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To realize nanoscale manufacturing based on laser direct writing technology, objective lenses with high numerical apertures immersed in water or oil are necessary. The use of liquid medium restricts its application in semiconductors. Achieving nanoscale features on silicon by laser direct writing in a low refractive index medium has been a challenge. In this work, a microsphere assisted femtosecond laser far-field induced dewetting approach is proposed. A reduction in the full-width at half-maximum of the focused light spot is realized by modulating tightly focused light through microspheres and achieving a minimum feature size of 9 nm on silicon in ambient air with energy smaller than the ablation threshold. Theoretical analysis and numerical simulation of laser processing are performed based on a two-temperature model. Furthermore, we explored the potential of femtosecond laser-induced dewetting in nanolithography and demonstrated its ability to achieve an arbitrary structure on silicon. Our work enables laser-based far-field sub-10-nm feature etching on a large-scale, providing a novel avenue for nanoscale silicon manufacturing.

IntroductionBrain computer interfaces (BCI), which establish a direct interaction between the brain and the external device bypassing peripheral nerves, is one of the hot research areas. How to effectively convert brain intentions into instructions for controlling external devices in real-time remains a key issue that needs to be addressed in brain computer interfaces. The Riemannian geometry-based methods have achieved competitive results in decoding EEG signals. However, current Riemannian classifiers tend to overlook changes in data distribution, resulting in degenerated classification performance in cross-session and/or cross subject scenarios.MethodsThis paper proposes a brain signal decoding method based on Riemannian transfer learning, fully considering the drift of the data distribution. Two Riemannian transfer learning methods based log-Euclidean metric are developed, such that historical data (source domain) can be used to aid the training of the Riemannian decoder for the current task, or data from other subjects can be used to boost the training of the decoder for the target subject.ResultsThe proposed methods were verified on BCI competition III, IIIa, and IV 2a datasets. Compared with the baseline that without transfer learning, the proposed algorithm demonstrates superior classification performance. In contrast to the Riemann transfer learning method based on the affine invariant Riemannian metric, the proposed method obtained comparable classification performance, but is much more computationally efficient.DiscussionWith the help of proposed transfer learning method, the Riemannian classifier obtained competitive performance to existing methods in the literature. More importantly, the transfer learning process is unsupervised and time-efficient, possessing potential for online learning scenarios.

The dynamic spreading mechanism of liquid on a specific surface is vital for understanding interface wetting and antifouling. Whereas, how to control the spreading process and accelerate the spreading speed is a major challenge. The rock‐climbing fish is characterized by its alepidote feature that lives in stream habitats dominated by strong currents. The mucus on its body surface plays a vital role in its adherence and maintenance of antifouling and antibacterial properties. However, the rapid, uniform, and efficient spreading mechanism of mucus on the fish body surface remains largely unknown. Herein, it is revealed that the surface of the rock‐climbing fish is overlaid fully by the microhexagonal texture structure. This hexagonal structure shows a superspreading effect on liquid diffusion, resulting from testing with bionic microfabrication inspired by the rock‐climbing fish. It is demonstrated that the microhexagonal‐textured surface can enhance liquid spreading quickly and evenly on the surface by regulating the moving contact line of the liquid. This kind of superspreading mechanism has great potential applications in the antifouling, electroencephalogram electrode interfaces, flexible skin sensors, and interfacial lubrication of underwater surfaces.

Abstract Flexible pressure sensors based on micro‐/nanostructures can be integrated into robots to achieve sensitive tactile perception. However, conventional symmetric structures, such as pyramids or hemispheres, can sense only the magnitude of a force and not its direction. In this study, a capacitive flexible tactile sensor inspired by skin structures and based on an asymmetric microhair structure array to perceive directional shear force is designed. Asymmetric microhair structures are obtained by two‐photon polymerization (TPP) and replication. Owing to the features of asymmetric microhair structures, different shear force directions result in different deformations. The designed device can determine the directions of both static and dynamic shear forces. Additionally, it exhibits large response scales ranging from 30 Pa to 300 kPa and maintains high stability even after 5000 cycles; the final relative capacitive change (ΔC/C0) is

Cell mechanics is essential to cell development and function, and its dynamics evolution reflects the physiological state of cells. Here, we investigate the dynamical mechanical properties of single cells under various drug conditions, and present two mathematical approaches to quantitatively characterizing the cell physiological state. It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate, and can be mathematically characterized by a linear time-invariant dynamical model. It is shown that the transition matrices of dynamical cell systems significantly improve the classification accuracies of the cells under different drug actions. Furthermore, it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties, and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model. This study builds a relationship between the cellular mechanical properties and the cellular physiological state, adding information for evaluating drug efficacy.

