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Cellular transfection is a method by which exogenous biomolecules can be introduced into the cells. In the fields of molecular and cellular biology, cellular transfection is considered an essential tool, specifically for applications such as drug delivery, cellular therapy, and biomedical imaging. Photoporation based cellular transfection approach uses high-intensity light energy to create membrane pores, sometimes nanoparticles are incorporated to achieve the result at low intensity. In this work, hybrid nanoparticles, composed of gold and polystyrene are used to mediate the photoporation. Laser fluence, exposure time, wavelength, the concentration of nanoparticles, and concentration of exogenous molecules are optimized for the successful delivery of propidium iodide dye, quantum dots, and plasmid into CL1-0, AGS, and P-19 cells. The best results (delivery efficiency of 92% and cell viability of 98%) are achieved in delivering propidium iodide dye into CL1-0 cells.

Human electromyogram (EMG) contains abundant body movement information, which is often used as the information medium of human-robot interaction. Precisely analyzing the muscle activity information contained in the patient's EMG and using it for the motion control of the rehabilitation robot is of great significance in the rehabilitation training process. Aiming at the problem that ankle rehabilitation robot needs to use the patient's EMG to identify the ankle motion intention and estimate the angle of continuous motion in the human-robot interactive rehabilitation training, this paper proposes a new method based on the patient's EMG to directly identify the type of ankle motion and estimate the continuous motion angle of the joint. Considering the nonlinear relationship between EMG and joint motion angles, Hammerstein model is selected to describe the relationship between them. The linear and nonlinear structure of the Hammerstein model simplifies the difficulty of model identification. First, obtain the real motion angle of the ankle joint while collecting the EMG of the muscles related to the ankle joint motion, and use the threshold judgment method to complete the recognition of the ankle joint motion intention. Then, use the EMG as the input of the motion model and the real motion angle of the ankle joint as the motion model output, identify and obtain the Hammerstein motion model of plantarflexion motion and dorsiflexion motion respectively. Finally, use EMG as the input of the recognized model to estimate the continuous motion angle of the ankle joint. The experiment shows that the motion model established by the method in this paper can realize the recognition of the motion intention of the ankle joint and the accurate estimation of the continuous motion angle, this method is worth promoting.

Detecting memory leak at industrial scale is still not well addressed, in spite of the tremendous effort from both industry and academia in the past decades. Existing work suffers from an unresolved paradox - a highly precise analysis limits its scalability and an imprecise one seriously hurts its precision or recall. In this work, we present Smoke, a staged approach to resolve this paradox. In the first stage, instead of using a uniform precise analysis for all paths, we use a scalable but imprecise analysis to compute a succinct set of candidate memory leak paths. In the second stage, we leverage a more precise analysis to verify the feasibility of those candidates. The first stage is scalable, due to the design of a new sparse program representation, the use-flow graph (UFG), that models the problem as a polynomial-time state analysis. The second stage analysis is both precise and efficient, due to the smaller number of candidates and the design of a dedicated constraint solver. Experimental results show that Smoke can finish checking industrial-sized projects, up to 8MLoC, in forty minutes with an average false positive rate of 24.4%. Besides, Smoke is significantly faster than the state-of-the-art research techniques as well as the industrial tools, with the speedup ranging from 5.2X to 22.8X. In the twenty-nine mature and extensively checked benchmark projects, Smoke has discovered thirty previously-unknown memory leaks which were confirmed by developers, and one even assigned a CVE ID.

In this paper we propose a nano-shield mechanism via polystyrene beads (PSBs) to resist the chemical etching, simultaneously produce a highly selective etching ratio to create more hot-spots for Surface-enhanced Raman spectroscopy (SERS) enhancement of a Janus-Biosensor. In this paper reports an improved method for processing nona-pillar array structure characterized by High-Aspect-Ratio, which extend the third dimension of hot-spots distribution. After depositing gold, nano-pillar array produce more hot-spots for greater SERS enhancement around 10 times than original substrate, which sensor could be proposed as high sensitivity bio-sensing application purpose.With this SERS substrate, we can improve the sensitivity to distinguish clearly of the hybridization process by Raman spectrum in label-free way. With this method, we will have a widespread implication in DNA analysis. Especially detecting biomarkers in liquid biopsy field, to achieve the final purpose of early cancer screening.

