Sensing with FETs - once, now and future

In this paper a short overview is given of the several FET-based sensor devices and the operational principle of the ISFET is summarized. Some of the shortcomings of the FET sensors were circumvented by an alternative operational mode, resulting in a device capable of acid/base concentration determination by coulometric titrant generation as well as in an original pH-static enzyme sensor. A more recent example is presented in which the ISFET is used for the on-line monitoring of fermentation processes. Future research is directed towards direct covalent coupling of organic monolayers on the silicon itself. In addition, the field-effect can be applied to the so-called semiconducting nanowire devices, ultimately making single molecule detection of charged species possible

Quantitative Determination of Glucose Transfer Between Cocurrent Laminar Water Streams in a H-Shaped Microchannel

To explore the applicability of a laminar fluid diffusion interface (LFDI) for the controlled feeding of microbioreactors, glucose diffusion experiments were carried out in a rounded H-shaped microstructure etched in a glass substrate. The diffusion channel of the microstructure had a length of 4 mm and a depth of 50 μm with a trapezoidal cross section with a width of 100 μm at the bottom and 200 μm at the surface of the channel. The microchannel was operated at residence times of less than 1 s ensuring high-mass-transfer rates. It was confirmed, both by microscopic observations as well as computational fluid dynamics (CFD) studies that the flow characteristics in the microchannel were fully laminar. Special attention was paid to flow splitting at the end of the channel, because the CFD simulations indicated that the performance of the device was sensitive to unequal flow splitting. The difference in outflow volume of the two streams was measured to be small (1.25% ± 0.6%). The measured glucose concentration in both exit ports at a fixed residence time was found to be stable in time and reproducible in multiple experiments. CFD simulation was shown to be a powerful tool for estimating the mass transfer in the LFDI, even at very short residence times. The results obtained in this work show the applicability of LFDI for the controlled diffusive supply of a solute to a water stream, with as possible application substrate and/or precursor feeding to microreactors

Aortic valve calcification volumes and chronic brain infarctions in patients undergoing transcatheter aortic valve implantation

Chronic silent brain infarctions, detected as new white matter hyperintensities on magnetic resonance imaging (MRI) following transcatheter aortic valve implantation (TAVI), are associated with long-term cognitive deterioration. This is the first study to investigate to which extent the calcification volume of the native aortic valve (AV) measured with cardiac computed tomography angiography (CTA) predicts the increase in chronic white matter hyperintensity volume after TAVI. A total of 36 patients (79 ± 5 years, median EuroSCORE II 1.9%, Q1–Q3 1.5–3.4%) with severe AV stenosis underwent fluid attenuation inversion recovery (FLAIR) MRI < 24 h prior to TAVI and at 3 months follow-up for assessment of cerebral white matter hyperintensity volume (mL). Calcification volumes (mm3) of the AV, aortic arch, landing zone and left ventricle were measured on the CTA pre-TAVI. The largest calcification volumes were found in the AV (median 692 mm3) and aortic arch (median 633 mm3), with a large variation between patients (Q1–Q3 482–1297 mm3 and 213–1727 mm3, respectively). The white matter hyperintensity volume increased in 72% of the patients. In these patients the median volume increase was of 1.1 mL (Q1–Q3 0.3–4.6 mL), corresponding with a 27% increase from baseline (Q1–Q3 7–104%). The calcification volume in the AV predicted the increase of white matter hyperintensity volume (Δ%), with a 35% increase of white matter hyperintensity volume, per 100 mm3 of AV calcification volume (SE 8.5, p < 0.001). The calcification volumes in the aortic arch, landing zone and left ventricle were not associated with the increase in white matter hyperintensity volume. In 72% of the patients new chronic white matter hyperintensities developed 3 months after TAVI, with a median increase of 27%. A higher calcification volume in the AV was associated with a larger increase in the white matter hyperintensity volume. These findings show the potential for automated AV calcium screening as an imaging biomarker to predict chronic silent brain infarctions

