Microcalorimetry is a critical technique for the measurement of cell metabolism, the identification of drug effects on specific cell types, and the study of protein folding, structural transitions and other biological phenomena. We propose to revolutionize this field with a micromachined biocalorimeter that is faster (15 msec time constant) than conventional devices, more sensitive (2 picocalories for 10 second integration) and inexpensive enough to be disposable. The device will feature one or more sample spaces etched into a silicon chip. Unlike earlier micromachined calorimeters, the high sensitivity is obtained in air, and without the need of a surrounding vacuum, making the new device ideal for studies of cellular metabolism. The high sensitivity will enable detection of much smaller sample volumes than ever before, thereby reducing the time to prepare and investigate many biological reactions. It will also permit the detection of metabolic changes in many fewer cells than before, in some cases in a single cell. Besides basic research in cellular metabolism, enzyme function, functional genomics, and others, disposable """"""""PicoCalorimeters"""""""" will have a major commercial application to drug development and evaluation, and the detection of a wide range of toxins in liquid samples.
The proposed """"""""PicoCalorimeter"""""""" will enable pharmaceutical researchers to evaluate the effects of experimental drugs on specific cell types, in a rapid, disposable test that will require very small volumes of drug. They will also contribute to an understanding of gene function, by identifying protein folding and other transitions controlled by genes.
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