Development of low-fluorescence thick photoresist for high-aspect-ratio microstructure in bio-application

In this study, we propose and evaluate a novel low-auto-fluorescence photoresist (SJI photoresist) for bio-application, e.g., in gene analysis and cell assay. The spin-coated SJI photoresist has a wide thickness range of ten to several hundred micrometers, and photoresist microstructures with an aspect ratio of over 7 and micropatterns of less than 2 μm are successfully fabricated. The emission spectrum intensity of the SJI photoresist is found to be over 80% less than that of the widely used SU-8 photoresist. To evaluate the validity of using the proposed photoresist in bio-application for fluorescence observation, we demonstrate a chromosome extension device composed of the SJI photoresist. The normalized contrast ratio of the SJI photoresist exhibits a 50% improvement over that of the SU-8 photoresist; thus, the SJI photoresist is a versatile tool for bio-application.     

China's first ZnO nanorod field-effect transistor developed at CAS

Recently,an zinc oxide (ZnO) nanorod field-effect transistor (FET), the first of its kind as a nano-device in China, was successfully fabricated by scientists with the CAS Institute     

Polydimethylsiloxane microfluidic chip with integrated microheater and thermal sensor

A microheater and a thermal sensor were fabricated inside elastomeric polydimethylsiloxane microchannels by injecting silver paint (or other conductive materials) into the channels. With a high-precision control scheme, microheaters can be used for rapid heating, with precise temperature control and uniform thermal distribution. Using such a microheater and feedback system, a polymerase chain reaction experiment was carried out whereas the DNA was successfully amplified in 25 cycles, with 1 min per cycle.     

Centrifugal multiplexing fixed-volume dispenser on a plastic lab-on-a-disk for parallel biochemical single-end-point assays

In this study, a multiple sample dispenser for precisely metered fixed volumes was successfully designed, fabricated, and fully characterized on a plastic centrifugal lab-on-a-disk (LOD) for parallel biochemical single-end-point assays. The dispenser, namely, a centrifugal multiplexing fixed-volume dispenser (C-MUFID) was designed with microfluidic structures based on the theoretical modeling about a centrifugal circumferential filling flow. The designed LODs were fabricated with a polystyrene substrate through micromachining and they were thermally bonded with a flat substrate. Furthermore, six parallel metering and dispensing assays were conducted at the same fixed-volume (1.27 μl) with a relative variation of ±0.02 μl. Moreover, the samples were metered and dispensed at different sub-volumes. To visualize the metering and dispensing performances, the C-MUFID was integrated with a serpentine micromixer during parallel centrifugal mixing tests. Parallel biochemical single-end-point assays were successfully conducted on the developed LOD using a standard serum with albumin, glucose, and total protein reagents. The developed LOD could be widely applied to various biochemical single-end-point assays which require different volume ratios of the sample and reagent by controlling the design of the C-MUFID. The proposed LOD is feasible for point-of-care diagnostics because of its mass-producible structures, reliable metering/dispensing performance, and parallel biochemical single-end-point assays, which can identify numerous biochemical.     

Microfluidics based on ZnO/nanocrystalline diamond surface acoustic wave devices

Surface acoustic wave (SAW) devices with 64 μm wavelength were fabricated on a zinc oxide (ZnO) film deposited on top of an ultra-smooth nanocrystalline diamond (UNCD) layer. The smooth surface of the UNCD film allowed the growth of the ZnO film with excellent c-axis orientation and low surface roughness, suitable for SAW fabrication, and could restrain the wave from significantly dissipating into the substrate. The frequency response of the fabricated devices was characterized and a Rayleigh mode was observed at ∼65.4 MHz. This mode was utilised to demonstrate that the ZnO/UNCD SAW device can be successfully used for microfluidic applications. Streaming, pumping, and jetting using microdroplets of 0.5 and 20 μl were achieved and characterized under different powers applied to the SAW device, focusing more on the jetting behaviors induced by the ZnO SAW.     

Double stochastic resonance induced by varying potential-well depth and width

The role of potential-well depth and width on stochastic resonance (SR) driven by colored noise with different noise correlation times is explored and evaluated by deriving the analytic expression of output signal-to-noise ratio (SNR) as a most widely used indicator for quantifying SR phenomenon. Double resonance peaks are observed and shifted between single peak and double peaks when SNR is expressed as the function of varying potential-well depth, varying potential-well width, additive noise intensity, multiplicative noise intensity and the intensity ratio between two noise, respectively. Moreover, the SR behavior induced by varying potential-well depth is different from that induced by varying potential-well width. Even the shapes of SNR curves under different correlation times and coupling strength for potential-well depth are opposite to those for potential-well width and furthermore they are also of dependence on initial conditions. Above clues may be helpful to the precise control of SR by varying potential-well depth and width separately for weak signal enhancement.     

