Nanoscale Hydrodynamic Film for Diffusive Mass Transport Control in Compartmentalized Microfluidic Chambers

A compartmentalized
microfluidic chamber array that offers not
only separate cell culture environments but also independent control
of the diffusion of small molecules provides an extremely useful platform
for cell cultivations and versatile cellular assays. However, it is
challenging to incorporate both cell compartmentalization and active
diffusion control in real-time and precise manners. Here, we present
a novel nanoscale hydrodynamic film (NHF) that is formed between a
solid substrate and a polydimethylsiloxane (PDMS) surface. The thickness
of the NHF can be adjusted by varying the pressure applied between
them so that the mass transfer through the NHF can also be controlled.
These novel phenomena are characterized and applied to develop a compartmentalized
microchamber array with diffusion-tunable and solution-switchable
chemostat-like versatile bacterial assays. The NHF-based compartmentalization
technique is ideal for not only continuous bacterial cultivation by
consistently refreshing various nutrient sources but also various
diffusion-based microbial assays such as chemical induction of synthetically
engineered bacterial cells and selective growth of a specific bacterial
strain with respect to chemical environments. In addition, we show
that tight compartmentalization protects cells in the chambers, while
biofilm formation and nutrient contamination are eliminated by loading
a lysis buffer, which typically hinders long-term continuous cultures
and accurate microbial assays on a chip. Therefore, we ensure that
the NHF-based compartmentalization platform proposed in this work
will facilitate not only fundamental studies in microbiology but also
various practical applications of microbes for production of valuable
metabolites and byproducts in a high-throughput and highly efficient
format.