Development of a bioelectric nerve conduit using solenoid technology, and nano fabrication

Martin, Christopher (2013) Development of a bioelectric nerve conduit using solenoid technology, and nano fabrication. PhD thesis, University of Glasgow.

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Abstract

Peripheral nerve repair outcomes have lagged behind comparable surgical techniques for many decades. A number of advanced approaches have been adopted over the last ten years. In particular the application of electrical stimulation during a repair is of great interest. It is clear that electrical stimulation of regenerating nerve tissue has a great many effects and can improve functional outcomes for patients. This work has focused on developing systems capable of applying accurate electric fields on the microscale within a biodegradable conduit, powered wirelessly. Experiments were conducted in vitro with a view to making progress towards an in vivo implementation. Electrical stimulation was applied to regenerating sensory neurons in vitro, from a rat dorsal root ganglion. Mechanical guidance cues aligned neurons towards different microelectrode configurations in order to record the effect of applied electrical stimulation. This was performed using custom stimulation modules. SU-8 microgrooves and Ti/Au electrodes acted as mechanical and electrical cues respectively. This method was employed to great effect, identifying the effect of a number of electrical stimulation parameters. This led to a stimulation protocol featuring a 1:4 duty cycle, 20 mV amplitude, 100 Hz sinusoidal signal. This produced a number of interesting effects, including neuronal turning and a barrier formation. These results, demonstrated at the cellular level using a custom device and an autonomous stimulation system illustrates progress towards an optimised electrical stimulation waveform for neuronal growth control. A novel transfer printing process was developed to produce patterned gold films on the biodegradable polymer, polycaprolactone. Patterned Au, 400 nm thick, was transferred to a sheet of the polymer, producing a 15 turn, spiral inductor. The inductor was then electroplated to a thickness of 30 μm and wire-bonded. Power and data were transferred wirelessly to the receiver circuit. Receiver circuits, connected to stimulation test modules in planar form, delivered electrical stimulation waveforms to regenerating sensory neurons on polycaprolactone. This stimulation resulted in confinement of the cells between two pairs of electrodes, demonstrating the efficacy of the novel receiver circuits. This was achieved with four electrodes in a twin-barrier configuration. These results illustrate progress towards implantation in vivo, using remotely powered electronics to guide regenerating neurons to their targets with microelectrodes. Sensing cell growth through changes in electrical impedance is a well-documented technique. A receiver inductor has been connected to caco-2 cells in culture. Power was transmitted to the receiver inductor through an inductive link. Changes in the cell-monolayer have been detected at the transmitter output circuit, showing that the impedance changes are of sufficient magnitude to be reflected to the transmitter. Trypsin or EDTA were added to confluent layers of caco-2 cells, detaching them from the surface of the microchannel electrode array. This detachment was seen at the transmitter in the form of transient voltage changes. Data was acquired in using Labview programming and PXI hardware systems. This work illustrates progress towards biodegradable, passive cell sensing inspired by radio frequency identification technology, and electric cell impedance sensing.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Nerve Repair, Electronics, Inductive Powering, Biodegradable, Flexible Electronics, Electrical Stimulation of Neurons,
Subjects: T Technology > TK Electrical engineering. Electronics Nuclear engineering
Colleges/Schools: College of Science and Engineering > School of Engineering > Electronics and Nanoscale Engineering
Funder's Name: UNSPECIFIED
Supervisor's Name: Cumming, Professor David R. S. and Riehle, Dr. Mathis O.
Date of Award: 2013
Depositing User: Mr Christopher Martin
Unique ID: glathesis:2013-5278
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 16 Jun 2014 10:01
Last Modified: 02 Jul 2014 08:41
URI: http://theses.gla.ac.uk/id/eprint/5278

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