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PHY435

PROJECT PROPOSAL

1 DETAILS OF PROPOSAL
Organisation where grant would be held

Organisation: University of Sheffield

Division or Department: Physics & Astronomy, Neuroscience

Address: The Department of Physics and Astronomy


Hicks Building
Hounsfield Road
Sheffield
S3 7RH
United Kingdom

Proposer

Title/Initials Dr G T
Surname Fletcher
Post held Research Follow
Organisation University of Sheffield
Division or Department Physics & Astronomy
Telephone 0114 22 23519
Fax 0114 22 23555
E-mail phb07gf@shef.ac.uk
Hours per week on project 45

Title of Research Project


Investigation into replacing a damaged motor neuron with an optoelectronic
system.

Summary of Financial Resources Required for Project

Total £
Staff 400,000
Travel and subsidence 9,600
Consumables 79,200
Exceptional items 0
Equipment 27,400
Large Capital 0
Total 516,200

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Duration

Duration of the grant (months) 36

Objectives:
Physics side
 Find the most suitable optical fibre for integration into the human body.
 Develop the laser diode triggering system.
 Develop a motor neuron triggering system.
 Match the benchmarks set by a biological system.
 Find the most suitable power source for the electronics.

Neuroscience side
 Investigate which neurons are suitable to be replaced.
 Investigate how neurotransmitter can trigger the electrical systems.
 Research into how the biomechanical neuron affects the human body.
 Research if chemical or electric is best when triggering other neuron cells.
 Make sure the artificial neuron is safe and does not harm the human body.

Summary

The project will be to research into the possibility of replacing damaged motor
neurons with optical fibres. The project will involve designing a possible
biomechanical artificial neuron that can replace damaged motor neurons in
the human body. This biomechanical neuron would have to be cost effective,
robust, flexible and easy to integrate into the human body.

The main signal carrier will be an optical fibre or another form of light guide,
with a small laser diode one end and a small photodetector at the other end.
The project will run for 36 months and will be joint run with my associate in the
in neuroscience department, this is required for their expertise of integrating
biomechanical devices into the nervous system.
At the end of the project we expect to have learnt: which type of system
is most suitable for integration into the human body, produced a way of
powering the device, created a reliable triggering system and finally a way of
triggering other motor neurons with our device.
The project will also hopefully produce some media hype, two PhD
theses and presentations at international conferences on the applications of
optoelectronic devices and ALS/MND.

Beneficiaries
The main beneficiaries would be people researching into curing and
developing treatments for physiological conditions that are caused by
damaged or degraded neurons, such as MND (motor neuron disease) and
paraplegia. If the research proves successful it could improve the lives of

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many people in the long run and could provide the stepping stones to curing
some of these diseases.

This research will also help many industries and research groups that use
advance fibre optics and optoelectronics; such as the telecommunications
industry. The research is also beneficial to the smart fibre industry as the
system will develop can have other applications, and a chemical sensitive
fibre system can have security or defence applications.

Travel and Subsidence

Destination and purpose Total £


SOPO 2011,2012,2013 — International Symposium on Photonics and 3600
Optoelectronics, China . To look at the latest optoelectronic devices. x2
(£600PPPA)

International Symposium on ALS/MND – Conference 2011,2012,2013. x2 3000


(£500PPPA)

Emergency conferences and Travel allowance (£1000PA) 3000

Total £ 9600

Consumables

Specify Total £

General running of the optoelectronics lab. (optical fibre, photo-


detectors, laser diodes) £1000 per month. 36,000

General running of the neuroscience lab. (disinfectant, petri dishes,


chemicals and growth mediums) £1200 per month. 43,200

Total £ 79,200

Staff

Specify Total £
2 x Postgraduate researcher 300,000

2 x PhD researcher 100,000

400,000
Total £

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Equipment (single items under £100,000)

Description of items and country of Basic Import VAT £ Total £


manufacture Price £ Duty £
Lecroy Waverunner 64Xi-A oscilloscope 12,500 0 2,500 15,000
(UK)
NIR Spectrometer (UK) 8,666 0 1,734 10,400

Laptop x 2 + software (UK) 833 0 167 2,000

27,400
Total £

Large Capital (single items £100,000 and over)

Description of items and country of Basic Import VAT £ Total £


manufacture price £ duty £

Total £

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Case for support
I.A - Introduction to the project
The project is focused on designing a biomechanical neuron which would be
able to replace a damaged or degraded motor neuron in the human body.
This is important as nerve cells do not grow or divide into new cells they are in
a continual state of G0 on the cell cycle. In most cases as well they do not
regenerate after damage, this means if a nerve cell is damaged the body can’t
replace it and the person can experience loss of functionality of what that
nerve controls. This ranges from loss of Feeling to complete loss of
functionality.
The project will hopefully show that it is possible to use an
optoelectronic system as a neuron. For this to be true the system must match
up to a biological neuron.