A sensitivity silicon p-n diodes for detecting backscattering electrons in SEM was proposed and fabricated. The multi-annular configuration enables to provide higher sensitivity of Z-contrast and better surface topography contrast of BSE image. In this study, the multi-annular backscattered electron detector (BSED) can provide enhancement of surface topography contrast and image contrast with 105% and 42% as compared with commercial BSED which with the multi-fan configuration. We also designed a high sensitivity to low energy electrons detector which with lateral p-n junctions and Al metal grids.

Present work lies in the fact that we have demonstrated that highly stable oxygen Nano bubbles (NBs) could be generated and stabilized in a liquid environmental transmission electron microscope (LETEM), using an in house fabricated quasi-2D system. The size of the stabilized NBs varies in the range from 10 to 50 nm, its formation occurred via decomposition of 0.025% hydrogen peroxide on Platinum/CNT nanocomposite. The characterization of growth and long-term stability of NBs has been successfully carried out. In our system, the long-term stability of oxygen NB comes from supersaturation of oxygen molecules and compact arranged of NB. We have also developed the theoretical model derived from Henry's law by which we can predict the stability stage of NBs.

We propose the synergic operation of two devices that consist of a high quality sperm sorter and an oocytes zona-removal as well as incubation device for promoting the successful rate and the efficiency of In-vitro fertilization (IVF). The high quality sperm sorter can gently sort out large number of sperms in few minutes and keep high survival rate for oligospermia patients. The oocytes zona-removal and incubation device can rapidly reduce enzyme contraction after gently removing oocytes shell. Experiment results showed that these two devices not only provide an easier and faster method to sort out motile sperms as well as better preserve the viability of dezona oocytes, but also increase the attachment rate of sperms on oocytes for enhancing fertilization.

Immunofluorescence is widely used in detection and characterization of circulating tumor cells (CTCs). The process of immunofluorescence staining on cells needs centrifugal force to wash residual fluorescence, which is not only time consuming but also cells harmful. To speed up the staining process, a three-dimensional (3D) microfluidic device is employed in this work. This study also reports the rapid selection of identified live CTCs from whole blood on SACA chip for further characterization by automatic imaging and in-situ cell capturing process. The whole process takes 120 minutes for examining 4 ml whole blood sample and the recognition sensitivity can approach 1/108 by using the integrated chip and automatic image system. All cells are remained highly viable after the rapid selection process for further applications.

In this study, we propose two devices that provide an easier and faster method to execute in-vitro fertilization (IVF) technique. The devices consist of a high quality sperm sorter and an oocytes zona-removal and incubation device to aid promoting the success rate and the efficiency of IVF technique. Comparing with the traditional IVF process, the high quality sperm sorter can gently sort out large number of sperms in few minutes and keep high survival rate for oligospermia patients. At the same time, the oocytes zona-removal and incubation device also gently decreases the enzyme contraction with removing oocytes shell rapidly. Experiment results showed that sorted sperms could easily attach on dezona oocytes surface, and the oocytes are still in complete shape. These two devices not only provide an easier and faster method to sort out motile sperms and dezona oocytes, but also increase the attachment rate of sperms on oocytes.

In this study, we design and fabricate a PMMA-based mini-direct methanol fuel cell. This device consists of commercial membrane electrode assembly (MEA) and PMMA-based fuel channels. Different proportion of commercial catalyst and ionomer (Nafion®) is tested by cyclic voltammetry (CV) in order to optimize the activation performance. The structure of PMMA-based fuel channels are manufactured by Computer Numerical Control (CNC) technology, in addition, Au film is deposited on PMMA surface to make electrode. For durability, the Au conducting layer is conjugated with PMMA surface by chemical modification. The single cell test indicated the PMMA-based fuel cell can provide 2 mW and oxygen is applied by air-breathing mode in room temperature. In this process, methanol is pumped in the fuel cell and raises the leakage issue.

This paper proposes a selection and extraction strategy to acquire high quality sperms from a biomimetic microfluidic device capable of generating a dual gradient flow field for motile sperm sorting. The sorter consists of a straight flow zone, a rapidly expansion sector for sperm sorting by gradient up-stream flow, and a dumbbell channel for dead sperms separation at the outlet. A collateral runner is set at the front area of the expansion sector, but mostly kept in dry state without affecting the sorting process. At the end of sorting, a pressure was applied from both the inlet and outlet to flush the high quality sperms into the collateral runner for collection. Controllable numbers, ranging from 1 to 15000, of sperms can be collected with a motility (>60µm) ratio higher than 60%, suitable for in-vitro fertilization (IVF).