A significant number of stroke patients are permanently left with a hemiparetic upper limb after the poststroke six-month golden recovery period, resulting in a drastic decline in their quality of life. This study develops a novel foot-controlled hand/forearm exoskeleton that enables patients with hemiparetic hands and forearms to restore their voluntary activities of daily living. Patients can accomplish dexterous hand/arm manipulation on their own with the assistance of a foot-controlled hand/forearm exoskeleton by utilizing foot movements on the unaffected side as command signals. The proposed foot-controlled exoskeleton was first tested on a stroke patient with a chronic hemiparetic upper limb. The testing results showed that the forearm exoskeleton can assist the patient in achieving approximately 107° of voluntary forearm rotation with a static control error less than 1.7°, whereas the hand exoskeleton can assist the patient in realizing at least six different voluntary hand gestures with a success rate of 100%. Further experiments involving more patients demonstrated that the foot-controlled hand/forearm exoskeleton can help patients in restoring some of the voluntary activities of daily living with their paretic upper limb, such as picking up food to eat and opening water bottles to drink, and etc. This research implies that the foot-controlled hand/forearm exoskeleton is a viable way to restore the upper limb activities of stroke patients with chronic hemiparesis.

ABSTRACT: The increasing consumption of ducks and chickens in China demands characterizing carcasses of domestic birds efficiently. Most existing methods, however, were developed for characterizing carcasses of pigs or cattle. Here, we developed a noncontact and automated weighing method for duck carcasses hanging on a production line. A 2D camera with its facilitating parts recorded the moving duck carcasses on the production line. To estimate the weight of carcasses, the images in the acquired dataset were modeled by a convolution neuron network (CNN). This model was trained and evaluated using 10-fold cross-validation. The model estimated the weight of duck carcasses precisely with a mean abstract deviation (MAD) of 58.8 grams and a mean relative error (MRE) of 2.15% in the testing dataset. Compared with 2 widely used methods, pixel area linear regression and the artificial neural network (ANN) model, our model decreases the estimation error MAD by 64.7 grams (52.4%) and 48.2 grams (45.0%). We release the dataset and code at https://github.com/RuoyuChen10/Image_weighing.

Abstract Background Combinatorial drug therapy for complex diseases, such as HSV infection and cancers, has a more significant efficacy than single-drug treatment. However, one key challenge is how to effectively and efficiently determine the optimal concentrations of combinatorial drugs because the number of drug combinations increases exponentially with the types of drugs. Results In this study, a searching method based on Markov chain is presented to optimize the combinatorial drug concentrations. In this method, the searching process of the optimal drug concentrations is converted into a Markov chain process with state variables representing all possible combinations of discretized drug concentrations. The transition probability matrix is updated by comparing the drug responses of the adjacent states in the network of the Markov chain and the drug concentration optimization is turned to seek the state with maximum value in the stationary distribution vector. Its performance is compared with five stochastic optimization algorithms as benchmark methods by simulation and biological experiments. Both simulation results and experimental data demonstrate that the Markov chain-based approach is more reliable and efficient in seeking global optimum than the benchmark algorithms. Furthermore, the Markov chain-based approach allows parallel implementation of all drug testing experiments, and largely reduces the times in the biological experiments. Conclusion This article provides a versatile method for combinatorial drug screening, which is of great significance for clinical drug combination therapy.

