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In Part II, we present the use and application of the Compliant Building Elements (CBE) method to generate practical designs for different multiple degree-of-freedom (DOF) compliant mechanisms. We first create a compliant mechanism library based on the combination of prismatic beams, which includes commonly used basic elements (BEs), serial elements (SEs), and parallel elements (PEs). Examples are given during the construction of the library. Based on the library and CBE method, we demonstrate the design of a six-axis nanopositioner, a compliant steering mechanism, and a one-dimensional mechanical metamaterial structure. The outcome of each design process yields a flexure topology that meets the design requirements as well as the corresponding parametric stiffness and compliance matrices, from which we can efficiently obtain the kinematic characteristics of the flexure system and optimize the stiffnesses in selected axes. • CBE is a new design methodology to generate practical designs for multiple degree-of-freedom mechanisms. • CBE combines the advantages of screw theory, matrix-based method, and practical experience to synthesize complex flexures. • A compliant mechanism library is provided based on the combination of prismatic beams to facilitate the design process. • We demonstrate the design process of compliant nanopositioners, steering mechanisms, and metamaterial structures via CBE. [ABSTRACT FROM AUTHOR]

In this paper, we present a new design method and principle, i.e., Compliant Building Elements (CBE), for compliant mechanisms that adopts a systematic and synthetic approach to generate practicable flexure designs. The CBE is unique in that it encodes a compliant system's quantitative information, including elasticity, geometry, location, and orientation, in a parametric matrix. Based on the matrix, a degree-of-freedom (DOF) concept is defined to describe permitted motions of a flexure; next, the screw theory is used to guide the design and synthesis of compliant mechanisms from DOF decomposition to actuator layout selection. In CBE, a compliant system consists of three types of compliant elements, i.e., compliant elements formed by serial or parallel connections and basic compliant elements. The synthesis procedure is a top-down and iterative process, starting from laying out the stage topology to finally optimizing the compliant connection elements and types (i.e., serial or parallel), where the iteration stops when the stage characteristics meet the design requirements. A library of various compliant elements is provided to help the designers quickly generate the initial stage topological designs and optimize the performance with reduced design iterations. The matrix-based design method for compliant mechanisms, i.e., CBE, which is analogous to the screw-based type synthesis for rigid parallel mechanisms, enables early-stage flexure system design via building compliant blocks just like building LEGO® bricks. • Compliant Building Elements (CBE) is a systematic and synthetic design method to generate designs for compliant mechanisms. • In CBE, the synthesis of compliant mechanisms is guided by screw theory and verified by the parametric stiffness/compliance matrices. • The CBE method can be automated to expedite the design process owing to its systematic and matrix operation nature. • The CBE method can benefit inexperienced flexure designers to quickly generate practical design concepts. [ABSTRACT FROM AUTHOR]

Neurons interact with astrocytes, microglia, and vascular cells. These interactions become unbalanced in disease states, resulting in damage to neurons and synapses, and contributing to cognitive impairment. Importantly, synaptic loss and synaptic dysfunction have been considered for years as a main pathological factor of cognitive impairment in Alzheimer's disease (AD). Recently, miRNAs have emerged as essential regulators of physiological and pathological processes in the brain. Focusing on the role of miRNAs in regulating synaptic functions, as well as different cell types in the brain, offers opportunities for the early prevention, diagnosis, and potential treatment of AD-related cognitive impairment. Here, we review the recent research conducted on miRNAs regulating astrocytes, microglia, cerebrovasculature, and synaptic functions in the context of AD-related cognitive impairment. We also review potential miRNA-related biomarkers and therapeutics, as well as emerging imaging technologies relevant for AD research. [ABSTRACT FROM AUTHOR]

The main purpose of this paper is experimentally comparing of organic Rankine cycle (ORC) system, by using R245fa, R123 and their mixtures to generate maximum net power on simulated low-temperature industrial waste heat. Four mass fractions of R245fa:R123 have been injected into the system with the ratios of 1:0, 2:1, 1:2 and 0:1 to test the system performance separately. To imitate industrial low-temperature waste heat, the heat source temperature is fixed at 110 °C and 120 °C with specified mass flow rate of heat source. Focusing on the change of mass flow rate of working fluid and expander inlet superheating, experiment results show that the system heat input increases when mass flow rate of working fluid increases. All four mass fractions of working fluids generate maximum net power when the system mass flow rate is around 0.15 kg/s. The case of pure R245fa generates a maximum net power 1.56 kW with an electrical efficiency of about 3.9% when heat source temperature is fixed at 110 °C. While, the case of mixture R245fa:R123 = 2:1 generates a maximum net power 1.66 kW with an electrical efficiency of about 4.4% when heat source temperature input is fixed at 120 °C. [ABSTRACT FROM AUTHOR]

In their Progress Report, Hahn et al. assessed the state‐of‐the‐art of 3D printing but excluded temporally focused two‐photon polymerization (2PP) from the comparison because they concluded that it does not represent a full 3D printing capability. This comment highlights the flaws in their scientific arguments, clarifies the misinterpretation of private communications, and shows that 3D structures with distinct z‐layers can be printed using temporally focused 2PP. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents the design of a small-scale nanopositioner, the μHexFlex, which is comprised of a six-axis compliant mechanism and three pairs of two-axis thermo-mechanical micro-actuators. In this paper, we cover the modeling, design and fabrication of the μHexFlex. Specific attention is given to: (1) the use of constraint-based design in generating the compliant mechanism design, (2) the modeling of the actuators, and (3) the system model which links the actuator input and mechanism response. The measured, quasi-static performance of a 3mm diameter prototype shows a maximum range of 8.4μm×12.8μm×8.8μm and 19.2mrad×17.5mrad×33.2mrad (1.1°×1.0°×1.9°). Experimental results indicate that a constant mechanical/electrical material property system model may be used to predict the position and orientation over a range of 3.0μm×4.4μm×3.0μm and 6.3mrad×6.3mrad×8.7mrad (0.36°×0.36°×0.5°). The dynamic characteristics of the device were investigated experimentally. Experimental results show a lowest natural frequency of 4kHz. The resolution characteristics of the device have been measured at 1Å/mV. The device was created using deep reactive ion etching (DRIE). Bulk fabrication costs are estimated at less than $ 2 per device. [Copyright &y& Elsevier]

