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High-throughput droplet-based microfluidic optical calorimeter
Conferences & Talks


5 February 2018



Screening campaigns, including high-throughput screening (HTS), often rely on assays using labeled ligands or enzyme substrates. The attachment of fluorescent tags, development of fluorescent substrates, or immobilization of reactants requires additional assay development time, and these modifications of the ligand or substrate can have adverse effects on binding/catalysis, leading to false positives/false negatives. A label-free, solution-based HTS method will help identify compounds acting specifically on the intended targets with the added benefit of a shorter assay development time. We have developed a novel microfluidic calorimeter to measure the enthalpy change of reactions occurring in 100 µm diameter aqueous droplets in fluoropolymer oil. Aqueous reactants are flowed into a microfluidic droplet generation chip, and the temperature change in the droplets due to the heat of reaction is measured optically by recording the reflectance spectra of encapsulated thermochromic liquid crystals (TLC) that are added to one of the reactant streams. As the droplets traverse the microfluidic channel, the peak spectral reflectivity of the TLC tracks the internal temperature, enabling optical temperature measurements with a precision of approximately 5 mK. Position-resolved optical temperature measurements of the droplets allow calculation of the heat of reaction by analyzing the droplet temperature profile over time. Compared to conventional microcalorimeters, this new continuous flow droplet calorimeter has the potential to perform titrations ?1000-fold faster while using ?400-fold less reactants per titration.