

Sub-Resolution Assist Features (SRAF) are widely used for Process Window (PW) enhancement in computational lithography. Rule-Based SRAF (RB-SRAF) methods work well with simple designs and regular repeated patterns, but require a long development cycle involving Litho, OPC, and design-technology co-optimization (DTCO) engineers. Furthermore, RB-SRAF is heuristics-based and there is no guarantee that SRAF placement is optimal for complex patterns. In contrast, the Model-Based SRAF (MB-SRAF) technique to construct SRAFs using the guidance map is sufficient to provide the required process window for the 32nm node and below. It provides an improved lithography margin for full chip and removes the challenge of developing manually complex rules to assist 2D structures. The machine learning assisted SRAF placement technique developed on the ASML Brion Tachyon platform allows us to push the limits of MB-SRAF even further. A Deep Convolutional Neural Network (DCNN) is trained using a Continuous Transmission Mask (CTM) that is fully optimized by the Tachyon inverse lithography engine. The neural network generated SRAF guidance map is then used to assist full-chip SRAF placement. This is different from the current full-chip MB-SRAF approach which utilizes a guidance map of mask sensitivity to improve the contrast of optical image at the edge of lithography target patterns. We expect that machine learning assisted SRAF placement can achieve a superior process window compared to the MB-SRAF method, with a full-chip affordable runtime significantly faster than inverse lithography. We will describe the current status of machine learning assisted SRAF technique and demonstrate its application on the full chip mask synthesis and how it can extend the computational lithography roadmap.

A wearable tactile device on fabrics based on Electrical Contact Resistance (ECR) variation mechanism is developed for the first time. The device consists of one top and one bottom fabric substrates, which are screen-printed with conductive materials then faced-to-face assembled. Due to its exclusive features of surface roughness and material compressibility, the fabric substrate is favorable in ECR variation mechanism. The device is optimized with different conductive materials to create microscale pillars and further enhance the device sensitivities. Device characteristics and practical applications are investigated in monitoring human wrist pulses with wireless module and smartphone, showing its capability in fast response and high sensitivity for internet-of-thing and medical applications.

We present a timing-valve mechanism on a paper-based device to conduct competitive ELISA procedures. The device consists of multiple channels, where timing-valves regulate each individual liquid flow, to automate sequential steps. The timing-valve is achieved using surfactants to dissolve the hydrophobic barriers and to allow fluid to pass through in a timed duration. Imidacloprid (small molecule pesticide) is tested in our proposed device, while the results validate a simplified fluidic manipulation procedure and permits only single-step application of the sample solution for on-site detection.

The mechatronic system to drive and control a digital microfluidics (DMF) microchip was introduced and explained. It features two key functionalities for digital microfluidics: (1) application of different driving forces/frequency through integrated electronic circuitry, and (2) capability of programming a series of DMF actuations on electrodes for automation with friendly graphical user interface (GUI). The system can further expand its functionality with a real-time monitoring system as a fully closed-loop control for practical applications. This article will provide readers a guideline to construct a mechatronic system for DMF, which thus allows the utilization of a DMF microchip as convenient tools to achieve the automation of biological laboratory procedures.

A lack of effective educational materials is limited general public awareness of, and interest in, nanoscience. This paper presents a conceptual atomic force microscope (AFM) model built by using the LEGO® MINDSTORMS series. AFMs are perhaps one of the most fundamental and widely-used instruments in nanoscience and nanotechnology, thus the introduction of this LEGO® AFM should be beneficial to nanoscience education. Programmed in LabVIEW, this LEGO® model has the ability to scan the samples and construct a three-dimensional (3D) surface graphs of the sample, based on the mechanism used for AFM. With this LEGO® AFM, the students can directly access nanoscience concepts through hands-on experience constructing an AFM model. This interaction will lead to a better understanding of nanoscience principles, and motivate learners to further explore both the theoretical and experimental aspects of the domain.

This paper introduces a passive degassing mechanism using textured surfaces to trap and transport bubbles, and then using hydrophobic porous membranes to vent out bubbles in a microfluidic system. The bubble trapping ability is achieved by creating nanostructures to promote bubble nucleation and coalescence on the sidewalls of KOH-etched concave pits in a silicon substrate. The substrate, which is bonded with a porous membrane, is placed in a liquid system with chemically generated CO2 bubbles to examine the degassing ability. The results validate that the bubbles can be easily trapped on the surfaces with nanostructures, and then vented through the porous membrane. Our proposed approach possesses the advantage of simple fabrication, great structure robustness, and effective bubble trapping and removing abilities, which show their great potential as economic, passive means of preventing the gas byproducts from blocking surfaces and improving the efficiency of microfluidic systems during operations.