• A combined machining approach using laser cutting and W-ECM process for Inconel-718 is explored. • Parametric study for laser cutting and W-ECM was carried out. • Analysis of reduction in surface roughness by W-ECM after laser cutting is explored. • A change of ∼95% in surface quality of machined surfaces is obtained after combined machining. In the paper, we present a combined gas–assisted laser machining and wire electrochemical machining (W-ECM) process to improve the surface quality of slits produced in Inconel-718, a high-strength nickel-based alloy widely used in aircraft engine parts. First, a laser cutting was applied to produce the slit structure in Inconel-718, where the power and feed rate were varied to identify the optimal processing parameters. Subsequently, the slits were processed by a custom-developed W-ECM process. The results were evaluated by characterizing the surface roughness and kerf width of the slits. Through this combined approach, a 90% average improvement on surface finish was achieved with a 10% increase in kerf width. In addition, the typical striation marks and thermal damages from laser machining processes were entirely eliminated in all slits. The new process is precise and low-cost, which may find important applications in high-precision laser machining applications. [ABSTRACT FROM AUTHOR]

The study of aging and neurodegenerative processes in the human brain requires a comprehensive understanding of cytoarchitectonic, myeloarchitectonic, and vascular structures. Recent computational advances have enabled volumetric reconstruction of the human brain using thousands of stained slices, however, tissue distortions and loss resulting from standard histological processing have hindered deformation‐free reconstruction. Here, the authors describe an integrated serial sectioning polarization‐sensitive optical coherence tomography (PSOCT) and two photon microscopy (2PM) system to provide label‐free multi‐contrast imaging of intact brain structures, including scattering, birefringence, and autofluorescence of human brain tissue. The authors demonstrate high‐throughput reconstruction of 4 × 4 × 2cm3 sample blocks and simple registration between PSOCT and 2PM images that enable comprehensive analysis of myelin content, vascular structure, and cellular information. The high‐resolution 2PM images provide microscopic validation and enrichment of the cellular information provided by the PSOCT optical properties on the same sample, revealing the densely packed fibers, capillaries, and lipofuscin‐filled cell bodies in the cortex and white matter. It is shown that the imaging system enables quantitative characterization of various pathological features in aging process, including myelin degradation, lipofuscin accumulation, and microvascular changes, which opens up numerous opportunities in the study of neurodegenerative diseases in the future. [ABSTRACT FROM AUTHOR]

Roll-to-roll (R2R) printing technologies have been widely adopted in a variety of engineering fields, e.g., organic photovoltaics and flexible electronics, owing to the advantages of cost and throughput. Although a minimum feature size of 100 nm has been demonstrated on R2R systems, the layer to layer registration accuracy (i.e., overlay accuracy) still remains as low as tens of microns, which prevents the fabrication of common electronic and functional devices, such as transistors. To realize the full potential of R2R technologies, the registration accuracy must be improved to match the printing resolution, i.e., 100s nm. To address the issue, we have developed a multi-layer R2R system with multiple-input multiple-output (MIMO) closed-loop control that achieves submicron level alignment precision for large-scale continuous printing processes. The enabling elements in the multi-layer R2R system include: (1) new vision-based alignment algorithm/method, which provides 100s nm position detection capability based on low-cost cameras; and (2) custom-built five-axis compliant roller positioner. Experimental results show that the compliant roller positioner has a ±1 mm range with 100s nm precision in X, Y, and Z axes respectively. For correcting in-plane web errors, the roller positioner can achieve a range of 1 mm with < 1 μm precision, realizing multi-layer R2R printing with submicron overlay accuracy. Based on the new methods, a gate/source-drain multi-layer electrode structure for field-effect transistors (FETs) has been designed and fabricated on a 4-inch PET web, demonstrating better than 1 μm overlay precision in fabricating flexible electronics on a R2R platform for the first time. • The first demonstration of a multi-layer R2R printing system that achieves better than 1 μm overlay accuracy. • The five-axis roller positioner actively corrects position errors with a precision of ±200 nm and ±2 μrad. • The new alignment solution achieves a large detection range (> 1 mm) with high-resolution (10s nm) based on low-cost cameras. • R2R printing of a multi-layer structure, i.e., FETs, was demonstrated on a 4-inch PET web with < 1 μm overlay precision. [ABSTRACT FROM AUTHOR]

This paper presents a comprehensive review of mechanical design and synthesis methods for piezo-actuated compliant micro-positioning stages, which play an important role in areas where high precision motion is required, including bio-robotics, precision manufacturing, automation, and aerospace. Unlike conventional rigid-link mechanisms, the motion of compliant mechanisms is realized by using flexible elements, whereby deformation requires no lubrication while achieving high movement accuracy without friction. As compliant mechanisms differ significantly from traditional rigid mechanisms, recent research has focused on investigating various technologies and approaches to address challenges in the flexure-based micro-positioning stage in the aspects of synthesis, analysis, material, fabrication, and actuation. In this paper, we reviewed the main concepts and key advances in the mechanical design of compliant piezo-actuated micro-positioning stages, with a particular focus on flexure design, kineto-static modeling, actuators, material selection, and functional mechanisms including amplification and self-guiding ones. We also identified the key issues and directions for the development trends of compliant micro-positioning stages. [ABSTRACT FROM AUTHOR]

Abstract Sectioning soft tissues, e.g., brain, into thin slices is frequently performed using an oscillating blade microtome; it is generally observed that a combination of normal and shear cutting forces at an appropriate frequency will minimize the material deformation, leading to better sectioning results. To understand and better exploit this phenomenon, we theoretically and experimentally study the cutting mechanism of soft materials using a custom-built oscillating blade microtome. Analytical models are derived to deterministically link the sectioning quality to the cutting parameters, including blade oscillation frequency, amplitude, and sample feed rate. Experiments have been performed on 2% agarose gels to verify the predicted results over a range of operating parameters. Importantly, for the first time the study reveals that the sectioning results given by microtomes can be greatly enhanced when the cutting frequency is above 150 Hz due to the material stiffening effect—a unique trait of viscoelastic materials. The model may be used to predict the optimal cutting parameters for various tissues. As most state-of-the-art microtomes operate below 100 Hz, the results also set the new requirements for the next-generation tissue sectioning and surgical instruments. Highlights • A new parametric model that explains the cutting mechanisms of soft materials using an oscillating blade. • For the first time, the analytical modeldeterministically links the sectioning quality to the cutting parameters. • The sectioning quality will be enhanced at high cutting frequency (> 150 Hz) due to the material stiffening effect. • As all microtomes operate < 100 Hz, the model sets new requirements for future tissue sectioning and surgical instruments. [ABSTRACT FROM AUTHOR]

