This work reports measurements to elucidate the reaction mechanisms of sensitive materials containing primary amino groups with CO2. The sensing mechanism is based on their ability to perform reversible acid-base reactions. The effect discussed for most of the previously used sensing layers concerns the formation of bicarbonate species, which requires H2O as well as an increased temperature. By using work function readout technology an operation at room temperature of the sensing layers is enabled providing satisfying sensor responses in terms of SNR (signal noise ratio) and response time. In contrast to the previously investigated higher operation temperature, the response resulting from a room temperature measurement appears to be dominated by the reversible formation of carbamate, which does not require the presence of water. The presence of carbamate is considered to be the reason of the improved sensing performance of this sensing material at room temperature with work function readout.To confirm this hypothesis, DRIFT-MIR, Raman, XPS and NMR spectroscopy were employed to investigate the formation of species after manufacturing of the sensitive layers. Besides the formation of bicarbonate, the results show a strong indication for carbamate formation. (C) 2010 Elsevier B.V. All rights reserved.

Polycrystalline β-Ga2O3/platinum thick films can be used as a novel sensing layer for the detection of VOC (volatile organic compounds) in sensors based on the readout of the work function (Kelvin probe, Floating Gate FET). An intermittent short thermal activation at 175°C enables a subsequent room temperature operation. The supposed mechanism is based on the formation of oxygen species during this thermal activation. After cooling down to room temperature those species remain on the surface for some hours to days. The sensing mechanism at room temperature is assumed to be based on a reaction of reducing gases with this oxygen species resulting in a change of the work function due to the change of the surface properties. The addition of platinum as catalyst is necessary to obtain a response to various VOC. Pt clusters with varying size are investigated which are responsible for improving the VOC sensitivity. Therefore platinum on micro- and nanoscale was used. The best variants are capable to detect small concentrations (ppb–ppm) of different VOC (aldehydes, alcohols, esters, ketones, and hydrocarbons) as well as toxic CO well below their odor or toxicity threshold. Meaningful responses are still present some days after the thermal activation.

In this contribution we present a new disposable micro-fluidic biosensor array for the online analysis of adherent Madin Darby canine kidney (MDCK-II) cells on quartz crystal resonators (QCRs). The device was conceived for the parallel cultivation of cells providing the same experimental conditions among all the sensors of the array. As well, dedicated sensor interface electronics were developed and optimized for fast spectra acquisition of all 16 QCRs with a miniaturized impedance analyzer. This allowed performing cell cultivation experiments for the observation of fast cellular reaction kinetics with focus on the comparison of the resulting sensor signals influenced by different cell distributions on the sensor surface. To prove the assumption of equal flow circulation within the symmetric micro-channel network and support the hypothesis of identical cultivation conditions for the cells living above the sensors, the influence of fabrication tolerances on the flow regime has been simulated. As well, the shear stress on the adherent cell layer due to the flowing media was characterized. Injection molding technology was chosen for the cheap mass production of disposable devices. Furthermore, the injection molding process was simulated in order to optimize the mold geometry and minimize the shrinkage and the warpage of the parts. MDCK-II cells were cultivated in the biosensor array. Parallel cultivation of cells on the gold surface of the QCRs led to first observations of the impact of the cell distribution on the sensor signals during cell cultivation. Indeed, the initial cell distribution revealed a significant influence on the changes in the measured acoustic load on the QCRs suggesting dissimilar cell migrations as well as proliferation kinetics of a non-confluent MDCK-II cell layer.

Zhou et al. [1] and Endres et al. [2] reported on CO2-sensing using primary amino groups of Heteropolysiloxanes at higher temperatures (50-70°C) by means of a mass sensitive and a capacitive readout. Based on this work the read out of the change in the work function is investigated. The reversible interaction of CO2 with spin-coated Heteropolysiloxanes sensitive layers results in changes of the work function with typical signal heights of 15-20 mV (from 400 ppm up to 4000 ppm). Results are presented regarding variations in the chemical nature of the films. This opens up the possibility for a new ambient temperature CO2-sensor which shows fast response times as well as a high sensitivity for concentrations exceeding 400 ppm CO2 (background in atmosphere).

