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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

A multifocal confocal fluorescence microscopy system is designed and developed by incorporating photopolymer (PQ-PMMA) based volume holographic optical element in the illumination path for generating multifocal super Gaussian (SG) beam spots to reduce the scanning time.

For acquiring optically sectioned images of volumetric samples from multiple depths without axial scanning, a confocal system which is able to obtain multi-plane images with a Digital Micro-Mirror Device (DMD) has been proposed. The focal points of the laser beam can be arbitrarily positioned to any multiple planes in the three dimensional object space by switching multiplexed binary hologram encoded in the DMD by Lee hologram. The radius of the spherical wavefronts generated directly determines the location of the focal points and DMD can function either as a convex or concave mirror. The optical sectioning capabilities of system are verified and which can be applicable in various biomedical imaging applications.

An FPGA module has been developed to control a quantitative differential phase contrast microscope, which can perform three functions: asymmetric-illumination to obtain intensity images, high-speed image acquisitions and phase image reconstruction.

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.

A volume holographic optical element is designed and fabricated using photopolymer (PQ- PMMA) for multifocal super Gaussian (SG) beam spots and can be used for illuminating sample in confocal microscopy to reduce the scanning time.

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.

Confocal endoscopy has been widely used to obtain fine optically sectioned images. However, confocal endomicroscopic images are formed by point-by-point scanning in both lateral and axial directions, which results in long image acquisition time. Here, an endomicroscope with telecentric configuration is presented to achieve nonmechanical and rapid axial scanning for volumetric fluorescence imaging. In our system, optical sectioning in wide-field fashion is obtained through HiLo imaging with a digital micromirror device. Axial scanning, without mechanical moving parts, is conducted by digital focus adjustment using an electrically tunable lens, offering constant magnification and contrast. We demonstrate imaging performance of our system with optically sectioned images using fluorescently labeled beads, as well as ex vivo mice cardiac tissue samples. Our system provides multiple advantages, in terms of improved scanning range, and reduced image acquisition time, which shows great potentials for three-dimensional biopsies of volumetric biological samples.

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.

Optical phase shifts generated by the spatial variation of refractive index and thickness inside the transparent samples can be determined by intensity measurements through quantitative phase contrast imaging. In this review, we focus on isotropic quantitative differential phase contrast microscopy (qDPC), which is a non-interferometric quantitative phase imaging technique that belongs to the class of deterministic phase retrieval from intensity. The qDPC is based on the principle of the weak object transfer function together with the first-order Born approximation in a partially coherent illumination system and wide-field detection, which offers multiple advantages. We review basic principles, imaging systems, and demonstrate examples of DPC imaging for biomedical applications. In addition to the previous work, we present the latest results for isotropic phase contrast enhancements using a deep learning model. We implemented a supervised learning approach with the U-net model to reduce the number of measurements required for multi-axis measurements associated with the isotropic phase transfer function. We show that a well-designed and trained neural network provides a fast and efficient way to predict quantitative phase maps for live cells, which can help in determining morphological parameters of cells for detailed study. The prospects of deep learning in quantitative phase microscopy, particularly for isotropic quantitative phase estimation, are discussed.

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.

Oxygen is necessary for the nutrition of living cells in a human body, and a low oxygen supply can damage the human tissues and cause hypoxia and loss of consciousness. Moreover, oxygen deficiency in the brain can directly damage the nervous system, resulting in memory loss and unconsciousness if the deficiency persists. Therefore, the determination of oxygen saturation (SpO2) in the human body in a short time is crucial for clinical diagnosis and treatment. In response to this need, we developed a no-contact skin oxygen-saturation imaging (SOSI) system to determine SpO2 in the human body. The measuring method uses the reflected image of shallow tissue skin to create a SpO2 distribution map of the entire measuring region, which then can be used to evaluate heart rate (HR) and blood flow velocity (BFV). It facilitates the determination of the status of patients' cardiovascular systems.

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.

This paper presents a novel tactile sensing array with adjustable sensing range and sensitivity. The sensing array consists of a deformable PDMS spacer layer, two Al glass substrates, and two dielectric liquids. The two dielectric liquids form a composite dielectric material, which is a low-dielectric-constant (ɛr) droplet covered with a high-ɛr liquid. The composite dielectric material is sandwiched between the upper and lower electrodes. By adjusting the electric flux passing through the electrodes, the contact angle of the droplet can be controlled. The sensing range and sensitivity were adjusted by varying the droplet shape. The results show that the device's sensing range can be adjusted in the ranges 0.05–0.29 N and 0.42–1.12 N. Compared with other devices, which are often used in a large force range, this device can be used in a smaller force range and provides 1.88 times greater sensitivity. Besides, the sensitivity can be adjusted during the sensing process.

In this study, conductive polyaniline (PANI) was coated on Si3N4/Si substrates and reacted with hydroxyl radicals created by mixing ferrous ions and hydrogen peroxide in a buffer solution, as known as the Fenton reaction. The hydroxyl radicals reacted with PANI, resulting in the decreased conductivity of PANI. The reduction in the conductivity of PANI was found to be proportional to the concentration of hydroxyl radicals in the buffer solution. The concentration of hydroxyl radicals was calibrated by comparing the fluorescence intensities of the Amplex ultrared molecules oxidized by radicals and hydrogen peroxide via the catalysis of horseradish peroxidase (HRP), respectively. The conductivity change of the PANI shows a linear relationship to the concentration of hydroxyl radicals, ranging from 0.2 μM to 0.8 μM. The conductivity of PANI does not respond to either ferrous ions or hydrogen peroxide alone. Only when both ferrous ions and hydrogen peroxide are present in the solution, the conductivity of PANI decreases, indicating that the conductivity change of PANI is attributed to the existence of hydroxyl radicals. The simple process for the sensor fabrication allows the sensor to be cost-effective and disposable. This electronic sensor can detect one of the most important reactive oxygen species (ROS), the hydroxyl radical, and therefore is promising for studying oxidative stress.

