Laboratory for Integrated Micro-Mechatronic Systems

The organization of cells into epithelium depends on cell interaction with both the extracellular matrix (ECM) and adjacent cells. The role of cell-cell adhesion in the regulation of epithelial topology is well-described. ECM is better known to promote cell migration and provide a structural scaffold for cell anchoring, but its contribution to multicellular morphogenesis is less well-understood. We developed a minimal model system to investigate how ECM affects the spatial organization of intercellular junctions. Fibronectin micropatterns were used to constrain the location of cell-ECM adhesion. We found that ECM affects the degree of stability of intercellular junction positioning and the magnitude of intra- and intercellular forces. Intercellular junctions were permanently displaced, and experienced large perpendicular tensional forces as long as they were positioned close to ECM. They remained stable solely in regions deprived of ECM, where they were submitted to lower tensional forces. The heterogeneity of the spatial organization of ECM induced anisotropic distribution of mechanical constraints in cells, which seemed to adapt their position to minimize both intra- and intercellular forces. These results uncover a morphogenetic role for ECM in the mechanical regulation of cells and intercellular junction positioning.

The fluidic channel in the flexible probe has three functions: (i) to inject chemicals into the tissues, (ii) to measure the neural activities from the tissues, and (iii) to improve the mechanical stiffness of the probe by filling the channel with a solid material. A 10-microm-thick microfluidic channel was embedded into the probe by using sacrificial photoresist patterns. Polyethylene glycol (PEG), which is solid at room temperature and dissolves when in contact with water, was used to fill the channel and increase the stiffness of the probe before insertion into the tissue. The impedance of the electrode inside the fluidic channel was around 100 kOmega at 1 kHz when the channel was filled with saline solution. We were able to insert the probe into a rat's brain and measure the neural signals with the electrode.

Living organisms perform and control complex behaviours by using webs of chemical reactions organized in precise networks. This powerful system concept, which is at the very core of biology, has recently become a new foundation for bioengineering. Remarkably, however, it is still extremely difficult to rationally create such network architectures in artificial, non-living and well-controlled settings. We introduce here a method for such a purpose, on the basis of standard DNA biochemistry. This approach is demonstrated by assembling de novo an efficient chemical oscillator: we encode the wiring of the corresponding network in the sequence of small DNA templates and obtain the predicted dynamics. Our results show that the rational cascading of standard elements opens the possibility to implement complex behaviours in vitro. Because of the simple and well-controlled environment, the corresponding chemical network is easily amenable to quantitative mathematical analysis. These synthetic systems may thus accelerate our understanding of the underlying principles of biological dynamic modules.

Almost 15 years have gone ever since the discovery of graphene as a single atom layer. Numerous papers have been published to demonstrate its high electron mobility, excellent thermal and mechanical as well as optical properties. We have recently seen more and more applications towards using graphene in commercial products. This paper is an attempt to review and summarize the current status of the research of the thermal properties of graphene and other 2D based materials including the manufacturing and characterization techniques and their applications, especially in electronics and power modules. It is obvious from the review that graphene has penetrated the market and gets more and more applications in commercial electronics thermal management context. In the paper, we also made a critical analysis of how mature the manufacturing processes are; what are the accuracies and challenges with the various characterization techniques and what are the remaining questions and issues left before we see further more applications in this exciting and fascinating field.

This paper presents an innovative high-frequency- based biosensor, which combines both microwave detection and microfluidic network for time-efficient and accurate biological analysis. It is composed of a coplanar waveguide with a microfluidic channel placed on top. With the help of an appropriate de-embedding technique and modeling of the measurements, the relative effective permittivity of human umbilical vein endothelial cells has been evaluated successfully. Furthermore, experiments have been performed with the sensor on various cell concentrations in suspension, which validates its use in bioengineering applications such as cell quantification and counting in solution. This sensor requires no direct contact or use of labels on the cells, contrary to other usual types of biosensors (optical, mechanical or dc/low-frequency-detection-based ones).

We report the fabrication of InAs/GaAs quantum dot solar cells (QDSCs) with enhanced photocurrent and no degradation in open circuit voltage (VOC) compared to a solar cell grown without QDs and composed solely of wetting layers. Notably, the achievement of such high VOC does not require electronic coupling. We report QDSCs with a light absorption range extended up to 1.3 μm and evidence a trade-off between VOC and QD ground-state energy. These results are of major significance to the design of high efficiency QDSCs.

A 3D flexible multichannel microprobe array was designed, fabricated and tested. Since each probe had several recording pads, the probe array could be used to measure neural activity at various depths in the brain. They were batch fabricated with interconnections, using a specific folding process to fold the planar probe structures. This flexible probe array was inserted into a rat's brain without fracturing and was successfully used to measure neural signals.

