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Liver function test is the first step to diagnose various liver diseases by measuring certain proteins and liver enzymes from the blood sample. After getting the required data of the clinical parameters from the blood test it is possible to calculate Child-Pugh (CTP), AST to PLT ratio (APRI) and Model for end-stage liver disease (MELD) clinical scores that help the doctors about the severity of the disease progression. Volatile organic compounds (VOCs) found in-breath and monitoring their concentration may be a prevailing method for disease diagnosis. In this work, Isoprene, Limonene, and Dimethyl sulphide (DMS) are considered as a potential breath biomarker related to liver disease. A dataset is designed, that includes the biomarkers concentration analysed from the breath sample before and after study subjects performed an exercise. Four regression methods are performed to predict the clinical scores using breath biomarkers data as features set by the machine learning techniques. Regression methods on the dataset for prediction are evaluated by mean absolute error and root mean square error. A significant difference observed for isoprene concentration (p

Indium tin oxide (ITO) is widely used as a substrate for fabricating chips because of its optical transparency, favorable chemical stability, and high electrical conductivity. However, the wettability of ITO surface is neutral (the contact angle was approximately 90&deg, ) or hydrophilic. For reagent transporting and manipulation in biochip application, the surface wettability of ITO-based chips was modified to the hydrophobic or nearly hydrophobic surface to enable their use with droplets. Due to the above demand, this study used a 355-nm ultraviolet laser to fabricate a comb microstructure on ITO glass to modify the surface wettability characteristics. All of the fabrication patterns with various line width and pitch, depth, and surface roughness were employed. Subsequently, the contact angle (CA) of droplets on the ITO glass was analyzed to examine wettability and electrical performance by using the different voltages applied to the electrode. The proposed approach can succeed in the fabrication of a biochip with suitable comb-microstructure by using the optimal operating voltage and time functions for the catch droplets on ITO glass for precision medicine application. The experiment results indicated that the CA of droplets under a volume of 20 &mu, L on flat ITO substrate was approximately 92&deg, &plusmn, 2&deg, furthermore, due to its lowest surface roughness, the pattern line width and pitch of 110 &mu, m exhibited a smaller CA variation and more favorable spherical droplet morphology, with a side and front view CA of 83&deg, 1&deg, and 78.5&deg, 2.5&deg, respectively, while a laser scanning speed of 750 mm/s was employed. Other line width and pitch, as well as scanning speed parameters, increased the surface roughness and resulted in the surface becoming hydrophilic. In addition, to prevent droplet morphology collapse, the droplet&rsquo, s electric operation voltage and driving time did not exceed 5 V and 20 s, respectively. With this method, the surface modification process can be employed to control the droplet&rsquo, s CA by adjusting the line width and pitch and the laser scanning speed, especially in the neutral or nearly hydrophobic surface for droplet transporting. This enables the production of a microfluidic chip with a surface that is both light transmittance and has favorable electrical conductivity. In addition, the shape of the microfluidic chip can be directly designed and fabricated using a laser direct writing system on ITO glass, obviating the use of a mask and complicated production processes in biosensing and biomanipulation applications.

Multifocal illumination can improve image acquisition time compared to single point scanning in confocal microscopy. However, due to an increase in the system complexity, obtaining uniform multifocal illumination throughout the field of view with conventional methods is challenging. Here, we propose a volume holographic lenslet array illuminator (VHLAI) for multifocal confocal microscopy. To obtain uniform array illumination, a super Gaussian (SG) beam has been incorporated through VHLAI with an efficiency of 43%, and implemented in a confocal microscope. The design method for a photo-polymer based volume holographic beam shaper is presented and its advantages are thoroughly addressed. The proposed system can significantly improve image acquisition time without sacrificing the quality of the image. The performance of the proposed multifocal confocal microscopy was compared with wide-field images and also evaluated by measuring optically sectioned microscopic images of fluorescence beads, florescence pollen grains, and biological samples. The proposed multifocal confocal system generates images faster without any changes in scanning devices. The present method may find important applications in high-speed multifocal microscopy platforms.

Optical sectioning fluorescence microscopy provides high contrast images of volumetric samples and has been widely used for many biological applications. However, simultaneously acquiring multi-color fluorescence images require additional optical elements and devices, which are bulky, wavelength specific, and not cost-effective. In this paper, wavelength-coded volume holographic gratings (WC-VHGs) based optical sectioning fluorescence microscopy is proposed to simultaneously offer multi-color fluorescence images with fine out-of-focus background rejection. Due to wavelength degeneracy, multiplexed WC-VHGs are capable of acquiring multi-wavelength fluorescence images in a single shot, and displaying the laterally separated multi-wavelength images onto CCD. In our system optical sectioning capability is achieved through speckle illumination and HiLo imaging method. To demonstrate imaging characteristics of our system, dual-wavelength fluorescence images of both standard fluorescent microspheres and ex vivo mT/mG mice cardiac tissue are presented. Current results may find important applications in hyperspectral imaging for biomedical research.

