Microfluidic memory and control devices

We demonstrate microscopic fluidic control and memory elements through the use of an aqueous viscoelastic polymer solution as a working fluid. By exploiting the fluid's non-Newtonian rheological properties, we were able to demonstrate both a flux stabilizer and a bistable flip-flop memory. These circuit elements are analogous to their solid-state electronic counterparts and could be used as components of control systems for integrated microfluidic devices. Such miniaturized fluidic circuits are insensitive to electromagnetic interference and may also find medical applications for implanted drug-delivery devices.     

Directed assembly of one-dimensional nanostructures into functional networks

One-dimensional nanostructures, such as nanowires and nanotubes, represent the smallest dimension for efficient transport of electrons and excitons and thus are ideal building blocks for hierarchical assembly of functional nanoscale electronic and photonic structures. We report an approach for the hierarchical assembly of one-dimensional nanostructures into well-defined functional networks. We show that nanowires can be assembled into parallel arrays with control of the average separation and, by combining fluidic alignment with surface-patterning techniques, that it is also possible to control periodicity. In addition, complex crossed nanowire arrays can be prepared with layer-by-layer assembly with different flow directions for sequential steps. Transport studies show that the crossed nanowire arrays form electrically conducting networks, with individually addressable device function at each cross point.     

Programmed adsorption and release of proteins in a microfluidic device

A microfluidic device has been developed that can adsorb proteins from solution, hold them with negligible denaturation, and release them on command. The active element in the device is a 4-nanometer-thick polymer film that can be thermally switched between an antifouling hydrophilic state and a protein-adsorbing state that is more hydrophobic. This active polymer has been integrated into a microfluidic hot plate that can be programmed to adsorb and desorb protein monolayers in less than 1 second. The rapid response characteristics of the device can be manipulated for proteomic functions, including preconcentration and separation of soluble proteins on an integrated fluidics chip.     

Electrochemical principles for active control of liquids on submillimeter scales

Electrochemical methods were combined with redox-active surfactants to actively control the motions and positions of aqueous and organic liquids on millimeter and smaller scales. Surfactant species generated at one electrode and consumed at another were used to manipulate the magnitude and direction of spatial gradients in surface tension and guide droplets of organic liquids through simple fluidic networks. Solid microparticles could be transported across unconfined surfaces. Electrochemical control of the position of surface-active species within aqueous films of liquid supported on homogeneous surfaces was used to direct these films into periodic arrays of droplets with deterministic shapes and sizes.     

Flexible control of mutual inhibition: a neural model of two-interval discrimination

Networks adapt to environmental demands by switching between distinct dynamical behaviors. The activity of frontal-lobe neurons during two-interval discrimination tasks is an example of these adaptable dynamics. Subjects first perceive a stimulus, then hold it in working memory, and finally make a decision by comparing it with a second stimulus. We present a simple mutual-inhibition network model that captures all three task phases within a single framework. The model integrates both working memory and decision making because its dynamical properties are easily controlled without changing its connectivity. Mutual inhibition between nonlinear units is a useful design motif for networks that must display multiple behaviors.     

A mobile lab-on-a-chip device for on-site soil nutrient analysis

In this paper, a mobile sensor for on-site analysis of soil sample extracts is presented. As a versatile tool for scanning ion concentrations in liquid samples, it especially allows the analysis of NO₃, NH₄, K and PO₄. The sensor mainly consists of a microfluidic chip in which the sample ions are separated in an electric field (capillary electrophoresis) and the individual ion concentrations are detected by a conductivity measurement. For the adaption of the device to field conditions, two major concerns were addressed. Firstly, nano-porous material was used as a barrier between the sample container and the analysis channel of the microfluidic chip. This prevents pressure driven leakage of the sample into the chip due to non-horizontal orientation of the device. Secondly, a new method for the injection of the sample into the chip was used. It reduces the number of fluidic connections between chip and operation device to three instead of the commonly used four connections. The sensor performance was tested on multi-ion solutions with calibration series for NO₃, NH₄, K and PO₄. For the first on-site test, a quick soil nutrient extraction procedure with water was used. The sensor data was compared to standard laboratory results. The potential of the sensor for soil nutrient analysis is discussed together with required improvements of the sensor performance and of the nutrient extraction procedure.     

