PhD Defence Dean de Boer | Self-aligned nanofabrication for neuroscience

Self-aligned nanofabrication for neuroscience

Dean de Boer is a PhD student in the Department of Mesoscale Chemical Systems. (Co)Promotors are dr.ir. N.R. Tas and prof.dr. J.G.E. Gardeniers from the Faculty of Science & Technology and dr. L.N. Cornelisse from Amsterdam UMC.

In this thesis the use of self-aligned cleanroom fabrication techniques was investigated as an alternative framework for producing micro and nanostructures related to electrophysiology for personalized medical neuronal models. Many designs have been presented in literature to address aspects of this topic, however limitations in the chosen fabrication methods hamper flexibility in design and high volume production.

Chapter 1 introduces the state of the art nanostructures related to in vitro electrophysiology on chip, providing an overview of the extracellular and intracellular approaches. Relevant background on key concepts is provided, such as seal and access resistance, as well as the role for commercially available multielectrode arrays and microfluidic integration. The challenges in existing approaches are discussed, such as the reliance on fabrication techniques suitable for prototyping which limit flexibility to modify designs or to integrate different approaches into a single fabrication flow, such as the combination of functionalized gold nanorings with microfluidics. The direction of the thesis is described and the proposed solution of using waferscale self-aligned nanofabrication techniques in combination with a novel gold-silicon inversion approach is introduced.

Chapter 2 introduces the various nanofabrication concepts which are used throughout the thesis, including corner lithography, edge retraction, and sidewall oxidation, with emphasis placed on the self-aligned and wafer scale way these techniques can be employed, and how they can be used be used to produce tunable structures to be used as templates. The chapter then continues by applying these self-aligned techniques to produce nanoscale silicon rings with critical dimensions below 20 nm coaxially aligned around a central microfluidic channel, demonstrating a potential path from combining the microfluidic and functionalized nanoring approaches described in chapter 1. The process is also demonstrated for producing platinum silicide nanowires through silicidation of a sacrificial amorphous silicon template, although is built upon further in chapter 3 with gold nanostructures. Finally, sapphire is investigated as a future substrate material,  offering material properties which allow for finer control over the nanostructures, down to below 15 nm, due to the excellent chemical resistance with respect to other materials in the fabrication flow. The advantages of this approach are described and the substrates produced in this manner are used in subsequent processing in chapter 3.

Chapter 3 provides an overview of existing fabrication techniques for producing gold nanofeatures, including those employed in the state of the art electrophysiology devices introduced in chapter 1. The advantages and key limitations of these approaches are discussed and need to a more flexible approach is explained. The key concepts behind a novel method for microscale and nanoscale patterning gold using sacrificial silicon molds are then explained, as well as relevant literature on the subject. The fabrication approach is demonstrated for producing microscale gold interconnects, focusing on parameter space optimizations for device performance and yield, achieving near bulk resistivities. This was then applied to the nanoscale using templates produced using the concepts in chapter 2, and achieves gold features as small as 12.5 nm, with a radius of curvature less than 2 nm, providing an alternative approach which could be used in functionalized gold nanoring electrophysiology devices without the contamination and geometric limitations of existing approaches.

Chapter 4 presents a potential bridge between silicon based nanostructures for electrophysiology  and the typical PDMS based microfluidic structures used for providing structure to neuronal microcircuits. A convergent feedforward microcircuit based on two different populations of neurons is demonstrated for directional axon guiding using a silicon-on-insulator and glass based material stack. Such an approach may enable future integration of gigaseal nanostructures presented in chapters 2 and 3 with microfluidics for personalized medical assays, providing a path to a scalable production which would be needed for population scale personalized medicine.

Chapter 5 consists of the conclusions and outlook of the work presented in the thesis, focusing on the novel achievements and potential directions of future work. Recommendations concerning next steps as well as adjacent fields which may benefit from these self-aligned fabrication, gold nanofabrication, and microfluidic integration approaches are discussed, finally followed with conclusions on future device integration.