A high-throughput silicon microphysiometer

We report on a micromachined silicon chip that is capable of providing a hi gh-throughput functional assay based on calorimetry. A calorimeter has been fabricated by IC technology process steps in combination with micromachine d techniques. A rubber membrane supports two identical chambers, situated at the cold and hot junction sites of a thermopile. The thermopile consists of 666 aluminu m/p(+)-polysilicon thermocouples. The chambers can house up to 10(6) eukary otic cells cultured to confluence, in volumes of 10-600 mu l. Power and tem perature sensitivity of the sensor are 23 V/W and 130 mV/K, respectively. T he response time of the sensor is 70 s, when filled with 50 mu l of water. Biological experiments were done with cultured kidney cells of Xenopus laev is (A6). The thermal equilibration time of the device is 45 min. Basal meta bolism is measured to be 330 pW/cell. Stimulation of transport mechanisms b y reducing bath osmolality by 50% increased metabolism by 40 pW/cell. Stimu lation of transport mechanisms by adding the oxytocin hormone increased met abolism by 106 pW/cell. (C) 2000 Elsevier Science S.A. All rights reserved.