Controlling the formation of disinfection by-products (DBPs) is a major issue in the drinking water industry, and understanding the characteristics of DBP precursors in treatment processes for micro-polluted raw water is key to improving water quality. In this study, a sampling program was undertaken to investigate the fate of dissolved organic matter (DOM) and the characteristics of DBP precursors in a pilot constructed wetland imitating the Yanlong Lake ecological project. Using XAD resin adsorption and ultrafiltration techniques, the dissolved organic carbon, UV254, and DBP formation potential (DBPFP) were measured in different DOM fractions in raw water and wetland effluents. After the constructed wetland treatment, the low molecular weight fraction (3 kDa) of DOM increased. The specific DBPFP (SDBPFP) was much higher in the

Femtosecond laser processing is fast becoming a pervasive method for fabricating micro/nanostructures because it can be used to produce micro/nanostructures on myriads of materials with high precision and resolution, requires little control over environmental conditions, and is simple to implement. Here, we review recent developments in the use of femtosecond lasers for the fabrication of micro/nanostructures through ablation and two-photon polymerization (TPP). Moreover, the applications of some of the fabricated micro/nanostructures are also discussed. We highlight the advantages of femtosecond laser processing by explaining the underlying principles of laser ablation and TPP. We also show the use of this method to fabricate new devices with outstanding performance in several application realm, such as sensors, optical devices, microfluidic chips, and soft robotics.

Abstract With the rapid evolution of microelectronics and nanofabrication technologies, the feature sizes of large‐scale integrated circuits continue to move toward the nanoscale. There is a strong need to improve the quality and efficiency of integrated circuit inspection, but it remains a great challenge to provide both rapid imaging and circuit node‐level high‐resolution images simultaneously using a conventional microscope. This paper proposes a nondestructive, high‐throughput, multiscale correlation imaging method that combines atomic force microscopy (AFM) with microlens‐based scanning optical microscopy. In this method, a microlens is coupled to the end of the AFM cantilever and the sample‐facing side of the microlens contains a focused ion beam deposited tip which serves as the AFM scanning probe. The introduction of a microlens improves the imaging resolution of the AFM optical system, providing a 3–4× increase in optical imaging magnification while the scanning imaging throughput is improved ≈8×. The proposed method bridges the resolution gap between traditional optical imaging and AFM, achieves cross‐scale rapid imaging with micrometer to nanometer resolution, and improves the efficiency of AFM‐based large‐scale imaging and detection. Simultaneously, nanoscale‐level correlation between the acquired optical image and structure information is enabled by the method, providing a powerful tool for semiconductor device inspection.

Background Endothelial cells (ECs) are a critical component of the hematopoietic niche, and the cross-talk between ECs and leukemia was reported recently. This study aimed to determine the genes involved in the proliferation inhibition of endothelial cells in leukemia. Methods Human umbilical vein endothelial cells (HUVEC) were cultured alone or co-cultured with K562 cell lines. GeneChip assays were performed to identify the differentially expressed genes. The Celigo, MTT assay, and flow cytometric analysis were used to determine the effect of RNAi DIDO on cell growth and apoptosis. The differently expressed genes were verified by qRT-PCR (quantitative real-time PCR) and western-blot. Results In K562-HUVEC co-cultured cell lines, 323 down-regulated probes were identified and the extracellular signal-regulated kinase 5 (ERK5) signaling pathway was significantly inhibited. Among the down-regulated genes, the death inducer-obliterator gene (DIDO) is a part of the centrosome protein and may be involved in cell mitosis. As shown in the public data, leukemia patients with lower expression of DIDO showed a better overall survival (OS). The HUVEC cells were infected with shDIDO lentivirus, and reduced expression, inhibited proliferation, and increased apoptosis was observed in shDIDO cells. In addition, the expression of Cyclin-Dependent Kinase 6 (CDK6) and Cyclin D1 (CCND1) genes was inhibited in shDIDO cells. Finally, the public ChIP-seq data were used to analyze the regulators that bind with DIDO, and the H3K4me3 and PolII (RNA polymerase II) signals were found near the Exon1 and exon2 sites of DIDO. Conclusion The knock-down of DIDO will inhibit the proliferation of endothelial cells in the leukemia environment. The expression of DIDO may be regulated by H3K4me3 and the inhibition of DIDO may lead to the down-regulation of CDK6 and CCND1. However, how DIDO interacts with CDK6 and CCND1 requires further study.

