Parallelized ultra-high throughput microfluidic emulsifier for multiplex kinetic assays

Droplet-based microfluidic technologies are powerful tools for applications requiring high-throughput, for example, in biochemistry or material sciences. Several systems have been proposed for the high-throughput production of monodisperse emulsions by parallelizing multiple droplet makers. However, these systems have two main limitations: (1) they allow the use of only a single disperse phase; (2) they are based on multiple layer microfabrication techniques. We present here a pipette-and-play solution offering the possibility of manipulating simultaneously 10 different disperse phases on a single layer device. This system allows high-throughput emulsion production using aqueous flow rates of up to 26 ml/h (>110 000 drops/s) leading to emulsions with user-defined complex chemical composition. We demonstrate the multiplex capabilities of our system by measuring the kinetics of β-galactosidase in droplets using nine different concentrations of a fluorogenic substrate.     

Perspectives in translating microfluidic devices from laboratory prototyping into scale-up production

Transforming lab research into a sustainable business is becoming a trend in the microfluidic field. However, there are various challenges during the translation process due to the gaps between academia and industry, especially from laboratory prototyping to industrial scale-up production, which is critical for potential commercialization. In this Perspective, based on our experience in collaboration with stakeholders, e.g., biologists, microfluidic engineers, diagnostic specialists, and manufacturers, we aim to share our understanding of the manufacturing process chain of microfluidic cartridge from concept development and laboratory prototyping to scale-up production, where the scale-up production of commercial microfluidic cartridges is highlighted. Four suggestions from the aspect of cartridge design for manufacturing, professional involvement, material selection, and standardization are provided in order to help scientists from the laboratory to bring their innovations into pre-clinical, clinical, and mass production and improve the manufacturability of laboratory prototypes toward commercialization.     

Thiolene-based microfluidic flow cells for surface plasmon resonance imaging

Thiolene-based microfluidic devices have been coupled with surface plasmon resonance imaging (SPRI) to provide an integrated platform to study interfacial interactions in both aqueous and organic solutions. In this work, we develop a photolithographic method that interfaces commercially available thiolene resin to gold and glass substrates to generate microfluidic channels with excellent adhesion that leave the underlying sensor surface free from contamination and readily available for surface modification through self-assembly. These devices can sustain high flow rates and have excellent solvent compatibility even with several organic solvents. To demonstrate the versatility of these devices, we have conducted nanomolar detection of streptavidin-biotin interactions using in situ SPRI.     

基于DEA窗口模型的中国碳减排技术研发效率评估

通过评价我国碳减排技术研发效率,探索促进二氧化碳减排的可行技术路径.基于不同的技术减排机理,将碳减排技术分为能源生产技术和能源利用技术,并利用DEA窗口模型对2005-2017年的碳减排技术研发效率进行了评估.结果发现,(1)研究期内,能源生产技术研发效率总体上没有取得进步,基本上维持在0.77左右,能源利用技术的研发...     

Vimentin networks at tunable ion-concentration in microfluidic drops

The structure and function of biological systems, for example, cells and proteins, depend strongly on their chemical environment. To investigate such dependence, we design a polydimethylsiloxane-based microfluidic device to encapsulate biological systems in picoliter-sized drops. The content of each individual drop is tuned in a defined manner. As a key feature of our method, the individual chemical composition is determined and related to the drop content. In our case, the drop content is imaged using microscopy methods, while the drops are immobilized to allow for long-time studies. As an application of our device, we study the influence of divalent ions on vimentin intermediate filament networks in a quantitative way by tuning the magnesium concentration from drop to drop. This way we are able to directly image the effect of magnesium on the fluorescently tagged protein in a few hundreds of drops. Our study shows that with increasing magnesium concentration in the drops, the compaction of the networks becomes more pronounced. The degree of compaction is characterized by different morphologies; freely fluctuating networks are observed at comparatively low magnesium concentrations of 5–10 mM, while with increasing magnesium concentration reaching 16 mM they develop into fully aggregated networks. Our approach demonstrates how a systematic study of interactions in biological systems can benefit from the exceptional controllability of microfluidic methods.     

Three-phase slug flow in microchips can provide beneficial reaction conditions for enzyme liquid-liquid reactions

Here, we introduce a solution to low stability of a two-phase slug flow with a chemical reaction occurring at the phase interface in a microfluidic reactor where substantial merging of individual reacting slugs results in the loss of uniformity of the flow. We create a three-phase slug flow by introducing a third fluid phase into the originally two-phase liquid-liquid slug flow, which generates small two-phase liquid slugs separated by gas phase. Introduction of the third phase into our system efficiently prevents merging of slugs and provides beneficial reaction conditions, such as uniform flow pattern along the whole reaction capillary, interfacial area with good reproducibility, and intensive water-oil interface renewal. We tested the three-phase flow on an enzyme hydrolysis of soybean oil and compared the reaction conversion with those from unstable two-phase slug flows. We experimentally confirmed that the three-phase slug flow arrangement provides conversions and pressure drops comparable or even better with two-phase liquid-liquid arrangements.     

