(257r) Developing highly sensitive chip nanocalorimeters based on the thermoelectric effect

Microcalorimeters have great potential as biosensors due to their ability to make measurements on very small samples and their short thermal equilibration times. They are not, however, sensitive enough to analyze nano/micro-scale samples or individual cells, and fluid handling is a critical issue. This work aims to break through the current limitations by measuring sub nano-Watt power levels quantitatively through use of micromachined sensors. Individual sensors consist of a combination of thermistors and thermopiles on a thin silicon nitride membrane that allow direct differential measurements between a sample and a reference. To maximize sensitivity, sensor geometry and materials were optimized based on the temperature field that develops around a typical sample and on calculations of the corresponding noise equivalent power and minimum detectable power (P_min). Specifically, thermopiles that consist of Constantan and Nichrome couples are capable of sensing below nW level power over a broad range of thermopile lengths, 10 - 10³ µm. Arrays of calorimeter sensors were fabricated using silicon micromachining techniques and characterized as a function of thermopile dimensions. We use a similar thermopile design to fabricate a flexible sensor array based on polymer membranes to facilitate integration with various fluid handing techniques. This highly sensitive thermopile-based calorimeter offers particular promise for quantitative measurement of cellular bioenergetics and systems that are limited in analytic volume.