Abstract
A microfluidic probe (MFP) is a mobile channel-less microfluidic system under which a fluid is injected from an aperture into an open space, hydrodynamically confined by a surrounding fluid, and entirely re-aspirated into a second aperture. Various MFPs have been developed, and have been used for applications ranging from surface patterning of photoresists to local perfusion of organotypic tissue slices. However, the hydrodynamic and mass transfer properties of the flow under the MFP have not been analyzed, and the flow parameters are adjusted empirically. Here, we present an analytical model describing the key transport properties in MFP operation, including the dimensions of the hydrodynamic flow confinement (HFC) area, diffusion broadening, and shear stress as a function of: (i) probe geometry (ii) aspiration-to-injection flow rate ratio (iii) gap between MFP and substrate and (iv) reagent diffusivity. Analytical results and scaling laws were validated against numerical simulations and experimental results from published data. These results will be useful to guide future MFP design and operation, notably to control the MFP “brush stroke” while preserving shear-sensitive cells and tissues.
Highlights
A microfluidic probe (MFP) is a mobile channel-less microfluidic system under which a fluid is injected from an aperture into an open space, hydrodynamically confined by a surrounding fluid, and entirely re-aspirated into a second aperture
Open microfluidic systems overcome some of these problems by using hydrodynamic flow confinement (HFC) to confine a fluid stream such as in microfluidic probes (MFP)[4,5,6] or capillary effects to confine droplets between a probe tip and a surface, such as in the “chemistrode” configuration[10,7,8]
Using the HFC property of MFPs, reagents injected by the probe can be confined within close proximity of the probe, allowing their delivery to a surface with high spatial resolution and lower shear stress than in channel-based microfluidics systems
Summary
A microfluidic probe (MFP) is a mobile channel-less microfluidic system under which a fluid is injected from an aperture into an open space, hydrodynamically confined by a surrounding fluid, and entirely re-aspirated into a second aperture. Fashion[4], maskless lithography by dissolving photoresist on a coated surface[10], lysis of human breast cancer cells and collecting and analysis of mRNA released from the lysate[11], pharmacokinetic studies on cells[12], staining of tissue sections13,analysis of neutrophil dynamics during chemotaxis[14,15], and perfusion of organotypic brain slices[16] In all these studies[17], the MFP design, flow rates and gap height were optimized empirically and calibrated experimentally based on a trial and error method. Their hydrodynamic pressure measurements at several points underneath the probe, supported by numerical models and relevant pressure scales thoroughly confirm the validity of potential flow assumptions when modeling the flow behavior under the probe Their analysis does not provide an analytical framework to quantify neither advection nor diffusion in two-aperture MFPs. Advection and diffusion are essential parameters to operating MFPs and control diffusion gradient generation, shear stress at the surface, confinement area, and the effect of port geometry. The shear stress on the substrate was calculated for various operating conditions and a working range based on the tolerance of cells to shear stress was established
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