Development of an Infrared Nerve Stimulator

Vanderbilt University School of EngineeringBME 273, Group 20

Submitted on April 26, 2011

Group Members:Gregory Wigger

Chris TedderMelanie Gault

Advisors:E. Duco Jansen, PhDKurt Schoener, PhD

Abstract

In the United States, approximately 1.7 million people are affected by limb loss and 6

million are living with paralysis. There is a need for implantable devices that will reliable

stimulate individual nerve fascicles to restore motor function in paralyzed limbs or prosthetic

devices. Recent scientific discoveries have found infrared laser light to be capable of neural

stimulation in a way that is damage-free, artifact-free, and spatially selective. Furthermore,

optical stimulation by an infrared laser does not require contact and has spatial selectivity that

can precisely excite only one nerve. Through a partnership with the Vanderbilt Biomedical

Photonics Laboratory, the design of a single channel side-firing nerve stimulator described in this

paper will enable the activation of individual nerve fascicles in a therapeutic device for future

implantation. Three large-scale prototypes ranging in complexity of design were developed to

accomplish this task: a 45-degree angle polished fiber, a flat polished fiber with an angled

concave mirror, and a flat polished fiber with an angled flat mirror. Each prototype was

compared based on their spot size, radiant exposure, energy loss, cost, and biocompatibility.

These nerve stimulators are designed with the ultimate goal of their inclusion in a biocompatible

cuff or flattened device with multiple channels for the activation of many individual fascicles.

The concave mirror prototype was chosen for the final multiple channel stimulator design based

on its high spatial precision (spot size = 0.028 cm2) and its high radiant exposure output (50.51

J/cm2). This design is more complex than the other two prototypes, and much consideration must

be taken into account on the focal length of the concave mirror. During the design process, the

nylon encasement was seen to scatter light in the infrared spectrum. The future implantation of a

multi-channel nerve stimulator will lead to innovations that can be integrated in the next

generation of prosthetic devices and other future long-term therapeutic modalities.

Introduction

Figure 1. Probable design of future nerve cuff.

For two centuries electrical stimulation has been used to stimulate neural tissue. By

increasing the transmembrane potential to activate the voltage-gated ion channels, an action

potential is induced and propagates down the axon. Unfortunately, electrical stimulation of

neurons has proven to be imprecise and unable to stimulate single neurons. In addition, electrical

stimulation induces a stimulation artifact, which masks the desired signal.

The Vanderbilt Biomedical Photonics Laboratory has been completing extensive research

in the area of infrared nerve stimulation. Several grants and projects have lead to the

department’s research collaboration with other educational institutions including Southern

Methodist University, University of Texas in Dallas, University of North Texas, and Case

Western Reserve University.

A recent study associated with Vanderbilt Biomedical Photonics Laboratory determined

that the infrared laser energy results in an increased transient temperature gradient that leads to

initiation of an action potential (Wells, 2007). Furthermore, research also indicates that optical

stimulation of the neural tissue has advantages over other excitation modalities such as electrical

nerve stimulation. Neural stimulation by an infrared laser has spatial selectivity in that the light

can focus to precisely excite single nerves. Neural stimulation by infrared light also lacks

stimulation artifacts and does not require contact with the tissue (Izzo, 2006).

A nerve cuff has yet to be

designed or created, however a

depiction of a potential

design/prototype can be seen in Figure

1. Figure 1 shows how the cuff

surrounds a nerve fiber and has

Figure 2. Optic fiber must side-fire to stimulate nerve in parallel in order to cause an action potential

multiple stimulation channels. The cuff is wrapped around the endoneurium of a nerve fiber so

that the individual infrared channels can stimulate individual nerves within the nerve fiber using

the signal from an infrared laser.

With this emerging technology, this design project strove to perform initial proof-of-

concept experiments and develop a prototype towards designing a nerve cuff that contains

optical fibers which deliver the infrared laser signals around the periphery of the peripheral nerve

bundle to stimulate neural activity in a spatially precise fashion. The future implantation of a

nerve cuff will lead to innovations that can be integrated in the next generation of prosthetic

devices. The implantable nerve cuff will be biocompatible and eventually have the capability to

be wrapped around an entire nerve bundle and optically activate single nerves (Veraart, 1998).