In the above-named paper [ibid., vol. 21, no. 2, pp. 340-349, 2012], the displacement data below 0 were omitted in Fig. 14(a). A replacement figure with correct data and caption is presented. [ABSTRACT FROM AUTHOR]

Objective: Serial sectioning optical coherence tomography (OCT) enables accurate volumetric reconstruction of several cubic centimeters of human brain samples. We aimed to identify anatomical features of the ex vivo human brain, such as intraparenchymal blood vessels and axonal fiber bundles, from the OCT data in 3D, using intrinsic optical contrast. Methods: We developed an automatic processing pipeline to enable characterization of the intraparenchymal microvascular network in human brain samples. Results: We demonstrated the automatic extraction of the vessels down to a 20 ${\boldsymbol{\mu }}$ m in diameter using a filtering strategy followed by a graphing representation and characterization of the geometrical properties of microvascular network in 3D. We also showed the ability to extend this processing strategy to extract axonal fiber bundles from the volumetric OCT image. Conclusion: This method provides a viable tool for quantitative characterization of volumetric microvascular network as well as the axonal bundle properties in normal and pathological tissues of the ex vivo human brain. [ABSTRACT FROM AUTHOR]

With the increasing demand for devices and systems with nanometer precision in the modern manufacturing industry, tip-based nanofabrication (TBN) has become an indispensable part of manufacturing process. However, a common issue that needs to be addressed is to increase the throughput of TBN, which is sequential and inherently slow. To overcome the difficulty, in this paper we present the design and control of a flexure-based five-axis nanopositioner with dynamic-tuning capability for parallel nanomanufacturing applications. The dynamic-tuning method enables trade-offs between the range and speed of the nanopositioner so as to increase the throughput of the nanomanufacturing system. The experimental results indicate that the nanopositioner conforms with the in-plane range and resolution requirements, i.e., ±5 mm/100 nm in X / Y axis, while its natural frequencies in X / Y axis can be increased by two to three times at the expense of decreased stroke, i.e., elastic range. In addition, real-time dynamic-tuning experiments show active vibration cancellation techniques can be implemented on the nanopositioner and effectively eliminate the unwanted dynamics and improve the overall dynamic performance. Lastly, we performed nano-scratching experiments using an 18 tip AFM array to fabricate optical grating patterns on gold coated silicon substrates of 5 × 1 mm 2 to demonstrate the practicality of the new method. The experiment confirmed good parallelism had been achieved during the experiments, where the scratched gold lines have a consistent depth of ∼160 nm. [ABSTRACT FROM AUTHOR]

Femtosecond laser-induced periodic surface structure (fs-LIPSS) is a high-throughput parallel laser patterning method to fabricate various surface structures of sub-micrometer scale; the morphology and regularity of the structured surface determine its function. In this paper, single and double femtosecond laser beams are used to fabricate nanostructures on a silicon substrate. In the experiments, it is found that the appearance of supra-wavelength structures with periods longer than the laser wavelength not only deteriorate the regularity of the sub-wavelength periodic ripples but also hinder the fabrication of the deep sub-wavelength ripples when a single femtosecond laser is used. In addition, when double time-delayed femtosecond laser beams are used, 2D nanostructures, such as hexagonally arranged nano-hole array, cannot be fabricated once the supra-wavelength structures appear. The formation mechanism of the supra-wavelength periodic structures, which cannot be explained by the interference between the incident laser and surface plasmon polaritons, may be attributed to the hydrothermal wave on the molten surface layer. These findings provide insights to understand the mechanisms of 1D and 2D nanostructures produced by single and dual femtosecond laser beams, which is critical for fabricating functional surfaces. [ABSTRACT FROM AUTHOR]

Abstract: The prediction of bank performance is an important issue. The bad performance of banks may first result in bankruptcy, which is expected to influence the economics of the country eventually. Since the early 1970s, many researchers had already made predictions on such issues. However, until recent years, most of them have used traditional statistics to build the prediction model. Because of the vigorous development of data mining techniques, many researchers have begun to apply those techniques to various fields, including performance prediction systems. However, data mining techniques have the problem of parameter settings. Therefore, this study applies particle swarm optimization (PSO) to obtain suitable parameter settings for support vector machine (SVM) and decision tree (DT), and to select a subset of beneficial features, without reducing the classification accuracy rate. In order to evaluate the proposed approaches, dataset collected from Taiwanese commercial banks are used as source data. The experimental results showed that the proposed approaches could obtain a better parameter setting, reduce unnecessary features, and improve the accuracy of classification significantly. [Copyright &y& Elsevier]

