  For high-throughput cell culture and associated analytics, droplet-based
cultivation systems open up the opportunities for parallelization and rapid
data generation. In contrast to microfluidics with continuous flow, sessile
droplet approaches enhance the flexibility for fluid manipulation with usually
less operational effort. Generating biologically favorable conditions and
promoting cell growth in a droplet, however, is particularly challenging due to
mass transfer limitations, which has to be solved by implementing an effective
mixing technique. Here, capillary waves induced by vertical oscillation are
used to mix inside a sessile droplet micro-bioreactor (MBR) system avoiding
additional moving parts inside the fluid. Depending on the excitation
frequency, different patterns are formed on the oscillating liquid surface,
which are described by a model of a vibrated sessile droplet. Analyzing mixing
times and oxygen transport into the liquid, a strong dependency of mass
transfer on the oscillation parameters, especially the excitation frequency, is
demonstrated. Oscillations at distinct capillary wave resonant frequencies lead
to rapid homogenization with mixing times of 2 s and volumetric liquid-phase
mass transfer coefficients of more than 340 h-1. This shows that the mass
transfer in a droplet MBR can be specifically controlled via capillary waves,
what is subsequently demonstrated for cultivations of Escherichia coli BL21
cells. Therefore, the presented MBR in combination with vertical oscillation
mixing for intensified mass transfer is a promising tool for highly parallel
cultivation and data generation.
