non-transcranial electroanesthesia...

Non-transcranial Electroanesthesia Device

Vanderbilt University

Dr. James Berry, Supporting Faculty Member

Ryan Demnter, Matthew Jackson, Caroline Schulman, Matthew Whitfield

Problem to be solved

Present anesthesiology techniques primarily utilize gas and liquid anesthetics. Gas anesthesia is complicated to administer and the equipment is expensive, while intravenous anesthetics are expensive to purchase (Clarke 155-160). In many cases, intravenous anesthesia is between three and nine times more expensive than gas anesthesia per volume (Kurpiers et. al., 69-75). However more gas is required per treatment raising the cost to around twenty to forty dollars a patient (Kurpiers et. al., 69-75). Anesthesia and analgesia may be produced through the application of electromagnetic fields to the brain. Electroanesthesia will reduce the high cost of anesthesia for surgery and other procedures by reducing the need to keep large quantities of liquid and gas anesthesia on hand. In addition, because electroanesthesia may be delivered non-invasively through the skin, a highly trained anesthesiologist will not be required. By combining the premedication and paramedication capacity of liquid, electroanesthesia as a method for administering general anesthesia is a more cost effective design. Electroanesthesia is thought to affect the same areas of the brain as chemical anesthesia and therefore provide the same effects. Due to apprehension about the long term effects of passing electrical current across the brain voiced by the Food and Drug Administration, an alternative method for administering electroanesthesia must be developed to bring electroanesthesia to market in the United States (Fries 2005).

Problem objective statement

By utilizing the vagal nerves’ direct connections to the brain, a theoretical alternative method for the application of electroanesthesia is proposed. Vagal nerve stimulation (VNS) currently offers the “analgesia” aspects of anesthesia (Kirchner et al., Ness et al.). There are fewer side-effects with transcranial electroanesthesia than conventional anesthesia techniques due to its biological benefits (Sances and Larson and Larson 1975), and non-transcranial electroanesthesia may also boast these benefits. Through the development of and further research into VNS, full anesthesia (hypnosis and analgesia) may be achieved. The goal of this design project is to develop a device to control and administer non-transcranial electroanesthesia using the vagal approach. The device will be portable, self sustaining, and rechargeable. Further research into VNS and other methods for administering electroanesthesia will be addressed in a later project. The exact parameters for stimulation will be variable allowing the device to be adaptable to altered stimulation parameters determined with any future research. The electrical pulses required for the electroanesthesia will be generated by the computer’s soundcard and then output from the sound jack to an external amplification circuit. This circuit will amplify



the signal to the desired voltage and a set of electrodes will deliver the signal to the surface of the skin.

Documentation of the final design, including applicable standards and risk analysis

The device is classified as a Class III medical device because insufficient information exists to ensure safety and effectiveness solely through general or special controls. Because the FDA relies upon only valid scientific evidence to determine whether there is reasonable assurance that the device is safe and effective1, further extensive investigation of the device will be necessary upon completion and production of the final design before use.

Using the Design Safe 3 program, some possible risks of our device and their solutions were investigated (See Report in Appendix G). One of the conceivable risks of this device or any device creating electrical pulses is the possibility of shocking the physician or patient during use or the maintenance technician during normal upkeep or repair of the device. In our device, this risk is small due to the low currents (sub mA) and voltages used. To further mitigate this risk, the amplification circuit will be enclosed within the device housing and all wires properly insulated. The laptop, circuit, and internal fans will also be grounded to prevent static charges from building up creating the possibility of shocking the user. The most serious risks associated with this device involve the cessation of function of the device. If it stops working for any reason, the anesthetic effects will almost immediately cease creating a serious problem if it occurs during a procedure. This failure could result if there is an error in the LabVIEW code, an error in the computer function, the battery dies, or the applicator becomes dislodged from the patient. Thorough testing of the code will be conducted under all possible parameters until all bugs have been removed. Although it is impossible to completely eliminate the risk of computer failure, by having a computer with a fast processor and an excess of memory that only runs our desired program this risk will be minimized. While not in our prototype, the laptop used for the device should have two battery ports allowing for extended battery life and the ability to recharge one battery while the other is powering the device. The electrodes themselves are highly adhesive to the skin and have a low probability of accidentally falling off the patient (Appendix D(a).iv). To further reduce this risk, a self-adhesive medical tape will be wrapped around the head or neck across both electrodes, securing them to the patient.

Prototype of the final design

The operation of our device will be controlled by a laptop running a LabVIEW virtual instrument (vi) (See Appendix E(d)). The program will accept the input of patient information either manually or from a patient database. Based on the patient information 1 Valid scientific evidence is evidence from well-controlled investigations, partially controlled studies, studies and objective trials without matched controls, well-documented case histories conducted by qualified experts, and reports of significant human experience with a marketed device, from which it can fairly and responsibly be concluded by qualified experts that there is reasonable assurance of the safety and effectiveness of a device under its conditions of use. (FDA title 21.860.7)



such as age, sex, or any special conditions, the pulse duration, amplitude, and frequency of the waveform will be set. When our unit is first turned on, the computer will boot up and automatically open the LabVIEW vi. The ON/OFF button turns the signal generation on or off but does not close the program. There are dials to control pulse duration, amplitude, and frequency of the output signal. The STOP button exits the program completely. There is also a SAVE command which saves the data from all of the plots. During waveform generation, a plot showing the current waveform generation and a plot showing a ten second window of all of the pulses during the session are displayed. The user can access a complete log of the signal by using the scroll bar at the bottom of the graph. The program also has a third plot space which will be utilized to display patient vital signs when the device is attached to appropriate vital signs equipment (See Appendix D(a).iii).