Significance: Differential phase contrast (DPC) is a well-known imaging technique for phase imaging. However, simultaneously acquiring multidepth DPC images is a non-trivial task. We propose simultaneous multiplane DPC imaging using volume holographic microscopy (VHM). Aim: To design and implement a new configuration of DPC-VHM for multiplane imaging. Approach: The angularly multiplexed volume holographic gratings (AMVHGs) and the wavelength-coded volume holographic gratings (WC-VHGs) are used for this purpose. To obtain asymmetric illumination for DPC images, a dynamic illumination system is designed by modifying the regular Köhler illumination using a thin film transistor panel (TFT-panel). Results: Multidepth DPC images of standard resolution chart and biosamples were used to compare imaging performance with the corresponding bright-field images. An average contrast enhancement of around three times is observed for target resolution chart by DPC-VHM. Imaging performance of our system is studied by modulation transfer function analysis, which suggests that DPC-VHM not only suppresses the DC component but also enhances high-frequency information. Conclusions: Proposed DPC-VHM can acquire multidepth-resolved DPC images without axial scanning. The illumination part of the system is adjustable so that the system can be adapted to bright-field mode, phase contrast mode, and DPC mode by controlling the pattern on the TFT-panel.

Differential phase contrast (DPC) microscopy provides isotropic phase images by applying asymmetric illumination patterns on the sample. The movement of specimens during series image acquisition may lead to motion blur artifacts, which are difficult to prevent. Here, we propose a new method based on pupil engineering and color multiplexing to obtain an isotropic phase transfer function and to reduce the required frames simultaneously. Radially asymmetric color pupils are implemented in a DPC microscope using a programmable thin-film transistor as a digital pupil, which gives flexibility and dynamic control for projecting illumination patterns on samples. With our approach, an isotropic quantitative phase map can be obtained using only pairwise color images for phase reconstruction. A radially asymmetric color pupil is synthesized by encoding the red, green, and blue colors. To recover accurate phase values, a color-leakage correction algorithm is applied to calibrate each color channel. Compared to a half-circle illumination pupil, our method can significantly enhance the image acquisition speed. The phase recovery accuracy is more than 97%. To show the imaging performance of our proposed method, quantitative phase imaging of living 3T3 mouse fibroblast cells is performed. Our quantitative phase measurement method may find important applications in biomedical research.

A volume holographic (VHG) grating-based multi-plane differential confocal microscopy (DCM) is proposed for axial scan-free imaging. Also, we briefly reviewed our previous works on volume holographic-based confocal imaging. We show that without degrading imaging performance, it is possible to simultaneously obtain two depth-resolved optically sectioned images with improved axial resolution using multi-plane DCM. The performance of our multi-plane DCM was evaluated by measuring the surface profile of a silicon micro-hole array with depths separation around 10 µm. The axial sensitivity of the system is around 25 nm. Our system has the advantages of multi-plane imaging with high axial sensitivity and high optical sectioning ability. Our method can be used for reflective surface profiling and multi-plane fluorescence imaging. The present methods may find important applications in surface metrology for label-free biological samples, as well as industrial applications.

Breath ammonia is an important biomarker linked to liver malfunction. Acetone is the most abundant compound in the breath, acts as major interference for selective detection of ammonia gas. Here, a novel method based on viscosity modulation of the silicone oil absorbent is reported for selectivity improvement of ammonia over acetone gas. ATD-GC-MS and T201 ammonia analyzer are used to measure the absorption of acetone and ammonia respectively into the silicone oil. The absorption of ammonia and acetone gas is measured in different absorbent viscosities at a constant flow rate (50 cc min−1). Absorption results of ammonia are 7.37%, 16.3%, and 17.1% and acetone absorption results are 35%, 68%, and 78% respectively into 500 cSt, 100 cSt, and 20 cSt viscous silicone oil at room temperature. More bubbles of smaller diameter are formed at a lower viscosity, increases the contact time of the gas with absorbent. Consequently, the absorption of acetone into silicone oil at lower viscosity increases as compared to ammonia. The absorption of acetone is about 4.6-fold higher than the ammonia. Hence, it proves to be an effective technique for enhancing selectivity. This novel concept can be incorporated with any sensor for portable breath ammonia sensing in the detection of liver dysfunction.

A non-axial-scanning multi-plane microscopic system incorporating multiplexed volume holographic gratings and slit array detection to simultaneously acquire optically sectioned images from different depths is presented. The proposed microscopic system is configured such that multiplexed volume holographic gratings are utilized to selectively produce axial focal points in two or more planes inside the sample, and then to use confocal slit apertures to simultaneously image these multiple planes onto corresponding detection areas of a CCD. We describe the design, implementation, and experimental data demonstrating this microscopic system’s ability to obtain optically sectioned multi-plane images of fluorescently labeled standard micro-spheres and tissue samples without scanning in axial directions.

During the thinning and machining processes, surface defects or cracks are easily induced on a silicon chip. The defects or cracks may cause stress concentration and become one of the failure sources for silicon chips. One of our previous papers reported that the stress concentration at the crack tip on a silicon chip with nanostructure was greatly reduced for the case of four-point bending. In this paper, the finite element analysis was used to further study the effect of nanostructures on the stress distribution near the surface crack for a silicon chip. Since the stress distribution near the surface crack was our main concern for a chip under four-point bending, nanostructures were introduced in the area near the crack on the chip surface in the analysis for computational efficiency. The spacing and depth of the nanostructure, and the crack depth on the silicon chip surface were varied to access their effects on the stress distributions near the crack on the silicon chip.

AlGaN/GaN high electron mobility transistors (HEMTs) were used to sense the binding between double stranded DNA (dsDNA) and the severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid protein (N protein). The sensing signals were the drain current change of the HEMTs induced by the protein–dsDNA binding. Binding-site models using surface coverage ratios were utilized to analyze the signals from the HEMT-based sensors to extract the dissociation constants and predict the number of binding sites. Two dissociation constants, K D 1 = 0.0955 nM, K D 2 = 51.23 nM, were obtained by fitting the experimental results into the two-binding-site model. The result shows that this technique is more competitive than isotope-labeling electrophoretic mobility shift assay (EMSA). We demonstrated that AlGaN/GaN HEMTs were highly potential in constructing a semiconductor-based-sensor binding assay to extract the dissociation constants of nucleotide–protein interaction.

