Recent Research

Controlled nanoconfinement in a microfluidic modular bead array device via elastomeric diaphragm collapse for enhancing biomolecular binding kinetics

Nanoconfinement is used to reduce diffusion limitations during biomolecular binding reactions in micro/nanofluidic environments. Under nanoconfined conditions, biomolecules experience an increased collision frequency, thereby enhancing binding efficiency. In this study, we employed a controllable deformation of an elastomeric diaphragm, which collapses onto microbeads featuring micropillar structures to create a nanoconfined space between the diaphragm and the bead surfaces. In addition, liquid-metal-based sensors are integrated within the diaphragm to provide real-time measurements of its displacement. Through a continuous and dynamic operation mode, a microbead array-based microfluidic device is established, offering efficient mixing. The device’s performance was validated using two biomolecular reaction models. In the case of thiol-modified DNA probe immobilization, the nanoconfined environment reduced the reaction time from over one hour to just six minutes. For the protein–aptamer binding reaction, the aptamer binding amount was enhanced by approximately 20-fold within five minutes, with strong binding specificity. This device offers promising potential for high-throughput biomolecular interaction screening, enabling simultaneous binding reactions between multiple targets and ligands, and is beneficial for drug development and biosensor applications. This research is a collaborative effort by Dr. Chia-Fu Chou, Dr. Deng-Kai Yang, and Dr. Jui-Hong Weng from the Institute of Physics, Academia Sinica, along with Dr. Nathan Swami and PhD candidate Abdullah-Bin Siddique from the University of Virginia. The results have been published in Small 2025, 2412474.

Journal Links: https://doi.org/10.1002/smll.202412474