Preconcentration modeling for the optimization of a micro gas preconcentrator applied to environmental monitoring.

This paper presents the optimization of a micro gas preconcentrator (µ-GP) system applied to atmospheric pollution monitoring, with the help of a complete modeling of the preconcentration cycle. Two different approaches based on kinetic equations are used to illustrate the behavior of the micro gas preconcentrator for given experimental conditions. The need for high adsorption flow and heating rate and for low desorption flow and detection volume is demonstrated in this paper. Preliminary to this optimization, the preconcentration factor is discussed and a definition is proposed.

Development of a new generation of ammonia sensors on printed polymeric hotplates.

Conducting polyaniline-based chemiresistors on printed polymeric micro-hotplates were developed, showing sensitive and selective detection of ammonia vapor in air. The devices consist of a fully inkjet-printed silver heater and interdigitated electrodes on a polyethylene naphthalate substrate, separated by a thin dielectric film. The integrated heater allowed operation at elevated temperatures, enhancing the ammonia sensing performance. The printed sensor designs were optimized over two different generations, to improve the thermal performance through careful design of the shape and dimension of the heater element. A vapor-phase deposition polymerization technique was adapted to produce polyaniline sensing layers doped with poly(4-styrenesulfonic acid). The resulting sensor had better thermal stability and sensing performance when compared with conventional polyaniline-based sensors, and this was attributed to the polymeric dopant used in this study. Improved long-term stability of the sensors was achieved by electrodeposition of gold on the silver electrodes. Response to sub-parts-per-million concentrations of ammonia even under humid conditions was observed.

Mid-infrared spectroscopy for gases and liquids based on quantum cascade technologies.

In this paper we present two compact, quantum cascade laser absorption spectroscopy based, sensors developed for trace substance detection in gases and liquids. The gas sensor, in its most integrated version, represents the first system combining a quantum cascade laser and a quantum cascade detector. Furthermore, it uses a toroidal mirror cell with a volume of only 40 cm(3) for a path length of up to 4 m. The analytical performance is assessed by the measurements of isotope ratios of CO2 at ambient abundance. For the (13)CO2/(12)CO2 isotope ratio, a measurement precision of 0.2‰ is demonstrated after an integration time of 600 s. For the liquid sensor, a microfluidic system is used to extract cocaine from saliva into a solvent (PCE) transparent in the mid-infrared. This system is bonded on top of a Si/Ge waveguide and the concentration of cocaine in PCE is measured through the interaction of the evanescent part of the waveguide optical mode and the solvent flowing on top. A detection limit of <100 µg mL(-1) was achieved with this system and down to 10 µg mL(-1) with a simplified, but improved system.

Microfluidic droplet-based liquid-liquid extraction and on-chip IR spectroscopy detection of cocaine in human saliva.

We present a portable microsystem to quantitatively detect cocaine in human saliva. In this system, we combine a microfluidic-based multiphase liquid-liquid extraction method to transfer cocaine continuously from IR-light-absorbing saliva to an IR-transparent solvent (tetrachloroethylene) with waveguide IR spectroscopy (QC-laser, waveguide, detector) to detect the cocaine on-chip. For the fabrication of the low-cost polymer microfluidic chips a simple rapid prototyping technique based on Scotch-tape masters was further developed and applied. To perform the droplet-based liquid-liquid extraction, we designed and integrated a simple and robust droplet generation method based on the capillary focusing effect within the device. Compared to well-characterized and commonly used microfluidic H-filters, our system showed at least two times higher extraction efficiencies with potential for further improvements. The current liquid-liquid extraction method alone can efficiently extract cocaine and pre-concentrate the analytes in a new solvent. Our fully integrated optofluidic system successfully detected cocaine in real saliva samples spiked with the drug (500 µg/mL) and allowed real time measurements, which makes this approach suitable for point-of-care applications.

A portable lab-on-a-chip instrument based on MCE with dual top-bottom capacitive coupled contactless conductivity detector in replaceable cell cartridge.