• We present a new model to predict and analyze errors associated with wavefront modulation based on digital holography and binary masks, e.g., digital micromirror devices or ferroelectric liquid crystal-based spatial light modulators, which has been a widely-adopted method in the optical engineering community. • To demonstrate the accuracy and practical use of the model, we present three case studies, including (1) beam shaping, (2) 3D random-access scanning, and (3) multi-focus generation based on binary masks. • The results show the analytical model can precisely predict the wavefront distortion, power efficiency, position accuracy, and intensity uniformity for multi-focus generation as a function of binary mask parameters including pixel size, pixel gentry, fill factor, and aperture. • As digital systems are highly repeatable, the predicted errors, e.g., position errors, can be compensated by adding appropriate phase to the designed holograms. The model and the simulation results will be a useful tool for optical engineers to select appropriate binary devices and optimization algorithms for specific engineering applications, e.g., nanofabrication or nonlinear microscopy. Binary holography has been applied with fast switching digital masks, e.g., digital micromirror device (DMD), to modulate light in recent years for a wide range of optical and scientific applications, such as trapping of cold atoms and 3D random-access two-photon fluorescence microscopy. However, the binarized modulation errors associated with the effect of discrete sampling, finite pixels, and intrinsic noises of algorithms have yet to be systematically investigated. In this paper, we present the development of an analytical model for a general binary mask with finite pixels. The model has established a deterministic link between the quality of the reconstructed wavefront to important parameters of the binary mask, including pixel size, pixel geometry, fill factor, and aperture. Based on the model, three case studies are presented, including (1) beam shaping, (2) 3D random-access scanning, and (3) multi-focus generation based on binary masks. The results show the model can precisely predict the wavefront distortion, power efficiency, position accuracy, and intensity uniformity for multi-focus generation as a function of binary mask parameters. As digital systems are highly repeatable, the predicted errors, e.g., position errors, can be compensated by adding appropriate phase to the designed holograms. The model and the simulation results may provide useful guidance to select appropriate binary devices and optimization algorithms for specific optical engineering applications, e.g., nanofabrication or nonlinear microscopy. [ABSTRACT FROM AUTHOR]

Microscale additive manufacturing is one of the fastest growing areas of research within the additive manufacturing community. However, there are still significant challenges that exist in terms of available materials, resolution, throughput, and ability to fabricate true three-dimensional geometries. These challenges render commercialization of currently available microscale additive manufacturing processes difficult. This paper is the last one in a four-part series of articles which review the current state-of-the-art of microscale additive manufacturing technologies and investigate the factors that currently limit each microscale additive manufacturing technology in terms of materials, resolution, throughput, and ability to fabricate complex geometries. Parts I, II and III offer prognoses about the future viability and applications of each technology along with suggested future research directions that could be used to bring each process technology in line with its fundamental, physics-based limitations. This paper brings together the general design guidelines that must be followed while designing scalable microscale AM processes. Finally, the paper concludes with an analysis of the role of precision engineering in the future advancement of microscale additive manufacturing technologies. This series of publications is a joint effort by the members and affiliates of the Micro-Nano Technical Leadership Committee of the American Society for Precision Engineering (ASPE). [ABSTRACT FROM AUTHOR]

The Part III of the four-part series of articles discusses the challenges and opportunities in microscale additive manufacturing processes, specifically focusing on energy-induced deposition and electrochemical processes. Compared to the direct ink write (DIW) and laser-based processes, the energy-induced deposition methods can fabricate high-resolution, high aspect ratio and complex parts, while the hybrid electrochemical process can be used to fabricate complex parts using a wide range of conductive and photoactive materials. However, the volumetric throughput of these processes is lower than their DIW and laser-based counterparts. The processes that have been explored in this process are Focused-ion Beam Induced Deposition (FIBID), Laser Chemical Vapor Deposition (LCVD), Menicus-confined Electrodeposition (MCED) and Laser-Enabled Electrochemical Printing (LECP). The range of processable materials, feature-size resolution, geometry and volumetric throughput are used as factors to evaluate the current state-of-the-art for these processes. Novel approaches have been proposed in the article to address these challenges associated with microscale AM processes. [ABSTRACT FROM AUTHOR]

In this paper, we present the development of a high-speed dual-beam stealth laser dicing (D-SLD) method for processing semiconductor wafers based on electrically tunable lenses (ETLs). An SLD system utilizes a laser beam to dice a wafer by inducing interior defects without modifying the surface characteristics of a wafer, thereby presenting significant advantages over conventional dicing methods, e.g., blade dicing or laser ablation. Currently, the throughput of SLD is limited by the serial scanning process; in addition, wafer misalignment and the warpage effects together deteriorate the dicing quality and yield and demand high-cost multi-axis precision stages. To address the issue, we parallelize the dicing process by splitting the laser focus into two foci, where the laser intensity at different depths are automatically adjusted to achieve optimal dicing condition. By combining the height sensor and ETLs, each laser focus, i.e., laser scan lines, can be rapidly controlled axially to compensate the wafer curvature and misalignment errors in real time, leading to substantially improved precision (kerf width < 2 μm) and speed, demonstrated by our experimental results. The new dual-beam laser dicing system presents an effective solution for high-speed wafer dicing as well as other important engineering applications, e.g., fabrication of micro-devices and optical components. • A new dual-beam stealth laser dicing method based on electrically tunable lenses that achieves a kerf of <2 μm • The two foci can be independently controlled to compensate wafer geometric and alignment errors. • Experimental characterization of optimal wafer dicing parameters including laser power, pulsed energy, and repetition rate. [ABSTRACT FROM AUTHOR]

Significance: High-speed 3D imaging methods have been playing crucial roles in many biological discoveries. Aim: We present a hybrid light-field imaging system and image processing algorithm that can visualize high-speed biological events. Approach: The hybrid light-field imaging system uses the selective plane optical illumination, which simultaneously records a high-resolution 2D image and a low-resolution 4D light-field image. The high-resolution 4D light-field image is obtained by applying the hybrid algorithm derived from the deconvolution and phase retrieval methods. Results: High-resolution 3D imaging at a speed of 100-s volumes per second over an imaging field of 250 × 250 × 80 μm3 in the x, y, and z axis, respectively, is achieved with a 2.5 times enhancement in lateral resolution over the entire imaging field compared with standard light-field systems. In comparison to the deconvolution algorithm, the hybrid algorithm addresses the artifact issue at the focal plane and reduces the computation time by a factor of 4. Conclusions: The new hybrid light-field imaging method realizes high-resolution and ultrafast 3D imaging with a compact setup and simple algorithm, which may help discover important applications in biophotonics to visualize high-speed biological events. [ABSTRACT FROM AUTHOR]

In this paper, we present a new multi-focus microscope (MFM) system based on a phase mask and HiLo algorithm, achieving high-speed (20 volumes per second), high-resolution, low-noise 3-D fluorescent imaging. During imaging, the emissions from the specimen at nine different depths are simultaneously modulated and focused to different regions on a single CCD chip, i.e., the CCD chip is subdivided into nine regions to record images from the different selected depths. Next, HiLo algorithm is applied to remove the background noises and to form clean 3-D images. To visualize larger volumes, the nine layers are scanned axially, realizing fast 3-D imaging. In the imaging experiments, a mouse kidney sample of ~ 60 × 60 × 16 μm3 is visualized with only 10 raw images, demonstrating substantially enhanced resolution and contrast as well as suppressed background noises. The new method will find important applications in 3-D fluorescent imaging, e.g., recording fast dynamic events at multiple depths in vivo. [ABSTRACT FROM AUTHOR]

