A mid-infrared lab-on-a-chip for dynamic reaction monitoring

Mid-infrared spectroscopy is a sensitive and selective technique for probing molecules in the gas or liquid phase. Investigating chemical reactions in bio-medical applications such as drug production is recently gaining particular interest. However, monitoring dynamic processes in liquids is commonly limited to bulky systems and thus requires time-consuming offline analytics. In this work, we show a next-generation, fully-integrated and robust chip-scale sensor for online measurements of molecule dynamics in a liquid solution. Our fingertip-sized device utilizes quantum cascade technology, combining the emitter, sensing section and detector on a single chip. This enables real-time measurements probing only microliter amounts of analyte in an in situ configuration. We demonstrate time-resolved device operation by analyzing temperature-induced conformational changes of the model protein bovine serum albumin in heavy water. Quantitative measurements reveal excellent performance characteristics in terms of sensor linearity, wide coverage of concentrations, extending from 0.075 mg ml^-1 to 92 mg ml^-1 and a 55-times higher absorbance than state-of-the-art bulky and offline reference systems.