Micropatterning of Digital Microfluidic Chips: Applications in Bio-Assay Development and Materials Synthesis

Digital microfluidics (DMF) emerged recently as a promising liquid handling technology for a wide variety of applications. DMF chips manipulate individual fluid droplets on planar surfaces by using electrostatic actuation forces. By applying series of electrical potentials to arrays of electrodes coated with a hydrophobic insulator, droplets containing reagents and samples can be transported, split, merged, mixed, and dispensed from fluid reservoirs. DMF is capable of manipulating low volumes of scarce samples and expensive reagents with great precision, while enabling parallelization and automation of fluid handling for high-throughput applications. DMF has been applied in diagnostics, biology, and chemical synthesis for which it demonstrated great potential both in terms of miniaturization and automation. Recent research demonstrated that the introduction of hydrophilic, functional zones in the fluorocarbon chip surfaces has the potential to enable a new fluidic operation called passive dispensing. In passive dispensing, tiny fluid volumes are deposited onto these hydrophilic elements when a droplet passes over them due to their selective wettability compared to the fluorocarbon layer. However, the exploration of this technique is hindered by the lack of a suitable microfabrication technique that allows accurate micropatterning of the fluorocarbon chip surface on a biocompatible way. First, a novel microfabrication technique is introduced in order to micropattern hydrophobic fluorocarbon surfaces on a biocompatible way. This novel microfabrication technique facilitates the fabrication of patterns down to low micrometer dimensions inside the fluorocarbon chip surface, while biomolecules can be selectively deposited inside these micropatterns with great precision. As such, DMF devices containing hydrophilic cell adhesion islands were fabricated for performing automated and miniaturized cell-based applications. When droplets containing suspended mammalian cells were transported over these cell adhesion islands, nanoliter droplets are split off from the original droplet and remain on the hydrophilic islands. This facilitates fully automated seeding, culturing, treating, and staining of cells and demonstrates DMF's great potential for automated drug screening applications. Subsequently, a DMF device is patterned with hydrophilic-in-hydrophobic microwells designed to trap and seal single magnetic microbeads. These microbeads are used to capture single protein or nucleic acid molecules before being printed and sealed inside the microwells on the DMF chip. When a fluorescent reaction is initiated due to the presence of an enzyme or an enzyme-labeled nucleic acid molecule, the fluorophores accumulate inside the small microwells on the chip and ensure sensitive detection of single molecules with fluorescence microscopy. Next, it is shown how micropatterned DMF chips present exciting new ways of performing miniaturized materials synthesis. This is exemplified by the on-chip synthesis of metal-organic frameworks (MOFs), an emerging class of crystalline, porous materials. By transporting droplets of MOF synthesis solutions over hydrophilic-in-hydrophobic micropatches on the DMF chip surface, MOFs can be patterned as arrays of single crystals or crystalline membranes. DMF proved to be an excellent tool for such highly controlled crystal patterning purposes, which will benefit the future applicability of these materials in functional devices. Finally, it is demonstrated that micropatterning the fluorocarbon chip surface enables the integration of optical components on DMF chips for integrated, on-chip sensing of droplet contents. Therefore, silicon microring resonator sensors were integrated in the DMF chip and were directly contacted by fluid droplets where the fluorocarbon chip surface was locally removed. This facilitated integrated optical sensing of droplet content in an automated and plug-and-play setting.status: publishe