I.B Neurons

[1] – fig.1 shows a typical


neuron.

A neuron can be split into three main sections.


1) Dendrites and cell body – These collect signals from other neurons,
they are the biological triggering system of the nerve cell. Once enough
neurotransmitter has been collected at the Dendrites it triggers and an
action potential to take place.

2) The Axon is the signal carrier, it is one long biological fibre in sections
insulated by a layer of cells called the mylene sheath. It is kept at a
constant voltage when resting. The resting voltage of -70mV this is
done via pumping out Na+ and K+ ions from the cell.
The Axon carries the action potential across the nerve to the
terminals at the far end of the neuron.

3) The Terminals are the other end of nerve cell when an action potential
reaches them they release neurotransmitter across synapses to trigger
other neurons.

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I.C Action potentials
Action potentials are how electrical signals are carried across the neurons.
They are electronical pulses that travel across the axon by opening ion
channels in-between sections of the mylene sheath. The pulse shape is
below.

[2] Fig.2 - shows the voltage at each stage of an action potential and what is
happening in the cell.
Stages of an action potential [3],[4]
1) In the resting stage where there is no external stimulus, the ion pumps
are active keeping the axon at -60 to -70mV.
2) When the threshold for an action potential is reached ~ -40mV due to a
response to a stimulus, the Na+ channels open and the neuron
depolarises (no longer charges against each side of the cell
membrane). There is a large influx of Na+ ions and an outward flux of
K+ due to diffusion.
3) This causes the cell voltage to change to ~ +50mV.
4) After the action potential (electrical pulse) propagates past the section
of axon the ion channels are in then repolarization takes place; where
the ion pumps are reactivated and the neuron will go back to the
resting stage.

This process takes ~10ms, this is the time in which the artificial neuron needs
to match. This will require fast electronics and data processing; this means
the research project will have to see if silicon chips are fast enough to match
this if not GaAs chips maybe used.

I.D optoelectronics
The Fibre optics industry is very well developed; there should be many
different types of light guides which can be researched to find the most
suitable fibre for to join electronic system.

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Fig.3. – diagram of a possible replacement nerve system.

Key parts of the system


 The system requires a trigger system at the laser diode end which will
only emit light pulses when the threshold is reached; like a biological
neuron.
 The power supplies need to be long lasting and reliable; as replacing
them maybe difficult in some areas of the body. Possible options for
power supplies include: batteries similar that are found in pacemakers,
a photovoltaic cell and battery and kinetic rechargeable battery.
 The optical part of the system will be an optical fibre or light guide. This
has to be strong, flexible and durable to be suitable for the human
body.
 The photodetector will detect the optical signal from the laser diode,
and then output an electrical or chemical signal to stimulate other
neurons.

II. Previous Research


The replacement of nerves with optical fibres has been considered before,
with research into trying to replace the optical nerve in the eye with an optical
fibre. This is a much more complex system to replace than motor neurons.

Optical fibre nerve systems have also already been developed by the
University of Tokyo in Japan[5]. These optical nerve systems were for use in
safety and security systems they measured stretching and strain properties to
to measure temperature, much like the human body. The fibres were used to
detect damage to the material they were imbedded in.

Smart fibres have also been developed for medical applications, such as the
research by Two MIT researchers Fink and Bayindir[6], who have developed
fibre optics connected to heat-sensitive electronics which are able to detect if
the laser light down the fibre defects and is able to shut the laser down before
any damage is done to healthy tissue or organs[6]. These smart fibres are
being proposed for surgical use to destroy tumours by using the fibre as a
laser light guide [6].

There are many other applications for smart optical fibres, some
multifunctional fibres that can sense their environment [6]. Many research
groups around the world looking into optoelectronics and their applications
such as University of Southampton [7].

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III. Programme and Methodology

III.A Objectives
Physics side
 Find the most suitable optical fibre for integration into the human body.
 Develop the laser diode triggering system.
 Develop a motor neuron triggering system.
 Match the benchmarks set by a biological system.
 Find the most suitable power source for the electronics.

Neuroscience side
 Investigate which neurons are suitable to be replaced.
 Investigate how neurotransmitter can trigger the electrical systems.
 Research into how the biomechanical neuron affects the human body.
 Research if chemical or electric is best when triggering other neuron cells.
 Make sure the artificial neuron is safe and does not harm the human body.

III.B Methodology and Work Plan


The research will be undertaken in two labs, the neuroscience labs will focus
on the integration of the neuron into a biological system. This will involve how
its presence affects the biological material around it, by running simulations
and testing to see how the immune system will respond and how cells will
grow around it. This will mainly be experimental lab work and computational
work.
At the start the project the neuroscience team will also have to
separate some nerve cells for the physics lab to examine their properties. This
will allow us to identify the strengths and weaknesses of neurons. This will
help in deciding which properties should be reproduced in the artificial neuron
and which need to be improved.