For an effective and plausible nerve cuff design, an optical fiber must be laid in parallel

with a nerve bundle and be capable of side-firing. Side-firing is the ability of an optical fiber to

fire an infrared signal at a 90° angle as shown in Figure 2. This project aims to explore the

potential methods in accomplishing a successful side-firing optical fiber that is properly encased

for implantation.

The study of infrared optics has led to three

possible models to accomplish the goal of infrared

side-firing; these are illustrated in Figure 3. The first

model is a 400µm optical fiber polished at 45°. By

polishing it in this manner, total internal reflection of

the optical fiber is utilized, as the light will be

reflected 90° from its axis of origin. The other two

models contain 400µm flat-polished fibers and

mirrors positioned at 45° to the fiber to reflect the

beams at 90°. One model uses a flat, single surface mirror, while the other uses a concave mirror.

There are still questions surrounding the ideal orientation of the target nerve. Figure 4a

depicts a cuff model that surrounds a flattened axon bundle; the optical fibers run in parallel in

the same plan above and below the

nerve. However, if it is seen that

deforming the axon hinders its

ability to transmit a nerve signal, a

radial cuff will be required, where

channels will be positioned around

the nerve at the 12, 3, 6, and 9

o’clock positions, as shown in

Figure 4b.

Figure 3. 45° angle-polished fiber model (top), single-surface mirror model (middle), and concave mirror model (bottom)

Figure 4. (a) Basic model of radial stimulation cuff surrounding flattened axon bundle. (b) Basic model of radial stimulation cuff surrounding cylindrical axon bundle

(a)

(b)

Materials

Laser Light Source

Three separate lasers were used along the course of this project. To test the polishing of

the optical fibers, a continuous wave He-Ne laser with a wavelength of 633 nm was coupled into

the fiber. Once the prototypes were made, a Lockheed-Martin Aculight Capella pulsed diode laser

(Model R-1850) with a wavelength of 1875 nm was used to assess the beam profile. This laser

emits a red pilot light, making it easy to visualize the spot area of the side-firing prototype. A

bulk of our characterization experiments were performed using a Holmium:YAG laser. This

laser emits infrared light at a wavelength of 2100 nm with pulse duration of 350 µs. The

repetition rate was set to 2 Hz, and the voltage was set to 970 V.

Prototype components

The optical fibers used in each prototype were 400 µm core diameter fibers (Edmund

Optics, Barrington, NJ). To encase the side-firing prototypes, Nylon 12 was obtained from AP

Extrusion with an inner diameter of 9.66 mm. Nylon 12 is advertised to be transparent in the

infrared spectrum, which we later found out to not be true at 2100 nm. A gold concave mirror

with a diameter of 9 mm and a focal length of 4.5 mm was used for the concave mirror

prototype. A silver flat first surface mirror with a 5 mm diameter was used in the flat mirror

prototype. A cylindrical aluminum insert with a 45-degree angle cut was used in the flat mirror

and the concave mirror prototype. These aluminum molds were fabricated in the physics

machine shop at Vanderbilt University.

Methodology

Prototype Construction

Prototype construction began with polishing the optical fibers. The angled fiber prototype

required a precise 45-degree polish at the fiber tip. A fiber polisher with a rotating wheel was

covered with polishing paper of varying grit. The polishing began with a rough grit,

approximately 12 µm in size. The fiber was lightly pressed onto the rotating wheel at a 45 degree

angle until the tip was flattened. The paper was removed and replaced with a smaller grit paper,

as low as 2µm. The tip was examined under a microscope to ensure completion in the polishing

job. The same process was completed for the flat polished fiber, except that the tip was pressed

orthogonally onto the polishing wheel.

The angled fiber prototype was constructed by inserting the jacketed fiber into a piece of

Nylon 12. The spot that light emitted was carefully marked on the prototype to ensure that all

future measurements would be made with maximal light output. The concave mirror prototype

was constructed by using a 1 minute drying epoxy to secure the concave mirror to the angled

surface of the aluminum insert. The aluminum insert was inserted into the nylon piece. The flat

polished optical fiber was inserted from the other end such that none of the light emitted from the

optical fiber would fall outside the diameter of the mirror due to beam divergence. The beam

profile was visualized using the pilot light emitted from the Aculight Capella laser. The flat

mirror prototype was constructed in the same fashion as the concave mirror prototype except that

a flat first surface mirror was secured to the aluminum insert instead of the concave mirror.

