Development of high-sensitivity chip calorimeters for cellular metabolic heat sensing

TL;DR

This paper introduces high-sensitivity chip calorimeters with integrated microfluidics and thermistors, enabling precise, label-free measurement of cellular metabolic heat, advancing cell biology research and drug discovery applications.

Contribution

Development of a microfluidic chip calorimeter with enhanced power resolution and reliable fabrication for measuring cellular metabolic heat.

Findings

Achieved temperature resolution of ~15 μK.

Demonstrated measurements with both adherent and nonadherent cells.

Three orders of magnitude improvement in volume-specific power resolution.

Abstract

Cellular metabolic rate is a good indicator of the physiological state of cells and its changes, which can be measured by total heat flux accompanying metabolism. Chip calorimeters can provide label-free and high throughput measurements of cellular metabolic rate, however, lack of high power resolution and microfluidic sample handling capability has been preventing their wide applications. We report high-resolution chip calorimeters integrated with thin-film parylene microfluidics, which can reliably measure metabolic heat from mammalian cells with controlled stimuli. The molding and bonding technique allowed fast and reliable parylene microfluidic channel fabrications and highly sensitive vanadium oxide thermistor enabled temperature resolution as small as ~ 15 {\mu}K, which led to a three-orders-of-magnitude improvement in volume specific power resolutions. Measurements of metabolic heat were successfully demonstrated with adherent and nonadherent cells. We expect the chip calorimeter will provide a universal platform for fundamental cell-biology studies and biomedical applications including cell-based assay for drug discovery.