In micro-plants, as used in chemical micro-process engineering, an integrated inline analytics is regarded as an important factor for the development and optimization of chemical processes. Up to now, there is a lack of sensitive, robust and low-priced micro-sensors for monitoring mixing and chemical conversion in micro-fluidic channels. In this paper a novel sensor system combining an impedimetric sensor and a novel pressure stable thermoelectric flow sensor for monitoring chemical reactions in micro-plants is presented. The CMOS-technology-based impedimetric sensor mainly consists of two capacitively coupled interdigital electrodes on a silicon chip. The thermoelectric flow sensor consists of a heater in between two thermopiles on a perforated membrane. The pulsed and constant current feeds of the heater were analyzed. Both sensors enable the analysis of chemical conversion by means of changes in the thermal and electrical properties of the liquid. The homogeneously catalyzed synthesis of n-butyl acetate as a chemical model system was studied. Experimental results revealed that in an overpressure regime, relative changes of less than 1% in terms of thermal and electrical properties can be detected. Furthermore, the transition from one to two liquid phases accompanied by the change in slug flow conditions could be reproducibly detected.

New sensor principles based on the resonant effect are introduced. Lateral field excitation (LFE) of the well-known quartz crystal microbalance leaves the sensing surface free of a metallic electrode. On the one hand it gives access to a large variety of silane based surface chemistry for achieving chemical sensitivity. On the other hand the electrical field penetrates into the adjacent substance allowing the determination of electrical properties of liquids. A second concept with the same advantages applies magnetic excitation. Here, piezoelectric materials are not required. Si membranes can serve as high-Q resonators. Capacitively driven micromechanical ultrasonic transducers consisting of a large number of resonators can serve as platform for sensor arrays. Finally, propagation of ultrasonic waves at specific frequencies inside the band gap of phononic crystals is a phenomenon about to be discovered for sensing purposes. The perspectives of these principles with regard to chemical and biosensors are discussed.

In this contribution capillary type thermal mass flow sensors based on the thermo-transfer principle were applied for monitoring esterification reactions in residence time micro-reactors. A novel micro-reactor with an integrated sensor network was developed that enables the inline analysis of six stages of chemical conversion in parallel. The device was optimized for residence times in the range of several tens of minutes. Conversion can be monitored by means of changes in the isobaric heat capacity. Methods for the compensation of offsets and flow pulsation in the linear operation range of the sensor were developed. The novel micro-reactor was used for studies on the homogeneously catalyzed synthesis of butyl acetate. The phase separation at a certain residence time could be successfully detected. The formation of aggregates/plugs with different phases led to oscillations in the measurement signal. Insofar, robust sensors emerge as low cost tool for the inline analysis and control of esterification reactions.

Gas sensors based on the work function read out of (hetero-) polysiloxane sensing layers containing primary amino groups (-NH2) can be used for the detection of CO2. The sensing mechanism is assumed to be an acid/base reaction between primary amino groups and CO2. In literature, both a bicarbonate formation and a carbamate formation are discussed. To investigate the reaction with CO2, different polymers based on modified polysiloxanes are examined. It is shown that the CO2 response of work function type sensors can be systematically improved by modifying the polymeric network on the one hand (adjoining primary amino groups) and by increasing the hydrophobicity on the other hand. The findings summarized in this paper indicate the possibility for new ambient temperature CO2 sensors with short response (<1 min) and recovery times (<5 mm), a high long-term stability (months to years) as well as a high SNR (signal noise ratio) of ca. 25 (exposure from 400 ppm up to 4000 ppm CO2). Furthermore, the fast establishment of the chemical equilibrium is remarkable when humidity is changed in atmosphere. (C) 2010 Elsevier B.V. All rights reserved.