This paper describes an easy-to-handle approach to create three-dimensional millimeter-scale (or submillimeter-scale) polymeric structures on various substrates that have been used as molds in order to develop a polymeric-based manufacturing procedure for making in vitro diagnostic devices with mass production capacity and portability. These polymeric structures were made by using UV-activated materials, adhesive tapes as the mask, and a UV-LED flashlight as the portable light source. This straightforward approach can be easily performed and has great potential for use in resource-limited settings. The ability to conduct three common metabolic assays – for glucose, total cholesterol, and nitrite ions in this study – in both a buffer system and human serum (analytical validation, US FDA regulations) with clinically relevant sensitivity has been demonstrated using these polymeric-based in vitro diagnostic devices. This study, we believe, would provide for a wide range of potential applications such as the development of in vitro diagnostic devices, and a large-scale, low-cost, and easy-to-handle fabrication procedure for either developing regions or resource-limited settings, and, ultimately, for the development of “zero-cost” diagnostic devices for global public health.

The detection of Volatile Organic Compounds (VOCs) biomarkers from the exhaled breath has opened the new techniques for medical diagnostics because of its noninvasive and inexpensive way of disease detection. Exhaled breath contains more than 1840 VOCs 1 which concentration may vary in ppb or in ppt range. The signature of some VOCs present in breath abruptly change with the specific disease, called biomarkers. Ammonia is an important biomarker for liver disease 2. There are many conventional techniques to detect ammonia in sub-ppm range including, proton transfer reaction mass spectrometry (PTR-MS), selected ion flow tube coupled mass spectrometry (SIFT-MS) 3, but these instruments are bulky and very costly. Metal Oxide (MOS) based gas sensors are very promising sensors for detection of breath biomarkers, but it also has a disadvantage of high operation temperature (more than 300ºC). Extensive attention has been paid recently to the indium nitride (InN) epitaxial layers and devices for gas sensing application because of its exceptional electronic properties, including excellent electron mobility, high electron density and comparatively low operation temperature ~200ºC. Moreover, an unusual phenomenon of strong electron accumulation at the surface of InN makes it highly sensitive gas sensor for VOCs detection 4. In this work, two InN based gas sensors of different thickness of the sensing film T1 (40nm) and T2 (60nm) are used respectively, for gas sensing. When the various concentration (0.3ppm, 0.5ppm, 1 ppm and 2ppm) of NH3 gas are exposed on the sensors, the current response is obtained at different thickness shown in (Figure 1a and 1b) respectively. The current variation response of 2 ppm NH3 gas on T1 is approx. 10 fold higher than T2 as shown in (Figure 1c). The current variation response for 0.5ppm on T1 is 0.04% while T2 showed negligible response as shown in (Figure 1d). The change at the surface of InN epilayer will be more significance on the total conductivity of thin layer as compare to thick layer 5. Hence, the lower thickness of the InN epilayer has higher response as compare to higher thickness. Therefore, lower thickness (40 nm) is suitable for diagnosis of liver malfunction. References B. de Lacy Costello, A. Amann, H. Al-Kateb, C. Flynn, W. Filipiak, T. Khalid, D. Osborne, and N. M. Ratcliffe, Journal of breath research, 8 (1), 014001 (2014). A. Kundra, A. Jain, A. Banga, G. Bajaj, and P. Kar, Clinical biochemistry, 38 (8), 696-699 (2005). S. T. Krishnan, J. P. Devadhasan, and S. Kim, Analytical and bioanalytical chemistry, 409 (1), 21-31 (2017). S. Rai, K.-W. Kao, S. Gwo, A. Agarwal, W. Lin, and J. Yeh, Sensors, 18 (11), 3887 (2018). H. Lu, W. J. Schaff, and L. F. Eastman, Journal of applied physics, 96 (6), 3577-3579 (2004). Figure 1: (a) current response at T1 (40 nm thickness), (b) current response at T2 (60 nm thickness), (c) current variation response at 2 ppm NH3 gas at T1 and T2, (d) current variation response at 0.5 ppm NH3 gas at T1 and T2. Figure 1

Photovoltaic, microelectromechanical systems, and integrated circuit industries are demanding a technology to enable the high rupture resistant silicon wafer production to improve the manufacturing yield. The presented silicon nanotexture patterning on the edges and sidewalls by wet chemical etching process can protect single-crystalline and multicrystalline silicon samples from rupture. Bending tests indicate a mechanical strength enhancement of ~ 72%-75% for sc-silicon and ~71%-73% for mc-silicon samples. In addition, the front and back surfaces of the samples remain intact and appropriate for any further semiconductor processes. This technology was implemented in solar cells that exhibited a strength improvement of nearly 73% without affecting their photovoltaic performances, anticipating an effective solution for the solar cell manufacturing industry.

In an alkaline condition, ammonium can be efficiently reduced with hydroxide ion using a spinning disk reactor at room temperature. To some extent, illumination can boost the processing efficiency by warming water. A homogeneous 8 nm crystallized platinum thin film deposited on a B270-glass substrate by plasma-enhanced atomic layer deposition absorbs light from 350 nm to 2500 nm. The absorbed light transforms plasmonic resonance energy on the platinum thin film and forms a high temperature hot layer. The plasmonic heating effect, or plasmonic photocatalytic reaction, enhances the activity of the Pt thin film for the oxidation of NH4+.