Characterization Studies

Characterization studies were performed to compare each of the three prototypes on the

basis of spot area, radiant exposure, and energy loss. Spot area was quantified using “the knife

edge technique.” In the knife edge technique, a razor blade is attached to a micromanipulator and

positioned over a power meter detector head as shown in Figure 5. The side-firing prototype was

positioned such that the outer diameter of the nylon was 1.5 mm away from the knife edge. This

distance was measured using a pair of digital calipers. The Ho:YAG laser was turned on at 970

V, 2 Hz repetition rate, and 2100 nm, while the knife edge was completely covering the emitted

beam from hitting the detector. Using a Molectron Power Meter, the reading was zeroed at this

position. The knife edge was moved away from complete coverage of the detector head, and the

maximum power output was recorded. The 10% and 90% of the minimum and maximum power

output was calculated. The knife edge was then moved perpendicularly to the incident light until

the 90% output was measured. Using the knobs of the micromanipulator, the distance from this

position to the position at which power meter read a 10% output was calculated. This was

determined to be the spot diameter in a single direction. For each prototype, the spot diameter in

four radial directions was determined.

Figure 5: Overview of the Knife Edge technique to determine beam profile of the side-firing prototypes.

The spot area was assumed to be elliptical in shape. It was calculated using equation 1

shown below where “r1” is the radius in the x-axial direction and “r2” is the radius in the y-axial

direction.

Areaof Ellipse=π r1r2 (Equation 1)

To visualize the beam profile, MATLAB was used. The output of the side-firing

prototypes is a three-dimensional Gaussian. Using the spot size measurements and the maximum

output for each prototype, the beam profile was fitted to Equation 2 below, where “G” is the

Intensity of the Gaussian at a given point in two-dimensional space, "a" is the maximum energy

output, and “c” is a variable that controls the width of the Gaussian.

G=a∗e−√x2+ y2

2c2 (Equation 2)

The maximum radiant exposure (J/cm2) was calculated for each prototype. The output of

the power meter in mW was divided by the repetition rate to get the output in mJ. The maximum

energy output was divided by the beam spot size and converted to J/cm2. These values were

compared in a bar graph for each of the three prototypes.

Energy losses were measured by comparing the energy output straight from the Ho:YAG

laser aperture, the energy straight from the bare fiber, and the energy straight out of the nylon .

The percent losses from the fiber, from the nylon and overall were calculated using Equation 3.

This equation shows the calculation of the loss from the fiber, but can also be applied to the other

categories of energy loss.

` Percent Energy Loss=LLaser−L fiber

LLaser∗100 (Equation 3)

Nylon issues

To determine if the Nylon 12 used to encase the side-firing prototype was infrared

transparent, several experiments were done. This was first assessed quantitatively by examining

the Nylon before shining laser light through it and after. Up to 1040 V of laser light from the

Ho:YAG was incident onto the nylon. Pictures were taken before and after. A qualitative

measurement of light absorption was performed using a FLIR infrared camera. The prototype

was positioned such that the light was directed downward. The FLIR camera was positioned

above it so that it could visualize the nylon on which the light was incident. For 3 minutes, the

temperature at the spot of light incidence was measured when the laser was on. A plot of the

temperature over time was recorded

A qualitative measurement of light scattering from the Nylon was performed by placing

the nylon approximately 2 inches from the laser aperture. The power meter detector head was

positioned in five locations at various degrees around the nylon. The reflections from the nylon

were determined based on whether there was power output at various angles surrounding the

nylon.

Results

Experimental Results

The design project successfully created

the three side-firing neural stimulation prototypes

that it was designed to test. As can be seen in

Figure 6, all three of the prototypes (flat mirror,

curved mirror, and 45° polished fiber prototypes)

were able to successfully transmit signal from a

pilot light laser at a 90° angle, i.e. “side-fire” light

waves. The knife-edge technique was used to

characterize the spot shape and spot area of the

angled infrared laser’s signal.

