J. Samitier

Effects of artificial micro- and nano-structured surfaces on cell behaviour.

Substrate topography, independently of substrate chemistry, has been reported to have significant effects on cell behaviour. Based on the use of fabrication techniques developed by the silicon microtechnology industry, numerous studies can now be found in the literature analyzing cell behaviour as to various micro- and nano-features such as lines, wells, holes and more. Most of these works have been found to relate the micro- and nano-sized topographical features with cell orientation, migration, morphology and proliferation. In recent papers, even the influence of substrate nanotopography on cell gene expression and differentiation has been pointed out. However, despite the large number of papers published on this topic, significant general trends in cell behaviour are difficult to establish due to differences in cell type, substrate material, feature aspect-ratio, feature geometry and parameters measured. This paper intends to compile and review the relevant existing information on the behaviour of cells on micro- and nano-structured artificial substrates and analyze possible general behavioural trends.

Improvement of the quality factor of RF integrated inductors by layout optimization

A systematic method to improve the quality (Q) factor of RF integrated inductors is presented in this paper. The proposed method is based on the layout optimization to minimize the series resistance of the inductor coil, taking into account both ohmic losses, due to conduction currents, and magnetically induced losses, due to eddy currents. The technique is particularly useful when applied to inductors in which the fabrication process includes integration substrate removal. However, it is also applicable to inductors on low-loss substrates. The method optimizes the width of the metal strip for each turn of the inductor coil, leading to a variable strip-width layout. The optimization procedure has been successfully applied to the design of square spiral inductors in a silicon-based multichip-module technology, complemented with silicon micromachining postprocessing. The obtained experimental results corroborate the validity of the proposed method. A Q factor of about 17 have been obtained for a 35-nH inductor at 1.5 GHz, with Q values higher than 40 predicted for a 20-nH inductor working at 3.5 GHz. The latter is up to a 60% better than the best results for a single strip-width inductor working at the same frequency.

Micropatterning of single endothelial cell shape reveals a tight coupling between nuclear volume in G1 and proliferation.

Shape-dependent local differentials in cell proliferation are considered to be a major driving mechanism of structuring processes in vivo, such as embryogenesis, wound healing, and angiogenesis. However, the specific biophysical signaling by which changes in cell shape contribute to cell cycle regulation remains poorly understood. Here, we describe our study of the roles of nuclear volume and cytoskeletal mechanics in mediating shape control of proliferation in single endothelial cells. Micropatterned adhesive islands were used to independently control cell spreading and elongation. We show that, irrespective of elongation, nuclear volume and apparent chromatin decondensation of cells in G1 systematically increased with cell spreading and highly correlated with DNA synthesis (percent of cells in the S phase). In contrast, cell elongation dramatically affected the organization of the actin cytoskeleton, markedly reduced both cytoskeletal stiffness (measured dorsally with atomic force microscopy) and contractility (measured ventrally with traction microscopy), and increased mechanical anisotropy, without affecting either DNA synthesis or nuclear volume. Our results reveal that the nuclear volume in G1 is predictive of the proliferative status of single endothelial cells within a population, whereas cell stiffness and contractility are not. These findings show that the effects of cell mechanics in shape control of proliferation are far more complex than a linear or straightforward relationship. Our data are consistent with a mechanism by which spreading of cells in G1 partially enhances proliferation by inducing nuclear swelling and decreasing chromatin condensation, thereby rendering DNA more accessible to the replication machinery.

Highly sensitive detection of pathogen Escherichia coli O157:H7 by electrochemical impedance spectroscopy

The presence of enterohemorrhagic Escherichia coli bacteria in food can cause serious foodborne disease outbreaks. Early detection and identification of these pathogens is extremely important for public health and safety. Here we present a highly sensitive label-free immunosensor for the detection of pathogenic E. coli O157:H7. Anti-E. coli antibodies were covalently immobilised onto gold electrodes via a self-assembled monolayer (SAM) of mercaptohexadecanoic acid and the pathogenic bacteria were detected by electrochemical impedance spectroscopy (EIS). Surface Plasmon Resonance (SPR) was used to monitor the antibody immobilisation protocol and antibody patterned surfaces were used to demonstrate the specificity of the antibody coated surfaces against the pathogenic bacteria. The immunosensor showed a very low limit of detection (2CFU/mL) and a large linear range (3 × 10-3 × 10(4)CFU/mL). Finally, the selectivity of the sensor was demonstrated and no significant adsorption of Salmonella typhimurium was observed.