The LabVIEW vi consists of one general loop that runs the entire vi. Outside of the general loop there are sound property operators that condition the program for the creation of sound. In the general loop there are 3 conditional loops, conditional operators, string matrix constructors, and a light boolean. The string matrix constructor creates strings for saving data for each plot. The light boolean is used to indicated that the stimulus is active. The conditional operators allow for the selection of which type of patient information is being used for display and saving. These operators also control which type of patient information should be activated for input. In addition, they control whether the device is on or off and whether the stimulus is active or inactive.

Two conditional loops allow for access to patient information entry protocol and one for signal generation. The patient information protocol is contained in two separate conditional loops that are controlled by a conditional operator. The first conditional loop allows for manual input, while the second allows for the use of a local or network drive to access patient information from a database or file. The signal generation conditional loop controls the audible signal generation. This loop contains an audible signal player correlated to the square wave generated. The loop is activated when the stimulus is turned on. This loop contains the controls for the properties of the stimulus. There is a divider operator associated with the voltage control to ensure a mono-polar signal and a multiplier to amplify the signal going out. The design links pulse length to duty cycle to achieve the desired audible output, thus the duty cycle dial is inactive at all times.

The computer output uses a gain stage of 23 (See Appendix E(c)) to amplify the signal for patient delivery to any desired voltage between 13.8 and 59.8V. The circuit consists of a precision instrumentation amplifier, resistors, fans, and a battery power supply contained under the laptop (See Appendix D(a).ii). The instrumentation amplifier used is a Burr-Brown INA114AP-ND amplifier. This amplifier is used because of the wide power range of +/-2.25V to +/-18V. Other advantages of the amplifier are a high CMRR of 115dB and a gain range of 1 to 1000. The gain of the amplifier is determined by one resister. When testing the device, the gain may be changed by replacing the resistor. The power supply to the amplifier is a 9V rechargeable Nickel Metal Hydride battery with a voltage divider to reduce the voltage of the circuit to 4.5V.



Using a lower voltage prevents the amplifier from generating unnecessary heat without compromising function. The battery is also connected to a RadioShack 9V charger. A rechargeable battery maintains the portability of the device while also offering an easy way to recharge the system. A 5V Orion fan is used to cool the amplifier from the heat of the computer and insulation surrounding the circuit. The life expectancy of the fan is over 50,000 hours. Using a separate 9V Ni-MH battery and 9V RadioShack charger, the fans are powered. There is a power strip fed through the back of the box connecting all components in the housing. This allows for one cord to be plugged in while the device is charging. The circuit output is then connected to electrodes attached to patient.

Shielded wires run out of the housing for connection to either clips, for a generic 2.75 in. diameter pad electrode, or needle electrode for application purposes. The white foam backing of the pad electrode allows for stretch-ability and memory over repeated use. The carbon/silver film gives uniform current distribution and lower impedance levels for more comfort for up to 6 hours. A monopolar 1 in., 28 gauge conical tip needle electrode will be used to delivery the desired signal for any length of time. The conical tip of the needle electrode will provide for low penetration resistance. At a price of roughly $2 to $3 per electrode, the pad and needle electrode will offer the proper functions with a minimal cost. The placement of the electrodes (See Appendix D(a).iv) will be behind the ear on the vagal nerve..

The laptop and amplification circuit are be housed within an 18" x 18" x 10" compartment constructed from rigid high-density polyethylene from Tap plastics (See Appendix D(a).i). The top of the box is hinged allowing for access to the laptop which sits on a shelf near the top of the casing. The right side of the box has a fan to remove heat produced by the laptop and circuit. Underneath the laptop is space for the circuit, a battery and charger to run the circuit and fans, a power strip to connect all of the devices, and extra space for the storage of the recommended vital signs equipment (See Appendix E(b)).

Proof that the design is functional and will solve the problem

The use of the vagal nerve to administer “complete” electroanesthesia is theoretical. It has been shown that pain can be controlled by electrical stimulation of the vagal nerve (Kirchner et al., Ness et al.) or the transcutaneous nerve (Strassburg). These nerves lead into the brain and allow for the control of pain without using a transcranial method. Cork et al (2004) showed that pain control was possible via clips on the earlobes (possibly stimulating the brain via the facial nerve). Ammons et al. (1983) proposed that there are sites on the brainstem that can activate descending inhibitory pathways via the stimulation of the vagal and surrounding nerves. Noxious and non-noxious stimuli were inhibited in spinothalamic cells by stimulation of the left vagal nerve. Complete inhibition was observed in cells with low background activity while cells with high background activity showed partial inhibition (See Appendix E(a).iii). George et al. (2002) showed that motor cortex excitability was reduced while the vagal nerve was being stimulated. A descending mechanism of inhibition was confirmed by Garcia-Larrea



et al. (1999) when a reduction in spinal reflexes resulted from motor cortex stimulation. Hammond et al. (1992) showed that the action potential of a stimulus travels via afferent fibers to the nucleus of the solitary tract and the area postrema. Hammond also reported that “synchronous bursts of potentials could be dispersed to widespread areas of the brain.” When inhibitory neurons are tonically excited, other inhibitory neurons are excited through mutual inhibitory connections (Jefferys et al. 202-208). Kirchner et al. (2000) confirm the use of vagal nerve stimulation to suppress pain in an experimentally induced pain study. Postulating that the mechanism of VNS involves central inhibition and not peripheral nociceptive mechanisms, Kirchner and his colleagues showed that there was widespread distribution of inhibition in the central nervous system, confirming the findings of Jefferys et al. The finding that VNS has widespread effects is significant because pain perception and response results from sensory inputs that are modulated by feedback mechanisms and the influence of the central nervous system (Melzack et al. 971-979). The release of GABA and glycerin by stimulated C-fibers (Woodbury and Woodbury 94-107) mediates inhibition (See Appendix E(a).ii). Our stimulation parameters were estimated from the findings of George et al. (2002) who discovered that 5 Hz signals resulted in less of an effect in the brain than did VNS at 20 Hz. Additionally, a pulse length of 250 µs (Liporace et al. 885-886) at 50 µA (Kirchner et al. 1167-1171) and 25 V produced the best results. The exact stimulation parameters will be varied based on the age, sex, and other parameters of the patient.

