Katarina Verhaegen

A Biomedical Microphysiometer

We report on a micromachined silicon chip that is capable of providing a high-throughput functional assay based on calorimetry. A prototype twin microcalorimeter based on the Seebeck effect has been fabricated by using IC technology process steps in combination with micromachined postprocessing techniques. A biocompatible liquid rubber membrane supports two identical 0.5×2 cm2 measurement chambers, situated at the cold and hot junction sites of a thermopile. The thermopile consists of 666 aluminum/p+-polysilicon thermocouples. The chambers can house up to 106 eukaryotic cells cultured to confluence. The advantage of the device over microcalorimeters on the market, is the integration of the measurement channels on chip, rendering microvolume reaction vessels, ranging from 10 to 600 µl, in the closest possible contact with the thermopile sensor (no springs are needed). Power and temperature sensitivity of the sensor are 23 V/W and 130 mV/K, respectively. The small thermal inertia of the microchannels results in the short response time of 70 s, when filled with 50% of water.Biological experiments were done with cultured kidney cells of Xenopus laevis (A6). The thermal equilibration time of the device is 45 minutes. Stimulation of transport mechanisms by reducing bath osmolality by 50% increased metabolism by 20%. Our results show that it is feasible to apply this large-area, small-volume whole-cell biosensor for drug discovery, where the binding assays that are commonly used to provide high-throughput need to be complemented with a functional assay.Solutions are brought onto the sensor by a simple pipette, making the use of an industrial microtiterplate dispenser feasible on a nx96-array of the microcalorimeter biosensor. Such an array of biosensors has been designed based on a new set of requirements as set forth by people in the field.

Lable-free biosensor based on localized surface plasmon resonance in a multi-channel microfluidic chip

A label-free biosensor based on localized surface plasmon resonance (LSPR) was developed. A multi-channel microfluidic chip was integrated with the sensor, providing referencing channel to minimize noise level and improving the throughput. With a CCD as a detector, a sensitivity of 10™4 RIU was demonstrated. The adsorption of S-layer protein was detected successfully by the sensor system.

Fabrication and modeling of a silicon micro calorimeter

A prototype micro calorimeter was fabricated by IC technology processes and micromachined post-processing techniques. A rubber membrane supports two identical chambers, situated at the cold and hot junction sites of a thermopile. The thermopile consists of 666 aluminum/p/sup +/-polysilicon thermocouples. The power and temperature sensitivity of the sensor are 23 V/W and 130 mV/K, respectively. The response time of the sensor in air is 12 s. The chamber floors are 1 cm/sup 2/, while the chamber volumes are 10 to 600 /spl mu/l. This high surface to volume ratio is a requirement set by the application area of surface chemistry, for which the sensor was custom designed. In order to be able to redesign the sensor to fulfil other application requirements, the prototype sensor was modeled. Two of the model parameters, the thickness of the silicon layer on the rubber support layer and the convection coefficient in air, could not be determined by means available to us. Their values were adapted until the sensitivity, as simulated with ANSYS5.3 software, and the measured value were equal. The sensitivity was further checked by analytically solving the electrical equivalent circuit of the model.

The use of liquid rubber in micromachining focussed on flexible large area biocompatible membranes

This paper reports on a novel micromachining technique for fabricating rubber membranes with an area of tens of square centimetres and a thickness of a few micrometers. In the basic technique a silicon wafer is spincoated with liquid rubber, bonded to a second (sacrificial) wafer and locally thinned out by anisotropical wet etching. The potential of the technique is highlighted in a demonstration example where a 20 cm/sup 2/ large biocompatible membrane is used to mechanically support and thermally isolate a large active area thermopile in a microcalorimeter for medical use.