In this study, we mechanically strengthened a borosilicate glass wafer by doubling its bending strength and simultaneously enhancing its transparency using surface nanostructures for different applications including sensors, displays and panels. A fabrication method that combines dry and wet etching is used for surface nanostructure fabrication. Specifically, we improved the bending strength of plain borosilicate glass by 96% using these surface nanostructures on both sides. Besides bending strength improvement, a limited optical transmittance enhancement of 3% was also observed in the visible light wavelength region (400–800 nm). Both strength and transparency were improved by using surface nanostructures of 500 nm depth on both sides of the borosilicate glass without affecting its bulk properties or the glass manufacturing process. Moreover, we observed comparatively smaller fragments during the breaking of the nanostructured glass, which is indicative of strengthening. The range for the nanostructure depth is defined for different applications with which improvements of the strength and transparency of borosilicate glass substrate are obtained.

Defects and heterogeneities degrade the strength of glass with different surface and subsurface properties. This study uses surface nanostructures to improve the bending strength of glass and investigates the effect of defects on three glass types. Borosilicate and aluminosilicate glasses with a higher defect density than fused silica exhibited 118 and 48 % improvement, respectively, in bending strength after surface nanostructure fabrication. Fused silica, exhibited limited strength improvement. Therefore, a 4-μm-deep square notch was fabricated to study the effect of a dominant defect in low defect density glass. The reduced bending strength of fused silica caused by artificial defect increased 65 % in the presence of 2-μm-deep nanostructures, and the fused silica regained its original strength when the nanostructures were 4 μm deep. In fragmentation tests, the fused silica specimen broke into two major portions because of the creation of artificial defects. The number of fragments increased when nanostructures were fabricated on the fused silica surface. Bending strength improvement and fragmentation test confirm the usability of this method for glasses with low defect densities when a dominant defect is present on the surface. Our findings indicate that nanostructure-based strengthening is suitable for all types of glasses irrespective of defect density, and the observed Weibull modulus enhancement confirms the reliability of this method.

Antibody-immobilized AlGaN/GaN high electron mobility transistors (HEMTs) were used to detect a short peptide consisting of 20 amino acids. One-binding-site model and two-binding-site model were used for the analysis of the electrical signals, revealing the number of binding sites on an antibody and the dissociation constants between the antibody and the short peptide. In the binding-site models, the surface coverage ratio of the short peptide on the sensor surface is relevant to the electrical signals resulted from the peptide–antibody binding on the HEMTs. Two binding sites on an antibody were observed and two dissociation constants, 4.404×10−11 M and 1.596×10−9 M, were extracted from the binding-site model through the analysis of the surface coverage ratio of the short peptide on the sensor surface. We have also shown that the conventional method to extract the dissociation constant from the linear regression of curve-fitting with Langmuir isotherm equation may lead to an incorrect information if the receptor has more than one binding site for the ligand. The limit of detection (LOD) of the sensor observed in the experimental result (∼10 pM of the short peptide) is very close to the LOD (around 2.7–3.4 pM) predicted from the value of the smallest dissociation constants. The sensitivity of the sensor is not only dependent on the transistors, but also highly relies on the affinity of the ligand-receptor pair. The results demonstrate that the AlGaN/GaN HEMTs cannot only be used for biosensors, but also for the biological affinity study., Highlights ► AlGaN/GaN high electron mobility transistors detected a short peptide. ► Antibody immobilized on transistors bind the peptide to form a complex. ► Binding affinity of the complex was studied using binding-site models. ► Dissociation constants and the number of binding sites were revealed.

An Ultrathin (~10 nm) InN ion sensitive field effect transistor (ISFET) with gate regions functionalized with phosphotyrosine (p-Tyr) is proposed to detect calcium ions (Ca2+) in aqueous solution. The ISFET was miniaturized to a chip size of 1.1 mm by 1.5 mm and integrated at the tip of a hypodermic injection needle (18 G) for real-time and continuous monitoring. The sensor shows a current variation ratio of 1.11% with per decade change of Ca2+ and a detection limit of 10-6 M. The response time of 5 sec. reveals its great potential for accomplishing fast detection in chemical and physiological sensing applications. The sensor would be applied in medical diagnosis and used to monitor continuous and real-time variations of Ca2+ levels in human blood in the near future.

A new kind of microdroplet-based biological protein sensor is presented. The sensor was made by placing silicon oil on gold film with a self-assembled monolayer (SAM). The surface tension dominates the sensitivity of the sensor. Using mercaptoundecanoic acid (11-MUA) as the sensor’s SAM layer, the sensor can detect 0.5 mg/ml, 20 μg/ml, and 0.4 μg/ml bovine serum albumin (BSA) protein solutions in a control volume of 0.5ml. The sensor’s reaction time for concentrations of 0.5 mg/ml, 20 μg/ml, and 0.4μg/ml protein solutions was 15, 60 and 120 minutes, respectively. As the size of microdroplet decreased, the change of contact angle increased.

This article unveiled the development of an inexpensive, lightweight, easy-to-use, and portable fluorescence imaging device for paper-based analytical applications. We used commercial fluorescent dyes, as proof of concept, to verify the feasibility of our fluorescence imaging device for bioanalysis. This approach may provide an alternative method for nucleotide detection and semen analysis, using a miniaturized fluorescence reader that is more compact and portable than conventional analytical equipment.

