Calorimetry is a label-free technique to study molecular interaction and measure their enthalpy changes in solution. We have developed a microfluidic calorimetry platform that uses optical means to measure these enthalpy changes in sub-nanoliter aqueous droplets. Thermochromic liquid crystals act as optical transducers to convert temperature changes caused by the reaction heat to a shift in their reflectance spectrum. We implemented large area fiber coupled LED illumination optics and multi spot detection along the microfluidic channel to measure the temperature changes in moving microfluidic droplets. To calibrate the temperature response of our system we implemented localized laser heating of individual droplets at 1464nm and monitored the heat dissipation of those droplets in the microfluidic channel. We showed that we can observe milli-Kelvin temperature changes in droplets with millisecond time resolution.
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.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.