To solve the low implantation rate of in-vitro fertilization (IVF), zona-free oocyte is widely used in IVF [1]. However the process of zona-removal is not only tedious but also easy to harm the fragile oocyte. In this work we introduce a 3-dimensional microfluidic device to simplify the zona-removal process, and the applied gentle process is also capable to keep oocyte intact and precisely locate all oocytes in the well throughout the procedure.

For the first time, using wet cell in a liquid environmental transmission electron microscopy (LETEM), we have successfully generated highly stable oxygen nanobubbles with diameter 5∼7 nm by decomposition of 0.02% H2O2 on Pt/CNT nanocomposite. The nucleation, growth and stability of those nanobubbles have been characterized. Along with this, we also have studied the variation of the internal pressure with average radius of stable nanobubbles with respect to time.

In this paper we report the development of an ultrasensitive photonic sensor based on nanoporous silicon (NPS) substrate for heavy metal ions detection in a FTIR reflection system. A one-dimensional photonic crystal with disturbed Bragg reflector (DBR) fabricated by successive electrochemical etchings (ECE) is employed to enhance the reflected IR signals [1] [2]. This well-defined NPS nanostructures will be red shifted due to the increase in the refractive index of the Fe3+ ion solution (1 mM). The Fe3+ with difference concentration due to difference spectrum shift, and the average sensitivity is 22.3cm−1/mM corresponding to a detection limit of 10.8 ppm.

In this paper, we nano-engineered commercial atomic force microscope (AFM) probes with multi nano tip structures for high speed/resolution dynamic nanodetection. The tip radius could be shrunk down to 2.5 nm, and the time resolution could be approaching 10 ms for measuring particle movement. The multi tip AFM can be applicable for detecting the dynamic movement of bio-molecules in situ.

This study introduces a combinatory assay platform that allows high-throughput but low-drug-dosage screening of five anti-cancer drugs as a cocktail for personalized cancer treatment. Photosensitive PEGDA hydrogel was employed for drug dosage definition through drop array formation and selective UV crosslinking process. The finally defined cocktail drugs in hydrogel will be directly released in parallel when combined with cell chips. This device is capable to combine 5 drugs with 1000 folds dynamic range in 30 second with low drug consumption for in-parallel cocktail screening process.

A cochlear implant (CI) can partially restore hearing in patients with severe to profound sensorineural hearing loss. Proper programming and evaluation of the CIs are key aspects determining success in the restoration of hearing for patients. Recent evidence suggests that cortical auditory evoked potentials, elicited via an unattended oddball paradigm, can provide objective information on CI spectral discrimination abilities, which in turn may be useful for assessing speech perception performance. This study investigates the applicability of an acoustic change paradigm for objective evaluation of CI users' ability to resolve spectral content via single channel electroencephalography. Acoustic change complex (ACC) responses were obtained from 13 CI users and correlated with psychoacoustic spectral discrimination abilities. The applicability of the acoustic change paradigm was compared to that of the unattended oddball paradigm. The neural spectral discrimination threshold, estimated via the ACC responses, showed a non-significant correlation with the behavioral spectral discrimination threshold. In contrast, the neural spectral threshold estimated via an unattended oddball paradigm showed a significant correlation with the behavioral threshold. Results suggest that the unattended oddball paradigm is a more robust paradigm than the ACC to objectively evaluate CI users' ability to resolve spectral ripples. Nonetheless, the ACC can be used in some CI users and may be considered as an additional tool for objective evaluation of CI performance.

This paper reports a highly sensitive SERS Diagnosis system by incorporating three dimensional Nano-Mushrooms and Nano-Stars-Array sandwiched on Bacterial Aggregation. Through the action of ACEOF and nano-mushroom/bacteria/nano-stars-array self-aggregation process, the signal can be much enhanced by 5 orders of magnitude in 5 minutes. Detection limit can approach 1 bacterium/ml from the analysis result.