The world communicates to our senses of vision, hearing, and touch in the language of waves, because light, sound, and even heat essentially consist of microscopic vibrations of different media. The wave nature of light and sound has been extensively investigated over the past century and is now widely used in modern technology. However, the wave nature of heat has been the subject of mostly theoretical studies because its experimental demonstration, let alone practical use, remains challenging due to its extremely short wavelengths. We show a possibility to use the wave nature of heat for thermal conductivity tuning via spatial short-range order in phononic crystal nanostructures. Our experimental and theoretical results suggest that interference of thermal phonons occurs in strictly periodic nanostructures and slows the propagation of heat. This finding expands the methodology of heat transfer engineering to the wave nature of heat.

This paper describes a methodology for the rapid and highly selective detection of cocaine using a membrane protein channel combined with a DNA aptamer. The DNA aptamer recognizes the cocaine molecule with high selectivity. We successfully detected a low concentration of cocaine (300 ng/mL, the drug test cutoff limit) within 60 s using a biological nanopore embedded in a microchip.

The self-assembling of three-dimensional (3-D) MEMS from polysilicon surface micromachined part is very attractive. To avoid risky external manipulation, the practical use of integrated actuator to perform the assembling task is required. To that goal, this paper presents detailed characteristics of the electrostatic surface micromachined scratch drive actuator (SDA). First, from numerous SDA tests, it is shown that this actuator is able to produce a threshold force of 30 /spl mu/N, with a yield above 60%. With polysilicon devices consisting of SDA mechanically linked to buckling beam, a horizontal force of 63 mN has been demonstrated with /spl plusmn/112 V pulse, and up to 100 /spl mu/N can be obtained with higher voltage. With buckling beams, displacements up to 150 /spl mu/m have been obtained in the vertical direction. The generation of vertical force of 10 /spl mu/N was confirmed with a 100 /spl mu/m displacement producing 1 nJ work in the vertical direction. Finally, SDA overcomes the usual sticking of surface machined polysilicon by producing enough vertical force to completely release wide polysilicon plate (500 /spl mu/m/spl times/50 /spl mu/m) without external manipulation. The above characteristic, both in terms of structure releasing and vertical/horizontal forces and displacements provides the SDA with the capability of self-assembling complex 3-D polysilicon part, opening new integration capabilities and new application field of MEMS.

Fluorescent thermometry presents a cheap and efficient alternative for small-scale thermal characterization. The use of dried Rhodamine B (see image) as a probe for surface-temperature mapping is demonstrated. The approach is applied in the evaluation of the temperature distribution along resistively heated micro- and nanowires. The temperature is found to be highly uniform along metal wires on silicon.

Unlike classical heat diffusion at macroscale, nanoscale heat conduction can occur without energy dissipation because phonons can ballistically travel in straight lines for hundreds of nanometres. Nevertheless, despite recent experimental evidence of such ballistic phonon transport, control over its directionality, and thus its practical use, remains a challenge, as the directions of individual phonons are chaotic. Here, we show a method to control the directionality of ballistic phonon transport using silicon membranes with arrays of holes. First, we demonstrate that the arrays of holes form fluxes of phonons oriented in the same direction. Next, we use these nanostructures as directional sources of ballistic phonons and couple the emitted phonons into nanowires. Finally, we introduce thermal lens nanostructures, in which the emitted phonons converge at the focal point, thus focusing heat into a spot of a few hundred nanometres. These results motivate the concept of ray-like heat manipulations at the nanoscale.

Biological organisms use intricate networks of chemical reactions to control molecular processes and spatiotemporal organization. In turn, these living systems are embedded in self-organized structures of larger scales, for example, ecosystems. Synthetic in vitro efforts have reproduced the architectures and behaviors of simple cellular circuits. However, because all these systems share the same dynamic foundations, a generalized molecular programming strategy should also support complex collective behaviors, as seen, for example, in animal populations. We report here the bottom-up assembly of chemical systems that reproduce in vitro the specific dynamics of ecological communities. We experimentally observed unprecedented molecular behaviors, including predator-prey oscillations, competition-induced chaos, and symbiotic synchronization. These synthetic systems are tailored through a novel, compact, and versatile design strategy, leveraging the programmability of DNA interactions under the precise control of enzymatic catalysis. Such self-organizing assemblies will foster a better appreciation of the molecular origins of biological complexity and may also serve to orchestrate complex collective operations of molecular agents in technological applications.

Reaction networks displaying bistability provide a chemical mechanism for long-term memory storage in cells, as exemplified by many epigenetic switches. These biological systems are not only bistable but switchable, in the sense that they can be flipped from one state to the other by application of specific molecular stimuli. We have reproduced such functions through the rational assembly of dynamic reaction networks based on basic DNA biochemistry. Rather than rewiring genetic systems as synthetic biology does in vivo, our strategy consists of building simplified dynamic analogs in vitro, in an artificial, well-controlled milieu. We report successively a bistable system, a two-input switchable memory element, and a single-input push-push memory circuit. These results suggest that it is possible to build complex time-responsive molecular circuits by following a modular approach to the design of dynamic in vitro behaviors. Our approach thus provides an unmatched opportunity to study topology/function relationships within dynamic reaction networks.

