A high-throughput silicon microphysiometer

Abstract

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 μl. 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 μl 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.