The differentiation of neural cells is an important process during the development of the central nervous system. Studies on the mechanisms of the differentiation process is of special importance, e.g. in the field of regenerative medicine. In this contribution the cellular differentiation of gel matrix embedded neuronal cells was studied. The three-dimensional organization of neuronal cells represents a new cellular model system closer to the physiology than conventional two-dimensional cell cultures. Neuro2a (N2a) neuroblastoma cells were immobilized in different gel matrices and the grade of differentiation was compared. Furthermore, the impact of the cell number and selected differentiation factors were analyzed. Experimental results revealed that gel matrices based on collagen-laminin mixtures in contact with serum free medium enable neural differentiation. Therefore, collagen-laminin gels appear as a suitable three-dimensional model for drug screening in developmental neurobiology. Following optimization of the immobilization process, a novel impedimetric sensor and electrical impedance spectroscopy technique was applied to on-line monitor the differentiation process by means of changes in the dielectric and conductive properties. Experimental results showed an increase in the impedance magnitude that can be mainly attributed to differentiating cells accompanied by an increase in the specific resistivity of the bare gel mixture.

An automated method to non-destructively estimate ultrasonic bond pull force is presented and validated. Scanning white light interferometry (SWLI) measures bond geometry whereas the singular value decomposition of a SWLI image extracts the characteristics of the imaged bond geometry in terms of eigenvectors. Soft modeling selects those parts of the eigenvectors that are important for predicting the highest sustainable pull force. We show that SWLI measurement, statistical feature selection and bond pull force prediction can be combined to automatically perform non-destructive bond quality monitoring. Such automation removes subjectivity as well as operator limitations and errors present in earlier approaches (Schäfer et al., 2007), since no pre-selection of bond geometry or shape is needed. The proposed method was verified by experimental measurements on 132 single-point tape automated bonds. The results show that the method predicts maximum sustainable bond pull force with a prediction accuracy comparable to that of the operator based method. The three most important features in the image of the bond predicted the maximum sustainable bond pull force with an error of 11.4%. Not having to rely on the input of an experienced operator is the major advantage of this contribution.

Fluid waves at the interface of CMUTs (Capacitive Micromachined Ultrasound Transducers) to the surrounding fluid are an often discussed and unwanted effect for medical imaging applications, as they cause ringing artifacts. A new approach for a surface wave sensor is presented which uses these dispersive surface waves for sensing fluid properties like mass density and viscosity. After a short introduction to the theory and our FEM model we will present first results showing the sensitivity of the sensor to the viscosity of different silicone oil samples and will discuss the results.

Heating up Pt films or Pt dispersions supported on a metal oxide to a few hundred degree Celsius in ambient air for some minutes causes the formation of reactive species on the surface that are supposedly derivates of adsorbed oxygen. When the specimen is subsequently cooled down to room temperature, these species are still active for several days. They cause a gas response at room temperature to a large variety of hydrocarbons, as measured by change in work function. The interaction of volatile organic compounds (VOCs) and the activity duration heavily depend on the composition of the materials. The results provide the basis for room temperature gas detection with intermittent activation at elevated temperatures.

An 8-pixel micromachined quartz crystal resonator array with a fundamental resonance frequency of 66 MHz has been designed, fabricated, and tested. A compact impedance-spectrum-analyzer electronic interface has been developed and combined with the quartz resonator array to form the biosensing system. The sensor array was calibrated using water-glycerol solutions, and the performance was found to be exactly as expected. Measurement of the crosstalk between the sensor pixels showed an isolation of ~ 30 dB. Selective functionalization of the pixels was achieved through the use of aqueous 3, 3'-Dithiobis (sulfosuccinimidylpropionate) (DTSSP) molecules. The adsorption of avidin on DTSSP gave a frequency signal of 60 kHz in comparison to unfunctionalized pixels. The specific adsorption of avidin on functionalized pixels was confirmed through fluorescence microscopy. Comparing the performance of the micromachined quartz crystal microbalance (QCM) with a commercial 5-MHz device, we found that the micromachined QCM has a 4.25 times higher signal-to-noise ratio. Based on the measurement of the noise and using three times the frequency noise as the limit for the detection of avidin molecules, we expect to resolve a minimum of ~ 1/960 of a monolayer of avidin corresponding to an aerial mass density resolution of 0.7 ng/cm2.