• A low-cost method to perform precise non-contact displacement measurement by exploiting the near-field chrematistics of fiber specklegrams. • The fiber-optic sensor achieves a resolution and repeatability of 10 nm and a detection range of 3–4 μm at 100 Hz. • Advantages (1) low-cost, (2) compact device envelope, (3) high precision, and (4) insensitivity to sample/target materials. In this paper, we present a precision non-contact displacement sensor based on the near-field property of specklegrams, achieving a precision of 10 nm and a detection range of 3–4 μm. The compact device envelope enables the application of the new fiber-optic sensor in many space-limited applications, e.g., probe-based nanofabrication and micro-/mesoscale positioning systems. In the sensor system, the laser is first coupled into a 50/50 fiber coupler; the flexible fiber transmits the laser beam to the remote sensor head that is a few micrometers away from the sample surface; the reflected light is collected by the sensor head. The interference among the different eigenmodes propagating in the multimode fiber form unique specklegram images for different sample positions in space. By recording the varying specklegrams along the scanning path, highly precise and repeatable non-contact displacement detection can be realized by comparing the recorded specklegrams with the calibrated specklegram database through imaging processing techniques. In the experiments, we demonstrate the fiber-optic sensor can perform one-axis displacement sensing with a precision of 10 nm over a range of 3–4 μm at 100 Hz, where the specklegram acquisition rate is limited only by the speed of the camera. The new fiber-optic sensor is flexible, precise, and low-cost, which may find important applications in optical metrology and nanomanufacturing. [ABSTRACT FROM AUTHOR]

As an important branch of wearable electronics, flexible pressure sensors have attracted extensive research owing to their wide range of applications, such as human–machine interfaces and health monitoring. To fulfill the requirements for different applications, new material design and device fabrication strategies have been developed in order to manipulate the mechanical and electrical properties and enhance device performance. In this paper, the important progresses in flexible pressure sensor development over recent years are selectively reviewed from a material and application perspective. First, an overview of the fundamental working mechanism and the systematic design approach is presented. Particularly, how the theoretical modeling has been used as an auxiliary tool to achieve better sensing performance is discussed. A number of applications, including human–machine interfaces, electronic skin and health monitoring, and certain application‐driven functions, e.g., pressure distribution visualization and direction‐sensitive force detection, are highlighted. Lastly, various advanced manufacturing methods used for realizing large‐scale fabrication are introduced. Recent scientific and engineering progresses of flexible pressure sensors are reported in this review. First, the fundamental sensor assessment principles and latest material developments are introduced. The theoretical methods for sensor modeling are then discussed. Applications and new auxiliary functions of flexible pressure sensors are presented. Lastly, advanced manufacturing technologies for large‐scale fabrication of the sensors are reviewed. [ABSTRACT FROM AUTHOR]

Highlights • Experimental test of lubricant oil on a 3 kW ORC prototype using R123. • Operation characteristics at lubricant oil ratio and degree of superheating. • Lubricant oil deteriorates the expander shaft power and electrical power. • Thermal efficiency is insensitive on the lubricant oil ratio. Abstract The lubricant oil can prevent the leakages and reduce the expander friction losses, but blend with the pure working fluid because of the absence of oil separator and affect eventually the organic Rankine cycle (ORC) operation characteristic. Based on a 3 kW ORC experimental prototype, the effect of lubricant oil ratio (1.2%, 3.1%, 5.0%, 6.7% and 9.0%) using R123 on the system behavior under three different degree of superheating (5, 10 and 15 °C) has been investigated. The heat source temperature is fixed at 130 °C, while the mass flow rate is controlled by adjusting the pump frequency. The heat input is first amended, and the detailed components' behaviors are examined. The system overall performance, including thermal efficiency and system generating efficiency is explored. Results demonstrated that the deviation between the calculated heat input and modified heat input is no more than 5%. The lubricant oil enhances the pump behavior, whereas deteriorates the expander shaft power and electrical power. Meanwhile, the thermal efficiency is insensitive on the lubricant oil ratio for a degree of superheating higher than 10 °C. The system generating efficiencies for degree of superheating of 10 and 15 °C are in range of 5.44–5.61% (3.03%) and 5.34–5.69% (6.15%), respectively. [ABSTRACT FROM AUTHOR]

Understanding complex biological systems requires the system-wide characterization of both molecular and cellular features. Existing methods for spatial mapping of biomolecules in intact tissues suffer from information loss caused by degradation and tissue damage. We report a tissue transformation strategy named stabilization under harsh conditions via intramolecular epoxide linkages to prevent degradation (SHIELD), which uses a flexible polyepoxide to form controlled intra- and intermolecular cross-link with biomolecules. SHIELD preserves protein fluorescence and antigenicity, transcripts and tissue architecture under a wide range of harsh conditions. We applied SHIELD to interrogate system-level wiring, synaptic architecture, and molecular features of virally labeled neurons and their targets in mouse at single-cell resolution. We also demonstrated rapid three-dimensional phenotyping of core needle biopsies and human brain cells. SHIELD enables rapid, multiscale, integrated molecular phenotyping of both animal and clinical tissues. [ABSTRACT FROM AUTHOR]

An ultrafast spectrum programmable femtosecond laser may enhance the performance of a wide variety of scientific applications, e.g., multi-photon imaging. In this paper, we report a digital micromirror device (DMD)-based ultrafast pulse shaper, i.e., DUPS, for femtosecond laser arbitrary amplitude shaping — the first time a programmable binary device reported to shape the amplitudes of ultrafast pulses spectrum at up to 32 kHz rate over a broad wavelength range. The DUPS is highly efficient, compact, and low cost based on the use of a DMD in combination with a transmission grating. Spatial and temporal dispersion introduced by the DUPS is compensated by a quasi-4-f setup and a grating pair, respectively. Femtosecond pulses with arbitrary spectrum shapes, including rectangular, sawtooth, triangular, double-pulse, and exponential profile, have been demonstrated in our experiments. A feedback operation process is implemented in the DUPS to ensure a robust and repeatable shaping process. The total efficiency of the DUPS for amplitude shaping is measured to be 27%. [ABSTRACT FROM AUTHOR]