我国科技服务业与体制改革

通过对新中国成立70年来我国经济体制与科技体制改革过程的梳理,分析每个改革阶段体制的变化对科技服务业的制约、激励和双重影响。研究结果表明：（1）新中国成立初期集中统一的计划体制阻碍科技服务业的产生,市场化程度低、科技资源配置不合理与科技成果转化限制为制约因素;（2）随着改革的不断深化,基本体制保障、技术商品化的合法性、市场化程度的提高、科技成果产业化等因素激励科技服务业快速发展;（3）两种体制改革对科技服务业的人力要素、服务平台以及服务生态带来双重影响。并提出相关政策建议：持续深化体制改革,促进科技服务最大程度市场化,逐步完善科技服务生态以及提升科技服务组织专业能力与盈利能力。     

高科技企业的国际合作经验与启示——基于航空发动机产业的分析

目前有关高科技产业的研究，从“技术演进”的视角切入的较多，从“组织发展”尤其是“国际合作”视角出发的更少。鉴于此，本文从企业国际合作的视角出发，选取高科技产业中具有代表性的航空发动机产业，挖掘、梳理并详析英国、法国、美国、日本、德国等在航空发动机产业发展过程中的国际市场现状、国际合作方式、合作经验及教训、技术学习、军事安全、风险规避等。分析研究认为：航空发动机市场“寡头俱乐部”特征显著；对于研发周期长、研发风险高、科技含量高、军民融合的高科技产业来说，与世界“巨头”企业的合作，有利于促进技术学习和行业地位提升；为避免掉入“合作陷阱”，需根据企业的技术能力和资金实力选择最佳合作方式。     

Ultraviolet-assisted microfluidic generation of ferroelectric composite particles

We report on the feasible fabrication of microfluidic devices for ferroelectric polymers'' synthesis in a rapid and stable fashion. Utilizing micro-mixing and flow-focusing in microchannels, poly(vinylidene fluoride-trifluoroethylene) and copper phthalocyanine are uniformly dispersed in one hydrogel particle, which are then demonstrated to immediate and complete on-chip steady polymerization by moderate ultraviolet treatment. The advantage of our droplet-based microfluidic devices is generating versatile particles from simple spheres to disks or rods, and the lengths of particles can be precisely tuned from 30 to 400 μm through adjusting the flow rates of both disperse and oil phases. In addition, this mixed technique allows for the continuous production of dielectric microparticles with controlled dielectric properties between 10 and 160. Such a microfluidic device offers a flexible platform for multiferroic applications.     

基于专利分析的我国新能源汽车生产企业技术竞争力研究

新能源汽车是我国汽车工业发展的重点领域，目前有大量汽车企业在国家政策的支持下进行产业布局、技术创新和产品生产。新能源汽车企业的技术竞争力可以分为技术综合竞争力和技术创新竞争力。专利分析是研究企业技术竞争力的优良方法。通过专利分析可以得知，当前我国新能源汽车技术创新已经进入稳定期。我国新能源汽车企业技术竞争力处于两极分化状态，生产企业开始出现技术创新型企业和技术跟随型企业两个主类型。     

All-aqueous multiphase microfluidics

Immiscible aqueous phases, formed by dissolving incompatible solutes in water, have been used in green chemical synthesis, molecular extraction and mimicking of cellular cytoplasm. Recently, a microfluidic approach has been introduced to generate all-aqueous emulsions and jets based on these immiscible aqueous phases; due to their biocompatibility, these all-aqueous structures have shown great promises as templates for fabricating biomaterials. The physico-chemical nature of interfaces between two immiscible aqueous phases leads to unique interfacial properties, such as an ultra-low interfacial tension. Strategies to manipulate components and direct their assembly at these interfaces needs to be explored. In this paper, we review progress on the topic over the past few years, with a focus on the fabrication and stabilization of all-aqueous structures in a multiphase microfluidic platform. We also discuss future efforts needed from the perspectives of fluidic physics, materials engineering, and biology for fulfilling potential applications ranging from materials fabrication to biomedical engineering.     

