Using bioinspired thermally triggered liposomes for high-efficiency mixing and reagent delivery in microfluidic devices.

High-efficiency mixing is of fundamental importance for the successful development and application of lab-on-a-chip devices. In this report, we present the use of bioinspired thermally triggered liposomes for the controlled delivery and subsequent rapid mixing of reagents in a microfluidic device. In this technique, reagents are encapsulated inside the aqueous interior of liposomes that are dispersed evenly throughout a microfluidic system. Mixing of the encapsulated reagent and reaction do not occur until the reagent is released by a thermal trigger. This approach takes advantage of the dramatically increased lipid membrane permeability of liposomes near the gel-to-liquid phase transition temperature (T(m)) to deliver reagents at a precise location in the microfluidic device through the modulation of temperature. Implementation of this technique requires the encapsulation of the desired reagent in a liposome whose formulation has an appropriate T(m), as well as accurate spatial control of the temperature in the microfluidic device. As the liposomes are uniformly dispersed through the microfluidic channel, mixing occurs quite rapidly upon the release of the reagent. We demonstrate this technique by using several formulations of thermally triggered liposomes to release the hydrophilic fluorescent dyes at controlled locations in a polycarbonate microfluidic device. Additionally, we demonstrate a DNA labeling reaction using liposomes in a capillary-based microfluidic device. Under the conditions studied here, mixing and reaction are complete in approximately 200 microm of channel length. We believe this approach holds great promise for the performance of rapid high-throughput assays and in particular for biological analytes whose native environment is mimicked by the liposome.