Integrated electrochemical DNA biosensors for lab-on-a-chip devices

Analytical devices able to perform accurate and fast automatic DNA detection or sequencing procedures have many potential benefits in the biomedical and environmental fields. The conversion of biological or biochemical responses into quantifiable optical, mechanical or electronic signals is achieved by means of biosensors. Most of these transducing elements can be miniaturized and incorporated into lab‐on‐a‐chip devices, also known as Micro Total Analysis Systems. The use of multiple DNA biosensors integrated in these miniaturized laboratories, which perform several analytical operations at the microscale, has many cost and efficiency advantages. Tiny amounts of reagents and samples are needed and highly sensitive, fast and parallel assays can be done at low cost. A particular type of DNA biosensors are the ones used based on electrochemical principles. These sensors offer several advantages over the popular fluorescence‐based detection schemes. The resulting signal is electrical and can be processed by conventional electronics in a very cheap and fast manner. Furthermore, the integration and miniaturization of electrochemical transducers in a microsystem makes easier its fabrication in front of the most common currently used detection method. In this review, different electrochemical DNA biosensors integrated in analytical microfluidic devices are discussed and some early stage commercial products based on this strategy are presented.

Gas identification with tin oxide sensor array and self organizing maps: adaptive correction of sensor drifts

Low cost tin oxide gas sensors are inherently nonspecific. In addition they feature several non-desirable behaviors such as slow time response, nonlinearities and long term drifts. This paper shows that the combination of a gas sensor array together with self organizing maps can solve the gas classification problems. That is, the system is able to determine the gas present in the test chamber with error rates lower than 3%. The correction of the sensor drift with an adaptative SOM has also been investigated.

MICRON: Small Autonomous Robot for Cell Manipulation Applications

Manipulating in the micro- or even nano world still poses a great challenge to robotics. Conventional (stationary) systems suffer from drawbacks regarding integration into process supervision and multi-robot approaches, which become highly relevant to fight scaling effects. This paper describes work currently being carried out which aims to make automated manipulation of micrometer-scaled objects possible by robots with nanometer precision. The goal is to establish a small cluster of (up to five) micro robots equipped with on-board electronics, sensors and wireless power supply. Power autonomy has been reached using inductive energy transmission from an external wireless power supply system or a battery based system. Electronics requirements are fulfilled in the electronic module with the full custom integrated circuit design for the robot locomotion control and the closed loop force control for AFM tool in cell manipulation applications. The maximum velocity obtained is about 0.4 mm/s with a saw tooth voltage signals of 20Vpp and 2500 Hz. In order to keep a AFM tool on micro-robot a specific tip with integrated piezoresistance, instead of the classical laser beam methodology, is validated for force measurement.

Stem cell differentiation by functionalized micro- and nanostructured surfaces.

New fabrication technologies and, in particular, new nanotechnologies have provided biomaterial and biomedical scientists with enormous possibilities when designing customized supports and scaffolds with controlled nanoscale topography and chemistry. The main issue now is how to effectively design these components and choose the appropriate combination of structure and chemistry to tailor towards applications as challenging and complex as stem cell differentiation. Occasionally, an incomplete knowledge of the fundamentals of biological differentiation processes has hampered this issue. However, the recent technological advances in creating controlled cellular microenvironments can be seen as a powerful tool for furthering fundamental biology studies. This article reviews the main strategies followed to achieve solutions to this challenge, particularly emphasizing the working hypothesis followed by the authors to elucidate the mechanisms behind the observed effects of structured surfaces on cell behavior.

Power-Conditioning Circuitry for a Self-Powered System Based on Micro PZT Generators in a 0.13-

The concept and design of a power-conditioning circuit for an autonomous low-power system-in-package (SiP) is presented in this paper. The SiPs main power source is based on the use of micropiezoelectric generators. The electrical model of the power source, which has been obtained based on experimental measurements and implemented on Cadence Analog Artists Spectre simulation environment, is explained. The model has been used to simulate the power source with the power-conditioning electronics over the entire design process. Finally, the simulated and experimental results of the developed integrated power circuits, which are formed by a rectifier and a low-power bandgap reference voltage source to define the threshold voltage for the closed-loop regulation process, are also shown. These circuits have been designed using a commercial 0.13-mum technology from ST Microelectronics through the multi-projects circuits (CMP) techniques of informatics and microelectronics for integrated systems architecture (TIMA) service.

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A frequency-dependent compact model for inductors in high ohmic substrates, which is based on an energy point-of-view, is developed. This approach enables the description of the most important coupling phenomena that take place inside the device. Magnetically induced losses are quite accurately calculated and coupling between electric and magnetic fields is given by means of a delay constant. The later coupling phenomenon provides a modified procedure for the computation of the fringing capacitance value, when the self-resonance frequency of the inductor is used as a fitting parameter. The model takes into account the width of every metal strip and the pitch between strips. This enables the description of optimized layout inductors. Data from experiments and electromagnetic simulators are presented to test the accuracy of the model.