The shape and overall area of the spot are

important in order to determine the potential

precision of each side-firing technique. A general

ellipse shape was assumed for each of the spots

while the specific diameter length on the x and y-

axis was determined with the knife edge technique and used to calculate the spot area. As seen in

Figure 7, the curved mirror prototype was shown to emit a spot with the smallest area while the

45° polished fiber prototype emitted a spot with the largest area. The curved mirror prototype

emitted a spot from the infrared laser of the smallest overall area with an area of 0.028 cm². The

flat mirror prototype emitted a spot with the second smallest overall area equal to 0.036 cm². The

45-degree polished fiber prototype emitted a spot with a significantly larger area than both the

Figure 6. All three side-firing prototypes (1.Flat mirror prototype, 2.Curved mirror prototype, 3.45-Degree polished prototype) are shown to successfully side-fire light waves

curved and the flat mirror

prototypes that was equal

to 0.183 cm². The larger

area of the 45-degree

polished fiber prototype

displayed a significant

disadvantage in

comparison to the other

side-firing prototypes for

the neural stimulator.

Using a Molectron power meter, the power output from each of the side-firing prototypes was

measured. Using the power output and the spot area measured from each of the prototypes, the

radiant exposure of each of the side-firing prototypes was determined. Figure 8 displays the

results of this data and indicates that the curved mirror prototype exhibits the highest radiant

exposure with a measured value

of 50.505 J/cm². The flat mirror

prototype emitted the second

highest radiant exposure with a

value of 24.439 J/cm² and the

45-degree polished fiber

prototype emitted the smallest

radiant exposure with a value of

5.012 J/cm². With the largest

Side-Firing Prototypes0.0000.0200.0400.0600.0800.1000.1200.1400.1600.1800.200

0.183

0.0280.036

Spot Area of Prototypes

45-Degree Polish Curved Mirror Flat Mirror

Spot

Are

a (c

m²)

Figure 7. The curved mirror prototype emitted a spot from the infrared laser with the smallest overall area from its assumed elliptical shape

Side-Firing Prototypes0.0005.000

10.00015.00020.00025.00030.00035.00040.00045.00050.00055.000

5.012

50.505

24.439

Radiant Exposure of Prototypes

45-Degree Polish Curved Mirror Flat Mirror

Radi

ant E

xpos

ure

(J/cm

²)

Figure 8. The curved mirror prototype emitted an infrared signal of the highest radiant exposure with a value of 50.505 J/cm²

radiant exposure of the three side-firing prototypes, the curved mirror prototype proved to be the

most precise and most efficient in transmitting the infrared signal from the laser source.

The percent energy loss was measured for the three prototypes in each of the different

transmission steps of the infrared signal. A power meter was used to measure the power output

directly from the infrared laser, the power output directly from the optical fiber of each of the

prototypes, and the power output after passing through the nylon casing. The results of these

measurements are shown in Figure 9 and display a fairly equivalent energy loss in each of the

side-firing prototypes. The most

notable measurement from this

data is the energy loss from the

fiber through the nylon casing of

each of the side-firing prototypes.

A loss of nearly or above 80% of

the energy through the nylon was

far too high and introduced a

significant inefficiency for the

design. Our preliminary research indicated that nylon was transparent to infrared light, therefore

an investigation was done to determine if the nylon was tubing was absorbing, deflecting, or

reflecting the infrared light to cause such large energy loss in the prototypes.

From fiber From nylon Overall0.00

10.0020.0030.0040.0050.0060.0070.0080.0090.00

100.00

76.3

4

79.2

4

95.0

9

67.8

3

84.1

0

94.8

8

78.8

0

79.0

6

95.5

6

Percent Energy Loss of Prototypes

45-Degree Polish Curved Mirror Flat Mirror

Perc

ent L

oss

Figure 9. The three side-firing prototypes exhibited a fairly equivalent percent energy loss in each of the transmission steps for the infrared signal

Using an AROI camera, the heat

accumulation was measured on the nylon tubing

to determine if the nylon was absorbing the

infrared light signal. If a rise in temperature was

seen in the nylon tubing at the point where the

infrared light was passing through, it would be

confirmed that the nylon was absorbing infrared

light. Figure 10 displays a screenshot of the AROI camera with the black box indicating the area

of interest, the nylon tubing of the prototype, for a change in temperature. The temperature of the

nylon tubing was monitored over a period of time with the infrared laser at different frequencies

and different

voltage outputs.

As seen in

Figure 11,

despite the

change of

frequency and

voltage output of

the infrared

laser, no significant temperature change was seen in the nylon tubing. These results indicated

two possibilities. The first possibility was that the AROI camera was not sensitive enough to

detect the rise in temperature caused by the absorption of the infrared light. The second

15.0°C

22.0°CAR01

Figure 10. Screenshot of the AROI camera with the black box indicating the area of interest, the nylon tube of the prototype

Figure 11. No significant temperature change was seen in the nylon tubing during infrared stimulation, no matter the voltage output or the frequency

possibility was that the nylon tubing was not absorbing the infrared signal and instead reflecting

and/or deflecting a majority of the infrared light.

