A modular diffusion barrier based on phase separation for localized delivery of discrete drug volumes in aqueous environments

Abstract

We present a new tool for the precisely controlled transfer of individual picoliter (pL) droplets in the range of 150–950 pL at user defined local positions within aqueous liquid environments while avoiding any leakage by diffusion. This is achieved by a low-cost, disposable and biocompatible cap that can be placed on top of any pL-dispenser and generates a phase-gap between dispensing agent and target liquid when the dispenser is dipped into the latter. We developed two different working modes: (i) the standard mode enables an instant injection (≪ 1 ms) of the droplet into the liquid environment and (ii) the focus mode further increases the spatial resolution from 100 µm to 50 µm at the cost of slowing down the injection time. For the phase-gap we have proven an excellent long-term stability of more than 30 hours against capillary priming.