Serial femtosecond
crystallography (SFX) is a powerful technique
that uses X-ray free-electron lasers (XFEL) to determine structures
of biomolecular complexes. Specifically, it benefits the study of
atomic resolution structures of large membrane protein complexes and
time-resolved reactions with crystallography. One major drawback of
SFX studies with XFELs is the consumption of large amounts of a protein
crystal sample to collect a complete X-ray diffraction data set for
high-resolution crystal structures. This increases the time and resources
required for sample preparation and experimentation. The intrinsic
pulsed nature of all current X-ray sources is a major reason why such
large amounts of sample are required. Any crystal sample that is delivered
in the path of the X-ray beam during its “off-time”
is wasted. To address this large sample consumption issue, we developed
a 3D printed microfluidic system with integrated metal electrodes
for water-in-oil droplet generation to dynamically create and manipulate
aqueous droplets. We demonstrate on-demand droplet generation using
DC potentials and the ability to tune the frequency of droplet generation
through the application of AC potentials. More importantly, to assist
with the synchronization of droplets and XFEL pulses, we show that
the device can induce a phase shift in the base droplet generation
frequency. This novel approach to droplet generation has the potential
to reduce sample waste by more than 95% for SFX experiments with XFELs
performed with liquid jets and can operate under low- and high-pressure
liquid injection systems.