Hydrogel microspheres are sought
for a variety of biomedical applications,
including therapeutic and cellular delivery, sensors, and lubricants.
Robust fabrication of hydrogel microspheres with uniform sizes and
properties can be achieved using microfluidic systems that rely on
droplet formation and subsequent gelation to form microspheres. Such
systems work well when gelation is initiated after droplet formation
but are not practical for timed gelation systems where gelation is
initiated prior to droplet formation; premature gelation can lead
to device blockage, variable microsphere diameter due to viscosity
changes in the precursor solution, and limited numbers of microspheres
produced in a single run. To enable microfluidic fabrication of microspheres
from timed gelation hydrogel systems, an in situ mixing
region is needed so that various hydrogel precursor components can
be added separately. Here, we designed and evaluated three mixing
devices for their effectiveness at mixing hydrogel precursor solutions
prior to droplet formation and subsequent gelation. The serpentine
geometry was found to be the most effective and was further improved
with the inclusion of a pillar array to increase agitation. The optimized
device was shown to fully mix precursor solutions and enable the fabrication
of monodisperse polyethylene glycol microspheres, offering great potential
for use with timed gelation hydrogel systems.