Abstract Planar and curved microlens arrays (MLAs) are the key components of miniaturized microoptical systems. In order to meet the requirements for advanced and multipurpose applications in microoptical field, a simple manufacturing method is urgently required for fabricating MLAs with unique properties, such as waterproofness and variable field-of-view (FOV) imaging. Such properties are beneficial for the production of advanced artificial compound eyes for the significant applications in complex microcavity environments with high humidity, for instance, miniature medical endoscopy. However, the simple and effective fabrication of advanced artificial compound eyes still presents significant challenges. In this paper, bioinspired by the natural superhydrophobic surface of lotus leaf, we propose a novel method for the fabrication of waterproof artificial compound eyes. Electrohydrodynamic jet printing was used to fabricate hierarchical MLAs and nanolens arrays (NLAs) on polydimethylsiloxane film. The flexible film of MLAs hybridized with NLAs exhibited excellent superhydrophobic property with a water contact angle of 158°. The MLAs film was deformed using a microfluidics chip to create artificial compound eyes with variable FOV, which ranged from 0° to 160°.

Biosyncretic robots, which are new nature-based robots in addition to bionic robots, that utilize biological materials to realize their core function, have been supposed to further promote the progress in robotics. Actuation as the main operation mechanism relates to the robotic overall performance. Therefore, biosyncretic robots actuated by living biological actuators have attracted increasing attention. However, innovative propelling modes and control methods are still necessary for the further development of controllable motion performance of biosyncretic robots. In this work, a muscle tissue-based biosyncretic swimmer with a manta ray-inspired propelling mode has been developed. What is more, to improve the stable controllability of the biosyncretic swimmer, a dynamic control method based on circularly distributed multiple electrodes (CDME) has been proposed. In this method, the direction of the electric field generated by the CDME could be real-time controlled to be parallel with the actuation tissue of the dynamic swimmer. Therefore, the instability of the tissue actuation induced by the dynamic included angle between the tissue axis and electric field direction could be eliminated. Finally, the biosyncretic robot has demonstrated stable, controllable, and effective swimming, by adjusting the electric stimulation pulse direction, amplitude, and frequency. This work may be beneficial for not only the development of biosyncretic robots but also other related studies including bionic design of soft robots and muscle tissue engineering.

Flexible magnetic continuum robots (MCRs) can be fabricated in small dimensions with great manipulability as their tips can deflect under fields, without the need for complicated mechanical structures to govern control, and it helps improve operating conditions during retrograde intrarenal surgery (RIRS). However, the limited effective workspace of an electromagnet‐based magnetic navigation system (MNS) influences the practical applications. Herein, the method of steering a flexible MCR in the enlarged workspace of a common MNS for RIRS is presented. First, the field heterogeneity is parameterized to quantitatively analyze its influence on the motion of the MCR. Then, a kinematic model of the MCR is constructed, by coupling the heterogeneous‐field and Cosserat‐rod models, to predict its large deformation in the enlarged workspace with constraints. The model is validated with the maximum mean error of 0.53 ± 0.39 mm for the tip position in all the experiments. It is demonstrated that the effective workspace can be enlarged to 75% of the physical workspace. In addition, experiments in phantoms, which simulate two challenges during RIRS, are performed to prove its manipulability. This study enlarges the effective workspace of the MNS, which helps expand the practical application of the MCR.

Since cancer incidence and mortality are rapidly growing worldwide, it is imperative to develop the effective tumor models in vitro for anti-cancer drug screening. Cellular spheroid as an excellent simple 3D model can bridge the gap between cell culture and live tissue. Although numerous approaches for generating cellular spheroids emerges, the long cultivation time and the heterospheroids formation with multiple cell types are still challenging. In the present study, a mask-free method of multicellular heterospheroids arrays formation using digital micromirror device (DMD)-based hydrogel fabricating system and microfluidic system is proposed. Microwell arrays were designed and manufactured online based on shadowed light which shows high flexible. Besides, heterospheroids with multiple cells controlled in different ratios can be generated and cultured for a long time in microfluidic system. Furthermore, the drug screening shows that heterospheroids have high rate of drug resistance compared with homospheroids and combinatorial drugs works better than the single drugs. These studies provide a 3D heterospheroids generating process for high-throughput combinatorial anti-cancer drug screening with potential cancer therapeutic application. Keywords: 3D heterospheroids generation, Microwells fabrication, Drug screening