单粒微米珠-单根DNA复合物的微流控分离初步研究

定点单分子DNA芯片有重要用途,但其制备极具挑战性,用光镊、磁镊及原子力显微镜等方法分离单分子DNA,为此建立的平台设备昂贵,且分离效率太低,难以满足实验要求。本研究采用微流控技术,在层流基础上电泳分离与富集单粒微米珠-单根DNA的复合物,旨在为基于微米孔阵列承载这种复合物的定点单分子DNA芯片的制备提供样本。此技术的完善将为单分子DNA芯片制作开辟新的途径。     

Giant piezoelectricity on Si for hyperactive MEMS

Microelectromechanical systems (MEMS) incorporating active piezoelectric layers offer integrated actuation, sensing, and transduction. The broad implementation of such active MEMS has long been constrained by the inability to integrate materials with giant piezoelectric response, such as Pb(Mg(1/3)Nb(2/3))O(3)-PbTiO(3) (PMN-PT). We synthesized high-quality PMN-PT epitaxial thin films on vicinal (001) Si wafers with the use of an epitaxial (001) SrTiO(3) template layer with superior piezoelectric coefficients (e(31,f) = -27 ± 3 coulombs per square meter) and figures of merit for piezoelectric energy-harvesting systems. We have incorporated these heterostructures into microcantilevers that are actuated with extremely low drive voltage due to thin-film piezoelectric properties that rival bulk PMN-PT single crystals. These epitaxial heterostructures exhibit very large electromechanical coupling for ultrasound medical imaging, microfluidic control, mechanical sensing, and energy harvesting.     

Monolithic microfabricated valves and pumps by multilayer soft lithography

Soft lithography is an alternative to silicon-based micromachining that uses replica molding of nontraditional elastomeric materials to fabricate stamps and microfluidic channels. We describe here an extension to the soft lithography paradigm, multilayer soft lithography, with which devices consisting of multiple layers may be fabricated from soft materials. We used this technique to build active microfluidic systems containing on-off valves, switching valves, and pumps entirely out of elastomer. The softness of these materials allows the device areas to be reduced by more than two orders of magnitude compared with silicon-based devices. The other advantages of soft lithography, such as rapid prototyping, ease of fabrication, and biocompatibility, are retained.     

Early tagging of cortical networks is required for the formation of enduring associative memory

Although formation and stabilization of long-lasting associative memories are thought to require time-dependent coordinated hippocampal-cortical interactions, the underlying mechanisms remain unclear. Here, we present evidence that neurons in the rat cortex must undergo a "tagging process" upon encoding to ensure the progressive hippocampal-driven rewiring of cortical networks that support remote memory storage. This process was AMPA- and N-methyl-D-aspartate receptor-dependent, information-specific, and capable of modulating remote memory persistence by affecting the temporal dynamics of hippocampal-cortical interactions. Post-learning reinforcement of the tagging process via time-limited epigenetic modifications resulted in improved remote memory retrieval. Thus, early tagging of cortical networks is a crucial neurobiological process for remote memory formation whose functional properties fit the requirements imposed by the extended time scale of systems-level memory consolidation.     

A molecular shift register based on electron transfer

An electronic shift-register memory at the molecular level is described. The memory elements are based on a chain of electron-transfer molecules and the information is shifted by photoinduced electron-transfer reactions. This device integrates designed electronic molecules onto a very large scale integrated (silicon microelectronic) substrate, providing an example of a "molecular electronic device" that could actually be made. The design requirements for such a device and possible synthetic strategies are discussed. Devices along these lines should have lower energy usage and enhanced storage density.     

From micro- to nanofabrication with soft materials

Soft materials are finding applications in areas ranging from microfluidic device technology to nanofabrication. We review recent work in these areas, discuss the motivation for device fabrication with soft materials, and describe applications of soft materials. In particular, we discuss active microfluidic devices for cell sorting and biochemical assays, replication-molded optics with subdiffraction limit features, and nanometer-scale resonators and wires formed from single-molecule DNA templates as examples of how the special properties of soft materials address outstanding problems in device fabrication.     