嵌入式可编程存储器中的字宽配置实现

提出了一种利用同步双端口存储器IP和标准单元来实现嵌入式可编程存储器中的字宽配置的方案以降低设计的复杂性,提高设计效率. 通过寄存输出控制信号来优化嵌入式可编程存储器混合宽度配置的实现结构以增强读出数据的稳定性. 对比试验表明,优化后的结构还有利于提高复杂实现电路的性能. 该优化结构的嵌入式可编程存储器已在SMIC 0.18μm 1P6M CMOS工艺线上流片. 测试结果表明,其读出数据具有良好的稳定性,在读出时间方面与相近工艺、相同存储容量的采用全定制方法设计的商用嵌入式可编程存储器相当.     

A numerical study on the dynamics of droplet formation in a microfluidic double T-junction

In this study, droplet formations in microfluidic double T-junctions (MFDTD) are investigated based on a two-dimensional numerical model with volume of fluid method. Parametric ranges for generating alternating droplet formation (ADF) are identified. A physical background responsible for the ADF is suggested by analyzing the dynamical stability of flow system. Since the phase discrepancy between dispersed flows is mainly caused by non-symmetrical breaking of merging droplet, merging regime becomes the alternating regime at appropriate conditions. In addition, the effects of channel geometries on droplet formation are studied in terms of relative channel width. The predicted results show that the ADF region is shifted toward lower capillary numbers when channel width ratio is less than unity. The alternating droplet size increases with the increase of channel width ratio. When this ratio reaches unity, alternating droplets can be formed at very high water fraction (wf = 0.8). The droplet formation in MFDTD depends significantly on the viscosity ratio, and the droplet size in ADF decreases with the increase of the viscosity ratio. The understanding of underlying physics of the ADF phenomenon is useful for many applications, including nanoparticle synthesis with different concentrations, hydrogel bead generation, and cell transplantation in biomedical therapy.     

Microfluidic electrospinning of biphasic nanofibers with Janus morphology

In this paper a method of electrospinning conducting and nonconducting biphasic Janus nanofibers using microfluidic polydimethylsiloxane (PDMS)-based manifolds is described. Key benefits of using microfluidic devices for nanofiber synthesis include rapid prototyping, ease of fabrication, and the ability to spin multiple Janus fibers in parallel through arrays of individual microchannels. Biphasic Janus nanofibers of polyvinylpyrrolidone (PVP)+polypyrrole (PPy)∕PVP nanofibers with an average diameter of 250 nm were successfully fabricated using elastomeric microfluidic devices. Fiber characterization and confirmation of the Janus morphology was subsequently carried out using a combination of scanning electron microscopy, energy dispersion spectroscopy, and transmission electron microscopy.     

Microfluidic wet spinning of chitosan-alginate microfibers and encapsulation of HepG2 cells in fibers

The successful encapsulation of human hepatocellular carcinoma (HepG2) cells would greatly assist a broad range of applications in tissue engineering. Due to the harsh conditions during standard chitosan fiber fabrication processes, encapsulation of HepG2 cells in chitosan fibers has been challenging. Here, we describe the successful wet-spinning of chitosan-alginate fibers using a coaxial flow microfluidic chip. We determined the optimal mixing conditions for generating chitosan-alginate fibers, including a 1:5 ratio of 2% (w∕w) water-soluble chitosan (WSC) solution to 2% (w∕w) alginate solution. Ratio including higher than 2% (w∕w) WSC solution increased aggregation throughout the mixture. By suspending cells in the WSC-alginate solution, we successfully fabricated HepG2 cell-laden fibers. The encapsulated HepG2 cells in the chitosan-alginate fibers were more viable than cells encapsulated in pure alginate fibers, suggesting that cross-linked chitosan provides a better environment for HepG2 cells than alginate alone. In addition, we found that the adhesion of HepG2 cells on the chitosan-alginate fiber is much better than that on the alginate fibers.     

Fabrication of two dimensional polyethylene terephthalate nanofluidic chip using hot embossing and thermal bonding technique

We present in this paper a method for obtaining a low cost and high replication precision 2D (two dimensional) nanofluidic chip with a PET (polyethylene terephthalate) sheet, which uses hot embossing and a thermal bonding technique. The hot embossing process parameters were optimized by both experiments and the finite element method to improve the replication precision of the 2D nanochannels. With the optimized process parameters, 174.67 ± 4.51 nm wide and 179.00 ± 4.00 nm deep nanochannels were successfully replicated into the PET sheet with high replication precision of 98.4%. O₂ plasma treatment was carried out before the bonding process to decrease the dimension loss and improve the bonding strength of the 2D nanofluidic chip. The bonding parameters were optimized by bonding rate of the nanofluidic chip. The experiment results show that the bonding strength of the 2D PET nanofluidic chip is 0.664 MPa, and the total dimension loss of 2D nanochannels is 4.34 ± 7.03 nm and 18.33 ± 9.52 nm, in width and depth, respectively. The fluorescence images demonstrate that there is no blocking or leakage over the entire micro- and nanochannels. With this fabrication technology, low cost polymer nanochannels can be fabricated, which allows for commercial manufacturing of nano-components.     

