An integrated digital microfluidic lab-on-a-chip for clinical diagnostics on human physiological fluidsThe Science and Application of Droplets in Microfluidic Devices.Electronic supplementary information (ESI) available: five video clips showing: high-speed transport of a droplet of blood across 4 electrodes; sample injection into an on-chip reservoir using an external pipette; droplet formation from an on-chip reservoir using only electrowetting forces; droplets moving in-phase on a 3-phase transport bus;

Abstract

Clinical diagnostics is one of the most promising applications for microfluidic lab-on-a-chip systems, especially in a point-of-care setting. Conventional microfluidic devices are usually based on continuous-flow in microchannels, and offer little flexibility in terms of reconfigurability and scalability. Handling of real physiological samples has also been a major challenge in these devices. We present an alternative paradigm--a fully integrated and reconfigurable droplet-based "digital" microfluidic lab-on-a-chip for clinical diagnostics on human physiological fluids. The microdroplets, which act as solution-phase reaction chambers, are manipulated using the electrowetting effect. Reliable and repeatable high-speed transport of microdroplets of human whole blood, serum, plasma, urine, saliva, sweat and tear, is demonstrated to establish the basic compatibility of these physiological fluids with the electrowetting platform. We further performed a colorimetric enzymatic glucose assay on serum, plasma, urine, and saliva, to show the feasibility of performing bioassays on real samples in our system. The concentrations obtained compare well with those obtained using a reference method, except for urine, where there is a significant difference due to interference by uric acid. A lab-on-a-chip architecture, integrating previously developed digital microfluidic components, is proposed for integrated and automated analysis of multiple analytes on a monolithic device. The lab-on-a-chip integrates sample injection, on-chip reservoirs, droplet formation structures, fluidic pathways, mixing areas and optical detection sites, on the same substrate. The pipelined operation of two glucose assays is shown on a prototype digital microfluidic lab-on-chip, as a proof-of-concept.

Asymmetric electrowetting—moving droplets by a square wave

“…Certainly, a droplet can also be regarded as an independent liquid compartment, where chemical and biological reactions take place, and applied to lab-on-a-chip or m-TAS. 9,10 Electrowetting is one of the mechanisms to drive droplets, which is advantageous as the size of the droplet shrinks down for increased surface to volume ratio. Electrowetting-based devices can be divided into two categories depending on the driving scheme and device structure.…”

Electrowetting-Induced Oil Film Entrapment and Instability

“…Quilliet and Berge [9] found theoretically that the balance between electrical forces and the disjoining pressure should give rise to an equilibrium thickness of the films of approximately 10 -20 nm for typical values of the applied voltage. However, despite the importance of these layers-for instance for the reduction of contact angle hysteresis, but also for the protection of the surfaces from adsorption of biomolecules [10,14]their properties and formation mechanism remained elusive in previous experimental studies [11].In the present Letter we study the dynamics of moving contact lines in EW systems with a two-phase configuration, as just described. We show that a layer of oil is indeed entrapped under the drop with an initial thickness that is determined by the hydrodynamics of the moving contact line rather than by equilibrium properties.…”

Cell handling using microstructured membranes

“…Vented capillaries with a hydrophobic barrier [22][23][24] could trap the air bubbles between fluid segments that need to be mixed. Microdroplets on electrowetting platforms 25 have to be formed outside the device by pipetting; their minimum size is limited to the microliter range, and stickiness of blood proteins and cells on the hydrophobic surfaces may be problematic. Finally, valves have been designed to sample sub-microliter volumes of fluid and perform biochemical assays, 26 although the geometry of the valves is not friendly for cells.…”