A new design for a compact portable lab-on-a-chip instrument based on MCE and dual capacitively coupled contactless conductivity detection (dC(4) D) is described. The instrument is battery powered with total dimension of 14 × 25 × 8 cm(3) (w × l × h), and weighs 1.2 kg. The device consists of a front electrophoresis compartment which has the chip holder and the chip, the associated high-voltage electrodes for electrophoresis injection and separation and the detector. The detection cell is integrated into the device housing with an exchangeable plug-and-play cartridge format. The design of the dC(4) D cell has been optimized for maximum performance. The cartridge includes the top-bottom excitation and pick up electrodes incorporated into the cell and connected to push-pull self-latching pins that are insulated with plastic. The metal frame of the cartridge is grounded completely to eliminate electronic interferences. The cartridge is designed to clamp a thin fluidic chip at the detection point. The cartridges are replaceable whereby different cartridges have different detection electrode configurations to employ according to the sensitivity or resolution needed in the specific analytical application. The second compartment consists of all the electronics, data acquisition card, high-voltage modules of up to ±5 kV both polarity, and batteries for 10 h of operation. The improved detector performance is illustrated by the electrophoresis analysis of six cations (NH4 (+) , K(+) , Ca(2+) , Na(+) , Mg(2+) , Li(+) ) with a detection limit of approximately 5 µM and the analysis of the anions (Br(-) , Cl(-) , NO2 (-) , NO3 (-) , SO4 (2-) , F(-) ) with a detection limit of about 3 µM. Analytical capabilities of the instrument for food and medical applications were evaluated by simultaneous detection of organic and inorganic acids in fruit juice and inorganic cations and anions in rabbit blood samples and human urine samples are also demonstrated.

Double-side-coated nanomechanical membrane-type surface stress sensor (MSS) for one-chip-one-channel setup.

With their capability for real-time and label-free detection of targets ranging from gases to biological molecules, nanomechanical sensors are expected to contribute to various fields, such as medicine, security, and environmental science. For practical applications, one of the major issues of nanomechanical sensors is the difficulty of coating receptor layers on their surfaces to which target molecules adsorb or react. To have measurable deflection, a single-side coating is commonly applied to cantilever-type geometry, and it requires specific methods or protocols, such as inkjet spotting or gold-thiol chemistry. If we can apply a double-side coating to nanomechanical sensors, it allows almost any kind of coating technique including dip coating methods, making nanomechanical sensors more useful with better user experiences. Here we address the feasibility of the double-side coating on nanomechanical sensors demonstrated by a membrane-type surface stress sensor (MSS) and verify its working principle by both finite element analysis (FEA) and experiments. In addition, simple hand-operated dip coating is demonstrated as a proof of concept, achieving practical receptor layers without any complex instrumentation. Because the double-side coating is compatible with batch protocols such as dip coating, double-side-coated MSS represents a new paradigm of one-chip-one-channel (channels on a chip are all coated with the same receptor layers) shifting from the conventional one-chip-multiple-channel (channels on a chip are coated with different receptor layers) paradigm.

Batch fabrication of gold-gold nanogaps by E-beam lithography and electrochemical deposition.

We report on the successful development of a well-controlled two-step batch nano-fabrication process to achieve nanometer-size gaps at the wafer scale. The technique is based on an optimized electron-beam lithography process, which enables the fabrication of nanogaps in the range (15 ± 4) nm. Following this first step, the feedback-controlled electrochemical deposition of gold from an aqueous HAuCl4-based electrolyte is applied to further reduce the size of the gap down to about 0.3-1.0 nm. This protocol was successfully demonstrated by fabricating more than 385 nanogaps on a 4 inch wafer. The reproducible fabrication of nanogaps in the range between 0.3 and 1.0 nm opens up new perspectives for addressing the electrical and reactivity properties of single molecules and clusters in confined space under well-controlled conditions.

Two dimensional array of piezoresistive nanomechanical Membrane-type Surface Stress Sensor (MSS) with improved sensitivity.