Integrated sensor array for on-line monitoring micro bioreactors

The “Fed��?batch on a chip��?��?project, which was carried out in close cooperation with the Technical University of Delft, aims to miniaturize and parallelize micro bioreactors suitable for on-line screening of micro-organisms. This thesis describes an electrochemical sensor array which has been developed for this purpose. The sensor array is suitable for on-line monitoring pH, temperature, dissolved oxygen concentrations and viable biomass concentrations. pH is monitored using an Ion-Selective Field Effect Transistor (ISFET). Drift influence was effectively be reduced. The temperature sensor is a platinum thin-film thermistor with a nominal impedance of 1 kOhm. Dissolved oxygen concentration is monitored using an amperometric Ultra Micro Electrode Array (UMEA) which exhibits good selectivity and low flow dependence. Viable biomass concentration is monitored using impedance spectroscopy. Yeast suspension conductivity was found to increase linearly with the biomass concentration for frequencies above 1 MHz. The sensors were fabricated using cleanroom techniques and meet the floorplan of a 96-well microtiterplate. The sensor array was first calibrated with respect to conventional measurement methods in lab-scale fermentors with a working volume of 4 liters. The sensors were then applied in an array consisting of two microreactors with a working volume of 100 microliter. Therefore, the sensors were placed underneath bottomless wells taken from 96-well microtiterplates. A single aqueous Ag/AgCl reference electrode was placed in a separate reservoir connected to the microreactors using saltbridges consisting of Nafion hollow fiber membranes filled with medium. Mixing was achieved using a magnetic stirrer bar, fixated on an axle. Cultivations of Candida Utilis were performed and monitored. Immediately after the log phase, excessive cell death and sensor fouling appears to take place; this phenomenon requires further investigation. This thesis furthermore describes the development of microfluidics for pH control and fed-batch functionality. PDMS microvalves with a rounded to semicircular cross section were fabricated using a new fabrication process which takes advantage of isotropically etched microchannels in glass substrates. The valves were actuated using Braille displays, electromagnetically, and pneumatically. Pneumatic actuation leads to the most robust results, since the alignment between the actuator and the microchannel is fixed

Sensing with FETs - once, now and future

In this paper a short overview is given of the several FET-based sensor devices and the operational principle of the ISFET is summarized. Some of the shortcomings of the FET sensors were circumvented by an alternative operational mode, resulting in a device capable of acid/base concentration determination by coulometric titrant generation as well as in an original pH-static enzyme sensor. A more recent example is presented in which the ISFET is used for the on-line monitoring of fermentation processes. Future research is directed towards direct covalent coupling of organic monolayers on the silicon itself. In addition, the field-effect can be applied to the so-called semiconducting nanowire devices, ultimately making single molecule detection of charged species possible

Monitoring of yeast cell concentration using a micromachined impedance sensor

The paper describes the design, modelling and experimental characterization of a micromachined impedance sensor for on-line monitoring of the viable yeast cell concentration (biomass) in a miniaturized cell assay. Measurements in a Saccharomyces cerevisiae cell culture show that the permittivity of the cell suspension depends linearly on the biomass concentration within the range of 0 to 9 g/l. In order to compensate the measurements for changes in the dielectric properties of the background electrolyte, the use of a three-electrode configuration in combination with a semi-permeable pHEMA membrane was explored. Measurements showed that the impedance of the hydrated pHEMA varies with only the background electrolyte conductivity, and not with the concentration of cells, indicating that pHEMA is suitable for this purpose. The optimal pHEMA membrane thickness was determined using finite element modelling

Lab-scale fermentation tests of microchip with integrated electrochemical sensors for pH, temperature, dissolved oxygen and viable biomass concentration

Miniaturization and automation are highly important issues for the development of high-throughput processes. The area of micro total analysis systems (mu TAS) is growing rapidly and the design of new schemes which are suitable for miniaturized analytical devices is of great importance. In this paper we report the immobilization of self-assembled monolayers (SAMs) with metal ion sensing properties, on the walls of glass microchannels. The parallel combinatorial synthesis of sensing SAMs in individually addressable microchannels towards the generation of optical sensor arrays and sensing chips has been developed