Isotropically etched radial micropore for cell concentration, immobilization, and picodroplet generation.

To enable several on-chip cell handling operations in a fused-silica substrate, small shallow micropores are radially embedded in larger deeper microchannels using an adaptation of single-level isotropic wet etching. By varying the distance between features on the photolithographic mask (mask distance), we can precisely control the overlap between two etch fronts and create a zero-thickness semi-elliptical micropore (e.g. 20 microm wide, 6 microm deep). Geometrical models derived from a hemispherical etch front show that micropore width and depth can be expressed as a function of mask distance and etch depth. These models are experimentally validated at different etch depths (25.03 and 29.78 microm) and for different configurations (point-to-point and point-to-edge). Good reproducibility confirms the validity of this approach to fabricate micropores with a desired size. To illustrate the wide range of cell handling operations enabled by micropores, we present three on-chip functionalities: continuous-flow particle concentration, immobilization of single cells, and picoliter droplet generation. (1) Using pressure differentials, particles are concentrated by removing the carrier fluid successively through a series of 44 shunts terminated by 31 microm wide, 5 microm deep micropores. Theoretical values for the concentration factor determined by a flow circuit model in conjunction with finite volume modeling are experimentally validated. (2) Flowing macrophages are individually trapped in 20 microm wide, 6 microm deep micropores by hydrodynamic confinement. The translocation of transcription factor NF-kappaB into the nucleus upon lipopolysaccharide stimulation is imaged by fluorescence microscopy. (3) Picoliter-sized droplets are generated at a 20 microm wide, 7 microm deep micropore T-junction in an oil stream for the encapsulation of individual E. coli bacteria cells.

Model based design of a microfluidic mixer driven by induced charge electroosmosis.

Mixing chemical or biological samples with reagents for chemical analysis is one of the most time consuming operations on microfluidic platforms. This is primarily due to the low rate of diffusive transport in liquid systems. Additionally, much research has focused on detection, rather than sample preparation. In response, we describe a mixer for microfluidic sample preparation based on the electrokinetic phenomenon of induced-charge-electroosmosis (ICEO). ICEO creates microvortices within a fluidic channel by application of alternating current (AC) electric fields. The microvortices are driven by electrostatic forces acting on the ionic charge induced by the field near polarizable materials. By enabling mixing to be turned on or off within a channel of fixed volume, these electronically controlled mixers prevent sample dilution-a common problem with other strategies. A three-dimensional model based on the finite volume method was developed to calculate the electric field, fluid flow, and mass transport in a multi-species liquid. After preliminary experiments, the model was used to rapidly prototype a wide range of designs. A new microfabrication process was developed for devices with vertical sidewalls having conductive metal coatings and embedded electrodes. Mixing experiments were carried out in the devices and the results were compared to the model.