The device output has been verified using an oscilloscope. The oscilloscope confirmed that the device produces a square pulse with the parameters that are set in the vi (See Appendix D(b)). This confirms that the output of the device is being produced and administered properly. The device was able to run while unplugged for three hours without any changes in performance and should run indefinitely when plugged in. The output signal could be cleaned up by the use of a better sound card. By changing the BIOS shell of the computer, any lag in the signal can be eliminated.

Results of a patent search and/or search for prior art, assessment of patentability

A patent search revealed no patents involving non-transcranial electroanesthesia. A patent was found (4383522, 1983) that describes a transcranial method of delivering electroanesthesia using electrodes placed on the neck and the forehead. This method uses two power supplies to pass up to 2.5 mA at 100-200 Hz through the brain. In this patent, electric pulses are used in conjunction with muscle relaxants, nitrous oxide and oxygen to produce anesthesia. Considering another potentially patentable part of our design, our device will use the output of a computer’s soundcard to produce the pulses used to produce the electroanesthesia. A patent search revealed a conceptually similar although different use for the output of a soundcard. The paragraph below describes patent number 6,393,319 received on May 21, 2002.

“Data defining electrical waveforms for physical therapy is created on a computer and stored in a removable machine-readable medium such as a CD-ROM or semiconductor memory module. The data is played back, for example on a portable



CD-ROM player, to produce the physical therapy waveforms at any time and location convenient or desired by the patient. An interface circuit amplifies and conditions the resulting waveforms for applying them to the skin of the patient via leads and electrodes. Since most therapies use waveforms within the audio frequency range, ubiquitous low-cost audio playback equipment can be used. Advantages of the invention are providing physical therapy at any location and at low cost, without requiring presence of a clinician or other health care professional on location.” (US Patent Office online)

Instead of prerecorded data, our device will use a continuously tunable LabVIEW interface to produce the data stream output by the soundcard. This dynamic electroanesthesia signal will be administered to the patient without any chemical anesthesia during the procedure. The electrical stimuli will be delivered to the vagal nerve either behind the earlobe or at the side of the neck.

Anticipated regulatory pathway

To date, the FDA has not approved any electroanesthesia devices and considers them to be Class III medical devices under 21CFR868.5400. Approval for such a device needs to go through a Premarket Approval (PMA) or Product Development Protocol (PDP). Extensive clinical testing, the disclosure of specifications, intended use, manufacturing methods, and proposed labeling would be required for the PMA process. In order to collect preliminary data and show proof of concept, animal testing would have to be conducted first. Before proceeding with animal testing, Institutional Review Board (IRB) approval would need to be obtained. After these studies, an investigational device exemption (IDE) would need to be cleared for human trials to begin. Specific success criteria for each end-point would be determined in advance. If the protocol is approved and the clinical trial yields data that meet or exceed these criteria, the process would be completed and the device should be approved.

Although no electroanesthesia devices have been approved in the US as stated previously, a cranial electrotherapy stimulator (CES) has been cleared as substantially equivalent for insomnia. Under 21CFR882.5800, this device is considered Class III and requires a 510(k) approval. These devices typically deliver about 4mA of high frequency current via applicators at each temple. Manufactures of these devices claim that they are useful for a variety of applications from reducing pain, to improving sleep, to increasing brain power (Red Circuits). There are also several transcranial electroanesthesia devices approved in Europe. These devices can produce general anesthesia either alone or in conjunction with conventional drugs or muscle relaxants. These devices are different from our proposed device because they deliver the electroanesthesia across the whole head instead of across the vagal nerve as in our device. This difference could make our device much safer with a reduced chance of side-effects.

Estimated manufacturing costs



The cost to produce this device would be somewhere around $1000. This manufacturing cost includes $600 for the computer to run the stimulation program, $20 for the electrical components and connections, $150 for housing and constructive material, $2-3 for electrode applicator, $30 for manufacturing, and $200 for research and development and quality assurance of the device. Vital signs monitoring and interface equipment would be added to the device for $2,000. The initial production number is estimated to be 1,000 units.

The computer being used would not be an after market unit like that of the one in the prototype, thus it may cost less than the $600 estimate. The estimate is high to provide for the use of a high quality sound card and microprocessor, as these components are integral to the device and its operation. The final device housing would be injection molded instead of our current prototype design. By eliminating the need for many expensive brackets and fastenings, the housing costs will be reduced by $50. The electrical components will be less expensive when bought in bulk. Manufacturing costs will also decline with bulk production. The estimated cost for research and development and quality assurance includes provisions for defective units. Those units that are not shipped would be either fixed and sold at a discounted price or disassembled and parts salvaged. Research and development costs will be ongoing to continue to improve the device as technology improves. The initial production of 1,000 units is a conservative estimate considering the potential market size. This is an estimate of the number of units to beta test the device efficiently.

Market analysis

A non-transcranial electroanesthesia device could be used as a substitute for intravenous and gas anesthesia in any medical procedure requiring general anesthesia below the neck. According to Aspect Medical Systems over an estimated 20 million people undergo surgery using general anesthesia each year in the United States. Our device would be applicable for most of these making its market potential substantial. In less developed countries, the high cost of anesthesia and lack of medical expertise make anesthesia hard to administer. An electroanesthesia device would reduce the cost of anesthesia and the need for a highly trained anesthesiologist. In developed countries where advanced anesthesia devices are used, an electroanesthesia device would reduce the dependence of gas and liquid anesthesia. There is nothing on the market in the US similar to the proposed device; there are electroanesthesia devices in Europe that utilize transcranial methods, but these are not approved by the FDA (Takakura).