Bio-syncretic robots consisting of both living biological materials and non-living systems possess desirable attributes such as high energy efficiency, intrinsic safety, high sensitivity, and self-repairing capabilities. Compared with living biological materials or non-living traditional robots based on electromechanical systems, the combined system of a bio-syncretic robot holds many advantages. Therefore, developing bio-syncretic robots has been a topic of great interest, and significant progress has been achieved in this area over the past decade. This review systematically summarizes the development of bio-syncretic robots. First, potential trends in the development of bio-syncretic robots are discussed. Next, the current performance of bio-syncretic robots, including simple movement and controllability of velocity and direction, is reviewed. The living biological materials and non-living materials that are used in bio-syncretic robots, and the corresponding fabrication methods, are then discussed. In addition, recently developed control methods for bio-syncretic robots, including physical and chemical control methods, are described. Finally, challenges in the development of bio-syncretic robots are discussed from multiple viewpoints, including sensing and intelligence, living and non-living materials, control approaches, and information technology. Keywords: Bio-syncretic robot, Hybrid robot, Bio-actuator, Cardiomyocyte, Muscle cells

The ability to create controllable patterns of micro- and nanostructures on the surface of bulk silicon has widespread application potential. In particular, the direct writing of silicon oxide patterns on silicon via femtosecond laser-induced silicon amorphization has attracted considerable attention owing to its simplicity and high efficiency. However, the direct writing of nanoscale resolution is challenging due to the optical diffraction effect. In this study, we propose a highly efficient, one-step method for preparing silicon oxide nanopatterns on silicon. The proposed method combines femtosecond laser-induced silicon amorphization with a subwavelength-scale beam waist of photonic nanojets. We demonstrate the direct writing of arbitrary nanopatterns via contactless scanning, achieving patterns with a minimum feature size of 310 nm and a height of 120 nm. The proposed method shows potential for the fabrication of multifunctional surfaces, silicon-based chips, and silicon photonics.

In this paper, polymer solar cells with a tandem structure were investigated and optimized using a multiscale simulation scheme. In the proposed multiscale simulation, multiple aspects – optical calculation, mesoscale simulation, device scale simulation and optimal power conversion efficiency searching modules – were studied together to give an optimal result. Through the simulation work, dependencies of device performance on the tandem structures were clarified by tuning the thickness, donor/acceptor weight ratio as well as the donor–acceptor distribution in both active layers of the two sub-cells. Finally, employing searching algorithms, we optimized the power conversion efficiency of the tandem polymer solar cells and located the optimal device structure parameters. With the proposed multiscale simulation strategy, poly(3-hexylthiophene)/phenyl-C61-butyric acid methyl ester and (poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b]dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)])/phenyl-C61-butyric acid methyl ester based tandem solar cells were simulated and optimized as an example. Two configurations with different sub-cell sequences in the tandem photovoltaic device were tested and compared. The comparison of the simulation results between the two configurations demonstrated that the balance between the two sub-cells is of critical importance for tandem organic photovoltaics to achieve high performance. Consistency between the optimization results and the reported experimental results proved the effectiveness of the proposed simulation scheme.

Rare subcellular events can be tracked by correlating structural-information gathered by imaging with specific-molecule fluorescent identification. Here, the authors achieve this correlation in a quick and non-invasive way using microsphere-based scanning superlens microscopy.

The controlled patterning of microdroplets or microwires at precise positions plays an essential role in micro/nano device applications. In this context, we propose a novel and efficient method called tip-assisted electrohydrodynamic (EHD) printing that combines the tip-assisted electric field intensity enhancement effect and the high-resolution capability of EHD printing. The tip-assisted electric field enhancement effect is first systematically investigated by simulation analysis. Under optimized experimental conditions, we obtain microdroplet arrays and microwires down to sizes of 2.3 μm and controlled micropatterns composed of droplet arrays or microwires with sizes smaller than the inner diameter of nozzle by means of the tip-assisted technique. We find that with our designed tip-assisted nozzle, solutions with a high viscosity of >2000 cps can be extracted from the nozzle, and the printing resolution can increase by nearly five times the current resolution. Our results demonstrate that tip-assisted EHD printing provides a potential and flexible method for precision and controlled manufacturing of micropatterns. Keywords: Electrohydrodynamic (EHD) printing, Tip-assisted EHD, Micropatterning, High-resolution printing

Three-dimensional multicellular spheroids (MCSs) have received extensive attention in the field of biomedicine due to their ability to simulate the structure and function of tissues in vivo more accurately than traditional in vitro two-dimensional models and to simulate cell–cell and cell extracellular matrix (ECM) interactions. It has become an important in vitro three-dimensional model for tumor research, high-throughput drug screening, tissue engineering, and basic biology research. In the review, we first summarize methods for MCSs generation and their respective advantages and disadvantages and highlight the advances of hydrogel and microfluidic systems in the generation of spheroids. Then, we look at the application of MCSs in cancer research and other aspects. Finally, we discuss the development direction and prospects of MCSs