Focusing-enhanced mixing in microfluidic channels

A focusing-based microfluidic mixer was studied. The micromixer utilizes the focusing process required for cytometry to reduce the diffusion distance of molecules to be mixed in order to facilitate the passive diffusion-controlled mixing process. It was found that both the high flow rate ratio of the sheath flow to the flows to be mixed and the low flow rate of the mixing fluids resulted in the short mixing length required within the microfluidic channel. It was shown that a complete mixing was achieved within a distance of 4 mm in the micromixer for the focused mixing fluids at a flow rate of 2 μl∕min and a flow rate ratio of the sheath flow to the flows to be mixed at 4:1. The mixer described here is simple and can be easily fabricated and controlled.     

板宽对FRP-混凝土粘结界面应力影响的三维有限元分析

纤维增强塑料(FRP)与混凝土的粘结性能是混凝土结构外贴FRP板材这一加固技术的重要研究课题。本文通过对混凝土表面粘贴FRP板的单剪搭接接头进行三维有限元模拟,得出了胶和混凝土中在加载端和自由端附近的各应力分量的分布曲线以及FRP板中沿板长度方向的应力分布曲线,从而分析板宽对FRP-混凝土粘结界面应力分布的具体影响,以期为进一步的相关研究提供参考。研究结果表明:(1)沿着板宽度方向应力存在着严重的不均匀性;(2)随着板宽的增加,使得应力沿着板宽的方向渐趋于均匀,因而有利于应力的传递;(3)当宽度比较大时,易发生自由端混凝土的拉剪破坏。     

High-throughput single-cell manipulation system for a large number of target cells

A sequential and high-throughput single-cell manipulation system for a large volume of cells was developed and the successive manipulation for single cell involving single-cell isolation, individual labeling, and individual rupture was realized in a microhydrodynamic flow channel fabricated by using two-dimensional simple flow channels. This microfluidic system consisted of the successive single-cell handlings of single-cell isolation from a large number of cells in cell suspension, labeling each isolated single cell and the lysate extraction from each labeled single cell. This microfluidic system was composed of main channels, cell-trapping pockets, drain channels, and single-cell content collection channels which were fabricated by polydimethylsiloxane. We demonstrated two kinds of prototypes for sequential single-cell manipulations, one was equipped with 16 single-cell isolation pockets in microchannel and the other was constructed of 512 single-cell isolation pockets. In this study, we demonstrated high-throughput and high-volume single-cell isolation with 512 pocket type device. The total number of isolated single cells in each isolation pocket from the cell suspension at a time was 426 for the cell line of African green monkey kidney, COS-1, and 360 for the rat primary brown preadipocytes, BAT. All isolated cells were stained with fluorescence dye injected into the same microchannel successfully. In addition, the extraction and collection of the cell contents was demonstrated using isolated stained COS-1 cells. The cell contents extracted from each captured cell were individually collected within each collection channel by local hydrodynamic flow. The sequential trapping, labeling, and content extraction with 512 pocket type devices realized high-throughput single-cell manipulations for innovative single-cell handling, feasible staining, and accurate cell rupture.     

Scaffold fabrication in a perfusion culture microchamber array chip by O(2) plasma bonding of poly(dimethylsiloxane) protected by a physical mask

Extracellular matrix (ECM) proteins are required for cell culture. In this paper, we report the use of O(2) plasma bonding to fabricate a perfusion culture microchamber array chip with identical-size ECM spots in the isolated microchambers. The chip was fabricated by assembly of two poly(dimethylsiloxane) (PDMS) layers, a microfluidic network layer, and an ECM array layer, which were aligned and then bonded by O(2) plasma oxidation with protection of the ECM microarray with a physical mask made from PDMS. We successfully cultivated Chinese hamster ovary K1 cells in the microchambers with fibronectin. In the fibronectin microchambers, the cells adhered and extended after 12 h of static culture and then grew over the course of 1 d of perfusion culture.     

