Superimposed Electric Field Enhanced Electrospray for High-Throughput and Consistent Cell Encapsulation.

Cell encapsulation technology, crucial for advanced biomedical applications, faces challenges in existing microfluidic and electrospray methods. Microfluidic techniques, while precise, can damage vulnerable cells, and conventional electrospray methods often encounter instability and capsule breakage during high-throughput encapsulation. Inspired by the transformation of the working state from unstable dripping to stable jetting triggered by local electric potential, this study introduces a superimposed electric field (SEF)-enhanced electrospray method for cell encapsulation, with improved stability and biocompatibility. Utilizing stiffness theory, we quantitatively analyze the stability of the electrospray, whose stiffness is five times stronger under conical confinement. The SEF technique enabled rapid, continuous production of ∼300 core-shell capsules per second in an aqueous environment, significantly improving cell encapsulation efficiency. Our method demonstrated remarkable potential as exemplified in two key applications: 1) a 92-fold increase in human-derived induced pluripotent stem cells (iPSCs) expansion over 10 days, outperforming traditional 2D cultures in both growth rate and pluripotency maintenance, and 2) the development of liver capsules for steatosis modeling, exhibiting normal function and biomimetic lipid accumulation. The SEF-enhanced electrospray method presents a significant advancement in cell encapsulation technology. It offers a more efficient, stable, and biocompatible approach, opening new possibilities in clinical transplantation, drug screening, and cell therapy. This article is protected by copyright. All rights reserved.