Developing a novel sensor technology for detecting neural activity based on surface plasmon resonance

One of the main goals of contemporary systems neuroscience is to understand how sensory inputs are processed, networks are formed and the resulting functional outputs. To achieve this, a recording technique is required that can detect action potentials with single-cell resolution for a long period of time across a large network. Current imaging techniques available are limited in at least one of the four elements needed to fulfill this aim (a) the technique needs to be able to detect every action potential (b) from every neuron (c) for a long period of time (d) from an entire network. Neural activity has been shown to produce fast intrinsic optical signals that are the result of refractive index changes causing light scattering and birefringence associated with membrane depolarisation. To date no one has successfully managed to exploit these intrinsic optical signals in a practical robust recording system. Surface plasmon resonance (SPR) is a technique that can detect extremely small changes in refractive index and is capable of detecting this membrane localised refractive index change with a high spatio-temporal resolution. This thesis describes the design and development of an imaging system based on surface plasmon resonance to detect the refractive index change of a cell membrane during neural activity. This thesis, first theoretically examines the different processes that occur during neural activity that could affect the resulting SPR response. The change in refractive index and therefore, light intensity was calculated considering the reorientation of dipoles and ion flux during an action potential. The planar gold surfaces required to produce surface plasmon resonances were characterised and the imaging system was shown to be sensitive enough to detect these small refractive index changes. There were no visible light intensity changes after recording the optical response from one action potential. This led to the development of the experimental protocol and a data analysis tool was developed to align and average over a number of action potentials to reduce the noise floor as much as possible and increase the signal-to-noise ratio. Unfortunately, it was determined to a high degree of certainty that no action potentials were detected by the planar gold SPR sensors. It was hypothesised the SPR signal from these cell membrane localised refractive index changes was averaged across the relatively large surface area of the planar gold sensor which was why no response was detected. A novel sensor design was investigated by reducing the gold sensor size to that of one cell to improve coupling or isolation of the plasmons to a single cell. SPR at planar metal/dielectric interfaces and localised SPR for metal nanoparticles have both been extensively studied, but it is less clear what happens to the optical properties at the micrometer scale. Gold patterns of different sizes in the micrometer range were therefore, produced using photolithography. Typical SPR responses were observed for all gold microstructures, however, as expected they were not as sensitive and were wider than that of the planar gold controls. This phenomenon became more pronounced as the length of the gold structure decreases, as expected because of the spatial constriction of the propagating surface plasmon. Although the sensitivity of the micron-sized gold surfaces was less than that of the planar gold surface, with the latter unable to detect these refractive index changes. The process still suggested that the SPR technique could be successfully implemented to detect individual action potentials. Reducing the sensor size to that of one cell could improve coupling and stop the signal being averaged across the sensor. Unfortunately, it was determined to a high degree of certainty that no action potentials were detected by the gold microstructure SPR sensors.