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.
We describe a method for integrating information from lens design into image system simulation tools. By coordinating these tools, image system designers can visualize the consequences of altering lens parameters. We describe the critical computational issues we addressed in converting lens design calculations into a format that could be used to model image information as it flows through the imaging pipeline from capture to display. The lens design software calculates information about relative illumination, geometrical distortion, and the wavelength and field height dependent optical point spread functions (PSF). These data are read by the image systems simulation tool, and they are used to transform the multispectral input radiance into a multispectral irradiance image at the sensor. Because the optical characteristics of lenses frequently vary significantly across the image field, the process is not shift-invariant. Hence, the method is computationally intense and includes a number of parameters and methods designed to reduce artifacts that can arise in shift-variant filtering. The predicted sensor irradiance image includes the effects of geometric distortion, relative illumination, vignetting, pupil aberrations, as well as the blurring effects of monochromatic and chromatic aberrations, and diffraction.
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