The device can be produced relatively inexpensively and the sale price can be set at a fraction of the cost of present anesthesia devices while still providing a profit for reimbursement. The long term effects of non-transcranial electroanesthesia can be approximated by the long term effects of vagal nerve stimulation. Considering the market size, the long term return on the production of a device of this type is considerable. If the device were sold for $3,500 including vital signs equipment, the profit would be $500. The cost of current anesthesia equipment is more than $20,000. So the sale of an



electroanesthesia device at $3,500 would be easily achieved. The price to include Vanderbilt royalties and company profit margins would be $4,500. This would provide a $1,500 profit, $900 of which would go to Vanderbilt in royalties and $600 for company profits. If the technology were bought outright from Vanderbilt, then the price could be adjusted to ensure company profit and amortization of the cost of the purchase of the IP.

Distribution of the device will be done through medical device companies on both a large scale and to private small medical equipment businesses. The sale price to these companies will be different as the volume of purchases will be different. Sales agreements will govern the price for these companies. This will assure the purchase of a set number of units per year. Sales for non-contracted purchases will be based upon the price for production of a set number of units a year for this purpose.

Executive Summary

Administering gas or intravenous anesthesia requires highly trained physicians using expensive equipment and expensive gas or liquid anesthetics (Clarke 155-160). Electroanesthesia will reduce the high cost of anesthesia for surgery and other procedures by reducing the need to keep large quantities of liquid and gas anesthesia on hand. In addition, because electroanesthesia will be delivered non-invasively through the skin, a highly trained anesthesiologist will not be required. These advantages provide a market for replacement of or the addition of another anesthesia device in all physicians' offices and hospitals when presented with findings from research and development.

Transcranial electroanesthesia boasts many advantages over gas and intravenous anesthesia such as a quicker recovery time and fewer biological effects during and after surgery (Photiades, 218-225) and non-transcranial electroanesthesia may also exhibit these benefits. Patients heal better when anesthetized with electroanesthesia and are less affected by the process (Sances and Larson, 21-27). With electroanesthesia there is less of a build up of naturally produced gases in the body compared to chemical anesthesia techniques because normal body functions are less impaired (Sances and Larson, 218-219). According to research done in Europe there is no harmful effect on electrocardiograms (ECG) or electroencephalograms (EEG). In mammalian testing, there was a change in the EEG (Sances and Larson, 55-58) but little on ECG and little neural tissue change. Hammond et al. (1992) states that in human testing there is obvious change in scalp recording of EEG with VNS. Furthermore the extracellular and intracellular fluid of the brain showed little change in potassium and sodium concentration levels with electroanesthesia (Sances and Larson, 148-175). These electrolytes are important to the function of many systems, homeostasis, and iron regulation in the body and play a role in nerve stimulation. This electrolyte concentration stabilization differs from research data for liquid anesthesia where electrolyte levels are decreased due to changes by the chemical agents (Sances and Larson, 148-175). Electroanesthesia also yields decreased gastric acid secretion (Sances and Larson, 33-46), leading to less of a chance for stomach ulcers seen with other anesthesia.



The use of the vagal nerve to administer electroanesthesia is theoretical. Through the development and further research into VNS, full anesthesia may be achieved. It has been shown that pain can be controlled by electrical stimulation of the vagal nerve (Kirchner et al., Ness et al.) or the transcutaneous nerve (Strassburg). These nerves lead into the brain and allow for the control of pain without passing current through the brain. Cork et al (2004) showed that pain control was possible via clips on the earlobes. Ammons et al. (1983) proposed that there are sites on the brain stem that can activate descending inhibitory pathways via the stimulation of the vagal nerves and the surrounding nerves. Noxious and non-noxious stimuli were inhibited in spinothalamic cells by stimulation of the left vagal nerve. A descending mechanism of inhibition was confirmed by Garcia-Larrea et al. (1999) when a reduction in spinal reflexes resulted from motor cortex stimulation. Hammond et al. (1992) showed that the action potential of a stimulus travels via afferent fibers to the nucleus of the solitary tract and the area postrema. Hammond also reported that “synchronous bursts of potentials could be dispersed to widespread areas of the brain.” When inhibitory neurons are tonically excited, other inhibitory neurons are excited through mutual inhibitory connections (Jefferys et al. 202-208). Kirchner et al. (2000) confirm the use of vagal nerve stimulation to suppress pain in an experimentally induced pain study. Kirchner and his colleagues showed that there was widespread distribution of inhibition in the central nervous system, confirming the findings of Jefferys et al.

To date, the FDA has not approved any electroanesthesia devices and considers them to be Class III medical devices under 21CFR868.5400. Approval for such a device needs to go through a Premarket Approval (PMA) or Product Development Protocol (PDP). Extensive clinical testing, the disclosure of specifications, intended use, manufacturing methods, and proposed labeling would be required for the PMA process. In order to collect preliminary data and show proof of concept, animal testing would have to be conducted first. Before proceeding with animal testing, Institutional Review Board (IRB) approval would need to be obtained. After these studies, an investigational device exemption (IDE) would need to be cleared for human trials to begin.

At the present time there is nothing on the market in the US similar to the proposed device; there are electroanesthesia devices in Europe that utilize transcranial methods, but these are not approved by the FDA (Takakura). One such device is the TRANSAIR system. When using this system, the patient is fitted with a headset of electrodes that are connected to one of 3 different signal generators. The first and most simple generator can be used by the patient or other non-professional operators. It generates a monopolar impulse and can run off rechargeable batteries. The second generator is for use by practitioners and is set to deliver either mono or bipolar impulses. This generator also comes with an LCD, timer, frequency control, alarm and other protection systems. The last generator is for use by hospitals and outpatient clinics only. Additional features for this device include automatic control and verbal dialogue with user (See Appendix E(e)). In the future, any competitive design would have to utilize non-transcranial methods to be approved for use in the United States. Alternative



methods are not known at this time and therefore speculation of possible other methods is difficult.