基于三阶段DEA与Malmquist指数分解的中国高技术产业全要素生产率研究

中国高技术产业全要素生产率（TFP）的提升为经济的可持续发展提供了重要支持。以中国30个省市为研究目标,采用三阶段DEA模型和Malmquist生产率指数对“十一五”至“十三五”期间各地区高技术产业TFP进行了静态和动态研究。研究发现：在剥离了外部环境因素和随机扰动因素后,综合效率和规模效率被高估,纯技术效率被低估,而规模效率偏低则是制约我国高技术产业TFP提升的主要原因。通过Malmquist指数及其分解可知,我国高技术产业技术效率改进由纯技术效率占据主导,但技术进步迟缓依旧是扼制我国高技术产业TFP提升的瓶颈。因此,持续扩大产业规模,保持研发投入和技术创新是推动我国高技术产业长远发展的重要途径。     

Finite element simulations of hydrodynamic trapping in microfluidic particle-trap array systems

Computational fluid dynamic (CFD) simulation is a powerful tool in the design and implementation of microfluidic systems, especially for systems that involve hydrodynamic behavior of objects such as functionalized microspheres, biological cells, or biopolymers in complex structures. In this work, we investigate hydrodynamic trapping of microspheres in a novel microfluidic particle-trap array device by finite element simulations. The accuracy of the time-dependent simulation of a microsphere''s motion towards the traps is validated by our experimental results. Based on the simulation, we study the fluid velocity field, pressure field, and force and stress on the microsphere in the device. We further explore the trap array''s geometric parameters and critical fluid velocity, which affect the microsphere''s hydrodynamic trapping. The information is valuable for designing microfluidic devices and guiding experimental operation. Besides, we provide guidelines on the simulation set-up and release an openly available implementation of our simulation in one of the popular FEM softwares, COMSOL Multiphysics. Researchers may tailor the model to simulate similar microfluidic systems that may accommodate a variety of structured particles. Therefore, the simulation will be of particular interest to biomedical research involving cell or bead transport and migration, blood flow within microvessels, and drug delivery.     

Making quantitative biomicrofluidics from microbore tubing and 3D-printed adapters

Microfluidic technology has tremendously facilitated the development of in vitro cell cultures and studies. Conventionally, microfluidic devices are fabricated with extensive facilities by well-trained researchers, which hinder the widespread adoption of the technology for broader applications. Enlightened by the fact that low-cost microbore tubing is a natural microfluidic channel, we developed a series of adaptors in a toolkit that can twine, connect, organize, and configure the tubing to produce functional microfluidic units. Three subsets of the toolkit were thoroughly developed: the tubing and scoring tools, the flow adaptors, and the 3D cell culture suite. To demonstrate the usefulness and versatility of the toolkit, we assembled a microfluidic device and successfully applied it for 3D macrophage cultures, flow-based stimulation, and automated near real-time quantitation with new knowledge generated. Overall, we present a new technology that allows simple, fast, and robust assembly of customizable and scalable microfluidic devices with minimal facilities, which is broadly applicable to research that needs or could be enhanced by microfluidics.     

构建我国第三代农机的创新体系

农业机械化和农业装备智能化是提高农业生产效率、转变农业发展方式、提高农村生产力的重要基础。70年来我国的农机工业从新中国成立时候的"一穷二白"发展到如今全球规模第一,取得了举世瞩目的成就。但是,我国的农机工业与世界农机强国相比依然存在着巨大的技术差距,"大而不强"成为现阶段的主要特征。如何实现农机工业"由大变强"的突破,根本路径是要建立适合中国农业生产作业方式的农机创新体系。文章以拖拉机作为农机行业的典型代表,回顾了我国农机工业体系的发展历程,并结合技术发展和土地制度的变革,对新中国的农机工业体系进行断代划分;着重阐述了未来第三代农机的创新体系建设目标和内容;探讨新的技术创新体系在黄河三角洲的应用与实践,介绍如何构建第三代农机的应用体系。最后,对全面构建自主可控的第三代农机创新体系提出规划建议。     

Three-dimensional fit-to-flow microfluidic assembly

Three-dimensional microfluidics holds great promise for large-scale integration of versatile, digitalized, and multitasking fluidic manipulations for biological and clinical applications. Successful translation of microfluidic toolsets to these purposes faces persistent technical challenges, such as reliable system-level packaging, device assembly and alignment, and world-to-chip interface. In this paper, we extended our previously established fit-to-flow (F2F) world-to-chip interconnection scheme to a complete system-level assembly strategy that addresses the three-dimensional microfluidic integration on demand. The modular F2F assembly consists of an interfacial chip, pluggable alignment modules, and multiple monolithic layers of microfluidic channels, through which convoluted three-dimensional microfluidic networks can be easily assembled and readily sealed with the capability of reconfigurable fluid flow. The monolithic laser-micromachining process simplifies and standardizes the fabrication of single-layer pluggable polymeric modules, which can be mass-produced as the renowned Lego^® building blocks. In addition, interlocking features are implemented between the plug-and-play microfluidic chips and the complementary alignment modules through the F2F assembly, resulting in facile and secure alignment with average misalignment of 45 μm. Importantly, the 3D multilayer microfluidic assembly has a comparable sealing performance as the conventional single-layer devices, providing an average leakage pressure of 38.47 kPa. The modular reconfigurability of the system-level reversible packaging concept has been demonstrated by re-routing microfluidic flows through interchangeable modular microchannel layers.     

