1. INVESTIGATION OF BURSTING OF HEATED DROPLETS FOR CHEMISTRY APPLICATIONS IN
DIGITAL MICROFLUIDICS
Gaurav J. Shah1,2*
, Andres Saucedo2
, Steven Jen-Zhu Pan2
and R. Michael van Dam2
1
Sofie Biosciences, Culver City, CA, USA, and
2
Department of Molecular & Medical Pharmacology and Crump Institute for Molecular Imaging, University of California Los Angeles (UCLA), Los Angeles, CA, USA
Background: Digital microfluidics for chemistry Motivation: Miniaturized high-temperature chemistry platform
Results and Discussion
Conclusions
Financial support from the Department of Energy Office of Biological and
Environmental Research (DE-SC0001249, DE-SC0005056) is greatly appreciated.
Droplet bursting at high temperatures
Envisioned microchemistry platform:
Automated, remotely-operated benchtop platform
“Consumables kit” is installed at start of each batch
 Reagents, EWOD chip and all fluidic
components
 Wetted components are single use, disposable
Automated, remote operations: reagent input, on-
chip high-temperature chemistry, product collection
Specific application: Radiochemistry for positron
emission tomography (PET) probes
Acknowledgment
Reactor Microreactor chip
React/evaporate (Heat, mix)
Add reagents
Reagent
droplet
Reagent
Reaction
mixtureReaction
mixture
Treact
Heat
Treact
Heat
Digital microfluidics on “EWOD” chip
Electrowetting-on-dielectric  electrical control of
fluid position
Electrode array buried under dielectric and
hydrophobic layers
Droplet paths controlled by voltage sequence applied
to electrodes
What is “digital microfluidics” (DMF)?
Manipulation of liquids in the form of discrete (digitized)
droplets
Droplets (typically 0.5-20 µL) are created, moved,
merged, split, reacted on-chip
High-temperature chemistry on digital
microfluidics platform
Microvolumes could reduce reagent consumption,
heating time, reaction time, contamination etc.
Heating can be provided on-chip (e.g. Joule heating) or
external heat source placed in contact with chip
Digital microfluidic reactor is at heart of the
microchemistry platform:
Reagents are introduced into heater region by EWOD
Heating is needed for evaporation and/or to speed up
biochemical reaction steps
Often need to heat above solvent boiling point (b.p.)
Above b.p., vapor pressure of gas bubble inside droplet
exceeds atmospheric pressure  could cause “bursting”
Reaction
mixture
Heater region
Heater region
Droplet before burst After droplet burst
Splattered
fragments
Droplet bursting in EWOD digital microfluidics during high
temperature reactions: Droplet (dotted blue line) being
heating by on-chip resistive heaters (inside dashed black
circle) on an EWOD chip. During high temperature reaction
steps, where the surface temperature needs to be above
the solvent boiling point, the droplet can sometimes burst or
splatter, causing loss of product and possible
chemical/radiation hazards. Our aim was to investigate
factors that influence the likelihood of bursting and thereby
find ways to prevent it.
Glass cover
Sandwiched
droplet
Thermoelectric module
Heated Al block
Spacers
Experimental setup (schematic (top) and image (bottom)) for
droplet bursting experiments. The metal surface is heated by
the thermoelectric module through an Al block below it. The
droplet and the Teflon-coated glass cover are then placed on it.
Droplet volume, gap height (between glass cover and bottom
substrate) and the surface temperature on the bottom substrate
are varied, while noting the frequency of droplet bursting
across multiple experiments.
Vapor pressure of
acetonitrile (blue) vs.
temperature.
Temperatures used in
the experiments range
from ~70 to 100 o
C,
corresponding to vapor
pressures below and
above atmospheric
pressure (red).
Droplets were placed on the preheated
surface, and immediately covered with
the glass cover. Bursting frequency is
influenced by several factors, including
droplet volume, geometry and surface
temperature. e.g. sudden violent
bursting occurs in (a-c), at 91 o
C, 0.34
mm gap in this case, causing the 20uL
droplet to undesirably splatter and/or
deform uncontrollably. On the other
hand, at 91 o
C, 0.51mm gap (d-f), the
20uL droplet evaporates without
bursting. Small droplets around the
central droplet are condensed solvent
vapor.
No bursts are observed below the boiling point, but droplet
evaporation takes very long in these cases. Smaller droplets have
lower bursting tendency, and can thus be heated to higher
temperatures without splattering. Increased gap height also
suppresses bursting. For instance, bursting can be prevented even
in 20 μL droplets instantly heated to ~10o
C above boiling point if
gap of 0.51 mm is used.
Sample image sequences showing the cases of
(a-c) bursting and (d-f) no bursting.
Summary of
results showing
influence of gap
height, droplet
volume and
surface
temperature on
bursting frequency
(n=10 for each).
While droplet bursting is a complex and dynamic phenomenon, processes can be
performed in a controlled manner above the solvent boiling point on a DMF chip
- Key factors include droplet volume, geometry and ramp time to desired
temperature
Future steps include studying the effect of droplet composition and gas-flow, and
utilizing the conclusions to speed up on-chip radiosyntheses