A non-transcranial electroanesthesia device could be used as a substitute for intravenous and gas anesthesia in any medical procedure requiring anesthesia below the neck. According to Aspect Medical Systems over an estimated 20 million people undergo surgery using general anesthesia each year in the United States. Our device would be applicable for most of these making its market potential substantial. In less developed countries, the high cost of anesthesia and lack of medical expertise make anesthesia hard to administer. An electroanesthesia device would reduce the cost of anesthesia and the need for a highly trained anesthesiologist. In developed countries were advanced anesthesia devices are used, an electroanesthesia device would reduce the dependence on gas and liquid anesthesia. The device can be produced very inexpensively and the sale price can be set at a fraction of the cost of present anesthesia devices. The cost of current anesthesia devices is more than $10,000. The price including Vanderbilt royalties and company profit margins would be $4,500. This would provide a $1,500 profit. If the technology were bought outright from Vanderbilt, then the price could be adjusted to assure company profit and amortization of the cost of the purchase of the IP.

Distribution of the device will be done through medical device companies to both large corporations and small, private medical equipment businesses via sales agreements. Sales for non-contracted purchases will be based upon the price for production. In this situation the buyer could be either a company or a hospital/physician's office. The end user in all cases would be the hospital staff/physician in non-hospital situations. These users would provide anesthesia to their patients at a reduced cost from that of present techniques and in non-hospital situations unlike present use of anesthesia.



Appendix

A. Student Résumésa. Matthew Wesley Jackson (Team Leader)

Phone: 239 - 340 - 8064email: [email protected]

b. Ryan Thomas DemeterPhone: 314 - 580 - 0151email: [email protected]

c. Caroline SchulmanPhone: 917 - 226 - 6079email: [email protected]

d. Matthew James WhitfieldPhone: 865 - 548 -4239email: [email protected]

B. Letter of SupportJames Berry Phone: 615-936-1206Email: [email protected]

C. IP policiesD. Photographs

a. Prototypei. Overall

ii. Circuitiii. Interfaceiv. Applicator

b. Oscilloscope display of stimulus from deviceE. Schematics

a. Nerve Informationi. Vagal Nerve Information

ii. Nerve Fiber Informationiii. Nerve/Stimulation Interaction

b. Final designc. Circuitd. LabVIEWe. European Devices

F. Business Plana. Budget

G. ReferencesH. Design Safe Report

mailto:[email protected]







Appendix A



Matthew W. [email protected]

Current Address: Permanent Address:Vanderbilt University 15821 Shamrock Dr.VU Station B #353886 Fort Myers, Fl 33912Nashville, TN 37235-3886 239-481-5083239-340-8064

EDUCATION Vanderbilt University Nashville, TN Bishop Verot Catholic High School Fort Myer, FL May 2002 Top 10% of class

HONORS Dean’s List-Fall 2002/2005ACTIVITIES Vanderbilt Student Volunteers for Science Participant Spring/Fall 2003, Spring/Fall 2004. Spring/Fall 2005. Teacher Coordinator Fall 05/Spring 06. Communicated between the program advisor and the coordinator teachers in the classrooms of the schools visited. Weekly e-mails were sent to the teachers each week informing them of the visitation of VSVS groups to the classroom. Feedback was collected and expressed to the executive board of the group, which I sat on at the end of the semester. Admissions Office Greeting Fall 2003, Spring 2004.Freshman Residential Advisor Fall 2004, Spring 2005.Head ResidentUpper-classman Summer 2005Freshman Fall 2005/Spring 2006The Head Resident (HR) is a part-time paraprofessional staff member for the Office of Housing & Residential Education. The Head Resident works closely with the Assistant Directors and supervision of the Resident Adviser staff in his building. The Head Resident provides staff leadership by demonstrating and encouraging responsible behavior for both his staff and students within their residential community. , . Lambda Chi Alpha international Fraternity (Greek social fraternity ΛΧΑ) – Steward April 2004 to March 2006Meals were arranged with local restaurants to feed the brothers of the fraternity after the weekly meetings. A 7 meal dinning plan was developed with the two dinners and 5 lunches a week for the Spring and Fall 2005 semesters. The Spring 2006 semester was reduced to one dinner and three lunches, with the same level of planning. . Member 2003 to present.Children’s Emergency Department Volunteer June 2004-present.EXPERIENCEProject DesignTeam member Fall 2002 (ES 130), Spring 2004 (BME 102) Fall 2004 (BME 210) Spring 2005 (BME 271).Worked to design various devises to satisfy design specification. Research in how our product would play a role in the market and in what market to enter into was necessary. Possible side-effect or after effect were researched. Photography and Resource Management Summer 2003Photographer for a picture book for a pool contracting company. Once pools were photographed, the photographs were organized by type of construction and then placed in binders for use in sales and on a data base for use in internet contact and the company web site. I was liaison to the web-site hosting company to help update and redesign the web site. Additionally I collected the input of the company’s customers about after construction comments. I also was a resource management consultant to a business student undergrad working at the company. Together the student and I were able to map out the location of customers and re-organize the pool service routes for the company. With the knowledge and comments fielded by the customers, pool service for the company was increased 5 fold within 3 months. . SKILLS & Certified SCUBA Diver. First Mate and cook on an Open Water SportsINTERESTS Fishing Boat. Proficient with Matlab, Microsoft WORD, Excel and



Power Point.

Ryan T. Demeter 14066 Boxford Court

Chesterfield, Mo 63017 Cell -(314) 580-0151

Home -(314) 576-4293 [email protected]

EDUCATION VANDERBILT UNIVERSITY Nashville, TN BE Biomedical Engineering – December 2006 GPA – 2.8

CHAMINADE COLLEGE PREP St. Louis, Mo May 2002. Top 10 % of class.