To test the possibility of the nylon

reflecting and/or deflecting the infrared

signal, a section of nylon tubing was cut

in half to create a flat section of nylon.

The nylon was then suspended in front of

the infrared laser as it emitted its infrared

signal. A power meter was then used to

measure the power coming off the nylon

as shown in Figure 12. Table 1 shows that

the nylon both deflected and reflected the infrared laser

signal. These measurements confirmed that the nylon was

deflecting and reflecting the infrared signal coming from the

laser. This redirection of the laser explains the power loss

seen from the fiber as it passes through the nylon tubing in the side-firing prototypes.

With such a large energy loss occurring due to the nylon casing, glass was tested as a

replacement material for future development of the side-firing prototypes. As seen in Table 2,

glass was a much more efficient material for casing

the side-firing prototypes with only a 12.24%

energy loss of the infrared signal. This significant

reduction in energy loss, compared to the nylon

Power (mJ) Percent Loss

Bare 2.353 -

With nylon tube 0.455 80.66%

With glass tube 2.065 12.24%Table 2. The glass capillary had significantly less energy loss than the nylon tube at the infrared signal passed through it

Figure 12. Scattering and deflection of the infrared laser light was measured by rotating a power detector head radially around a flattened piece of nylon tubing.

Power (mW)Left of nylon (Back) 0.21Left of nylon (Front) 0.31Top of nylon (Back) 0.22Top of nylon (Front) 0.00

Table 1. Power measurements indicated that the nylon tubing both reflected and deflected the infrared laser light

tubing, showed to be a proof-of-concept for glass. The future development and testing of the

side-firing prototypes should utilize another material for encasement to increase their efficiency.

Economic Analysis

The potential market for an implantable neural stimulator is very large and only continues

to grow with time. An implant that utilizes infrared neural stimulation is particularly appealing

due to its precision and the significantly less damage that infrared waves cause on nerve

fascicles. Future implantation of the infrared neural stimulator could incorporated into the next

generation of prosthetics with a market of over 1.7 million people currently affected by limb loss

in the United States. This implant could also be used in the future for safe stimulation of those

affected by paralysis which includes approximately 6 million people. With a vast array of

conditions it could treat, this infrared implantable neural stimulator has an increasingly large

potential market.

As seen in Table 3, the developmental cost for each of these prototypes was relatively

low with the deviation in

cost due to the type of mirror

needed. As the fabrication of

each prototype was

downsized to fit the

dimensions needed for an implantable device, the price of each prototype would likely change

since custom materials would be ordered.

The cost of maintenance for the implantable neural stimulator is fairly unknown at this

time and largely depends upon the future development of a downsized infrared laser. However,

45° Polished Fiber Flat Mirror Prototype Curved Mirror Prototype

Fiber $138 $138 $138

Nylon Tubing $25 $25 $25

Mirror $144 $117

Total $163 $307 $280Table 3. The developmental cost for each of the side-firing prototypes depended largely upon the type of mirror needed (if needed at all)

any future cost in maintenance would only deal with the replacement of the optical fiber or with

repairing/repowering the portable infrared laser source. Furthermore, the life cycle of the

implantable neural stimulator is also dependent upon the infrared laser source being used. The

mirrors, optical fiber, and packaging of the prototypes have an infinite life cycle. Therefore the

overall life cycle of the device relies solely upon the power supply and lifetime of the infrared

signal source.

The future of this device would also need much further research of the long term effects

of infrared neural stimulation on the body and its nervous system. This research, along with the

device’s overall biocompatibility, will be needed for the future FDA approval of the device

needed for implantation in future animal and human subjects.

Safety

The biocompatibility is a main concern in the end use of the nerve stimulator prototypes.

