Method To Directly Measure and Actively Control a Single Nucleation-Crystal Growth Process

Nucleation and subsequent phase transitions exist broadly in nature and engineered processes, from ice formation to protein crystallization and beyond. The lack of capable methods to analyze and to control the dynamic heterogeneous process is a fundamental problem, and constitutes overwhelming technical challenges in synthesizing crystalline structures with designed/predictable properties. By actively controlling mass transport through a single nano pipette, the extent of supersaturation is adjusted kinetically in a confined space immediately outside the nanopore. Using protein insulin as prototype, the formation of a single atto-femto-liter droplet, subsequent nucleation inside and further growth of a single crystal, is monitored electrically and optically, and actively controlled by an external electrical field. The generalizable method, referred to as nanoAC for nanoscale active control, not just provides fundamental insights at unprecedented single entity resolution, it enables active in situ control of growth of the newly formed phase locally around an individual precursor.