HONORS National Honor Society (2001 & 2002) Nation Merit Semi-Finalist (2002)

EXPERIENCE THE INFIELD St. Louis, Mo '00-'02 Attendant

Attendant for go-carts, batting cages, miniature golf. Assisted customers who experienced problems or that broke the ground rules.

Summer '03 Chili's Resteraunt Server. Gained experience in customer relations as a server at a bustling resteraunt near downtown Nashille.

Summer '04 AMI Pacific, Mo Automated Drill Operator Operated a drill designed to fabricate custom made plastics, synthetics, metals. Gained insight on the design process and large factory environments.

ACTIVITIES BMES (Biomedical Engineering Society) (2003-2005) Kappa Sigma MDA lock-up philanthropy event volunteer ( 2004 & 2005) Assisted in organizing the physical set-up of the event and coordinated the arrival of and placement of donors. Kappa Sigma assistant rush chair (2003) One of five people living in the fraternity house. Coordinated rush activities and other events for incoming freshman National Honor Society (2001 & 2002) Nation Merit Semi-Finalist (2002)

COMPUTER SKILLS Major Packages: Microsoft Office (including Work, Excel, PowerPoint, Access, and

Project), Matlab, LabView, AutoCAD LT



Caroline Schulman322 Central Park WestNew York, NY 10025

Phone (917) 226 - 6079Home Phone (212) 678 - 2096

Email [email protected]

P E R S O N A LBiomedical and Electrical Engineering Undergraduate Student

E D U C A T I O NSchool of Engineering, Vanderbilt University, Nashville, TN Class of 2006. Majoring in Biomedical and Electrical Engineering, Concentrating in Mathematics and SociologyDean’s List, Freshman and Junior Year

Canterbury School, New Milford, CTGraduating Class of 2002High Honor RoleHonor Society

E X P R I E N C EResearch Assistant, St. Luke’s Hospital 2004Robotic cardiac surgery unit, summer position, research involving robotic cardiac machine, virtual reality programs, aneurysm study. Published study below.

Studies in Health Technology and Informatics, Vol. 111/2005, pp. 414-417Server, Brinker International, Chili’s 2003- 2004Required interpersonal skills, organizational skills, punctuality, reliability, friendlinessVolunteer, Engineering World Health 2003- 2004Repair broken medical equipment, electrical experience with circuit designTeacher, Vanderbilt Student Volunteers for Science 2003- 2004Present scientific lessons and experiments to middle school students including basic chemical reactionsMember, Biomedical Engineering Society 2003- 2004Local school chapter; attend lectures, special events, tripsLab Assistant, Science Department of Canterbury 2001- 2002

I N T E R E S T S & A C T I V I T I E S National Biomedical Engineering Society Member (2003 - Present) Biomedical Engineering Society Conference Volunteer (2003) Heifer Project Participant (1995 - 2004) March of Dimes Participant (2001 - 2002) Visit and tour of Vanderbilt Clinical Research Center (2003)

S K I L L S Recent laboratory experience in Biology, Chemistry, Physics Highly organized, responsible; Strong problem-solver Basic computer programming in Matlab Familiarity and experience with Microsoft Excel, including statistical experience English and intermediate Spanish Web page design in Notepad, use of JavaScript Driver’s license



Matthew J. [email protected]

Vanderbilt University Permanent Address:VU Station B #354177 6641 Cate RdNashville, TN 37931 Knoxville, TN 37931865-548-4239 856-945-3243

Education Vanderbilt University, Nashville, TNBachelor of Engineering, Biomedical Engineering major, Neuroscience minorGPA: 3.76/4.00. May 2006

Karns High School, Knoxville, TNMay 2002, Valedictorian

Honors Dean’s List – every semesterPaul Harrawood Honors Undergraduate Scholarship – full tuitionTau Beta Pi – engineering honor societyNational Merit ScholarEagle Scout

Experience Vanderbilt University Medical Center – Department of OphthalmologyStudent Worker, September 2004 – presentUtilizing microscopic imaging and advanced computer analysis of rat optic nerves to observe the progression of macular degeneration. Created and modified programs and macros in Matlab, Visual Basic, and Image Pro to collect and interpret data.

Vanderbilt University – Department of Civil and Environmental EngineeringIntern, Summer 2004Conducted extensive field work collecting samples from streams in Davidson County. Performed bacterial, pH, temperature, and chlorine level tests, mapped locations with GPS system, and cataloged all data in Access.

Oak Ridge National Lab – Chemical Sciences DivisionIntern, Summer 2003Constructed and used an apparatus to test electrode arrays for byproduct formation in eye-like environments as part of an overall project to create an artificial retina.

University of Tennessee – Plant Molecular GeneticsLab Technician, Summer 2002Learned many basic laboratory techniques, assisted in experiments, managed MSDS inventories, conducted field work, assisted in setup of new laboratory.

Activities V^2 Mentor – Upperclassmen get paired with a group of freshmen and help them find classes, get settled into the university, and answer any questions.

Vanderbilt Students Volunteering for Science – Went to local middle schools and taught students simple science lessons for four semesters.Meals on Wheels – Delivered meals to shut-ins in the mornings for a couple of summers

Skills and Microsoft Office Suite (Word, Excel, PowerPoint, and Access), Matlab, Visual BasicInterests Ultimate Frisbee – traveling club team

Backpacking



Appendix B



April 3, 2005

National Collegiate Inventors and Innovators Alliance100 Venture WayHadley MA 01035

Re: “Non-Transcranial Electroanesthesia Device” proposal

Dear Sirs:

I am writing to offer my support to the applicants: Matthew Jackson, Ryan Demeter, Caroline Schulman, and Matthew Whitfield in their proposal entitled “Non-Transcranial Electroanesthesia Device.”

