UC Berkeley

This thesis describes three experimental thrusts applying nanotechnology to develop novel tools for the life sciences.

Part I (chapters 2 and 3) covers the development of a graphene based nanofluidic platform for in-situ electron microscopy. The Graphene Flow Cell (GFC), as we have referred to it, consists of a nanofluidic channel integrated into a SiN/SiO2/SiN stack on a Silicon chip, with a layer of graphene sealing the channel. The graphene serves as an electron transparent membrane as well as a scavenger of oxidative radicals during imaging. We discuss the fabrication and testing of the GFC, as well as a few demonstrations of its capabilities. The GFC outperforms commercial nitride cells in resolution and contrast, and allows for the introduction of reactants

during imaging and precise control of sample concentration, features sealed liquid cell architectures lack. These advantages have already allowed for advances in our understanding of nanobubble geometry and stability, as well nanoparticle dynamics. Finally, we discuss some future applications and improvements for the GFC.

Part II (chapters 4 and 5) discusses work towards carbon nanotube intracellular neural electrodes. Due to their nanoscale nature, extreme aspect ratios, and unique mechanical and electrochemical properties, carbon nanotubes make an ideal electrophysiological probe. We demonstrated their capability using a single-unit probe device, and further demonstrated that such a probe is scalable, having the potential to record from a high-density of neurons in a small volume. We walk through the micro- and nano-fabrication considerations in developing such a probe, and progress we have made towards this aim. Finally, we discuss an alternative application of CNTs as neural probes, using them to bias plasmonic nanoparticles to create a voltage sensitive optical probe.

Finally, Part III (chapters 6 and 7) covers ongoing work applying atomically precise nanopores in hexagonal boron nitride (hBN) to DNA sequencing. Previous work out of our lab has demonstrated that defects in hBN introduced by electron beam irradiation grow in atomically-quantized metastable triangles. Taking advantage of this property, it is possible to produce individual triangular nanopores in hBN with atomically precise diameters. This precision allows us to create nanopores for DNA sequencing in which the pore size is tailored to the size of DNA strands. Currently, solid-state nanopore sequencing has been limited by the speeds at which DNA passes through the pore, as well as limited blocking current signatures of the nucleotide bases. Atomically precise pores address both of these issues and will likely mark a significant advance in the field. We cover the progress we have made towards this goal, as well

as aims that are still outstanding.