Calorimetry is a label-free technique that can provide valuable insight into the thermodynamics of drug binding important to drug design and development. Nonetheless, conventional isothermal titration calorimetry is not used in highthroughput drug screening campaigns due to its high sample consumption and limited throughput. In previous work, we demonstrated an optical analog that involves measurements of the spectral reflectance of thermochromic liquid crystal (TLC) particles, and employs microfluidics to enable rapid measurement of reaction enthalpy in sub-nanoliter aqueous droplets. To optimize system performance, we have evaluated mixing of reactants in droplets with a custom-fabricated microfluidic chip. In addition, we constructed a large area illuminator and dichroic detection blocks to scale to multiple detection points along the droplet travel direction to probe the droplet temperature at several time points. Our platform’s current temperature resolution of 3 mK is on the same order as commercial ITCs and 10-fold better than most nanocalorimeters. This label-free microfluidic calorimeter with scalable optical read-out has the potential to accelerate the process of drug discovery in high-throughput screening campaigns.
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