Introducing functional macromolecules into a variety of living cells is challenging but important for biology research and cell-based therapies. We report a novel cell delivery platform based on rotating shape anisotropic magnetic particles (SAMPs), which make very small cuts on cell membranes for macromolecule delivery with high efficiency and high survivability. SAMP delivery is performed by placing commercially available nickel powder onto cells grown in standard cell culture dishes. Application of a uniform magnetic field causes the magnetic particles to rotate because of mechanical torques induced by shape anisotropic magnetization. Cells touching these rotating particles are nicked, which generates transient membrane pores that enable the delivery of macromolecules into the cytosol of cells. Calcein dye, 3 and 40 kDa dextran polymers, a green fluorescence protein (GFP) plasmid, siRNA, and an enzyme (β-lactamase) were successfully delivered into HeLa cells, primary normal human dermal fibroblasts (NHDFs), and mouse cortical neurons that can be difficult to transfect. The SAMP approach offers several advantages, including easy implementation, low cost, high throughput, and efficient delivery of a broad range of macromolecules. Collectively, SAMP delivery has great potential for a broad range of academic and industrial applications.

The unavoidable occurrence of microdefects in silicon wafers increase the probability of catastrophic fracture of silicon-based devices, thus highlighting the need for a strengthening mechanism to minimize fractures resulting from defects. In this study, a novel mechanism for manufacturing silicon wafers was engineered based on nanoscale reinforcement through surface nanotexturing. Because of nanotexturing, different defect depths synthetically emulated as V-notches, demonstrated a bending strength enhancement by factors of 2.5, 3.2 and 6 for 2-, 7- and 14-μm-deep V-notches, respectively. A very large increase in the number of fragments observed during silicon fracturing was also indicative of the strengthening effect. Nanotextures surrounding the V-notch reduced the stress concentration factor at the notch tip and saturated as the nanotexture depth approached 1.5 times the V-notch depth. The stress reduction at the V-notch tip measured by micro-Raman spectroscopy revealed that nanotextures reduced the effective depth of the defect. Therefore, the nanotextured samples were able to sustain a larger fracture force. The enhancement in Weibull modulus, along with an increase in bending strength in the nanotextured samples compared to polished single-crystal silicon samples, demonstrated the reliability of the strengthening method. These results suggest that this method may be suitable for industrial implementation.

Several sorts of MEMS (Microelectromechanical Systems) based have been demonstrated by using electrostatic actuation scheme up to date. The comb drive and parallel plate are the two most common electrostatic actuators that have been well studied in variable optical attenuator (VOA) applications. In addition to the known retro-reflection type of optical attenuation being realized by our new devices driven by electrothermal actuators in present study, a novel planar tilted mirror with rotational and translation moving capability is proposed by using electrothermal actuators as well. Using electrothermal actuators to provide said planar tilted mirror with rotational and translational displacement has granted us a more efficient way to perform the light attenuation for in-plane structure. The static and transient characteristics of devices operated at ambient room temperature environment show good repeatability and stability.

In this study, we fabricate an ultra-sensitive hydrogen peroxide sensor by using horseradish peroxidase (HRP)-immobilized conducting polymer, polyaniline (PANI). With the proposed detection mechanism, hydrogen peroxide first oxidizes HRP, which then oxidizes polyaniline, thus resulting in decreased conductivity of the polyaniline thin film. The reduced HRP can be further oxidized by hydrogen peroxide and the cycle of the oxidation/reduction would continue until all hydrogen peroxide are reacted, leading to the high sensitivity of the sensor due to the signal contributed from all hydrogen peroxide molecule. The detection limit of this sensor is only 0.7 nM. The detectable concentration of H2O2 is from 0.7 nM to 1 μM. Beyond 1 μM, the sensor gradually saturates and some H2O2 remains, indicating the inhibition of HRP activity at high concentration of H2O2. There is no response to hydrogen peroxide once the PANI is standalone without HRP immobilized, showing the enzymatic reaction is required in the process of hydrogen peroxide detection. The simple process for the sensor fabrication allows the sensor to be cost-effective and disposable. This electronic hydrogen peroxide sensor is promising in applications for low concentration hydrogen peroxide detections, such as the reactive oxygen species (ROS) in oxidative stress studies.

