A high-throughput silicon microphysiometer

We report on a micromachined silicon chip that is capable of providing a high-throughput functional assay based on calorimetry. A calorimeter has been fabricated by IC technology process steps in combination with micromachined 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(+)-polysilicon thermocouples. The chambers can house up to 10(6) eukaryotic cells cultured to confluence, in volumes of 10-600 mu l. Power and temperature sensitivity of the sensor are 23 V/W and 130 mV/K, respectively. The 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 laevis (A6). The thermal equilibration time of the device is 45 min. Basal metabolism is measured to be 330 pW/cell. Stimulation of transport mechanisms by reducing bath osmolality by 50% increased metabolism by 40 pW/cell. Stimulation of transport mechanisms by adding the oxytocin hormone increased metabolism by 106 pW/cell. (C) 2000 Elsevier Science S.A. All rights reserved.