VanderbiltUniversity
School of Engineering
Senior Design Project
Development of an Infrared Nerve Stimulator
Team Members:
Gregory Wigger
Melanie Gault
Advisor:
E. Duco Jansen, PhD
Biographical Information
Melanie Gault
Biomedical Engineering
Telephone: (847) 924-8824
Email:
Gregory Wigger
Biomedical Engineering
Telephone: (859) 512-1381
Email:
Dr. E. Duco Jansen
Principle Investigator
Vanderbilt University
Professor of Biomedical Engineering
Professor of Neurological Surgery
Director, Graduate Studies, Biomedical Engineering
Email:
Telephone: (615) 343-1911
Ms. Mary Judd
Administrative Contact
Vanderbilt University
Biomedical Engineering
Grants Manager
Email:
Telephone: (615) 322-4229
Fax: (615) 343-7919
Dr. Todd Giorgio
Department Chair
Vanderbilt University
Biomedical Engineering
Chair of Biomedical Engineering
Email:
Telephone: (615) 322-3756
Fax: (615) 343-7919
Grant Info
Team name/name of venture: Infrared Nerve Stimulator Development
Amount requested: $1695
Proposed grant period: 10/20/2010 - 4/12/2011
Abstract
Development of an infrared nerve stimulator
Recent scientific discoveries have found infrared laser light to be capable of neural stimulation. Unlike electrical stimulation, infrared stimulation has proven to be damage-free, artifact-free, and spatially selective (Wells, 2005). Furthermore, optical stimulation by an infrared laser does not require contact and has spatial selectivity that can precisely excite only one nerve (Izzo, 2006). Through a partnership with the Vanderbilt University Biomedical optics laboratory, the design team proposes to construct an infrared nerve stimulator cuff for implantation that can be used for treatment of neural disorders.We will perform initial proof-of-concept experiments and development of a large-scale prototype that contains optical fibers that lie in parallel with a nerve bundle and are capable of side-firing an infrared laser signal to stimulate neural activity in a spatially precise fashion. . This design may be extended out to four channels that are wrapped around the nerve for spatially selective stimulation of nerve fascicles.The future implantation of a nerve cuff will lead to innovations that can be integrated in the next generation of prosthetic devices, and be used as long term therapeutic modalities for a wide variety of diseases including Alzheimer’s disease.
Introduction
Recent scientific discoveries have found infrared laser light to be capable of neural stimulation. The use of fiber optics allows for the precise stimulation of individual neurons without affecting surrounding neurons in the nerve bundle. This low energy technology has proven to be novel method for neural stimulation that is damage-free, artifact-free, and spatially selective (Wells, 2005).
With this emerging technology, we strive to begin to perform initial proof-of-concept experiments and development of 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. Implantable nerve cuffwill be biocompatible and eventually have the capability to be wrapped around an entire nerve bundle and optically activate single nerves. The spatial selectivity of infrared stimulation will supersede the spatial selectivity and abilities of electrical stimulation nerve cuffs (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 1. Our project aims to explore the potential methods in accomplishing a successful side-firing optical fiber that is properly encased for implantation.
If time permits, we will expand our research and design a prototype for a multichannel infrared neural stimulation probe capable of simultaneously or sequentially stimulate multiple fascicles in the same nerve. Specifically, we will aim to design and perform further proof-of-concept experiments on a nerve cuff with four side-firing channels positioned around the nerve at the 12, 3, 6, and 9 o’clock positions.
History and Context
For two centuries electrical stimulation has been used to stimulate neurons. 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 stimulationinduces a stimulation artifact.
The Vanderbilt Biomedical Optics 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 Optics Laboratory determined that the infrared laser energy results in a transient temperature gradient increase which leads to the opening of ion channels and 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 focused to only precisely excite one nerve. Neural stimulation by infrared light also lacks stimulation artifacts and is a non-contact stimulation (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 2. Figure 2 shows how the cuff surrounds a nerve fiber and has multiple infrared 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 (not depicted in Figure 2).
Active industry participation will be needed for the eventual commercialization of this nerve cuff product. Lockheed Martin Aculight is dedicated to medical applications of lasers and photonic devices. Texas Instruments and National Instruments are also focused on creating new markets for their core signal processing product line.
Team
The infrared nerve stimulator development team is composed of two Vanderbilt undergraduate students. Melanie Gault is a biomedical engineering student pursuing a bachelor's degree and master's degree in biomedical engineering. She has worked in the biomedical optics laboratory for three years on a project involving infrared nerve stimulation. She will help select the optimal material for the components, design and make the prototype of the stimulator, and test its feasibility along with Greg Wigger.
Greg Wigger is a biomedical engineer who has previous design experience in his research with the Center for Perioperative Research in Quality and in an independent study utilizing cardiovascular image analysis in the Vanderbilt University Medical Center. Both Melanie and Gregory will perform proof-of-concept experiment to determine the best method for side-firing an infrared signal. In addition, they will design the optimal and biocompatible encasement for the eventual implantation of the fiber optics.