Biocompatibility is the compatibility of a foreign object in a living system. Materials that are not

biocompatible may potentially induce an immune response. The effects of this immune response

could be hypersensitivity (anaphylactic shock, cytotoxicity, immune complex, or a cell mediated

response), chronic inflammation, immunosuppression, or histological changes in tissue

(Guelcher and Hollinger, 2006). Nylon is not a biocompatible material and induces an immune

response in the body. Glass capillaries were another material investigated for use in the

stimulator cuff. However, glass is also not biocompatible. Although these materials are not

biocompatible on their own, there are several methods that can be implemented to improve

biocompatibility and minimize the body's immune response. PEGylation is one method of

attaching polyethylene glycol (PEG) to the surface of a biocompatible material. The body would

then only have to interface with the PEG, which is a biocompatible molecule. However, the

material that encases each single fiber stimulator does not need to be biocompatible because it

can be encased in another material that will come in contact with the neural tissue. Silicon based

materials are biocompatible and provide enough flexibility that the nerve will not be damaged by

the moving of the implant in the body. Polydimethylsiloxane (PDMS) is an ideal material to

embed the single channel stimulators. PDMS will likely be the material that is used in the end

product.

Conclusions

Several specifications were considered in determining the best of the three models.

Included in these specifications were radiant exposure, power loss, and design complexity; the

complete list of factors used in determining the optimal prototypes are detailed in Table 4. At

50.5 J/cm2, the concave mirror prototype’s

radiant exposure was greater than twice that of

the flat mirror and ten-fold greater than that of

the angle-polished fiber. As seen in Table 4,

this magnitude is not required for individual

nerve stimulation. However, for future use in a nerve cuff, the energy could be divided into four

to twelve different fibers, so the exposure must be great enough to provide adequate power to

multiple channels. The overall power loss was virtually identical for all three prototypes at 95%.

This includes coupling loss, loss within the fiber/mirror complex, and loss through the nylon.

After learning of nylon’s poor infrared transparency and the dependency of coupling loss on

other external factors (e.g. focusing lens), it was determined that the loss through the fiber/mirror

Table 4. Ideal prototype specifications

complex is the most critical consideration for throughput in the context of our experiments.

While these values were all with eleven percentage points of each other, the concave mirror

measurements was the lowest at 67.83% power loss.

Though the concave mirror prototype did outperform the other in radiant exposure and

throughput, it is by far the most complex of the three. The angle-polished fiber is the simplest

because of it lacks the requirement for a mirror. The flat mirror model is simpler than the

concave mirror model because one needs not consider the ramifications of the focal length (e.g.

fiber distance from mirror and nerve distance from mirror). Despite its greater complexity, its

quantitative advantages are too valuable to compromise. With the appropriate precision in

manufacturing the mirror and nerve cuff, it will be possible to construct a safe and effective

infrared nerve stimulator.

Recommendations

Engineers must overcome additional challenges before this method of nerve stimulation

can improve the quality of life for patients suffering from paralysis or limb loss. These

challenges include development of actual scale multi-channel nerve cuff and the incorporation of

a biocompatible and infrared transparent material. Vanderbilt University’s Duco Jansen, Ph.D is

working with the U.S. Department of Defense under the CIPhER (Centers in Integrated

Photonics Engineering Research) grant towards the eventual creation of such a cuff. He and his

team have decided to construct the cuff using the concave mirror design.

The nylon was used in the large-scale prototype construction based on its low cost and

presumably infrared transparent properties; its biocompatibility was ignored. Implantable cuffs

must be infrared transparent and biocompatible. Based on research, an ideal material for this

application is silicon-based PDMS (polydimethylsiloxane). Its infrared energy loss at 2.12µm

(wavelength of Ho:Yag laser) is between 0 and 5 dB/cm and it is known to be biocompatible

(Cai, 2008).

Appendix I: References

Agnella D. Izzo MS, Claus-Peter Richter MD, E. Duco Jansen PhD, Joseph T. Walsh Jr. PhD. “Laser stimulation of the auditory nerve.” Lasers in Surgery and Medicine. 2006 September; 38(8): 745-753.

Cai, D., A. Neyer, R. Kuckuk, and H. Heise. "Optical Absorption in Transparent PDMS Materials Applied for Multimode Waveguides Fabrication." Optical Materials30.7 (2008): 1157-161. Print.

Claude Veraart, Christian Raftopoulos, J. Thomas Mortimer, Jean Delbeke, Delphine Pins, Geraldine Michaux, Annick Vanlierde, Simone Parrini, Marie-Chantal Wanet-Defalque. “Visual sensations produced by optic nerve stimulation using an implanted self-sizing spiral cuff electrode.” Brain Research, vol. 813, Issue 1, 30 November 1998, Pages 181-186,

Guelcher SA, Hollinger JO (2006) An Introduction to Biomaterials. Taylor and Francis Group.