The study describes chitosan membrane platform modified with nanostructure pattern which using nanotechnology to fabricate. The cell-substrate interaction between neuro-2a neuroblasts cell lines and chitosan membrane (flat, nanostructure and nanostructure pattern types) was investigated. The adhered morphology of neuro-2a cells depends on the topography of chitosan surface. We have found that neuro-2a showed different morphogenesis when cells adhered on flat and nanostructure chitosan membrane. The cell projected area of neuro-2a on flat chitosan membrane is larger than on nanostructure chitosan membrane. In addition, neuro-2a cells preferred to adhere on flat chitosan surface region than on nanostructure chitosan membrane to immobilize and differentiation. The experiment suggests surface topography can be used as a critical mechanism to isolate group of neuro-2a to a particular rectangle area on chitosan membrane. Our finding will provide a platform to take patch clamp to record electrophysiological behavior about neurons in vitro in the future., {"references":["N. Li and A. Folch, \"Integration of topographical and biochemical cues\nby axons during growth on microfabricated 3-D substrates,\" Exp. Cell\nRes., vol. 311, pp. 307- 316, Nov. 2005.","H. G. Craighead, S. W. Turner, R. C. Davis, C. James, A. M. Perez, P. M.\nSt. John, M. S. Isaacson, L. Kam, W. Shain, J. N. Turner and G. Banker,\n\"Chemical and Topographical Surface Modification for Control of\nCentral Nervous System Cell Adhesion,\" Biomed. Microdevices, vol. 1,\npp. 49-64, Sep. 1998.","M. Arnold, E. A. C. Adam, R. Glass, J. B. Mmel, W. Eck, M. Kantlehner,\nH. Kessler, and J. -P. Spatz, \"Induction of Cell Polarization and Migration\nby a Gradient of Nanoscale Variations in Adhesive Ligand Spacing,\"\nNano Lett., vol. 8, pp. 2063-2069, June 2008.","B. Zhua, Q. Zhangb, Q. Lua, Y. Xub, J. Yina, J. Hub and Z. Wanga,\n\"Nanotopographical guidance of C6 glioma cell alignment and oriented\ngrowth,\" Biomaterials, vol. 25, pp. 4215-422, Aug. 2004.","M. Cecchini, G. Bumma, M. Serresi and F. Beltram, \"PC12\ndifferentiation on biopolymer nanostructures,\" Nanotechnology, vol.18,\npp.505103, Nov. 2007.","M. Cheng, J. Deng, F. Yang, Y. Gong, N. Zhao and X. Zhang, \"Study on\nphysical properties and nerve cell affinity of composite films from\nchitosan and gelatin solutions,\" Biomaterials, vol. 24, pp. 2871-2880,\nAug. 2003.","G. Haipeng, Z. Yinghui, L. Jianchun, G. Yandao, Z. Nanming and Z.\nXiufang, \"Studies on nerve cell affinity of chitosan-derived materials,\" J.\nBiomed. Mater. Res., vol. 52, pp. 285-95, Nov. 2000."]}

This paper presents a new actuation mechanism to drive comb-drive actuators. An asymmetric configuration of the finger overlap was used to generate capacitive coupling for the actuation mechanism. When the driving voltages were applied on the stators, a voltage would be induced at the rotor due to the capacitive coupling. Then, an electrostatic force would be exerted onto the rotor due to the voltage differences between the stators and the rotor. The actuator’s static displacement and resonant frequency were theoretically analyzed. To verify the design, a comb-drive actuator with different initial finger overlaps, i.e., 159.3 μm and 48.9 μm on each side, was fabricated and tested. The results show that the actuator worked well using the proposed actuation mechanism. A static displacement of 41.7 μm and a resonant frequency of 577 Hz were achieved. Using the actuation mechanism, no electrical connection is required between the rotor and the outside power supply. This makes some comb-drive actuators containing heterogeneous structures easy to design and actuate.

An indium nitride (InN) gas sensor of 10 nm in thickness has achieved detection limit of 0.4 ppm acetone. The sensor has a size of 1 mm by 2.5 mm, while its sensing area is 0.25 mm by 2 mm. Detection of such a low acetone concentration in exhaled breath could enable early diagnosis of diabetes for portable physiological applications. The ultrathin InN epilayer extensively enhances sensing sensitivity due to its strong electron accumulation on roughly 5–10 nm deep layers from the surface. Platinum as catalyst can increase output current signals by 2.5-fold (94 vs. 37.5 μA) as well as reduce response time by 8.4-fold (150 vs. 1,260 s) in comparison with bare InN. More, the effect of 3% oxygen consumption due to breath inhalation and exhalation on 2.4 ppm acetone gas detection was investigated, indicating that such an acetone concentration can be analyzed in air.

Multicrystalline silicon (mc-Si) photovoltaic (PV) solar cells with nanoscale surface texturing by metal-nanoparticle-assisted etching are proposed to achieve high power efficiency. The investigation of average nanorod lengths from 100 nm to 1 μm reveals that the Si wafer decorated with 100 nm thick nanorods has optical reflection of 9.5% inferior than the one with 1 μm thick nanorods (2%). However, the short nanorods improve the doping uniformity and effectively decrease metal contact resistance. After surface passivation using the hydrogenated SiO[subscript 2]/SiN[subscript x] (5 nm/50 nm) stack, the minority carrier lifetime substantially increases from 1.8 to 7.2 μs for the 100 nm-thick nanorod solar cell to achieve the high power efficiency of 16.38%, compared with 1 μm thick nanorod solar cell with 11.87%., National Science Council of Taiwan (project 100-2120-M-007-011-CC2)

The importance for manipulating an incorporated scaffold and directing cell behaviors is well appreciated for tissue engineering. Here, we developed newly nano-topographic oxidized silicon nanosponges capable of being various chemical modifications to provide much insight into the fundamental biology of how cells interact with their surrounding environment in vitro. A wet etching technique is exerted to allow us fabricated the silicon nanosponges in a high-throughput manner. Furthermore, various organo-silane chemicals enabled self-assembled on the surfaces by vapor deposition. We have found that Chinese hamster ovary (CHO) cells displayed certain distinguishable morphogenesis, adherent responses, and biochemical properties while cultured on these chemical modified nano-topographic structures in compared with the planar oxidized silicon counterparts, indicating that cell behaviors can be influenced by certain physical characteristic derived from nano-topography in addition to the hydrophobicity of contact surfaces crucial for cell adhesion and spreading. Of particular, there were predominant nano-actin punches and slender protrusions formed while cells were cultured on the nano-topographic structures. This study shed potential applications of these nano-topographic biomaterials for controlling cell development in tissue engineering or basic cell biology research., {"references":["R. Langer and J. P. Vacanti, \"Tissue engineering,\" Science, vol. 260,\nMay. 1993, pp. 920-926.","R. Singhvi, A. Kumar, G. Lopez, G. N. Stephanopoulos, D. I. C. Wang,\nand G. M. 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A cell rotation method by using optoelectronic tweezers (OET) is reported. The binary image of a typical OET device, whose light and dark sides act as two sets of parallel plates with different ac voltages, was used to create a rotating electric field. Its feasibility for application to electrorotation of cells was demonstrated by rotating Ramos and yeast cells in their pitch axes. The electrorotation by using OET devices is dependent on the medium and cells’ electrical properties, the cells’ positions, and the OET device’s geometrical dimension, as well as the frequency of the electric field.