Gently down the stream: A microfluidic technique uses a continuous fluid stream to generate monodisperse unilamellar phospholipid vesicles from a single bilayer (see picture). Since the vesicles are robust and efficiently encapsulate high concentrations of various molecules, they are useful as delivery vehicles and as model cellular systems.

We present a micromechanical device designed to be used as a non-volatile mechanical memory. The structure is composed of a suspended slender nanowire (width: 100 nm, thickness: 430 nm, length: 8 to 30 µm) clamped at both ends. Electrodes are placed on each side of the nanowire to (1) actuate the structure during the data writing and erasing mode and (2) determine its position by measuring the capacitive bridge in the reading mode. The structure is patterned by electron beam lithography on a pre-stressed thermally grown silicon dioxide layer. When later released by plasma etching, the stressed material relaxes and the beam buckles by itself to a position of lower energy. These symmetric bistable Euler beams exhibit two stable deformed. This paper presents the microfabrication process and analysis of the static buckling of nanowires. Snapping of these nanowires from one stable position to another by mechanical or electrical means will also be discussed.

A carbon-nanotube architecture based on ceramic microparticles allows for strikingly reducing the number of thermal contact resistances between carbon nanotubes (CNT). The result is a 130% enhancement of the thermal conductivity of the nanocomposites at a remarkably low CNT mass fraction of 0.15 wt%.

In this work, the friction anisotropy of hexagonal MoS(2) (a well-known lamellar compound) was theoretically investigated. A molecular dynamics method was adopted to study the dynamical friction of two-layered MoS(2) sheets at atomistic level. Rotational disorder was depicted by rotating one layer and was changed from 0° to 60°, in 5° intervals. The superimposed structures with misfit angle of 0° and 60° are commensurate, and others are incommensurate. Friction dynamics was simulated by applying an external pressure and a sliding speed to the model. During friction simulation, the incommensurate structures showed extremely low friction due to cancellation of the atomic force in the sliding direction, leading to smooth motion. On the other hand, in commensurate situations, all the atoms in the sliding part were overcoming the atoms in counterpart at the same time while the atomic forces were acted in the same direction, leading to 100 times larger friction than incommensurate situation. Thus, lubrication by MoS(2) strongly depended on its interlayer contacts in the atomic scale. According to part I of this paper [Onodera, T., et al. J. Phys. Chem. B 2009, 113, 16526-16536], interlayer sliding was source of friction reduction by MoS(2) and was originally derived by its material property (interlayer Coulombic interaction). In addition to this interlayer sliding, the rotational disorder was also important to achieve low friction state.

We report the experimental observation of traveling concentration waves and spirals in a chemical reaction network built from the bottom up. The mechanism of the network is an oscillator of the predator-prey type, and this is the first time that predator-prey waves have been observed in the laboratory. The molecular encoding of the nonequilibrium behavior relies on small DNA oligonucleotides that enforce the network connectivity and three purified enzymes that control the reactivity. Wave velocities in the range 80-400 μm min(-1) were measured. A reaction-diffusion model in quantitative agreement with the experiments is proposed. Three fundamental parameters are easy to tune in nucleic acid reaction networks: the topology of the network, the rate constants of the individual reactions, and the diffusion coefficients of the individual species. For this reason, we expect such networks to bring unprecedented opportunities for assaying the principles of spatiotemporal order formation in chemistry.

Angiogenesis is the formation of new capillaries from pre-existing blood vessels and participates in proper vasculature development. In pathological conditions such as cancer, abnormal angiogenesis takes place. Angiogenesis is primarily carried out by endothelial cells, the innermost layer of blood vessels. The vascular endothelial growth factor-A (VEGF-A) and its receptor-2 (VEGFR-2) trigger most of the mechanisms activating and regulating angiogenesis, and have been the targets for the development of drugs. However, most experimental assays assessing angiogenesis rely on animal models. We report an in vitro model using a microvessel-on-a-chip. It mimics an effective endothelial sprouting angiogenesis event triggered from an initial microvessel using a single angiogenic factor, VEGF-A. The angiogenic sprouting in this model is depends on the Notch signaling, as observed in vivo. This model enables the study of anti-angiogenic drugs which target a specific factor/receptor pathway, as demonstrated by the use of the clinically approved sorafenib and sunitinib for targeting the VEGF-A/VEGFR-2 pathway. Furthermore, this model allows testing simultaneously angiogenesis and permeability. It demonstrates that sorafenib impairs the endothelial barrier function, while sunitinib does not. Such in vitro human model provides a significant complimentary approach to animal models for the development of effective therapies.