In addition to the undergraduate members, faculty from the Vanderbilt School of Engineering will be advising the engineering aspects of the project, such as design and engineering principles.Dr. E. Duco Jansen, principal investigator of the biomedical optics lab at Vanderbilt will be providing input and assistance with his experience doing nerve stimulation.
Work Plan and Outcomes
The engineering aspects of this project include designing a large scale prototype for a single channel implantable nerve stimulator. Geometric features of the stimulator ideal for implantation and suitable light delivery will be determined. Materials will be assessed for biocompatibility. Characterization studies will be done on the nerve stimulator to determine amount of energy that is reaching the neural tissue. Light loss and light profiles will be assessed to ensure that the energy reaching the tissue is adequate for stimulation but does not reach the damage threshold of the tissue. The nerve stimulator will be redesigned if the characterization studies show tissue incompatibility or insufficient light delivery. Other engineering components include testing the stress and strain modulus of the materials in order to protect against damage of neural tissue. The work plan for this project is summarized in Figure 3. The project will span from the end of October to the middle of April when the prototype will be presented.
Figure 3: Summary of the work plan for design of infrared nerve stimulator.
At the end of the grant period, the project has the opportunity to continue by expanding into multi-channel stimulation. Four single channel nerve stimulators will be placed radially around the nerve. In order to achieve this multichannel design, the single channel prototype must be scaled down in order to fit around the diameter of a nerve fiber. A way of attaching the implant to the body must be considered in this design. A mechanism of delivering light to each fiber individually will be determined. The laser hardware will be incorporated into the design. The optimal packaging method for implantation will be determined.
Through collaboration with the Vanderbilt University Biomedical Optics Laboratory in the School of Engineering, biomedical engineers with interests in research, industry, and medicine will work together to design a functional prototype that meets the performance and financial specifications of the target market. The proposed nerve stimulator project is an extension of work done in the research laboratory performing nerve stimulation by light coupled through fibers perpendicular to the nerve. A perpendicular orientation is not practical for implantation. Therefore, creating this nerve stimulator presents an opportunity to take an existing technique from lab bench to bedside and improve the quality of life for many with neural disorders.
Evaluation and Sustainability Plan
This project will be considered successful if a prototype for a fiber optic is designed that can lie in parallel with a nerve bundle and have the ability to side-fire an infrared signal. The prototype must include the most effective means of reflection and be completely encased within a biocompatible material for future implementation. Dependent upon the delays met in the design process, ambitious success in this project would be the complete design of a four-channel capable of simultaneously side-firing an infrared signal from its four separate optical fibers.
Success of the delivery of the infrared laser signal will be based upon three sources of measurement. Measurement of the intensity of received signal and number photons delivered to nerve will be compared to the signals original intensity and photon output. A percent error of 20% or less for these two measurements would be considered a successful side-firing. Furthermore, a laser beam profile of the side-fired signal from the optical fiber and a graph of the signal’s intensity as a function of θ (θ is the angle around the nerve cuff) will be completed to offer a visualization of the infrared signal. The magnitude of the intensity must be above the threshold for stimulation and below the threshold for tissue ablation.
The measurements of the intensity and photons delivered will also be done on the four-channel infrared neural stimulation probe if time permits. A percent error of 35% from each fiber will be considered successful in this particular prototype.
Appendix A - Budget
- Research of the Prototype
- No Cost
- Total=$0
- Building of the Prototype
- Polydimethylsiloxane (PDMS) – $40
- Petri dishes - $10
- Mirrors- $400
- Four fiber optic probes – $500
- Machine Shop/Fabrication - $50
- Safety Equipment $20
- Miscellaneous supplies $100
- Total=$1120
- Publication/Promotion
- Poster-$75
- Kinko's Budget-$200
- Total=$275
- Total = $1395
- Contingencies= $300
- GRAND TOTAL = $1695
Budget Justification
Four mirrors and four optical fibers will be purchased at approximately $100 each.
Most of the fabrication will be done on our own, but $50 is set aside for more complex fabrication steps
$200 for Kinko's need to print material for presentations.
Appendix B- Team Member Expertise
Melanie Gault
Melanie Gault is a senior at Vanderbilt University majoring in Biomedical Engineering. She is simultaneously pursuing her Master's degree in Biomedical engineering. She is doing her thesis work in the Vanderbilt biomedical optics lab on a project involving infrared neural stimulation of the sea slug Aplysia californica. With her knowledge of nerve stimulation and stimulation constraints, she can design and test the nerve stimulator prototype. Her previous experience working with nerve preparations of different model organisms will contribute valuable input to the design of the stimulator prototype. She is currently applying PhD programs in the area of neural engineering for the fall of 2011.
Gregory Wigger
Gregory Wigger is a senior at Vanderbilt University majoring in Biomedical Engineering. He has previous experience in research involving design with the Center for Perioperative Care in Quality within Vanderbilt University Medical Center. In addition, he has experience involving scientific research and image analysis during an independent study analyzing the effect of insulin on the blood flow and dilation of blood vessels of mice. Gregory plans to attend medical school in the fall of 2011. These unique aspirations allow him to bring forth a unique perspective that will provide valuable input centered on the need for this project’s technology to keep future patients and physicians in mind.
Appendix C – Supporting Documents
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
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,
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.