Manipulating an incorporated scaffold to direct cell behaviors play a key role in tissue engineering. In this study, we developed novel nano-topographic oxidized silicon nanosponges capable of being modified with various chemicals of a few nm in thickness to gain further insight into the fundamental biology of cell-environment interactions in vitro. A wet etching technique was applied to fabricate the silicon nanosponges in a high-throughput manner and was followed by vapor deposition of various organo-silane chemicals to enable self-assembly on the surfaces of the silicon nanosponges. When Chinese hamster ovary cells were cultured on these chemically modified nano-topographic structures, they displayed distinct morphogenesis, adherent responses, and biochemical properties in comparison with those of their planar oxidized silicon counterparts. There were predominant nano-actin punches and slender protrusions formed while cells were cultured on the nano-topographic structures, indicating that cell behaviors can be influenced by the physical characteristic derived from nano-topography, in addition to the hydrophobicity of contact surfaces. This study demonstrates potential applications of these nano-topographic biomaterials for controlling cell development in tissue engineering as well as in basic cell biology research.

A packaged liquid lens driven by the dielectric force was demonstrated. The liquid lens consisted of a low dielectric constant droplet and a high dielectric constant sealing liquid. The two non-conductive liquids were sealed in a chamber under the condition of iso-density. Focal length of a liquid lens with an aperture of 3mm changed from 34mm to 12mm in the range of 0-200V. Hysteresis was observed in the liquid lens, with a maximum value measured of 12.5 degrees at 120 volts in terms of droplet's contact angle. The focal spot size measured approximately 80mum. Rise and fall times were 650ms and 300ms, respectively. The lens consumed 1mW of power when applying a 200 volt, 1 kHz signal. The longitudinal and transverse spherical aberrations were estimated to be nearly invariant when the focal length exceeded 20mm.

Microlens arrays were self-assembled from microballs using dielectrophoretic energy wells. Energy wells defined by patterned dielectric were used to produce microlens arrays with array patterns of desire. Microballs of 25microm in diameter were measured to have numerical aperture of 0.8 and focal length of 15.5microm. The optical resolution was found to be 0.4microm. Both the numerical aperture and the focal length were further adjusted to 0.66 and 19.0microm by a post-assembly heat treatment at 190 degrees C for 5 minutes.

The gas sensor based on platinum-catalyzed ultrathin indium nitride (Pt-InN) was used to detect liver disease by sub-ppm ammonia (NH3) concentration variation in an ambient environment simulating exhaled human breath. Because the InN with strong surface electron accumulation extensively enhanced sensitivity, the NH3 gas sensor minimum detection limit is 0.2 ppm. Meanwhile, the sensor enables to distinguish slight deviation in NH3 concentration between 0.2 and 0.8 ppm that brings simple diagnosis of liver disease for portable and homecare clinical applications. Liver cancer is first of the top ten causes of death in Asia. Abnormal concentrations of the breath volatile organic compounds (VOCs) are reported to correlate with unhealthy/injurious body/organ conditions; for instance, ammonia (NH3) gas for renal and liver disease. Therefore, the detection of ammonia concentration in exhaled breath more important. In this study, an indium nitride (InN) gas sensor of 10 nm in thickness has achieved detection limit of 0.2 ppm ammonia. The sensor has a size of 1 mm by 2.5 mm, while its sensing area is 0.25 mm by 2 mm and deposited with a 10 nm thick Pt film on the sensing window to investigate the effect of catalyst on ammonia gas detection, shown in Fig 1. The ultrathin InN epilayer extensively enhances sensing sensitivity due to its strong electron accumulation on roughly 5–10 nm deep layers from the surface. Sensitivity is expected to be much better due to the natural electronic characteristics of as-grown InN films, including a narrow band gap, excellent electron transport characteristics (mobility > 1,000 cm2·V·s), a background high electron density (typically in excess of 1 × 1018 cm-3), and the unusual phenomenon of strong surface electron (charge) accumulation (1.57 × 1013 cm- 2) for the InN films grown on AlN film on a buffer layer . We proposing the miniaturized prototype, and packaging the ammonia gas sensor system (Including: Pt-InN sensor chip, heater, K-type thermocouple) on the 8 pin dual in-line package (DIP) for the portable human breath liver disease physiological detection application, shown in Fig 2. The current variation (DI) of a Pt-InN ammonia sensor under exposure to various ammonia concentrations from 0.2 ppm to 0.8 ppm in synthetic air at 200 °C is depicted in Fig 3. The experiments were repeatedly performed while the ammonia gas was turned on for 5 minute and off (i.e., in pure synthetic air) for another 5 minute at various ammonia concentrations. The current went up as ammonia concentration increased; such current increment was induced by the reduction of pre-adsorbed oxygen atoms. When ammonia molecules are introduced to the sensing system, the hydrogen atoms on dissociated ammonia molecules react with pre-adsorbed oxygen atoms, reducing the effects of surface depletion. Platinum as catalyst can increase output current signals as well as reduce response in comparison with Pt-InN, indicating that such an ammonia concentration can be analyzed in air. The dynamic responses of the Pt-InN sensor indeed demonstrate the great ability to sense ammonia gas at the sub-ppm level, and promising device for the realization of non-invasive ammonia sensing to detect ammonia in exhaled breath as a marker for liver disease. Figure 1

