Systematic analysis of microfluidic probe design and operation

Microfluidic probes are an emerging tool used in a wide range of applications including surface biopatterning, immunohistology, and cell migration studies. They control flow above a surface by simultaneously injecting and aspirating fluids from a pen-like structure positioned a few tens of microns above a surface. Rather than confining flows inside microchannels they rely on recirculating flow patterns between the probe tip and the substrate to create a hydrodynamic flow confinement (HFC) zone in which reagents can be locally delivered to the surface. In this paper, we provide a theoretical model, supported by numerical simulations and experimental data, describing the extent of the HFC as a function of the two most important probe operation parameters, the ratio of aspiration to injection flow rate, and the distance between probe apertures. Two types of probes are studied: two-aperture microfluidic probes (MFPs) and microfluidic quadrupoles (MQs). In both cases, the model yields very accurate results and suggests a simple underlying theory based on 2D potential flows to understand probe operation. We further highlight how the model can be used to precisely control the probe´s “brush stroke” while in surface patterning mode. The understanding of probe operation made possible through the provided analytical model should lay the bases for computer-controlled probe calibration and operation.