Volume Management for Pin-Constrained Continuous-Flow Microfluidic Biochips

Microfluidic Biochips integrate functional components for biochemical analysis and sample preparation on a single chip. The implementation of conventional biochemical laboratory equipment on to a chip at sub-millimetre scale offers several advantages. This thesis is focused on continuous-flowbased biochip technology. Here, valves are used as basic building blocks to route reagents as desired along channels. Combining multiple valves allows to build more complex components to mimic the functionality of their conventional laboratory counterparts such as centrifuges, in cubatorsor analysers. Fabrication capabilities of biochips have seen a rapid growth in the last years, further miniaturizing valves to just few µm in size and thereby allowing thousands of components to be placed on a single chip. To keep up with the manufacturing technology, new design methodologies are required, and researchers have started to propose methods and tools for the physical design and programming of biochips. However, these tools have considered simplified models and unrealistic assumptions regarding other parts of the design process. To support the practical use of biochips, we have to consider the practical aspects that bridge the gap from research to functional verification and fabrication. Even though thousands of valves can be integrated on a biochip, their functionality is limited due to the number of control-pins that can be connected to an external controller. that satisfies all constraints while improving the efficiency of mixing operations. Furthermore, moving fluids within a biochip is simply referred to as fluid transport by researchers, ignoring the underlying complexity. Realistic biochip design has to offer the capabilities to provide specific volumes of fluid during the biochip’s operation. We therefore propose a component that provides metering, alignment and missing fluid detection capabilities for fluid transport. Current tools for physical design do not bridge the fabrication gap, which extends in to lacking functional verification. Instead, interdisciplinary specialist knowledge is required to verify, potentially adapt and then turn the synthesized design in to working biochips. Hence, in this thesis we consider three-layernormally-closed valve biochips that use two micromilled Polymethylmethacrylate (PMMA) layers sandwiching a sheet of Polydimethylsiloxane (PDMS), which are easier to fabricate. We have developed a software tool towards a more automated biochip designprocess, reducing the amount of manual and error-prone work required. Aiming to reduce the interdisciplinary knowledge required by the end-user to fabricate biochips, the tool generates G-Code from the created design usable for fabrication of the biochip’s PMMA layers in anymicro milling machine. Current tools for physical design do not bridge the fabrication gap, which extends in to lacking functional verification. Instead, interdisciplinary specialist knowledge is required to verify, potentially adapt and then turn the synthesized design in to working biochips. Hence, in this thesis we consider three-layer normally-closed valve biochips that use two micromilled Polymethylmethacrylate (PMMA) layers sandwiching a sheet of Polydimethylsiloxane (PDMS), which are easier to fabricate. We have developed a software tool towards a more automated biochip design process, reducing the amount of manual and error-prone work required. Aiming to reduce the interdisciplinary knowledge required by the end-user to fabricate biochips, the tool generates G-Code from the created design usable for fabrication of the biochip’s PMMA layers in any micromilling machine.