The objective of this study is to present an electrical characterization of metal electrodes deposited on flexible substrates for folding test. In order to quantize folding conditions, flexible-characteristic inspection system (FCIS) [1] for folding function is utilized to control radii of curvature of the flexible substrates. As a result, the new technique successfully measures electrical characteristics of flexible polydimethylsiloxane (PDMS)/gold electrodes for analysis during the 0/m to 200/m curvature folding cycles. Inspection results of folding characteristics depicted on flexible displays help a designer or maker of flexible displays design useful and comfortable flexible electronic products.

This paper presents optimized structural interface between 3D SU8 prism and SOI waveguide for reduced coupling loss at the interface, hence increasing light transmission efficiency over the system. The coupling loss reduced to 10 % at each optimized interface thanks to SU8 overlap on tip of SOI waveguide and partly etched BOX under the interface. With large tolerance up to 5 µm, the interface can be easily fabricated.

In this paper, an open-loop reduction system (OLRS) [1] is employed to produce the core-shell Pt (platinum)/Ru (ruthenium) catalysts on the carbon nanotube/carbon fiber supports (CNT/CF) for direct methanol fuel cell (DMFC) application. By adjusting pH value of the ionized reduction environment, Pt 4+ can be first converted into Pt 2+ to allow partial Ru replacement with Pt by redox transmetalation and produce Pt/Ru core-shell nano structures [2,3]. Methanol oxidation efficiency and carbon monoxide (CO) poisoning tolerance of the prepared core-shell nano catalysts can be greatly enhanced by our developed OLRS compared to conventional reflux system [4].

© 2014 IEEE. Today single cell research is a great interest to analyze cell to cell or cell to environment behavior with their intracellular compounds, where bulk measurement can provide average value. To deliver biomolecules precise and localized way into single living cell with high transfection rate and high cell viability is a challenging and promisible task for biological and therapeutic research. In this report, we present a nano-localized single cell nano-electroporation technique, where electroporation take place in a very precise and localized area on a single cell membrane to achieve high efficient delivery with high cell viability. We fabricated 60nm gap with 40 nm triangular Indium Tin Oxide (ITO) based nano-eletcrode tip, which can intense electric field in a nano-localized area of a single cell to permeabilize cell membrane and deliver exogenous biomolecules from outside to inside of the cell. This device successfully deliver dyes, proteins into single cell with high cell viability (98%). The process not only control precise delivery mechanism into single cell with membrane reversibility, but also it can provide special, temporal and qualitative dosage control, which might be beneficial for therapeutic and biological cell studies.

Podocytes are the mature glomerular epithelial cells that processes highly branched architecture essential for glomerular filtration in the kidney. To resemble the filtration barrier in vivo, we use porous membranes in podocyte culture to mimic the glomerular basement membrane. We found that the morphology of the podocytes were dependent on pore sizes and membrane material. Podocytes grew on anodic aluminum oxide (AAO) membranes have higher degree of cell spreading and grew faster than they did on polycarbonate (PC) membrane. The difference is even more significant when cultured on AAO with smaller pores. To study the porosity only, both membranes were coated with collagen. The results show that the difference of cell growing rate was reduced, while the degree of cell spreading was still higher in AAO membrane. This results show that the podocyte culture is dependent on the underneath porosity and material property, with the implication for “kidney on a chip” in the future pharmaceutical development.

Physical introduction of foreign biomolecules such as genes, proteins, DNA and RNA into living cells with high efficiency is a challenging task for biological and therapeutic research. Bulk electroporation technique, where high electric field pulses were applied to millions of cells together in-between two large electrodes, though widely employed, however is nonspecific resulting in variable efficiency with low cell viability. Here we demonstrate controllable nano-electroporation platform for HeLa cell and human Caucasian Gastric Adenocarcinoma (AGS) cell to achieve high efficient bimolecular delivery with high cell viability. Our system consists of 40nm triangular Indium Tin Oxide (ITO) metal tip with 60nm electrode gap to provide high intense electric filed into the local region of the single cell membrane. Therefore biomolecules can be delivered by much enhance electrophoresis and diffusion effects during pulsing process through a small specific nano-region of the single cell, where remaining other area of the cell membrane unaffected. This microfluidic device has great ability to offer spatial, temporal and qualitative dosage control as well as very high transfection efficiency and high cell viability.