We present a new generation of piezoresistive nanomechanical Membrane-type Surface stress Sensor (MSS) chips, which consist of a two dimensional array of MSS on a single chip. The implementation of several optimization techniques in the design and microfabrication improved the piezoresistive sensitivity by 3~4 times compared to the first generation MSS chip, resulting in a sensitivity about ~100 times better than a standard cantilever-type sensor and a few times better than optical read-out methods in terms of experimental signal-to-noise ratio. Since the integrated piezoresistive read-out of the MSS can meet practical requirements, such as compactness and not requiring bulky and expensive peripheral devices, the MSS is a promising transducer for nanomechanical sensing in the rapidly growing application fields in medicine, biology, security, and the environment. Specifically, its system compactness due to the integrated piezoresistive sensing makes the MSS concept attractive for the instruments used in mobile applications. In addition, the MSS can operate in opaque liquids, such as blood, where optical read-out techniques cannot be applied.

Multiple extra-synaptic spillover mechanisms regulate prolonged activity in cerebellar Golgi cell-granule cell loops.

Despite a wealth of in vitro and modelling studies it remains unclear how neuronal populations in the cerebellum interact in vivo. We address the issue of how the cerebellar input layer processes sensory information, with particular focus on the granule cells (input relays) and their counterpart inhibitory interneurones, Golgi cells. Based on the textbook view, granule cells excite Golgi cells via glutamate forming a negative feedback loop. However, Golgi cells express inhibitory mGluR2 receptors suggesting an inhibitory role for glutamate. We set out to test this glutamatergic paradox in Golgi cells. Here we show that granule cells and Golgi cells interact through extra-synaptic signalling mechanisms during sensory information processing, as well as synaptic mechanisms. We demonstrate that such interactions depend on granule cell-derived glutamate acting via inhibitory mGluR2 receptors leading causally to the suppression of Golgi cell activity for several hundreds of milliseconds. We further show that granule cell-derived inhibition of Golgi cell activity is regulated by GABA-dependent extra-synaptic Golgi cell inhibition of granule cells, identifying a regulatory loop in which glutamate and GABA may be critical regulators of Golgi cell­granule cell functional activity. Thus, granule cells may promote their own prolonged activity via paradoxical feed-forward inhibition of Golgi cells, thereby enabling information processing over long timescales.

Spectral phase, amplitude, and spatial modulation from ultraviolet to infrared with a reflective MEMS pulse shaper.

We describe the performance of a reflective pulse-shaper based on a Micro-ElectroMechanical System (MEMS) linear mirror array. It represents a substantial upgrade of a preceding release [Opt. Lett. 35, 3102 (2010)] as it allows simultaneous piston and tilt mirror motion, allowing both phase- and binary amplitude-shaping with no wavelength restriction. Moreover, we show how the combination of in-axis and tilt movement can be used for active correction of spatial chirp.

Continuous-flow multi-analyte biosensor cartridge with controllable linear response range.

This article presents the design and fabrication of a microfluidic biosensor cartridge for the continuous and simultaneous measurement of biologically relevant analytes in a sample solution. The biosensor principle is based on the amperometric detection of hydrogen peroxide using enzyme-modified electrodes. The low-integrated and disposable cartridge is fabricated in PDMS and SU-8 by rapid prototyping. The device is designed in such a way that it addresses two major challenges of biosensors using microfluidics approaches. Firstly, the enzymatic membrane is deposited on top of the platinum electrodes via a microfluidic deposition channel from outside the cartridge. This decouples the membrane deposition from the cartridge fabrication and enables the user to decide when and with what mixture he wants to modify the electrode. Secondly, by using laminar sheath-flow of the sample and a buffer solution, a dynamic diffusion layer is created. The analyte has to diffuse through the buffer solution layer before it can reach the immobilized enzyme membrane on the electrode. Controlling of the thickness of the diffusion layer by variation of the flow-rate of the two layers enables the user to adjust the sensitivity and the linear region of the sensor. The point where the buffer and sample stream join proved critical in creating the laminar sheath-flow. Results of computational simulations considering fluid dynamics and diffusion are presented. The consistency of the device was investigated through detection of glucose and lactate and are in accordance with the CFD simulations. A sensitivity of 157+/-28 nA/mM for the glucose sensor and 79+/-12 nA/mM for the lactate sensor was obtained. The linear response range of these biosensors could be increased from initially 2 mM up to 15 mM with a limit of detection of 0.2 mM.

