Simplified fabrication of complex multilayer microfluidics: enabling sophisticated lab-on-a-chip and point-of-care platforms
Creators: name: Szydzik, Crispin
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 400909
subject: Photonic and electro-optical devices, sensors and systems (excl. communications)

description: Complex multilayer microfluidics have generated a lot of interest in recent years. Early research introduced elastomer microvalves and postulated they would bring about a revolution for microfluidic systems, similar in scale to introduction of the transistor for electronic systems. In the following years, many researchers have been active in the use of complex multilayer microfluidic systems, with numerous high impact research outcomes using these systems as precise and active control components, providing fluidic isolation, switching or fluidic actuation, and allowing unprecedented sophistication and precise control and automation of experimental conditions. While application of complex multilayer microfluidic platforms has been demonstrated in numerous research settings, there is little evidence that the technology has become ubiquitously accepted, with a lack of evidence for point-of-care application, or widespread acceptance within the research community. While the advantages that the technology offers have been well documented, the field seems to have failed to gain traction, or facilitate the revolution that was predicted on its introduction.<br><br>There are various possible explanations for this lack of acceptance, as with any technology, there are caveats to the application of complex multilayer microfluidic systems, however given the broad range of demonstrated applications, it is unlikely that the bottleneck in their application is related to a fundamental application related limitation. In contrast, fabrication technology utilised in realisation of complex multilayer microfluidic systems, has not advanced at the same rate to the multitude of application-based publications in the past decade.<br><br>This thesis explores the hypothesis that one of the fundamental limiting factors in widespread application of complex multilayer microfluidic systems, is related to the challenges associated with fabrication of these systems. To explore this hypothesis, firstly, a new fabrication approach is introduced which aims to eliminate many of the challenges associated with traditional multilayer fabrication methods, this technique is demonstrated in a proof of concept capacity, fabricating common multilayer microfluidic structures and doing so with surprising ease. <br><br>Having developed method with simpler fabrication, it is possible to explore whether overcoming the multilayer fabrication bottleneck would allow the advantages inherent to complex multilayer microfluidic systems to be applied to fields which would otherwise be considered prohibitively difficult, if reliant on traditional fabrication methods. This hypothesis is investigated through harnessing the new, simplified fabrication technique to advance point-of-care photonic biosensor research through short term collaborative engagements.  It is found that the use of modular building blocks and the simple, rapid fabrication enables sophisticated microfluidic chip prototypes to be developed in a very short period of time achieving multiple iterations over a matter of weeks and even facilitating collaboration on these integrated platforms remotely. The outcomes of these short-term collaborations have produced publications automating the fluid handling of highly sensitive interferometric waveguide biosensors and environmental control for a single cell analysis platform utilising integrated plasmonic biosensors.       <br><br>Having demonstrated that simplifying complex microfluidic fabrication can accelerate the development and deployment of these systems to enhance research platforms, the next step was to explore whether this simplified system could also lower the barrier to deployment in a clinical setting. The ability for the fluidic system to handle whole blood was chosen as a deliberately challenging target with great sensitivity to fluid dynamics and large variability in patient samples and environmental factors, requiring large number of replicate devices to determine statistical significance. Here the fabrication technique is applied to enable a study investigating the hemocompatibility of common multilayer control components, paving the way for point of care blood handling devices.  It is shown that not only can the technique be used to rapidly develop platforms that can be used with blood, but the same technique can produce even hundreds of replicates required for limited clinical trials, leading the collaborating clinicians to seriously consider these complex microfluidics for future point of care diagnostics. <br><br>In Summary, it has been demonstrated that access to complex multilayer microfluidic systems without the fabrication overheads generally associated with these systems can allow their application to areas that would otherwise be prohibitively difficult. The fabrication method presented can allow rapid development, and rapid and reliable deployment to various research applications, while allowing the consistency and throughput required enabling large volume fabrication required for clinical investigations.  The fact that such a large advancement toward real world application within the scope of a single PhD is possible, supports the hypothesis that lowering the barrier to fabricating complex microfluidic devices has the potential to significantly increase their scope of application.