In this work, we present a compact and ultrasensitive bio-molecule sensor based on fiber specklegram, achieving a DNA detection sensitivity of 10 −16  M. To our knowledge, the new device is the most sensitive fiber-optic DNA sensor reported to date. Importantly, the well-known temperature cross-sensitivity issue in many fiber-optic devices has been entirely removed by the introduction of a reference fiber-optic channel embedded in microfluidic channels. In the experiment, we demonstrate label-free DNA hybridization detection at different concentrations, where normalized intensity inner product of the collected specklegrams are calculated and used for determining the DNA concentration. The result shows the exact ssDNA concentration can be precisely determined with a single experiment in 60 min. The new fiber sensor presents distinctive advantages over traditional bio-sensors in terms of sensitivity, precision and cost, which may find many practical applications in health and medicine, e.g., point-of-care testing and disease diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Optogenetics employs light to manipulate cellular events such as activation of molecular channels, signaling molecules, and gene transcription, by transfection with engineered light‐sensitive proteins. In the last decade, great progresses in life science have been made by optogenetics, but the gene transfection limits its further medical applications. In this study, it is reported that a short flash of femtosecond‐laser stimulation can directly activate extracellular signal‐regulated kinase (ERK), an essential signaling pathway, in target cells, without any optogenetic technology. This all‐optical approach can be easily accomplished by a two‐photon or confocal microscope coupled with a femtosecond laser. The photostimulation can initiate immediate ERK translocation into nucleus and exit back to cytosol. The nuclear ERK level can be regulated by combination of multiple photostimulations. Subsequent up‐regulation of phosphorylated endogenous eIF4E indicates successful activation of the ERK signaling pathway. Occasionally, ERK activation in the surrounding cells of the stimulation is observed. Some key signaling cascades in the ERK2 pathway activated by photostimulation is further clarified. Altogether, this all‐optical method can activate ERK without any exogenous chemicals or proteins and thus be with promissing potential for related research. [ABSTRACT FROM AUTHOR]

3D metal printing has become one of the critical manufacturing methods in recent years that enables a variety of applications across different disciplines, e.g. aerospace and medicine. In this work, we present a high-throughput 3D metal printing method based on a programmable femtosecond light sheet and electrodeposition, achieving submicron resolution in both lateral and axial directions. The light sheet, for parallel material removal, is generated by spatially and temporally focusing the ultrafast laser in the processing plane, which is in conjugation with a digital micromirror device (DMD), thereby allowing fast pattern generation in synchronization with laser pulses. High quality metal layers are formed successively via electrodeposition processes. Accordingly, 3D metal printing is realized by repeating the steps of (1) forming structural/sacrificial layers; and (2) laser micromachining. In the experiments, we demonstrate fast metal printing of various complex 3D structures within tens of laser pulses over an area of 100 × 60 μm 2 . Compared with the existing sequential metal printing techniques, the new method has substantially improved both the throughput and resolution by a factor of ∼100 times. [ABSTRACT FROM AUTHOR]

We present a parallel depth resolved laser fabrication technique for micro- and nano-machining metal substrates based on temporal focusing. In this system, the spectrum of a femtosecond laser pulse is first spatially separated by a digital micromirror device, which simultaneously serves as a diffraction grating and a programmable binary mask. After collimation and beam flattening, an objective lens recombines the spectrum to the focal region, forming a high-intensity, depth resolved light sheet for laser micromachining. The light sheet technology enables parallel fabrication of highly uniform micro-structures of close to diffraction-limited resolution. Experimental results demonstrate high-resolution (~800 nm) direct area patterning on various metal substrates, e.g., nickel and copper, over an area of ~100 × 60 µm 2 within tens of laser pulses. The relationship among material removal rate, surface flatness, laser power, and number of pulses have been experimentally studied; the results suggest the application of higher power with fewer number of laser pulses produce microstructures of better surface quality. The light sheet technology substantially improves the throughput of ultrafast laser machining, enabling direct area patterning without compromising the resolution. [ABSTRACT FROM AUTHOR]

This paper presents the design, characterization, and control of a flexure-based roll-to-roll (R2R) printing system that achieves nanometer level precision and repeatability. The R2R system includes an unwinding/rewinding module, a web guide mechanism, and a core positioning stage consisting of two monolithic compliant X–Y stages that control the position/force of the print roller. During the printing process, capacitance probes, eddy current sensors and load cells are used to monitor the displacements of the flexure stage and contact force in real time. Control strategies, including decoupling, PID, and cascade control, have been implemented to decouple the cross-axis and cross-stage motion coupling effect and improve the overall precision and dynamic performance. In actual printing processes, the contact force and roller position can be uniformly controlled within ±0.05 N and ±200 nm respectively across a 4 in. wide PET web. To demonstrate the performance, a positive microcontact printing (MCP) process is adapted to the R2R system, printing various fine metal patterns, e.g., optical gratings and electrodes, in a continuous fashion. [ABSTRACT FROM AUTHOR]

This paper reports a vacuum-assisted UV imprinting system for parallel fabrication of micro-lens arrays on a spherical dome for artificial compound eye applications. Artificial compound eyes are a kind of micro-optics structure inspired by insect eyes. They offer unique optical characteristics, e.g., wide field of view (FOV), high sensitivity and light weight, in a compact arrangement with miniaturized lens arrays on a curved surface. In practice, it has been a great challenge to precisely fabricate micro-lens arrays on curved substrates at reasonable cost. The UV imprinting system was developed to ensure conformal contact between a soft elastomeric stamp and a convex substrate, i.e., dome, coated with UV-curable resins. The pressure-driven stamp enables large-area direct formation of high fill factor hexagonal micro-lens arrays through soft UV imprint processes. The geometrical characteristics, surface quality and optical properties of the micro-lens array were characterized quantitatively, e.g., NA = 0.06; RMS ∼ λ /50. Lastly, the optical performance of the artificial compound eyes was demonstrated by an ultra-wide angle imaging experiment under uniform illumination. The vacuum imprinting system presents a new manufacturing platform for fabricating 3-dimensional structures on nonplanar substrates in a parallel and cost effective way. The fabricated compound eye structure will be particularly useful in the areas of multi-channel imaging, machine vision, and surveillance. [ABSTRACT FROM AUTHOR]