The physics lab will focus on building and testing the neuron. This will include
material stress tests, electrical tests, measuring how fast the signal takes to
cross the neuron and reset time. Over the first two years of the programme it
is expected that there will be several iterations of the biomechanical neuron in
which the system is developed and tested. Each iteration will be fully tested
and the results will provide information on how to improve the current system,
this will continue until we produce an effective design that is able to match the
biological neuron.

At this point the prototype neuron will be handed to the neuroscience lab for
biological testing and then both groups will work together on improving parts
of the prototype and building the triggering systems; like the chemical sensor
needed to trigger the artificial neuron.

Hopefully at the end of the project the prototype design will be fully developed
and the neuron will be safe in a biological environment. This project will not
include implanting the neuron into living biological systems.

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III.C Work Plan
Physics Group Neuroscience Group
Getting up to date with latest research in our area and technology

Material testing Extracting Neurons for research


Optical fibre research Researching which neurons are
Year 1 Ordering equipment able to be replaced

Measuring properties of the Simulations and testing of


extracted neurons. artificial neuron in biological
environments

Design, construction and Principles of Chemical


testing of prototype artificial stimulation from
neurons. neurotransmitter
Including:
 The fibre optics
Year 2
 Laser diode system
Research which method would
 Photodetector system be best when triggering other
motor neurons (chem. or Elect.)

Meeting targets for the


artificial neuron, e.g. response Biological Testing of prototypes
time, power consumption and made by physics group
cost.

Year 3
Improving design of artificial neuron.

Development of Chemical trigger system for triggering artificial neuron.

Development of triggering system for triggering other motor neurons.

Does not include time allocated for attending conferences or writing reports
and presentations of results showing progress of our research.

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IV. Beneficiaries of research
The main beneficiaries would be people researching into curing and
developing treatments for physiological conditions that are caused by
damaged and degraded neurons; such as MND (motor neuron disease) and
paraplegia. If the research proves successful it could improve the lives of
many people in the long run and could provide the stepping stones to curing
some of these diseases.

This research will also help many industries and research groups that use
advance fibre optics and optoelectronics; such as the telecommunications
industry. The research is also beneficial to the smart fibre industry as the
system will develop can have other applications, and chemical sensitive fibre
systems can have security or defence applications.

V. Dissemination and exploitation


As mentioned above the technology can be implemented into many other
devices, chemical sensitive fibre optic system could have many applications
from monitoring levels of chemical compounds for safety systems to
integration into building materials for producing smart materials.

The prototype neuron produced can go into further development for clinical
trials. This would be the best possible outcome of the research project.
Progress which is made during the project will be written into reports
and also presentations to be shared with other research groups in our area.
There will also be two PhD theses wrote on our research which will be
available for the scientific community to read.
Hopefully near the end the prototype will show real promise this will
generate media hype about our research showing promise to potential cure
some diseases.

VI. Justification of resources


The funding required for the project is high due to having to run two research
labs and also the number of researchers needed to make the research project
effective on the time scale of 36 months. The cost though is a small price to
pay for the potential of being able to improve so many people’s lives. Even if
the research does not succeed, the systems which will be developed during
the research project can be implemented into many other devices for uses in
other industries.
References
[1] J. A. Stone, “Stone’s Blog: neurons and synapses.”[Online]. Available:
http://jermaineadrianstone.blogspot.com/2011/03/neurons-and-synapses.html. [Accessed: 16-Mar-2011].
[2] “action-potantial2.jpg (JPEG Image, 648×468 pixels) - Scaled (54%).”[Online]. Available:
http://biologyclass.neurobio.arizona.edu/images/action-potantial2.jpg. [Accessed: 18-Mar-2011].
[3] “Nerve Impulses.”[Online]. Available: http://www.biologymad.com/NervousSystem/nerveimpulses.htm.
[Accessed: 19-Mar-2011].
[4] University of Bristol, School of Medical Sciences, “Neurotransmitters and receptors.”[Online].
Available: http://www.bris.ac.uk/synaptic/basics/basics-2.html. [Accessed: 16-Mar-2011].
[5] K. Hotate and H. Zuyuan, “Fiber-Optic Nerve Systems for Safety and Security,” Online
http://www.oecc2009.org/paper/538.pdf.
[6] K. Bullis, “Smart Fibers - Technology Review.”[Online]. Available:
http://www.technologyreview.com/NanoTech-Devices/wtr_15853,303,p1.html?a=f. [Accessed: 20-Mar-
2011].
[7] “Optoelectronics Research Centre University of Southampton.”[Online]. Available:
http://www.orc.soton.ac.uk/researchgroups.html. [Accessed: 20-Mar-2011].

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