High-throughput screening (HTS) is an essential step in the discovery and development of novel therapeutics. Droplet-based and continuous-flow microfluidic platforms offer improved sensitivity, reduced cost, and enhanced physiological relevance compared with conventional screening technologies such as microplates and flow cytometers. However, a challenge towards unlocking the full potential of microfluidic platforms for HTS in academic and industrial settings is the development of designs that accelerate the exploration of massive design spaces for insights beyond bulk measurements. While droplet-based microfluidics have been used to screen large libraries of enzyme variants and cell types with single-molecule and single-cell level resolution, these approaches are primarily limited to fluorescence-based assays at throughputs up to the 10 kHz range. Although continuous-flow microfluidic systems have been used to perform combinatorial drug screens across cell cultures, a lack of reliable strategies for reversible cellular access and incompatibility with certain single-cell manipulation techniques has hindered their functionality for high control, high throughput cellular assays.

In this talk, we discuss our work towards addressing these challenges, specifically by presenting two types of microfluidic platforms that enable accessible, throughput-scalable screening of functional biomolecules in biochemical and cellular assays. We present a microfluidic device that enables deformation-based separation of microgels using sequential bifurcations at moderate inertia. We investigate the dynamics of dilute suspensions of viscoelastic particles in confined microfluidic channels and demonstrate the utility of the device for enzymatically catalyzed hydrogel degradation assays. Additionally, we present our work to engineer a reversibly-sealable microfluidic platform for multi-molecule gradient delivery to large adherent cell cultures. We evaluate the spatiotemporal control of physiochemical gradients across centimeter-scale areas and show the power of the approach to simultaneously deliver combinations of multiple molecules to cells with tunable flow-induced shear stresses. In summary, our microfluidic platforms have the potential to identify optimal biomolecular at throughputs relevant for the discovery of drug candidates to address unmet therapeutic needs.