Physical properties of two-dimensional materials, such as graphene, black phosphorus, molybdenum disulfide (MoS2) and tungsten disulfide, exhibit significant dependence on their lattice orientations, especially for zigzag and armchair lattice orientations. Understanding of the atomic probe motion on surfaces with different orientations helps in the study of anisotropic materials. Unfortunately, there is no comprehensive model that can describe the probe motion mechanism. In this paper, we report a tribological study of MoS2 in zigzag and armchair orientations. We observed a characteristic power spectrum and friction force values. To explain our results, we developed a modified, two-dimensional, stick-slip Tomlinson model that allows simulation of the probe motion on MoS2 surfaces by combining the motion in the Mo layer and S layer. Our model fits well with the experimental data and provides a theoretical basis for tribological studies of two-dimensional materials.

Fabrication of hydrogel microstructures has attracted considerable attention. A large number of applications, such as fabricating tissue engineering scaffolds, delivering drugs to diseased tissue, and constructing extracellular matrix for studying cell behaviors, have been introduced. In this article, an ultraviolet (UV)-curing method based on a digital micromirror device (DMD) for fabricating poly(ethylene glycol) diacrylate (PEGDA) hydrogel microstructures was presented. By controlling UV projection in real-time using a DMD as digital dynamic mask instead of a physical mask, polymerization of the pre-polymer solution could be controlled to create custom-designed hydrogel microstructures. Arbitrary microstructures could also be fabricated within several seconds (

Since the late 1980s, additive manufacturing (AM), commonly known as three-dimensional (3D) printing, has been gradually popularized. However, the microstructures fabricated using 3D printing is static. To overcome this challenge, four-dimensional (4D) printing which defined as fabricating a complex spontaneous structure that changes with time respond in an intended manner to external stimuli. 4D printing originates in 3D printing, but beyond 3D printing. Although 4D printing is mainly based on 3D printing and become an branch of additive manufacturing, the fabricated objects are no longer static and can be transformed into complex structures by changing the size, shape, property and functionality under external stimuli, which makes 3D printing alive. Herein, recent major progresses in 4D printing are reviewed, including AM technologies for 4D printing, stimulation method, materials and applications. In addition, the current challenges and future prospects of 4D printing were highlighted.

Cell dielectric properties, a type of intrinsic property of cells, can be used as electrophysiological biomarkers that offer a label-free way to characterize cell phenotypes and states, purify clinical samples, and identify target cancer cells. Here, we present a review of the determination of cell dielectric properties using alternating current (AC) electrokinetic-based microfluidic mechanisms, including electro-rotation (ROT) and dielectrophoresis (DEP). The review covers theoretically how ROT and DEP work to extract cell dielectric properties. We also dive into the details of differently structured ROT chips, followed by a discussion on the determination of cell dielectric properties and the use of these properties in bio-related applications. Additionally, the review offers a look at the future challenges facing the AC electrokinetic-based microfluidic platform in terms of acquiring cell dielectric parameters. Our conclusion is that this platform will bring biomedical and bioengineering sciences to the next level and ultimately achieve the shift from lab-oriented research to real-world applications.

Optoelectrokinetics (OEK), a fusion of optics, electrokinetics, and microfluidics, has been demonstrated to offer a series of extraordinary advantages in the manipulation and fabrication of micro/nanomaterials, such as requiring no mask, programmability, flexibility, and rapidness. In this paper, we summarize a variety of differently structured OEK chips, followed by a discussion on how they are fabricated and the ways in which they work. We also review how three differently sized polystyrene beads can be separated simultaneously, how a variety of nanoparticles can be assembled, and how micro/nanomaterials can be fabricated into functional devices. Another focus of our paper is on mask-free fabrication and assembly of hydrogel-based micro/nanostructures and its possible applications in biological fields. We provide a summary of the current challenges facing the OEK technique and its future prospects at the end of this paper.

