Towards the development of open-chip digital microfluidics platform

includes bibliographical references and index

PhD; 2023; Centre for Nano Science and Engineering

Manipulating and utilizing fluid flows at microscale provides several
opportunities towards technological advancement in different domains such as (but not
limited to) lab-on-chip devices for mimicking biological laboratory settings in an
automated manner, wearable devices for continuous health monitoring, body-on-chip
devices towards personalized medicine goal, electronics cooling techniques for efficient
thermal management of semiconductor devices. Engineering such microscale fluid flow
devices comes under the study of microfluidics. There has been various development in
continuous, droplet and digital microfluidics approach. The microfluidic technology has
potential to automate the laboratory procedures while reducing the sample and reagent
consumption during analysis. However, there is plenty of room towards a fully
integrated lab-on-chip platform comprising of all the steps such sample preparation,
analyte separation/enrichments, detection, and final readouts.
In this doctoral work, an attempt has been made towards development of open digital
microfluidics platform that can be integrated with channel-based microfluidic devices.
The digital microfluidics techniques provide solution for automated sample preparation
by manipulating discrete droplets on a planar substrate. While the channel-based
devices are suitable for downstream analysis of samples e.g., single cell analysis. Thus,
bringing together these two techniques of manipulating fluid will help in the
development of integrated sampling and analysis device. However, the conventional
digital microfluidics devices comprise of squeezed droplets using cover slips. This
prevents accessibility to droplets and integration of other sampling and detection
devices. Thus, open digital devices provide an alternative solution in which droplet is not covered from top side. There are different techniques to manipulate droplets such as
surface acoustic wave (SAW), magnetic actuation, DEP and electro actuation. In this
work, electrowetting-on-dielectric (EWOD) based digital microfluidics devices has been
used. Open-chip droplet manipulation using electrowetting enables micro-total-analysis
systems with multiple sensor integration and re-routing capabilities. In literature,
researchers have explored unit processes like droplet transport and mixing on openchip digital microfluidics platform. But splitting of droplet has always been considered
as bottleneck. The splitting of droplet is crucial for sample separation and creating
dilution ratio.
Initially, the challenge in open-chip droplet splitting is explored. An energy-based
simulation modes is developed using surface evolver. It shows that splitting a sessile
water droplet is impossible on an open-chip configuration because of the low pad
contact angle requirement. Low contact angles cannot be achieved due to contact angle
saturation in electrowetting. Further, the splitting of surfactant-loaded single-phase
sessile droplets is presented and explain it using a preferential surface charging
phenomenon.
Later, an alternative solution has been proposed for droplet splitting using compound
droplet (droplet is engulfed in an oil shell). The planar electrode configurations and
regime of electrowetting numbers for which splitting can be achieved are identified. It
was observed that larger gaps and higher electrowetting numbers favour symmetrical
splitting because the electrostatic force driving the actuation is significantly higher than
the retarding interfacial forces. Conversely, asymmetrical splitting has been obtained
when the actuation force is barely sufficient In the later part of the thesis, a scalable open EWOD device is presented that can be used
for study of multi-droplets non-coalescence phenomenon using compound droplets. The
droplet non-coalescence is an interesting phenomenon that is observed in nature. This
phenomenon of non-coalescence is slightly counter-intuitive as we expect liquid
interfaces of the same surface tension to merge when they come in contact. However,
with the help of modulating oil film in between the liquid interface, non-coalescence is
observed for long durations. In this work, we have achieved the non-coalescence of
multiple compound droplets on a coplanar EWOD device. The effect of droplet volume
on the non-coalescence phenomenon has been studied in two-droplet systems. We have
obtained the non-coalescence regime map for different operating parameters of applied
voltage and frequency. We have also explored three-droplet systems and obtained a
non-coalescence regime.
For developing an integrated platform there is a need for channel-based sampling and
analysis device which can be integrated with digital microfluidic sample preparation
platform. However, for controlled sampling, in-situ pressure measurement is very
important. The pressure measurement in a microfluidic device is useful for several other
purposes as well such as fluid flow effect study on cells, measurement of mechanical
properties of cells, etc. This work presents a cleanroom-free and simple technique to
integrate pressure sensor in microfluidic devices. In this work, we demonstrated a novel
technique of patterning Ti3C2-MXene on PDMS membrane using inkjet printing. We
showed the piezoresistive response of inkjet printed MXene that has high sensitivity and
can detect low strain value of 0.0003. The response time of the sensor is around 200 ms.
The printed layer has been tested for 9000 cyclic loading for durability test and it shows very consistent behaviour. The printed MXene layer has been used as pressure sensor in
closed-chip microfluidic device. We developed a simple way to integrate sensors by
transferring thin PDMS layer followed by sensor integration using inkjet printing. Later,
we demonstrated the applicability of our process to print Wheatstone bridge on
microfluidic device to measure pressure. We also demonstrated touch sensor,
temperature sensor and ultra-sensitive pressure sensor by using 8 microns thick PDMS
membrane. This technique provides a way for localized pressure sensing in the
microfluidic device with simple electrical readout and opens further prospect to study
strain effect on endothelial cells, deformability of cells in microfluidic flow cytometry,
etc.
In the future work, the complete idea of integrated platform is presented that has been
envisioned to have multiple robotic limbs each armed with different sampling and
analysis device