Besides having a novel and potentially marketable device, these inventors have potentially opened a new line of investigation into electromagnetic influences on the central nervous system. This device represents a new approach to anesthesia and analgesia not previously explored, and it is clearly patentable as a novel application of portable computer soundcard-generated medical energy.

They have my full support and the support of the University and the Medical Center.

Please let me know if I may be of any further service to you.

Sincerely,

James Berry MDProfessor and Division ChiefDivision of Multispecialty AnesthesiologyMedical Director, Main Operating Rooms



Department of Anesthesiology

Appendix C

INTELLECTUAL PROPERTY RIGHTS FOR VANDERBILT SPONSORED SENIOR PROJECTS

If you use Vanderbilt resources (including funds, facilities, laboratories, or personnel) while conducting a senior project, any intellectual property generated as a result of the project work will be governed by the University’s “Policy on Technology and Literary and Artistic Works”. This Policy may be found in the Vanderbilt Faculty Manual, Pages 103 - 109, or it may be accessed on-line at: http://www.vanderbilt.edu/facman/. Click on "Part III. University Principles and Policies," and proceed to Page 103.

The Policy on Technology and Literary and Artistic Works states, in brief, that intellectual property, such as an invention or process improvement, generated as a result of work performed in this course shall be assigned to, and owned by, Vanderbilt University if it is created “with the use of University facilities or funds administered by the University.” In return, students are entitled to a portion of the royalties generated by the invention as provided in the Policy.

Students must inform their faculty sponsor and the Vanderbilt Office of Technology Transfer and Enterprise Development (OTTED) if there are any other agreements that involve the intellectual property to be created. OTTED will, in turn, determine whether to pursue patent or intellectual property rights protection, and, if so determined, will obtain that protection. Income received as a result of exploiting this intellectual property will be shared with the inventor(s)/creator(s) in accordance with the Policy. If the University waives, or elects not to pursue its intellectual property rights, and assuming that there are no other contractual rights with respect to the intellectual property, the inventors/creators will be offered the rights to the intellectual property.

By my signature below, I acknowledge that I am aware of Vanderbilt’s Policy on Technology and Literary and Artistic Works.

_____________________ _________Signature Date

_____________________Name (printed)



Appendix D

Section a

Part i

Overall



Appendix D

Section a

Part ii

Circuit



Appendix D

Section a

Part iii

User Interface



Appendix D

Section a

Part iv

Applicator

Needle Electrode Pad Electrode



Appendix D

Section b

Oscilloscope display of stimulus from device



Appendix E

Section a

Part i

Vagal Nerve Information



Appendix E

Section a

Part ii

Nerve Fiber Information

Compound nerveaction potentials



Appendix E

Section a

Part iii

Nerve/Stimulus Interaction

Normal Nerve reaction to a stimulus

“Relative refractory zone” Inhibition of function



Appendix E

Section b

Final Design



Appendix E

Section c

Circuit



Appendix E

Section d

LabVIEW



Appendix E

Section e

European Devices

A. Shape of impulses and limits of frequency modulation.B. 1 – Headset of electrodes 2 – Monopolar output impulse, rechargeable3 – For practictioners, mono- and bipolar output impulses, LCD, timer, frequency control, alarm 4 – For hospitals and outpatient clinics, mono- and bipolar output impulses with or without frequency modulation, LD indicators, timer, automatic control, alarm and protection systems, verbal dialogue with user in process of adjustment of parameters, plug in



Appendix FBusiness Plan

Section a

Budget

Box and mountings ($214.15) Case (Dimensions: 18" x 18" x 10") ($124.12) Foam Padding (VU BME Donated) Keyboard Hand Rest ($8.75) Hardware Mounting ($81.37)

Applicator ($0)

Pad Electrode (VU BME Donated) Needle Electrode (VUMC borrowed)

Circuit and Supplies ($155.78)

2 Fans ($18.00) 3 Amplifiers ($45) Supplies from Radio Shack ($92.78)

Computer ($0, VUMC Loaned)

1.6 GHz 1 GB Hard drive

Miscellaneous ($130)

Total Budget =$500



Appendix GReferences

Ammons, W. Steve, Robert W. Blair, and Robert D. Foreman. "Vagal Afferent Inhibition of Primate Thoracic Spinothalamic Neurons." Journal if Neurophysiology 50.4 (October 1983): 926-940. "Anethesia PAteint Information". Aspect Medical Systems. Accessed 11/14/05. <http://www.aspectmedical.com/patients/information/default.mspx> Clarke, H.L. "Anaesthesia for Out-Patient Procedures." The West African Medical Journal 11 (1962): 155-160.Cork, Randall C., Patrick Wood, Norbert Ming, and Clifton Shepherd et al. "The Effect of Cranial Electrotherapy Stimulation (CES) on Pain Associated with Fibromyalgia." The Internet Journal of Anesthesiology (2004): 1-7.“Cranial Electrotherapy Stimulator” Red Circuits. 27 March 2006. <http://www.redcircuits.com/Page19.htm>Fries, Richard. E-mail interview. 5 2005.“FDA: Significant Risk and Nonsignificant Risk Devices”. Mount Sinai School of Medicine. 1 September 2005. <http://www.mssm.edu/irb/pdfs/appendix/13.pdf>Garcia-Larrea, L., R. Peyron, P. Mertens, M.C. Gregoire, F. Lavenne, D. Le Bars, P. Convers, F. Mauguiere, M. Sidou, and B. Laurent. “Electrical stimulation of motor cortex for pain control: a combined PETscan and electrophysiological study.” Pain 83(1999): 259-273George, M.S. MD, Z. Nahas, MD D.E. Bohning, PhD F.A. Kozel, MD B. Anderson, RN J.-H. Chae, MD M. Lomarev, MD PhD S. Denslow, PhD X. Li, MD C. Mu, MD PhD. “Vagus Nerve Stimulation Therapy.” Neurology 59 (2002):s56-s61Hammond , EJ, BM Uthman, SA Reid, and BJ Wilder. "Electrophysiological studies of cervical vagus nerve stimulation in humans: I. EEG effects.." Epilepsia. 33 (1992): 1013-1020. Jefferys, John GR, Roger D. Traub, and Miles A. Whittington. "Neuronal networks for induced '40 Hz' rhythms." Trends in Neuroscience 19 (1996): 202-208. Kano, T, GS Cowan, and RH Smith. "Electroanesthesia (EA) studies: EA produced by stimulation of sensory nerves of the scalp in Rhesus monkeys." Anesthesia and Analgesia (1976): 536-541.Kirchner MD, A., F. Birklein MD, H Stefan PhD, and H.O. Handwerker PhD. "Left vagus nerve stimulation suppresses experimentally induced pain." Neurology 55.8 (2000): 1167-1171. Kurpiers EM, Scharine J, Lovell SL. “Cost-effective anesthesia: desflurane versus propofol in outpatient surgery.” American Association of Nurse Anesthetists Journal. 1996 Feb;64(1):69-75. Liporace MD, J., D. Hucko RN, BSN, R. Morrow MD, G. Barolat MD, M. Nei MD, J. Schnur BA, and M. Sperling MD. "Vagal nerve stimulation: Adjustments to reduce painful side effects." Neurology 57.5 (2001): 885-886.