Capacitively coupled contactless conductivity detection with dual top-bottom cell configuration for microchip electrophoresis.

An optimized capacitively coupled contactless conductivity detector for microchip electophoresis is presented. The detector consists of a pair of top-bottom excitation electrodes and a pair of pickup electrodes disposed onto a very thin plastic microfluidic chip. The detection cell formed by the electrodes is completely encased and shielded in a metal housing. These approaches allow for the enhancement of signal coupling and extraction from the detection cell that result in an improved signal-to-noise-ratio and detection sensitivity. The improved detector performance is illustrated by the electrophoretic separation of six cations (NH(4) (+), K(+), Ca(2+), Na(+), Mg(2+), Li(+)) with a detection limit of approximately 0.3 microM and the analysis of the anions (Br(-), Cl(-), NO(2) (-), NO(3) (-), SO(4) (2-), F(-)) with a detection limit of about 0.15 microM. These LODs are significantly improved compared with previous reports using the conventional top-top electrode geometry. The developed system was applied to the analysis of ions in bottled drinking water samples.

Ultraviolet and near-infrared femtosecond temporal pulse shaping with a new high-aspect-ratio one-dimensional micromirror array.

We demonstrate the capabilities of a new optical microelectromechanical systems device that we specifically developed for broadband femtosecond pulse shaping. It consists of a one-dimensional array of 100 independently addressable, high-aspect-ratio micromirrors with up to 3 µm stroke. We apply linear and quadratic phase modulations demonstrating the temporal compression of 800 and 400 nm pulses. Because of the device's surface flatness, stroke, and stroke resolution, phase shaping over an unprecedented bandwidth is attainable.

Potentiometric platform for the quantification of cellular potassium efflux.

Renewed interest in the measurement of cellular K(+) effluxes has been prompted by the observation that potassium plays an active and important role in numerous key cellular events, in particular cell necrosis and apoptosis. Although necrosis and apoptosis follow different pathways, both induce intracellular potassium effluxes. Here, we report the use of potassium-selective microelectrodes located in a microfluidic platform for cell culture to monitor and quantify such effluxes in real time. Using this platform, we observed and measured the early signs of cell lysis induced by a modification of the extracellular osmolarity. Furthermore, we were able to quantify the number of dying cells by evaluating the extracellular potassium concentration. A comparison between the potentiometric measurement with a fluorescent live-dead assay performed under similar conditions revealed the delay between potassium effluxes and cell necrosis. These results suggest that such platforms may be exploited for applications, such as cytotoxicological screening assays or tumor cell proliferation assays, by using extracellular K(+) as cell death marker.

Label-free detection of single protein molecules and protein-protein interactions using synthetic nanopores.

Nanofabricated pores in 20 nm-thick silicon nitride membranes were used to probe various protein analytes as well as to perform an antigen-antibody binding assay. A two-compartment electrochemical cell was separated by a single nanopore, 28 nm in diameter. Adding proteins to one compartment caused current perturbations in the ion current flowing through the pore. These perturbations correlated with both the charge and the size of the protein or of a protein-protein complex. The potential of this nanotechnology for studying protein-protein interactions is highlighted with the sensitive detection of beta-human chorionic gonadotropin, a hormone and clinical biomarker of pregnancy, by monitoring in real time and at a molecular level the formation of a complex between hormones and antibodies in solution. In this form, the assay compared advantageously to immunoassays, with the important difference that labels, immobilization, or amplification steps were no longer needed. In conclusion, we present proof-of-principle that properties of proteins and their interactions can be investigated in solution using synthetic nanopores and that these interactions can be exploited to measure protein concentrations accurately.

Characterization of a microfluidic dispensing system for localised stimulation of cellular networks.