Noninvasive and real-time cuffless blood pressure (BP) measurement realizes the idea of unobtrusive and continuous BP monitoring which is essential for diagnosis and prevention of cardiovascular diseases associated with hypertension. In this paper, a wearable sensor patch system that integrates flexible piezoresistive sensor (FPS) and epidermal electrocardiogram (ECG) sensors for cuffless BP measurement is presented. By developing parametric models on the FPS sensing mechanism and optimizing operational conditions, a highly stable epidermal pulse monitoring method is established and beat-to-beat BP measurement from the ECG and epidermal pulse signals is demonstrated. In particular, this study highlights the compromise between sensor sensitivity and signal stability. As compared with the current optical-based cuffless BP measurement devices, the sensing patch requires much lower power consumption (3 nW) and is capable of detecting subtle physiological signal variations, e.g., pre and postexercises, thus providing a promising solution for low-power, real-time, and home-based BP monitoring. [ABSTRACT FROM AUTHOR]

This paper presents the concept, theoretical analysis, microfabrication processes and experimental characterization of a micromirror with tunable resonant frequency. For scanning applications where a large scanning angle is required, comb-drive based micromirrors are typically operated at resonance due to the limited force/energy density of electrostatic actuators. However, errors in microfabrication processes often cause natural frequencies to offset from the design value. This issue may be resolved by a frequency-tunable micromirror. In our design, the shifting of the resonant frequency is achieved by adjusting the axial stress of the micromirror’s torsion hinge via integrated chevron thermomechanical actuators. The scanning motion of the micromirror is generated by double silicon-on-insulator (SOI) wafer-based electrostatic comb-drive actuators. The experimental results show that the micromirror has achieved a frequency tuning range of approximately 3%, which is close to the analytic model. With precise frequency control, the micromirror may compensate the undesired frequency shift due to fabrication errors, which is useful for applications requiring precise scanning synchronization such as the laser scanning endomicroscope systems. [ABSTRACT FROM AUTHOR]

Crystallization is one of the most crucial steps in the process of pharmaceutical formulation. In recent years, emulsion-based platforms have been developed and broadly adopted to generate high quality products. However, these conventional approaches such as stirring are still limited in several aspects, e.g., unstable crystallization conditions and broad size distribution; besides, only simple crystal forms can be produced. In this paper, we present a new flow-free droplet-based formation process for producing highly controlled crystallization with two examples: (1) NaCl crystallization reveals the ability to package saturated solution into nanoliter droplets, and (2) glycine crystallization demonstrates the ability to produce polymorphic crystallization forms by controlling the droplet size and temperature. In our process, the saturated solution automatically fills the microwell array powered by degassed bulk PDMS. A critical oil covering step is then introduced to isolate the saturated solution and control the water dissolution rate. Utilizing surface tension, the solution is uniformly packaged in the form of thousands of isolating droplets at the bottom of each microwell of 50–300 μm diameter. After water dissolution, individual crystal structures are automatically formed inside the microwell array. This approach facilitates the study of different glycine growth processes: α-form generated inside the droplets and γ-form generated at the edge of the droplets. With precise temperature control over nanoliter-sized droplets, the growth of ellipsoidal crystalline agglomerates of glycine was achieved for the first time. Optical and SEM images illustrate that the ellipsoidal agglomerates consist of 2–5 μm glycine clusters with inner spiral structures of ~35 μm screw pitch. Lastly, the size distribution of spherical crystalline agglomerates (SAs) produced from microwells of different sizes was measured to have a coefficient variation (CV) of less than 5%, showing crystal sizes can be precisely controlled by microwell sizes with high uniformity. This new method can be used to reliably fabricate monodispersed crystals for pharmaceutical applications. [ABSTRACT FROM AUTHOR]

• First demonstration of self-mode-locked dark solitons in a Tm-Ho doped fiber laser. • The self-mode-locking operation is achieved by inserting a long gain fiber. • Dark solitons are generated by exploiting the reverse saturable absorption effect. • Our simulation based on the NLSE equation confirms the dark soliton generation process. • Our method shows a higher damage threshold and a record laser power of 149.6 mW. We present the first experimental demonstration of self-mode-locked dark solitons in a Tm-Ho doped fiber laser at 1.93 μm with an average power of 149.6 mW and repetition rate of 15.9 MHz. In our system, the dark solitons are generated by self-mode-locking via exploiting the reverse saturable excited-state absorption of a gain fiber, which achieves a higher damage threshold and accordingly laser power over conventional methods based on extra saturable absorber or nonlinear polarization rotation. In the experiments, we study the evolution from high-order to low-order dark solitons by adjusting the pump power, which is attributed to the excited-state absorption in Tm3+ between 3F 4 and 3H 4 energy level. Simulations have been performed to show dark soliton generation by the reverse-saturable absorption mechanism in Tm-Ho doped fiber laser based on the extended nonlinear Schrödinger equation. The results confirm our new approach can generate stable dark solitons of high average power, which may find important applications in laser sensing and laser communications. [ABSTRACT FROM AUTHOR]

Significance: High-speed three-dimensional (3D) super-resolution microscopy is a unique tool to investigate various biological phenomena; yet the technology is not broadly adopted due to its high cost and complex system design. Aim: We present a compact, low-cost, and high-speed 3D structured illumination microscopy (SIM) based on a digital micromirror device and binary holography to visualize fast biological events with super-resolution. Approach: The 3D SIM uses a digital micromirror device to generate three laser foci with individually controllable positions, phases, and amplitudes via binary holography at the back aperture of objective lens to form optimal 3D structured patterns. Fifteen raw images are sequentially recorded and processed by the 3D SIM algorithm to reconstruct a super-resolved image. Results: Super-resolution 3D imaging at a speed of 26.7 frames per second is achieved with a lateral and axial resolution of 155 and 487 nm, which corresponds to a 1.65- and 1.63-times resolution enhancement, respectively, comparing with standard deconvolution microscopy. Conclusions: The 3D SIM realizes fast super-resolution imaging with optimal 3D structured illumination, which may find important applications in biophotonics. [ABSTRACT FROM AUTHOR]