Single nucleotide polymorphism (SNP) is not only one of the most common genetic variances in a human genome, but it also serves a crucial biomarker greatly affecting the phenotypes of individuals. Moreover, SNP had shown its importance by making contributions in many aspects, including species classification for pests, pesticide resistance detection, and disease diagnostic for human beings. Most of today’s SNP detection techniques utilize enzymes or modification of DNA, leading to the requirement of high reagent cost or complex procedures. Therefore, a new SNP genotyping scheme has been developed to address these issues by conducting melting curve analysis on the DNA target sequences, which are conjugated onto polystyrene microbeads in a microfluidic device. The microbeads function as a solid vehicle for capturing the DNA duplexes, providing a larger surface-to-volume ratio for reaction and allowing it to be hydrodynamically confined for melting curve analysis. A prototype device serving as a basis for this proposed scheme was successfully tested, detecting the SNP of ataxia–telangiectasia-mutated gene from both synthetic DNA and genomic DNA of Landrace sows. This bead-based SNP detection only required a minimal reagent amount and simplified the sample preparation procedures, thereby preserving it as a flexible and accurate detection scheme. All these characteristics show great promise in this bead-based SNP detection.

We propose the utilization of a microfluidic platform, which generates a defined temperature gradient, for on-chip microtubule (MT) polymerization. The temperature gradient allows the MTs to be asymmetrically polymerized in a spatially-restricted, nature-mimicking environment. MTs are unidirectionally assembled and neatly aligned along the temperature gradient direction. To quantify the MT alignment, a structure-tensor-based image processing technique is employed. At the similar temperature, the MTs show an alignment within 30° under the temperature gradient field, whereas they are widely dispersed under the uniform temperature field. Further, the MT polymerization and alignments at two different tubulin concentrations are examined. The MTs polymerized at the higher concentration are aligned for a longer distance than the ones at the lower concentration due to sufficient tubulin concentration.

A taxel device on flexible substrates based on the electrical contact resistance (ECR) variation mechanism is developed. The proposed taxel device consists of one top and one bottom substrates, which are coated with conductive polymer then face-to-face assembled. The device is tested with different substrate materials to show the viability of the ECR variation mechanism. It is found that when paper is used as the substrate material, because of its exclusive features of surface roughness and material compressibility, the ECR variation mechanism is greatly enhanced and the device exhibits higher sensitivity and larger working pressure range. Practical applications are investigated in elasticity measurement on phantom samples and biological tissues. The results are promising with our taxel device made on flexible substrates being capable of integration onto surgical tools and the potential to realize the psychical property of biological tissues.

Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taipei, TaiwanNanowire arrays with various agglomeration patterns were synthesized by adjusting the solventevaporation rates. Nanowires with 200 nm diameter and 2∼25 m in length were fabricated froman anodic aluminum oxide (AAO) porous template. Various drying treatments were applied todevelop nanostructured surfaces with topological differences. Due to surface tension forces, coppernanowires after thermal and evaporative drying treatments agglomerated into clusters, while super-critical drying technique provided excellent bundled-free and vertically-standing nanowire arrays.Although all dried surfaces exhibited hydrophobic nature, the contact angle hysteresis, or the dif-ference between advancing and receding angles, was found to be larger on those surfaces withbundled nanowire clusters. To explain the difference, the wetted solid fraction on each surface wascalculated using the Cassie-Baxter model to show that the hysteresis was contributed by liquid/solidcontact area on the textured surfaces.

Strong resist shrinkage effects have been widely observed in resist profiles after negative tone development (NTD) and therefore must be taken into account in computational lithography applications. However, existing lithography simulation tools, especially those designed for full-chip applications, lack resist shrinkage modeling capabilities because they are not needed until only recently when NTD processes begin to replace the conventional positive tone development (PTD) processes where resist shrinkage effects are negligible. In this work we describe the development of a physical resist shrinkage (PRS) model for full-chip lithography simulations and present its accuracy evaluation against experimental data.

A new technique is developed to directly grow Cu nanowire (CuNW) on Si substrate with electrochemical deposition to produce height-controlled hydrophilic nanowired surfaces for enhancing pool boiling performance. For broader heat transfer applications, CuNW and Si nanowires (SiNW) with various nanowire heights were fabricated and examined under pool boiling with water. The heat transfer performance of the samples with NW arrays is enhanced with increasing NW heights regardless of the NW materials. The surface with the tallest NW structure (35 mm-tall SiNW) yielded a heat flux of 134 W/cm 2 at 23 K wall superheat, about 300% higher than a plain Si surface at the same wall superheat.