Graphene and single-walled carbon nanotube (SWCNT) have been widely studied because of their extraordinary electrical, thermal, mechanical, and optical properties. This paper describes a novel and flexible method to fabricate all-carbon field-effect transistors (FETs). The fabrication process begins with assembling graphene grown by chemical vapor deposition (CVD) on a silicon chip with SiO2 as the dielectric layer and n-doped Si substrate as the gate. Next, an atomic force microscopy (AFM)-based mechanical cutting method is utilized to cut the graphene into interdigitated electrodes with nanogaps, which serve as the source and drain. Lastly, SWCNTs are assembled on the graphene interdigitated electrodes by dielectrophoresis to form the conductive channel. The electrical properties of the thus-fabricated SWCNT-graphene FETs are investigated and their FET behavior is confirmed. The current method effectively integrates SWCNTs and graphene in nanoelectronic devices, and presents a new method to build all-carbon electronic devices.

A modified Prandtl–Ishlinskii (PI) model, referred to as a direct inverse asymmetric PI (DIAPI) model in this paper, was implemented to reduce the displacement error between a predicted model and the actual trajectory of a piezoelectric actuator which is commonly found in AFM systems. Due to the nonlinearity of the piezoelectric actuator, the standard symmetric PI model cannot precisely describe the asymmetric motion of the actuator. In order to improve the accuracy of AFM scans, two series of slope parameters were introduced in the PI model to describe both the voltage-increase-loop (trace) and voltage-decrease-loop (retrace). A feedforward controller based on the DIAPI model was implemented to compensate hysteresis. Performance of the DIAPI model and the feedforward controller were validated by scanning micro-lenses and standard silicon grating using a custom-built AFM.

As an inhibitor of microtubule assembly, combretastatin A-4 (CA-4)-induced biological responses in tumor cells have been well known, but the corresponding changes in nano-biophysical properties were not investigated given the lack of an ideal tool. Using AFM technique, we investigated the alteration of nano-biophysical properties when CA-4-treated tumor cells underwent the different biological processes, including cell cycle arrest, apoptosis and autophagy. We found that CA-4-resistant cells were rougher with the presence of characteristic "ridges", indicating that the development of "ridge" structure may be a determinant of the sensitivity of cells to CA-4 compounds. CA-4 induced G2/M arrest and apoptosis in sensitive cells but triggered anti-apoptotic autophagy in resistant cells. CA-4 treatment caused an increase in stiffness in both sensitive and resistant cells. However, these cells exhibited different changes in cell surface roughness. CA-4 decreased Ra and Rq values in sensitive cells but increased these values in resistant cells. The reorganization of F-actin might contribute to the different changes of nano-biophysical properties in CA-4-sensitive and-resistant cells. Our results suggest that cellular nano-biophysical properties, such as "ridges", roughness and stiffness, could be applied as potential biomarkers for evaluating CA-4 compounds, and knowledge regarding how biological alterations cause changes in cellular nano-biophysical properties is helpful to develop a new high-resolution screening tool for anti-tumor agents.

Microsphere-assisted microscopy has received a lot of attention recently due to its simplicity and its capability to surpass the diffraction limit. However, to date, sub-diffraction-limit features have only been observed in virtual images formed through the microspheres. We show that it is possible to form real, super-resolution images using high-refractive index microspheres. Also, we report on how changes to a microsphere's refractive index and size affect image formation and planes. The relationship between the focus position and the additional magnification factor is also investigated using experimental and theoretical methods. We demonstrate that such a real imaging mode, combined with the use of larger microspheres, can enlarge sub-diffraction-limit features up to 10 times that of wide-field microscopy's magnification with a field-of-view diameter of up to 9 μm.

A single cell can be regarded as a complex network that contains thousands of overlapping signaling pathways. The traditional methods for describing the dynamics of this network are extremely complicated. The mechanical properties of a cell reflect the cytoskeletal structure and composition and are closely related to the cellular biological functions and physiological activities. Therefore, modeling the mechanical properties of single cells provides the basis for analyzing and controlling the cellular state. In this study, we developed a dynamical model with cellular viscoelasticity properties as the system parameters to describe the stress-relaxation phenomenon of a single cell indented by an atomic force microscope (AFM). The system order and parameters were identified and analyzed. Our results demonstrated that the parameters identified using this model represent the cellular mechanical elasticity and viscosity and can be used to classify cell types.

