Towards the development of open-chip digital microfluidics platform

Abstract

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 optical, surface acoustic wave (SAW), magnetic actuation 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 open-chip 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.