Fluid waves at the interface of CMUTs (Capacitive Micromachined Ultrasound Transducers) to the surrounding fluid are an often discussed and unwanted effect for medical imaging applications, as they cause ringing artifacts. A new approach for a surface wave sensor is presented which uses these dispersive surface waves for sensing fluid properties like mass density and viscosity. After a short introduction to the theory and our FEM model we will present first results. A mixture of water and glycerin was used to investigate the sensitivity of the sensor to dynamic viscosity.

In this contribution the impact of culture medium flow on the cultivation of Madin-Darby canine kidney cells on quartz crystal resonators (QCRs) was studied. Cells were cultivated at different medium flow rates in a bioreactor chip containing 4 QCRs. Confluency and motility of cells were analyzed based on light microscopical pictures and impedance spectra of the resonators. Results were compared with cells cultivated in culture flasks mounted on a shaker and CFD simulation results of the bioreactor chip. Based on our studies the flow-regime in the micro fluidic channel geometry has major impact e.g. on the cell division rate.

In this contribution we focus on the on-line analysis of neuronal cells embedded in gel matrices by means of variations in their dielectric and conductive properties. For impedance measurement of thin gel films in flow-through regime a novel impedimetric biosensor was developed. A technique for the preparation of gels containing Neuro-2a neuroblastoma cells (N2a) in between the measurement electrodes was set up. Impedance spectra of gels with N2a cells were analyzed and cell viability was tested. Experimental results showed that even at frequencies (>>1 MHz) and a gel concentration of 2 % with ~8300 cells/μL conductive properties dominate the spectrum.

A sensor system combining a novel pressure stable thermoelectric flow and impedimetric sensor for monitoring chemical conversion in micro fluidic channels was developed. Devices were optimized for hydraulic diameters ~1 mm and overpressure regime. Impedimetric sensors consist of a pair of interdigital electrodes deposited on a silicon substrate. Thermoelectric flow sensors consist of a perforated membrane with a heater in between two thermocouples. Based on our results both sensors can detect in parallel relative changes in thermal and electrical properties of less than 1 %. Thus the system enables the inline monitoring of chemical conversion by means of 4 parameters.

Polycrystalline Ga2O3/platinum-thick films can be used as a novel sensing layer for VOC detection in sensors based on the readout of the work function by GasFET devices. Room temperature operation can be used if an intermittent short thermal activation at 175°C is employed. This paper reports on how the stepwise addition of catalytic activity using platinum as catalyst incrementally improves the gas sensitivity of this material system towards VOCs. The best variants are capable to detect small concentrations even below the odor or medical exposure threshold.

In this contribution triggering of the acetylcholine receptor (AChR) in Neuro2a murine neuroblastoma (N2a) cells was studied by means of electrical impedance analysis. N2a cells were immobilized in a bactoagar gel matrix and stimulated with acetylcholine (ACh). Gel films were prepared in between the electrodes of a novel impedimetric sensor. Devices were integrated in a micro fluidic bioreactor for cell stimulation in flow-through regime. Shifts in the impedance spectra (10 to 110 MHz) of gels showed that AChR triggering is accompanied by an increase in the overall conductivity of the gel in a time scale of tens of minutes.

The influence of statistical variations in cell distribution on the proliferation of Madin-Darby canine kidney (MDCK-II) cells was analyzed. MDCK-II cells were cultivated in parallel on 4 quartz crystal resonators in a bioreactor chip. Results of proliferation experiments with different initial grade of confluence were compared. Light microscope pictures of the sensor surface and impedance spectra were continuously acquired. CFD simulation results of the bioreactor chip were employed to verify experimental conditions. Results show that especially at low confluency dissimilar development of non-confluent MDCK-II cell layers and resulting changes in acoustic load depend significantly on initial cell distribution.