完全有序的全同金属纳米点阵列的生长与研究

利用“幻数稳定团簇 模板”方法在半导体Si(111)衬底上第一次成功地外延生长出了尺寸相同、空间分布均匀的金属纳米团簇阵列。这种方法适用于不同的金属,制备出的纳米团簇阵列热稳定性非常高。用扫描隧道显微镜(STM)原位分析结合第一性原理计算确定了纳米团簇的原子结构以及阵列的形成机理。     

Geometrical optimization of microstripe arrays for microbead magnetophoresis

Manipulation of magnetic beads plays an increasingly important role in molecular diagnostics. Magnetophoresis is a promising technique for selective transportation of magnetic beads in lab-on-a-chip systems. We investigate periodic arrays of exchange-biased permalloy microstripes fabricated using a single lithography step. Magnetic beads can be continuously moved across such arrays by combining the spatially periodic magnetic field from microstripes with a rotating external magnetic field. By measuring and modeling the magnetophoresis properties of thirteen different stripe designs, we study the effect of the stripe geometry on the magnetophoretic transport properties of the magnetic microbeads between the stripes. We show that a symmetric geometry with equal width of and spacing between the microstripes facilitates faster transportation and that the optimal period of the periodic stripe array is approximately three times the height of the bead center over the microstripes.     

Cascaded spiral microfluidic device for deterministic and high purity continuous separation of circulating tumor cells

Inertial microfluidics is an emerging class of technologies developed to separate circulating tumor cells (CTCs). However, defining design parameters and flow conditions for optimal operation remains nondeterministic due to incomplete understanding of the mechanics, which has led to challenges in designing efficient systems. Here, we perform a parametric study of the inertial focusing effects observed in low aspect ratio curvilinear microchannels and utilize the results to demonstrate the isolation of CTCs with high purity. First, we systematically vary parameters including the channel height, width, and radius of curvature over a wide range of flow velocities to analyze its effect on size dependent differential focusing and migration behaviors of binary (10 μm and 20 μm) particles. Second, we use these results to identify optimal flow regimes to achieve maximum separation in various channel configurations and establish design guidelines to readily provide information for developing spiral channels tailored to potentially arbitrary flow conditions that yield a desired equilibrium position for optimal size based CTC separation. Finally, we describe a fully integrated, sheath-less cascaded spiral microfluidic device to continuously isolate CTCs. Human breast cancer epithelial cells were successfully extracted from leukocytes, achieving 86.76% recovery, 97.91% depletion rate, and sustaining high viability upon collection to demonstrate the versatility of the device. Importantly, this device was designed without the cumbersome trail-and-error optimization process that has hindered the development of designing such inertial microfluidic systems.     

A dynamically deformable microfilter for selective separation of specific substances in microfluidics

To study an environmental or biological solution, it is essential to separate its constituents. In this study, a 3D-deformable dynamic microfilter was developed to selectively separate the target substance from a solution. This microfilter is a fine metallic nickel structure fabricated using photolithography and electroplating techniques. It is gold-coated across its entire surface with multiple slits of 10–20 μm in width. Its two-dimensional shape is deformed into a three-dimensional shape when used for fluid separation due to hydrodynamic forces. By adjusting the pressure applied to the microfilter, the size of the gap created by deformation can be changed. To effectively isolate the target substance, the relationship between the solution flow rate and the extent of microfilter deformation was investigated. The filtration experiments demonstrated the microfilter’s ability to isolate the target substance with elastic deformation without undergoing plastic deformation. Additionally, modification of the microfilter surface with nucleic acid aptamers resulted in the selective isolation of the target cell, which further demonstrates the potential application of microfilters in the isolation of specific components of heterogeneous solutions.     

Structural design of a double-layered porous hydrogel for effective mass transport

Mass transport in porous materials is universal in nature, and its worth attracts great attention in many engineering applications. Plant leaves, which work as natural hydraulic pumps for water uptake, have evolved to have the morphological structure for fast water transport to compensate large water loss by leaf transpiration. In this study, we tried to deduce the advantageous structural features of plant leaves for practical applications. Inspired by the tissue organization of the hydraulic pathways in plant leaves, analogous double-layered porous models were fabricated using agarose hydrogel. Solute transport through the hydrogel models with different thickness ratios of the two layers was experimentally observed. In addition, numerical simulation and theoretical analysis were carried out with varying porosity and thickness ratio to investigate the effect of structural factors on mass transport ability. A simple parametric study was also conducted to examine unveiled relations between structural factors. As a result, the porosity and thickness ratio of the two layers are found to govern the mass transport ability in double-layered porous materials. The hydrogel models with widely dispersed pores at a fixed porosity, i.e., close to a homogeneously porous structure, are mostly turned out to exhibit fast mass transport. The present results would provide a new framework for fundamental design of various porous structures for effective mass transport.