96-Well plate has been the traditional method used for screening drug compounds libraries for potential bioactivity. Although this method has been proven successful in testing dose-response analysis, the microliter consumption of expensive reagents and hours of reaction and analysis time call for innovative methods for improvements. This work demonstrates a droplet microfluidic platform that has the potential to significantly reduce the reagent consumption and shorten the reaction and analysis time by utilizing nanoliter-sized droplets as a replacement of wells. This platform is evaluated by applying it to screen drug compounds that inhibit the tau-peptide aggregation, a phenomena related to Alzheimer's disease. In this platform, sample reagents are first dispersed into nanolitre-sized droplets by an immiscible carrier oil and then these droplets are trapped on-demand in the downstream of the microfluidic device. The relative decrease in fluorescence through drug inhibition is characterized using an inverted epifluorescence microscope. Finally, the trapped droplets are released on-demand after each test by manipulating the applied pressures to the channel network which allows continuous processing. The testing results agree well with that obtained from 96-well plates with much lower sample consumption (∼200 times lower than 96-well plate) and reduced reaction time due to increased surface volume ratio (2.5 min vs 2 h).

Automated control of individual droplets in microfluidic channels offers tremendous potential for applications requiring high accuracy and minimal user involvement.

With its ability to continuously separate and collect charged analytes, free-flow electrophoresis (FFE) has become a useful tool for the purification and real-time analysis of biological mixtures. This work presents a new free-flow counterflow gradient focusing (FF-CGF) mechanism that uses a novel velocity gradient to counterbalance electrophoretic migration. This counterflow gradient is created by simply introducing fluid flow through the sidewalls of the FFE chamber. The theoretical foundation and device design for FF-CGF are provided in this work, followed by implementation and validation, with a detailed discussion on future opportunities and challenges. Initial results show promise, with the potential to improve FFE resolution and offer versatility. Compared to existing focusing techniques, such as free-flow isotachophoresis and isoelectric focusing, no complex buffer compositions are required.

Free‐flow electrophoresis (FFE) enables the continuous separation and collection of charged solutes, and as a result, it has drawn interest as both a preparative and an analytical tool for biological applications. Recently, a free‐flow counterflow gradient focusing (FF‐CGF) mechanism has been proposed with the goal of improving the resolution and versatility of FFE. To realize this potential, the factors that influence solute dispersion deserve further attention, including the gradient strength and the parabolic profile of the counterflow. Therefore, the goal of this work is to develop a theoretical model to study the interplay between these factors and molecular diffusion. Overall, an asymmetric solute distribution emerges for a wide range of parameters, and this behavior can be characterized with an exponentially modified Gaussian function. Results show that FF‐CGF can achieve high‐resolution separations, with the potential for high‐throughput protein purification. Moreover, this work provides a practical guide for optimizing experimental conditions, as well as a strong framework for understanding and developing FF‐CGF further.