Interfacing Nanowire Sensors With Electrogenic Cells for In-Vitro Intracellular Electrophysiology

Abstract

Semiconductor nanowire (NW) devices that can record and/or illicit intracellular electrophysiological events with high sensitivity and spatial resolution are emerging as key tools in nanobioelectronics. In this thesis, I focus on the development of semiconducting NWs as intracellular sensors, beginning with the synthesis and functionalization of NW elements, moving to strategies for integrating NW transistors into functional sensing devices, and finally interfacing these sensors with electrogenic cells to enable facile and high quality recording of the intracellular action potential. First, I investigate the synthesis of a variety of NW building blocks including kinked and straight NWs and study the variability in their electrical properties. Second, I demonstrate a strategy to promote uptake of Si NWs into primarily neurons via surface functionalization with a cell-penetrating peptide (CPP). Notably, Si NWs functionalized with CPPs can be internalized into rat hippocampal neurons with ca. 15% efficiency with within ca. 6 hr, whereas Si NWs without CPP functionalization remained on the surface of the cell. Third, I develop a fabrication process to enable integration of straight p-typed NWs, using shape controlled NW transfer and selection metallization, into scalable U-shaped nanowire field effect transistor (U-NWFET) sensors, where the sensitive device region can be as short as ca. 50 nm. Finally, I use these U-NWFET probes to interface with and record intracellular action potentials from both primary rat neurons and human cardiac cells. I show that the intracellular action potential amplitude and signal-to-noise of the U-NWFET probes is comparable to that of patch clamp and that capacity to obtain high quality intracellular recordings is dependent on NW device geometry/size. Furthermore, the U-NWFET fabrication process allows design of multiple U-NWFET probes for multiplexed intracellular electrophysiology within a single cell or in cell networks. Together these results show the promise of integrating NW based probes seamlessly with cells to open up new opportunities in studying electrophysiology as well as pushing the boundaries towards long-term interfacing of cellular networks/tissues with electronic systems.