Melzack, Ronald, and Patrick D. Wall. "Pain Mechanisms: A New Theory." Science 150.3699 (1965): 971-979. Ness, T.J., R.B. Fillingim, A. Randich, and E.M. Backensto. "Low intensity vagal nerve stimulation lowers human thermal." Pain 86 (2000): 81-85. Photiades, Dimitri P., Janus Garwacki, K.C. Whittaker, and Andeas S. Lambis. "Electroaneasthesia in Major Surgery ." The West African Medical Journal (October 1963): 218-225.Sances Jr., Anthony, and Sanford J. Larson. Electroanesthesia Biomedical and Biophysical Studies. New York: Academic Press, Inc., 1975.Strassburg, H.M. "Influence of Transcutaneous Nerve Stimulations (TNS) on Acute Pain." Journal if Neurology 217.1 (1977): 1-10.Takakura, Kintomo. “Transcutaneous Electrical Nerve Stimulation for Relieving Pain: Physiological significance of the 1/f frequency fluctuation.” Accessed 11/4/05 <http://www.everbest.com.au/TENSforRelievingPain1ffrequencyfluctuation.html.> Woodbury, JW and DM woodbury. “Vagal Stimulation Reduces the Severity of Maximal Electroshock Siezures in Intact Rats: Use of a Cuff electrode for Stimulating and recording.” Pacing and clinical electrophysiology 14 (1991):94-107VUMC. E-mail interview. 10 2005.



Appendix H



maintenance technician

periodic maintenance

electrical / electronic shorts / arcing / sparking

bad circuit design, equipment damage Slight Remote Negligible Low

other design change, fixed enclosures / barriers


periodic maintenance

electrical / electronic

unexpected start up / motion

Improper shut down and powering down of device. Slight Remote Negligible Low

instruction manuals, on-the-job training (OJT)


set-up or changeover

material handling storing precarious positioning Minimal Remote Negligible Low

other design change, safety mats / contact strip


set-up or changeover

material handling

movement to / from storage heavy Minimal Remote Negligible Low other design change

maintenance technician clean up


energized equipment / live parts improper handling of tools Serious Remote Negligible Low

special procedures, on-the-job training (OJT), instruction manuals



lack of grounding (earthing or neutral)

could cause problems seen in 1-1-4 Slight Occasional Possible Moderate



electrical / electronic insulation failure improper handling of tools Serious Remote Negligible Low



electrical / electronic shorts / arcing / sparking improper handling of tools Slight Remote Negligible Low


All Usersnormal operation


energized equipment / live parts

electrodes carry current which could be dangerous at high voltages. computer is actively using elctricity Slight Remote Negligible Low

fixed enclosures / barriers, audible alarm or sounds, visible alarm or signal, instruction manuals



lack of grounding (earthing or neutral)

could cause problems seen in 1-1-4 Slight Occasional Possible Moderate prevent energy buildup


electrical / electronic insulation failure exposed wires or circuits Serious Remote Negligible Low

prevent energy release, fixed enclosures / barriers






electrical / electronic electrostatic discharge charge buildup and storage Serious Remote Unlikely Moderate

prevent energy buildup, grounding

Physician and/or Nurse

normal operation


energized equipment / live parts

electrodes carry current which could be dangerous at high voltages. computer is actively using elctricity Slight Remote Negligible Low

fixed enclosures / barriers, audible alarm or sounds, visible alarm or signal, instruction manuals


normal operation

electrical / electronic insulation failure exposed wires or circuits Serious Remote Negligible Low



normal operation



prevent energy buildup, fixed enclosures / barriers




normal operation

electrical / electronic software errors

computer virus, bad programming Catastrophic Occasional Possible High

thoroughly test prototype and incorporate backup mechanisms


normal operation

electrical / electronic power supply interruption

electrical outage, EMP, battery discharge, short circuit Catastrophic Remote Possible High

other design change (backup measures), other devices, audible alarm or sounds, visible alarm or signal, standard procedures


normal operation

material handling

movement to / from storage improper handling Minimal None Negligible Low

on-the-job training (OJT), instruction manuals

Physician and/or Nurse shut down

electrical / electronic electrostatic discharge improper grounding Serious Remote Unlikely Moderate


non-transcranial electroanesthesia...

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