This study involved developing a meter for rapidly evaluating the state of health (SOH) of lithium-ion batteries (LIBs). The key component was a magnetic induction antenna (MIA) module with an interdigital pattern fabricated using a 355-nm pulsed ultraviolet laser system. For inducing high voltage from the LIB to the MIA module for evaluating the SOH, interdigital patterns of four line widths (i.e., 0.25, 0.5, 0.75, and 1.0 mm) were designed. The experimental results indicate that patterns with wider lines induce higher voltages. However, patterns using the 0.75-mm line offer optimal SOH measurements, because those with the 1.0-mm line yielded lower power storage. The optimal operating frequency for enhancing SOH identification was found to be 700 kHz. In addition, this study established an empirical equation for expressing the relationship between the induced voltage and SOH of LIBs.

A 43-μm-thick Si(111) substrate was obtained using the stress-induced lift-off method with a screen-printed metal paste layer as the stress-generation layer. The reflection of the metal-removed side of the Si(111) substrate was lower than that of the exfoliated side because of high surface roughness resulting from the reaction between the metal paste and the silicon substrate at 700◦C. After aggressive etching with an alkaline solution for the peeled silicon substrate, the efficiency of the heterojunction silicon solar cell was improved from 0.87% to 12%. © The Author(s) 2015. Published by ECS. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 License (CC BY, http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse of the work in any medium, provided the original work is properly cited. [DOI: 10.1149/2.0171508jss] All rights reserved.

This study proposes a promising silicon (Si) solar cell structure for reducing the potential induced degradation (PID) of crystalline Si solar cells. Phosphorous silicate glass (PSG) layers were carefully designed on an emitter layer, and the thickness of these layers (dPSG) was controlled by adjusting the diffusion temperature and time. The results show that the power loss remarkably decreased from 31% (dPSG = 0 nm) to 11% (dPSG = 22.3 nm) and further decreased to less than 5% after a 48-h PID test when dPSG was higher than 23.3 nm. No additional process or equipment was required for producing this effective and low-cost solar cell. © The Author(s) 2015. Published by ECS. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 License (CC BY, http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse of the work in any

This paper purposes a portable multispectra tunable forensic lens for jadeite analysis. The visible and ultraviolet light are used to detect the absorption spectra of natural jadeite, implement jadeite, and jadeite color spectra around 550∼700 nm. Besides, tunable lens with three-step (5, 7 and 10 X) magnification is based on the dielectric liquid lens.

A 3 μm thick silicon layers with nano-scale honeycomb structure on the surface were fabricated using the mask-less process, “Thermal-stress Induced Pattern Transfer method”. The thin silicon layer was deposited on a patterned sapphire substrate with nano-scale pyramids, followed by a metal layer printing on the top of the thin silicon layer. After thermal treatment, a thin silicon layer was peeled off from the patterned sapphire substrate and was transferred to the metal layer. Meanwhile, the periodic patterns on the sapphire substrate were transferred to the thin silicon layer forming the honeycomb structure on the surface of the silicon layer. The whole process was operated at a low temperature below 250 °C without any mask process. Finally, the solar cell was fabricated on the silicon thin layer and its performance was measured. The short circuit current density is 0.11 mA/cm2.

Biomimetic materials are used for creating microsystems to control cell growth spatially and elicit specific cellular responses by combining complex biomolecules with nanostructured surfaces. Intercellular cell-to-cell and cell-to-extracellular matrix (ECM) interactions in biomimetic materials have demonstrated potential in the development of drug discovery platforms and regeneration medicine. In this study, we developed a biomimetic nanostructured matrix by using various ECM molecular layers to create a biomimetic and biocompatible environment for realizing neuronal guidance in neural regeneration medicine. Silicon-based substrates possessing nanostructures were modified using different ECM proteins and peptides to develop a biomimetic and biocompatible environment for studying neural behaviors in adhesion, proliferation, and differentiation. The substrates were flat glass, flat silicon wafers (FWs), and nanorod-structured wafers prepared using wet etching. The three substrates were then functionalized using laminin-1 peptide, PA22-2-contained active isoleucine-lysine-valine-alanine-valine (IKVAV) peptide, and poly-d-lysine (PDL), separately. When PC12 cells were cultured and differentiated on the modified substrates, the cells were able to elongate the neurites on the glass and FW, which was coated with three types of peptide. More differentiated neurons were observed on the nanorod-structured wafers coated with laminin than on those coated with IKVAV or PDL. For achieving directional guidance of neurite outgrowth, substrates exhibiting a grating pattern of nanorods were partially collapsed by the pulling force of water, leaving few nanorods, which support the net form of laminin on the surface. Furthermore, we fabricated the topological nanostructure-patterned wafer coated with laminin and successfully manipulated the extension and direction of neurites by using more than 80 μm of a single soma. This approach demonstrates potential as a facile and efficient method for guiding the direction of single axons and for enhancing neurite outgrowth in studies on nerve regenerative medicine.

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.