Abstract: Hepatocellular carcinoma (HCC) is a global public health problem which causes approximately 500,000 deaths annually. Considering that the limited therapeutic options for HCC, novel therapeutic targets and drugs are urgently needed. In this study, we discovered that 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran [7,6-b] xanthone (TDP), isolated from the traditional Chinese medicinal herb, Garcinia oblongifolia, effectively inhibited cell growth and induced the caspase-dependent mitochondrial apoptosis in HCC. A two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomics were performed to find the molecular targets of TDP in HCC cells. Eighteen proteins were identified as differently expressed, with Hsp27 protein being one of the most significantly down-regulated proteins induced by TDP. In addition, the following gain- and loss-of-function studies indicated that Hsp27 mediates mitochondrial apoptosis induced by TDP. Furthermore, a nude mice model also demonstrated the suppressive effect of TDP on HCC. Our study suggests that TDP plays apoptosis-inducing roles by strongly suppressing the Hsp27 expression that is specifically associated with the mitochondrial death of the caspase-dependent pathway. In conclusion, TDP may be a potential anti-cancer drug candidate, especially to cancers with an abnormally high expression of Hsp27. [Copyright &y& Elsevier]

• Single-point detection strategy for 2D SPR sensor array. • High-speed solid-state scanning by digital micro-mirror device (up to 32.5 kHz). • The measured resolution and CV% are 6.47 × 10−6 RIU and 1.45%, respectively. • The system can perform rapid high-throughput aptamer screening. • Screened aptamers can be antibody alternatives for diagnostic and therapeutic purpose. In this paper, we report a novel single-point detection strategy for 2D solid-state angular interrogated SPR (surface plasmon resonance) sensor array for multiple aptamer screening. The scheme operates with two DMDs (digital micro-mirror devices), which suffices a single-point detector for high-throughput 2D SPR measurements without sacrificing the sensitivity. After having verified the biosensing capability of the system, in terms of sensitivity and repeatability, using standard BSA-anti-BSA antibody interaction, we further conducted experiments to perform rapid screening of aptamer candidates for binding with tumor necrosis factor-α (TNF-α). The selected anti-TNF-α aptamers were subsequently evaluated as an in vitro cell protection agent against TNF-α-induced cell death. Our experiments confirm that the anti-TNF-α aptamer screening approach offers high potential as an alternative to that based on antibodies for diagnostic and therapeutic applications. [ABSTRACT FROM AUTHOR]

The surface plasmon resonance (SPR) sensor is an important tool widely used for studying binding kinetics between biomolecular species. The SPR approach offers unique advantages in light of its real-time and label-free sensing capabilities. Until now, nearly all established SPR instrumentation schemes are based on single- or several-channel configurations. With the emergence of drug screening and investigation of biomolecular interactions on a massive scale these days for finding more effective treatments of diseases, there is a growing demand for the development of high-throughput 2-D SPR sensor arrays based on imaging. The so-called SPR imaging (SPRi) approach has been explored intensively in recent years. This review aims to provide an up-to-date and concise summary of recent advances in SPRi. The specific focuses are on practical instrumentation designs and their respective biosensing applications in relation to molecular sensing, healthcare testing, and environmental screening. [ABSTRACT FROM AUTHOR]

Wearable pressure sensors enable long‐term real‐time health monitoring in a noninvasive and power‐efficient way; however, the sensors are often required to be precisely applied at the optimal measurement spot, e.g., nearby radial artery, for signal acquisition, causing inconvenience for untrained users or the elders. In this paper, a wearable liquid‐capsule sensor platform embedded with a piezo‐resistive pressure sensor is presented for continuous, accurate, and alignment‐relaxed physiological monitoring, i.e., heart rate (HR) and blood pressure (BP) tracking. The flexible capsule design ensures comfort and good device conformation to any skin regions. For HR and BP measurements, experiments are performed on 12 human subjects. The results show that the capsuled sensor can continuously track: 1) HR with a mean absolute difference (MAD) of 0.88 beats per minute (bpm) and 2) BP with a MAD<3 mmHg for both diastolic and systolic blood pressure. The new liquid‐capsule‐based sensor platform may help to realize an accurate, flexible, robust, and low‐power solution for next‐generation wearable health monitoring devices. A wearable liquid‐capsule sensor platform embedded with a piezo‐resistive pressure sensor for continuous, accurate, and alignment‐relaxed physiological monitoring, i.e., heart rate and blood pressure tracking, is realized. [ABSTRACT FROM AUTHOR]

N. Zhao and coworkers demonstrate, on page 1178, a low‐power, wearable sensor system that integrates a flexible piezoresistive sensor and epidermal electrocardiogram sensors, for extracting real‐time beat‐to‐beat blood pressure measurements. Through parametric modelling and operation optimization, highly stable epidermal pulse monitoring is achieved, and the compromise between sensor sensitivity and signal stability is highlighted. [ABSTRACT FROM AUTHOR]

A continuous roll-to-roll microcontact printing (MCP) platform promises large-area nanoscale patterning with significantly improved throughput and a great variety of applications, e.g. precision patterning of metals, bio-molecules, colloidal nanocrystals, etc. Compared with nanoimprint lithography, MCP does not require a thermal imprinting step (which limits the speed and material choices), but instead, extreme precision with multi-axis positioning and misalignment correction capabilities for large area adaptation. In this work, we exploit a flexure-based mechanism that enables continuous MCP with 500 nm precision and 0.05 N force control. The fully automated roll-to-roll platform is coupled with a new backfilling MCP chemistry optimized for high-speed patterning of gold and silver. Gratings of 300, 400, 600 nm line-width at various locations on a 4-inch plastic substrate are fabricated at a speed of 60 cm/min. Our work represents the first example of roll-to-roll MCP with high reproducibility, wafer scale production capability at nanometer resolution. The precision roll-to-roll platform can be readily applied to other material systems. [ABSTRACT FROM AUTHOR]