High-throughput droplet-based microfluidic optical calorimeter

Calorimetry is a powerful label-free technique for characterizing biochemical interactions. However, conventional calorimeters are limited by large sample requirements and low throughput, relegating their use to a limited number of high-value measurements. To increase the throughput and sensitivity of calorimetry, we have developed a novel microfluidic calorimeter that uses optical methods to measure the temperature change caused by reactions occurring in sub-nanoliter droplets. In this calorimeter, a microfluidic system creates a mixed droplet of reactants, a thermochromic liquid crystal (TLC) reporter converts the temperature change to a spectral shift, and a sensitive optical detector measures the spectral shift. Experimental measurements of the temperature change induced in droplets by the exothermic binding of EDTA to Ca2+ show good agreement with a thermal multiphysics model. Our ongoing work to improve the microfluidic mixing of reactants and increase the temperature resolution of the calorimeter has yielded a temperature resolution for this calorimeter of 2.4 mK, which corresponds to an energy resolution of 16 nJ. This resolution is on the same order as commercial isothermal titration calorimeter (ITC) systems and 10-fold better than most nanocalorimeters.