Hydrogen peroxide is a metabolic by-product and a kind of stable reactive oxygen species (ROS). When the ROS levels increase, it may causes several harmful effects of ROS on the cell structure, such as damage of DNA and protein oxidation, and this is known as oxidative stress. The oxidative stress is also the important clinical indicators of cause of aging, Alzheimer disease, and kidney diseases. Now the common test method of oxidative stress is Enzyme-linked immunosorbent assay (ELISA). ELISA needs color giving dyes, complicated preparation of sample, and optical system, so it is very expensive and inconvenient. In our study, we present a high sensitivity hydrogen peroxide sensor with ultra-low detection limit. The sensor can directly test the sample and only need very small amount of sample. And because of the simple structural design and fabrication, the sensor can be used as a cheap, efficient, and portable sensor system. In the future, the novel hydrogen peroxide sensor has various applications in studying oxidative stress and detecting reactive oxygen species for cells. Furthermore, we can combine the PANI sensor with different enzymes to fabricate other highly sensitive sensors to detect diverse materials, such as glucose, lactic acid and cholesterin. In our study, the PANI layer and gold electrodes were deposited on silicon nitride substrate, and the PANI was applied to fabricate a thin film between two electrodes. Then the PANI layer was sultonated by propane sultone and modified with HRP. During the measurement, the sensor was operated at 100mV and different concentrations of hydrogen peroxide citrate buffer solutions (pH=5.4) were dropped on it. The current change was measured when the hydrogen peroxide reacted with the HRP Immobilized PANI thin film. We tested the hydrogen peroxide solution from 0.1 nm to 1mM. The HRP-modified resistive sensors based on n-alkylated polyaniline(PANI) detect hydrogen peroxide in solution with very high sensitivity, ultra-low limit, and short response time. The sensitivity is higher than that of other sensing methods, such as electrochemical sensors or transistor sensors. The detection limit of PANI sensor is 0.7 nM (Figure 1. a, b). It is three orders smaller than that of other common methods with detection limit around 1 μM. To the best of our knowledge, it is the lowest detection limit that has ever been reported. And We combine the hydrogen peroxide sensor with glucose oxidase to build up the glucose sensor. In summary, the hydrogen peroxide sensor can provide a more exact hydrogen peroxide concentration and quick detection. The simple process for the sensor fabrication also allows the sensor to be cheap, disposable and combinable with other sensors to build up sensing system. This work was partially supported by National Science Council grant (No.99B20495A & 101-2221-E-007-102-MY3) and by the research grant (100N2049E1) at National Tsing Hua University.

Hydrogen peroxide attracts a great interest due to its important role in food, pharmaceutical, and clinical applications. Hydrogen peroxide is also a by-product in many enzyme catalytic reactions, such as glucose oxidase, lactate oxidase, cholesterol oxidase, alcohol oxidase, urate oxidase, aldehyde oxidase, and oxalate oxidase, which are implemented to detect glucose, lactic acid, cholesterol, ethanol, urea, formaldehyde, and oxalate, respectively. These biomolecules are significant markers in many biologically metabolic reactions. In our study, we present a cholesterol sensor based on a high sensitivity hydrogen peroxide sensor with ultra-low detection limit. The sensor can directly test the sample and only need very small amount of sample. And because of the simple structural design and fabrication, the sensor can be used as a cheap, efficient, and portable sensor system. The HRP-modified resistive sensors based on n-alkylated polyaniline(PANI) detect hydrogen peroxide in solution with very high sensitivity, ultra-low limit, and short response time. The sensitivity is higher than that of other sensing methods, such as electrochemical sensors or transistor sensors. The detection limit of PANI sensor is 0.7 nM. It is three orders smaller than that of other common methods with detection limit around 1 μM. To the best of our knowledge, it is the lowest detection limit that has ever been reported. And we combine the hydrogen peroxide sensor with cholesterol oxidase to build up the cholesterol sensor. In our study, the PANI layer and gold electrodes were deposited on silicon nitride substrate, and the PANI was applied to fabricate a thin film between two electrodes. Then the PANI layer was sultonated by propane sultone and modified with HRP. After that, the device was combined with dialysis membrane which was modified with cholesterol oxidase. During the measurement, the sensor was operated at 100mV and different concentrations of cholesterol PBS solutions (pH=7.0) were dropped on it. The cholesterol reacted with the cholesterol oxidase and created hydrogen peroxide on the PANI thin film (Figure 1). The current change was measured when the hydrogen peroxide reacted with the HRP immobilized PANI thin film. According to regular cholesterol level in human blood, we tested the cholesterol solution from 100 mg/dl to 400 mg/dl ,and we get a very good linear result (Figure 2). In summary, the cholesterol sensor can provide a more exact cholesterol concentration detection. The simple process for the sensor fabrication also allows the sensor to be cheap, disposable and combinable with other sensors to build up sensing system. This work was partially supported by National Science Council grant (No.99B20495A & 101-2221-E-007-102-MY3) and by the research grant (100N2049E1) at National Tsing Hua University.