PhaseScan: A High-Throughput Microfluidic Platform for Biomolecular Condensate Analysis and Drug Discovery

Abstract: Condensates are membraneless organelles within cells, composed of proteins and nucleic acids, playing critical roles in maintaining cellular homeostasis. These biomolecular assemblies are integral to various cellular processes, and their perturbations can lead to diseases such as cancer and neurological disorders.

Understanding the phase behavior of biomolecules is crucial for elucidating the mechanisms of condensate assembly and developing therapeutic strategies targeting these systems. Traditionally, phase diagrams, which are key to characterizing phase-separating systems, are constructed from numerous individual measurements. This conventional method is slow, low throughput, and requires significant sample consumption.

To overcome these challenges, we introduce the PhaseScan platform, a droplet microfluidic technology designed for the rapid and high-resolution acquisition of multidimensional biomolecular phase diagrams. We have developed an automated instrument capable of handling compounds stored in a standard well-plate format and delivering them into a custom-made microfluidic consumable in a highly repeatable manner. Utilizing our proprietary in-house screening instrumentation, PhaseScan enables large-scale quantitative studies of small molecule effects on biomolecular phase transitions, representing a significant breakthrough in the study and manipulation of biomolecular condensates.

In this talk, we will demonstrate the capabilities of PhaseScan by showcasing its application in identifying novel, functionally active small-molecule modulators for several projects within our discovery pipeline. This innovative technology promises to accelerate the understanding and therapeutic targeting of biomolecular condensates, paving the way for new treatments for diseases associated with condensate dysfunction.