Molecular diffusion analysis of dynamic blood flow and plasma separation driven by self-powered microfluidic devices

Integration of microfluidic devices with pressure-driven, self-powered fluid flow propulsion methods has provided a very effective solution for on-chip, droplet blood testing applications. However, precise understanding of the physical process governing fluid dynamics in polydimethylsiloxane (PDMS)-based microfluidic devices remains unclear. Here, we propose a pressure-driven diffusion model using Fick''s law and the ideal gas law, the results of which agree well with the experimental fluid dynamics observed in our vacuum pocket-assisted, self-powered microfluidic devices. Notably, this model enables us to precisely tune the flow rate by adjusting two geometrical parameters of the vacuum pocket. By linking the self-powered fluid flow propulsion method to the sedimentation, we also show that direct plasma separation from a drop of whole blood can be achieved using only a simple construction without the need for external power sources, connectors, or a complex operational procedure. Finally, the potential of the vacuum pocket, along with a removable vacuum battery to be integrated with non-PDMS microfluidic devices to drive and control the fluid flow, is demonstrated.     

Implementation of tetra-poly(ethylene glycol) hydrogel with high mechanical strength into microfluidic device technology

Hydrogels have several excellent characteristics suitable for biomedical use such as softness, biological inertness and solute permeability. Hence, integrating hydrogels into microfluidic devices is a promising approach for providing additional functions such as biocompatibility and porosity, to microfluidic devices. However, the poor mechanical strength of hydrogels has severely limited device design and fabrication. A tetra-poly(ethylene glycol) (tetra-PEG) hydrogel synthesized recently has high mechanical strength and is expected to overcome such a limitation. In this research, we have comprehensively studied the implementation of tetra-PEG gel into microfluidic device technology. First, the fabrication of tetra-PEG gel/PDMS hybrid microchannels was established by developing a simple and robust bonding technique. Second, some fundamental features of tetra-PEG gel/PDMS hybrid microchannels, particularly fluid flow and mass transfer, were studied. Finally, to demonstrate the unique application of tetra-PEG-gel-integrated microfluidic devices, the generation of patterned chemical modulation with the maximum concentration gradient: 10% per 20 μm in a hydrogel was performed. The techniques developed in this study are expected to provide fundamental and beneficial methods of developing various microfluidic devices for life science and biomedical applications.     

我国科技服务业发展效率测度及时空差异分析

通过运用DEA-Malmquist指数对我国2006-2016年省级科技服务业发展的技术效率以及全要素生产率进行测度,结果表明：科技服务业整体发展效率较低,已有生产要素投入潜力未能得到有效挖掘,处于规模不经济状态;科技服务业TFP以年均9.8%的速度增长,其中主要源动力来自技术进步变化,而技术效率变化对TFP增长的贡献较弱;生产率指数区域发展不均衡,高水平与较高水平区逐渐从东部地区向中西部地区扩散,地区间技术效率变化差异显著。要促使科技服务业效率提高,需要加大研发投入促进自主创新,完善制度环境加强管理创新,因地制宜缩小区域差异等。     

Microfluidic platform for isolating nucleic acid targets using sequence specific hybridization

The separation of target nucleic acid sequences from biological samples has emerged as a significant process in today''s diagnostics and detection strategies. In addition to the possible clinical applications, the fundamental understanding of target and sequence specific hybridization on surface modified magnetic beads is of high value. In this paper, we describe a novel microfluidic platform that utilizes a mobile magnetic field in static microfluidic channels, where single stranded DNA (ssDNA) molecules are isolated via nucleic acid hybridization. We first established efficient isolation of biotinylated capture probe (BP) using streptavidin-coated magnetic beads. Subsequently, we investigated the hybridization of target ssDNA with BP bound to beads and explained these hybridization kinetics using a dual-species kinetic model. The number of hybridized target ssDNA molecules was determined to be about 6.5 times less than that of BP on the bead surface, due to steric hindrance effects. The hybridization of target ssDNA with non-complementary BP bound to bead was also examined, and non-specific hybridization was found to be insignificant. Finally, we demonstrated highly efficient capture and isolation of target ssDNA in the presence of non-target ssDNA, where as low as 1% target ssDNA can be detected from mixture. The microfluidic method described in this paper is significantly relevant and is broadly applicable, especially towards point-of-care biological diagnostic platforms that require binding and separation of known target biomolecules, such as RNA, ssDNA, or protein.