Jonathon Wells, Chris Kao, E. Duco Jansen, Peter Konrad, and Anita Mahadevan-Jansen, J. “Application of infrared light for in vivo neural stimulation.” Biomed. Opt. 10, 064003 (2005), DOI:10.1117/1.2121772

Jonathon Wells, Chris Kao, Peter Konrad, Tom Milner, Jihoon Kim, Anita Mahadevan-Jansen, and E. Duco Jansen. “Biophysical Mechanisms of Transient Optical Stimulation of Peripheral Nerve.” Biophysical Journal. 2007 October 1; 93(7): 2567–2580.

Appendix II: Safety Report

Appendix III: Innovation Workbench

Ideation Process Project Initiation Project name: Design of an Infrared Nerve Stimulator Project timeline: October 2010 - May 2011 Project team: Melanie Gault, Greg Wigger, Chris TedderPrimary Objectives1. Develop three infrared nerve stimulator prototypes containing optical fibers running parallel to

the nerve for eventual implantation in a nerve cuff stimulator2. Compare the efficacy and infrared light output of each of the three designsImportance of the SituationDesign of the side-firing prototypes will provide the means for an implantable nerve stimulator. This implantable device will have the capabilities to be included in the next generation of prosthetic devices and for treatment of those suffering from paralysis.

Innovation Situation Questionnaire Brief description of the situation Researchers have determined that infrared light can stimulate nerve fascicles with greater precision, specificity, and less damage than electrical nerve stimulation. For future use and implantation of infrared nerve stimulators, a design must be created that can direct an infrared beam at a 90° angle, or “side-fire” the signal. Using mirrors and/or optical properties of an optical fiber, the side-firing of the beam is possible.

Detailed description of the situation In order for a nerve stimulator to be feasible for implantation, it must lay in parallel with the nerve fascicle of the patient. To lie in parallel and still stimulate the nerve, the infrared light must be directed at a 90° angle. By polishing an optical fiber at a 45° angle, the infrared light experiences total internal reflection so that it goes in the 90° direction. The other two strategies involve using a flat mirror or a concave mirror laid at a 45° angle so that the infrared light is reflected in a 90° direction.

Supersystem - System - Subsystems System name Infrared Nerve StimulatorSystem structure The infrared nerve stimulator must always contain an optical fiber that transmits the infrared light from the laser source. Ideally, this optical fiber has maximum flexibility and minimum size. All nerve stimulators must also include a casing, made of glass, nylon, or some other transparent material, to protect the air-fiber interface of the polished fiber or to contain the mirrors for the mirrored stimulators. The mirrored stimulators must contain either a concave or flat first-surface mirror with a minimum size.Supersystems and environment The infrared nerve stimulator must be attached to an infrared light source. This light source must emit an infrared laser with a high energy output and will therefore be connected to an external power source. In order for the nerve stimulator to be as precise and efficient as possible, the stimulator must lie, in parallel, on top of the nerve fascicle and aligned with pre-determined,

particular axons. This conditions requires that the patient be alive, healthy, and with a viable nerve system.

Systems with similar problems No other system experiences a similar problem since electric stimulation does not rely on “side-firing” methods. Electric stimulation simply attaches to the nerve fascicle for direct delivery of stimulation while infrared light must be delivered in less direct fashion. However in optical research, mirrors have been precisely fabricated and are used throughout to reflect light in any desired direction. Using this previous mirror usage, along with the known optical properties of an optical fiber, the three side-firing methods can utilize the solutions.

Input - Process - Output Functioning of the system Infrared light will be passed through the different side-firing prototypes and the various properties of infrared beam directed in the 90° angle will be measured.System inputs The input of our system is the infrared light and its energy. System outputs The output of our system is an infrared beam that has been directed in a 90°angle or “side-fired.” The output of this beam includes its beam size, radiant exposure, and energy loss in each stage of the infrared light’s movement.

Cause - Problem - Effect Problem to be resolved Infrared light must be directed at a 90° angle while maintaining a minimum beam size, a high energy throughput, and a sufficient radiant exposure for nerve stimulation.Mechanism causing the problem The human body anatomy requires that the infrared nerve stimulator lie in parallel with nerve fascicles in order for a patient to maintain functionality and a high quality of life. Undesirable consequences if the problem is not resolved Patient using an infrared nerve stimulator without side-firing abilities will lose original mobility and functionality of affected body areas.Other problems to be solved Reflection and transmission of the infrared light changes the beam’s characteristics and its energy output.