A novel micromanipulation technique of multi-objectives based on vibrating bubbles in an open chip environment is described in this paper. Bubbles were created in an aqueous medium by the thermal energy converted from a laser. When the piezoelectric stack fixed under the chip vibrated the bubbles, micro-objects (microparticles, cells, etc.) rapidly moved towards the bubbles. Results from numerical simulation demonstrate that convective flow around the bubbles can provide forces to capture objects. Since bubbles can be generated at arbitrary destinations in the open chip environment, they can act as both micromanipulators and transporters. As a result, micro- and bio-objects could be collected and transported effectively as masses in the open chip environment. This makes it possible for scientific instruments, such as atomic force microscopy (AFM) and scanning ion conductive microscopy (SICM), to operate the micro-objects directly in an open chip environment.

The advent of atomic force microscopy (AFM) has provided a powerful tool for investigating the behaviors of single native biological molecules under physiological conditions. AFM can not only image the conformational changes of single biological molecules at work with sub-nanometer resolution, but also sense the specific interactions of individual molecular pair with piconewton force sensitivity. In the past decade, the performance of AFM has been greatly improved, which makes it widely used in biology to address diverse biomedical issues. Characterizing the behaviors of single molecules by AFM provides considerable novel insights into the underlying mechanisms guiding life activities, contributing much to cell and molecular biology. In this article, we review the recent developments of AFM studies in single-molecule assay. The related techniques involved in AFM single-molecule assay were firstly presented, and then the progress in several aspects (including molecular imaging, molecular mechanics, molecular recognition, and molecular activities on cell surface) was summarized. The challenges and future directions were also discussed.

Early stage detection of lymphoma cells is invaluable for providing reliable prognosis to patients. However, the purity of lymphoma cells in extracted samples from human patients' marrow is typically low. To address this issue, we report here our work on using optically-induced dielectrophoresis (ODEP) force to rapidly purify Raji cells' (a type of Burkitt's lymphoma cell) sample from red blood cells (RBCs) with a label-free process. This method utilizes dynamically moving virtual electrodes to induce negative ODEP force of varying magnitudes on the Raji cells and RBCs in an optically-induced electrokinetics (OEK) chip. Polarization models for the two types of cells that reflect their discriminate electrical properties were established. Then, the cells' differential velocities caused by a specific ODEP force field were obtained by a finite element simulation model, thereby established the theoretical basis that the two types of cells could be separated using an ODEP force field. To ensure that the ODEP force dominated the separation process, a comparison of the ODEP force with other significant electrokinetics forces was conducted using numerical results. Furthermore, the performance of the ODEP-based approach for separating Raji cells from RBCs was experimentally investigated. The results showed that these two types of cells, with different concentration ratios, could be separated rapidly using externally-applied electrical field at a driven frequency of 50 kHz at 20 Vpp. In addition, we have found that in order to facilitate ODEP-based cell separation, Raji cells' adhesion to the OEK chip's substrate should be minimized. This paper also presents our experimental results of finding the appropriate bovine serum albumin concentration in an isotonic solution to reduce cell adhesion, while maintaining suitable medium conductivity for electrokinetics-based cell separation. In short, we have demonstrated that OEK technology could be a promising tool for efficient and effective purification of Raji cells from RBCs.

We present a rapid hydrogel polymerization and prototyping microfabrication technique using an optically induced electrokinetics (OEK) chip, which is based on a non-UV hydrogel curing principle. Using this technique, micro-scale high-aspect-ratio three-dimensional polymer features with different geometric sizes can be fabricated within 1–10 min by projecting pre-defined visible light image patterns onto the OEK chip. This method eliminates the need for traditional photolithography masks used for patterning and fabricating polymer microstructures and simplifies the fabrication processes. This technique uses cross-link hydrogels, such as poly(ethylene glycol) (PEG)-diacrylate (PEGDA), as fabrication materials. We demonstrated that hydrogel micropillar arrays rapidly fabricated using this technique can be used as molds to create micron-scale cavities in PDMS (polydimethylsiloxane) substrates. Furthermore, hollow, circular tubes with controllable wall thicknesses and high-aspect ratios can also be fabricated. These results show the potential of this technique to become a rapid prototyping technology for producing microfluidic devices. In addition, we show that rapid prototyping of three-dimensional suspended polymer structures is possible without any sacrificial etching process.