Hierarchical Hydrodynamic Flow Confinement: Efficient Use and Retrieval of Chemicals for Microscale Chemistry on Surfaces

Abstract

We devised, implemented, and tested a new concept for efficient local surface chemistry that we call hierarchical hydrodynamic flow confinement (hierarchical HFC). This concept leverages the hydrodynamic shaping of multiple layers of liquid to address challenges inherent to microscale surface chemistry, such as minimal dilution, economical consumption of reagent, and fast liquid switching. We illustrate two modes of hierarchical HFC, nested and pinched, by locally denaturing and recovering a 26 bp DNA with as little as 2% dilution and by efficiently patterning an antibody on a surface, with a 5 μm resolution and a 100-fold decrease of reagent consumption compared to microcontact printing. In addition, valveless switching between nanoliter volumes of liquids was achieved within 20 ms. We believe hierarchical HFC will have broad utility for chemistry on surfaces at the microscale.

Rapid Subtractive Patterning of Live Cell Layers with a Microfluidic Probe

“…The ratio of injection flows (Q I2 /Q I1 ) allows us to further modulate the size of the hHFC footprint ( Figure 3D and Figure 4B), with the underlying principle elaborated by Autebert et al 14 . Using the liquidshaping ability of the hHFC coupled with high-resolution scanning ability of MFP platform, we demonstrate live-cell grid generation at multiple scales and furthermore show the application of the given protocol in developing co-cultures ( Figure 4C).…”

“…However, we can address this using the liquid shaping ability of the hHFC. We have demonstrated that the resolution of cell removal can be tuned for a given set of aperture dimensions by controlling Q I2 /Q I1 (Figure 4b) and the apex-to-substrate gap 10,14 . The stages used in the current work has a minimum step size of 100 nm.…”

“…NOTE: The Z-stage controls the head-to-substrate distance, whereas the X-Y stage controls the scanning of the substrate (Figure 2). A detailed explanation can be found in our earlier work 14 .…”

“…This implies liquid flows in laminar regime with convection being the primary mode of mass transfer of chemical species. The numerical and analytical models for flow confinement are described elsewhere [12][13][14] .…”

“…In this paper, we use the approach of simultaneously confining multiple processing liquids, which is called hierarchical HFC (hHFC) 14 . To implement hHFC with the MFP, two additional apertures are needed to provide a secondary source of injection and aspiration.…”