基于微流控芯片电泳的番茄黄化曲叶病毒快速检测

【目的】探索微流控芯片电泳方法在PCR产物检测方面的效果,并建立针对番茄黄化曲叶病毒（Tomato yellow leaf curl virus,TYLCV）的微流控芯片电泳检测方法,弥补琼脂糖凝胶电泳方法在试剂消耗、所用时间、安全性方面的缺陷。【方法】通过对TYLCV的基因组进行分析后,在该基因组中相对稳定的位置设计引物,同时兼顾引用已被研究者研究过的引物,对这些选择的引物进行特异性、稳定性、灵敏度等方面的验证,筛选出用于后续试验的引物。选择DNA标准物φX174/BsuR I(Hae Ⅲ) marker,分别进行琼脂糖凝胶电泳和微流控芯片电泳,对二者在耗材、耗时和灵敏度方面进行比较,确定微流控芯片电泳在核酸检测方面的应用价值。利用筛选出的其中1对引物对番茄叶片的实际样品进行PCR扩增,随后通过微流控芯片电泳对其进行检测,以此探讨微流控芯片电泳在病毒检测方面的检测效果。【结果】共筛选出14对TYLCV备用引物,其中2对引自文献,12对为本文设计,每对引物均可满足微流控芯片检测要求。选择其中1对引物TYLCV-T作为随后的研究对象。利用琼脂糖凝胶电泳和微流控芯片电泳对DNA标准物检测,结果表明微流控芯片电泳在耗时方面不足琼脂糖凝胶电泳的1/10,约为13 min,试剂消耗为琼脂糖凝胶电泳的1/8,检测灵敏度方面至少比琼脂糖凝胶电泳高103倍,根据DNA标准物原液浓度计算可知,微流控芯片电泳至少可准确检测到浓度为5×10-6 μg?μL-1的核酸样品。利用微流控芯片电泳对TYLCV-T扩增的TYLCV PCR产物进行检测,将检测峰值图与DNA标准物的峰值图时间比较,就可判断出产物峰的大小范围。【结论】筛选出的关于TYLCV的备用引物可作为进一步研究微流控芯片技术在该病毒检测方面的基础;通过将琼脂糖凝胶电泳和微流控芯片电泳进行比较,确立了后者在核酸检测方面的应用价值;通过微流控芯片电泳对TYLCV PCR产物的检测,建立了基于微流控芯片电泳的TYLCV快速检测方法,为TYLCV的快速检测提供新的技术支持。     

Implementing the quantum von Neumann architecture with superconducting circuits

The von Neumann architecture for a classical computer comprises a central processing unit and a memory holding instructions and data. We demonstrate a quantum central processing unit that exchanges data with a quantum random-access memory integrated on a chip, with instructions stored on a classical computer. We test our quantum machine by executing codes that involve seven quantum elements: Two superconducting qubits coupled through a quantum bus, two quantum memories, and two zeroing registers. Two vital algorithms for quantum computing are demonstrated, the quantum Fourier transform, with 66% process fidelity, and the three-qubit Toffoli-class OR phase gate, with 98% phase fidelity. Our results, in combination especially with longer qubit coherence, illustrate a potentially viable approach to factoring numbers and implementing simple quantum error correction codes.     

Microprocessors: from desktops to supercomputers

Continuing improvements in integrated circuit technology and computer architecture have driven microprocessors to performance levels that rival those of supercomputers-at a fraction of the price. The use of sophisticated memory hierarchies enables microprocessor-based machines to have very large memories built from commodity dynamic random access memory while retaining the high bandwidth and low access time needed in a high-performance machine. Parallel processors composed of these high-performance microprocessors are becoming the supercomputing technology of choice for scientific and engineering applications. The challenges for these new supercomputers have been in developing multiprocessor architectures that are easy to program and that deliver high performance without extraordinary programming efforts by users. Recent progress in multiprocessor architecture has led to ways to meet these challenges.     

Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics

Microreactor technology has shown potential for optimizing synthetic efficiency, particularly in preparing sensitive compounds. We achieved the synthesis of an [(18)F]fluoride-radiolabeled molecular imaging probe, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), in an integrated microfluidic device. Five sequential processes-[18F]fluoride concentration, water evaporation, radiofluorination, solvent exchange, and hydrolytic deprotection-proceeded with high radio-chemical yield and purity and with shorter synthesis time relative to conventional automated synthesis. Multiple doses of [18F]FDG for positron emission tomography imaging studies in mice were prepared. These results, which constitute a proof of principle for automated multistep syntheses at the nanogram to microgram scale, could be generalized to a range of radiolabeled substrates.     

Long-term monitoring of bacteria undergoing programmed population control in a microchemostat

Using an active approach to preventing biofilm formation, we implemented a microfluidic bioreactor that enables long-term culture and monitoring of extremely small populations of bacteria with single-cell resolution. We used this device to observe the dynamics of Escherichia coli carrying a synthetic "population control" circuit that regulates cell density through a feedback mechanism based on quorum sensing. The microfluidic bioreactor enabled long-term monitoring of unnatural behavior programmed by the synthetic circuit, which included sustained oscillations in cell density and associated morphological changes, over hundreds of hours.     

Counting low-copy number proteins in a single cell

We have designed a microfluidic device in which we can manipulate, lyse, label, separate, and quantify the protein contents of a single cell using single-molecule fluorescence counting. Generic labeling of proteins is achieved through fluorescent-antibody binding. The use of cylindrical optics enables high-efficiency (approximately 60%) counting of molecules in micrometer-sized channels. We used this microfluidic device to quantify beta2 adrenergic receptors expressed in insect cells (SF9). We also analyzed phycobiliprotein contents in individual cyanobacterial cells (Synechococcus sp. PCC 7942) and observed marked differences in the levels of specific complexes in cell populations that were grown under nitrogen-depleted conditions.