Past - Present - Future History of the problem Electric stimulation of nerve fascicles have existed for over 150 years. Infrared stimulation of nerve fascicles has existed for less than 50 years however. Until now, infrared stimulation has only occurred by directing infrared light on the nerve fascicle in a perpendicular manner. With the future of implantation ensuing, side-firing techniques must be developed. Pre-process time Research into previous methods of nerve stimulation. Determining top prototype candidates through proof-of-concept modeling.Post-process time Research into afferent stimulation and a portable, infrared laser source are future directions.

Resources, constraints and limitations Available resources The substance resources that we have are optical fibers from Ocean Optics, transparent nylon tubing, glass tubing, and first-surface flat and concave mirrors from Edmund Optics. Our primary resources for space are Vanderbilt Optics lab facilities. We have two semesters to complete the project which is our time resource. Dr. Duco Jansen, Dr. Kurt Schoener, and Dr. Paul King are our information resources. Allowable changes to the system Small changes are allowed regarding the tubing/encasement of the side-firing prototypes. The fiber optic system must be encased in a material that is biocompatible and transparent to infrared light with maximum throughput. Constraints and limitations The system is constrained to emit an infrared beam with a minimum radiant exposure of 0.4 J/cm^2 to result in nerve stimulation. The air-fiber interface must remain on the 45° polished fiber prototype so that is optical properties retain its ability for side-firing.Criteria for selecting solution concepts Primary characteristics include radiant exposure and energy throughput. The ideal model will have the highest values in both of these categories. Other considerations include durability, cost, and design complexity.

Problem Formulation and Brainstorming

Infrared Nerve Stimulator

1.Infrared Nerve Stimulator produces Side-Firing Capabilities, Spatially selective stimulation and Need for nerve cuff produces Narrow energy window for effective stimulation.

2.

Side-Firing Capabilities produces Ability to lie fiber in parallel with nerve and Ability to fire infrared beam at 90 degree angle produces Difficulty in producing desired beam profile, Energy lost in reflection and Polished fiber requires air-fiber interface is produced by Infrared Nerve Stimulator.

3.Ability to lie fiber in parallel with nerve produces Ideal for implantation produces More contact with nerve that could induce damage to nerve is produced by Side-Firing Capabilities.

4. Ideal for implantation is produced by Ability to lie fiber in parallel with nerve and Ability to fire infrared beam at 90 degree angle.

5. Difficulty in producing desired beam profile produces Energy lost in reflection is produced by Side-Firing Capabilities.

6. Energy lost in reflection is produced by Side-Firing Capabilities and Difficulty in producing desired beam profile.

7. Spatially selective stimulation produces Ability to stimulate individual fascicle is produced by Infrared Nerve Stimulator and Need for nerve cuff.

8. More contact with nerve that could induce damage to nerve is produced by Ability to lie fiber in parallel with nerve.

9. Ability to stimulate individual fascicle is produced by Spatially selective stimulation.

10. Polished fiber requires air-fiber interface produces Need for material is produced by Side-Firing Capabilities.

11. Need for material produces Larger risk for immune response is produced by Polished fiber requires air-fiber interface.

12. Larger risk for immune response is produced by Need for material.

13.Narrow energy window for effective stimulation produces Below stimulation threshold results in no effect and Above safety range can cause tissue ablation is produced by Infrared Nerve Stimulator.

14. Below stimulation threshold results in no effect is produced by Narrow energy window for effective stimulation.

15. Above safety range can cause tissue ablation is produced by Narrow energy window for effective stimulation.

16. Ability to fire infrared beam at 90 degree angle produces Ideal for implantation is produced by Side-Firing Capabilities.

17.Need for nerve cuff produces Spatially selective stimulation, Stimulate multiple fascicles at once and Need for biocompatibility produces Must anchor cuff to nerve is produced by Infrared Nerve Stimulator.

18. Stimulate multiple fascicles at once is produced by Need for nerve cuff.

19. Must anchor cuff to nerve produces Potential damage to nerve is produced by Need for nerve cuff.

20. Potential damage to nerve is produced by Must anchor cuff to nerve.

21. Need for biocompatibility produces Limits use of materials is produced by Need for nerve cuff.

22. Limits use of materials is produced by Need for biocompatibility.