We present a 3-D microfluidic device designed for localized drug delivery to cellular networks. The device features a flow cell comprising a main channel for nutrient delivery as well as multiple channels for drug delivery. This device is one key component of a larger, fully integrated system now under development, based upon a microelectrode array (MEA) with on-chip CMOS circuitry for recording and stimulation of electrogenic cells (e.g. neurons, cardiomyocytes). As a critical system unit, the microfluidics must be carefully designed and characterized to ensure that candidate drugs are delivered to specific regions of the culture at known concentrations. Furthermore, microfluidic design and functionality is dictated by the size, geometry, and material/electrical characteristics of the CMOS MEA. Therefore, this paper reports on the design considerations and fabrication of the flow cell, including theoretical and experimental analysis of the mass transfer properties of the nutrient and drug flows, which are in good agreement with one another. To demonstrate proof of concept, the flow cell was mounted on a dummy CMOS chip, which had been plated with HL-1 cardiomyocytes. A test chemical compound was delivered to the cell culture in a spatially resolved manner. Envisioned applications of this stand-alone system include simultaneous toxicological testing of multiple compounds and chemical stimulation of natural neural networks for neuroscience investigations.

A high current density DC magnetohydrodynamic (MHD) micropump.

This paper describes the working principle of a DC magnetohydrodynamic (MHD) micropump that can be operated at high DC current densities (J) in 75-microm-deep microfluidic channels without introducing gas bubbles into the pumping channel. The main design feature for current generation is a micromachined frit-like structure that connects the pumping channel to side reservoirs, where platinum electrodes are located. Current densities up to 4000 A m(-2) could be obtained without noticeable Joule heating in the system. The pump performance was studied as a function of current density and magnetic field intensity, as well as buffer ionic strength and pH. Bead velocities of up to 1 mm s(-1) (0.5 microL min(-1)) were observed in buffered solutions using a 0.4 T NdFeB permanent magnet, at an applied current density of 4000 A m(-2). This pump is intended for transport of electrolyte solutions having a relatively high ionic strength (0.5-1 M) in a DC magnetic field environment. The application of this pump for the study of biological samples in a miniaturized total analysis system (microTAS) with integrated NMR detection is foreseen. In the 7 T NMR environment, a minimum 16-fold increase in volumetric flow rate for a given applied current density is expected.

Chemical and physical processes for integrated temperature control in microfluidic devices.

Microfluidic devices are a promising new tool for studying and optimizing (bio)chemical reactions and analyses. Many (bio)chemical reactions require accurate temperature control, such as for example thermocycling for PCR. Here, a new integrated temperature control system for microfluidic devices is presented, using chemical and physical processes to locally regulate temperature. In demonstration experiments, the evaporation of acetone was used as an endothermic process to cool a microchannel. Additionally, heating of a microchannel was achieved by dissolution of concentrated sulfuric acid in water as an exothermic process. Localization of the contact area of two flows in a microfluidic channel allows control of the position and the magnitude of the thermal effect.

A novel microfluidic concept for bioanalysis using freely moving beads trapped in recirculating flows.

There are only a few examples in which beads are employed for heterogeneous assays on microfluidic devices, because of the difficulties associated with packing and handling these in etched microstructures. This contribution describes a microfluidic device that allows the capture, preconcentration, and controlled manipulation of small beads (<6 microm) in etched microchannels using fluid flows only. The chips feature planar diverging and converging channel elements connected by a narrow microchannel. Creation of bi-directional liquid movement by opposing electro-osmotic and pressure-driven flows can lead to the generation of controlled recirculating flow at these elements. Small polymer beads can actually be captured in the controlled rotating flow patterns. The clusters of freely moving beads that result can be perfused sequentially with different solutions. A preliminary binding curve was determined for the reaction of streptavidin-coated beads and fluorescein-labelled biotin, demonstrating the potential of this bead-handling approach for bioanalysis.

Comparison of the performance characteristics of poly(dimethylsiloxane) and Pyrex microchip electrophoresis devices for peptide separations.

A comparative study of electrophoretic separations of fluorescently labeled peptides and amino acids on poly(dimethylsiloxane) (PDMS) and Pyrex microchips is presented. The separation parameters for each microchip substrate were compared, including electroosmotic flow, plate numbers, resolution, and limits of detection. The effect of buffer composition on the separation was also investigated. Acceptable separations were obtained for most peptides with both substrates; however, PDMS chips exhibited much lower separation efficiencies and longer analysis times.