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ATP-POWERED

NANO-BASED

COCHLEAR IMPLANT

Final Project

In partial fulfillment of the requirements of the

Coursera internet-course in

Nanotechnology and Nanosensors

Submitted by nanoTEAM:

Brown, Clifton (cww.brown@gmail.com) - USA. Senior Electronic Engineer, designing

research instrumentation for the Biotech industry (Gene Chip DNA scanners and Confocal Laser

Scanning Microscopes)

Haimov, Boris (boris.haimov2@gmail.com) – Israel. Ph.D. student in the multidisciplinary

program of Nano Science and Nano Technology in RBNI, Technion, Israel Institue of Technology

Kolbei, Ievgen (eugen.kolbey@gmail.com) – Ukraine. Bachelor of computer science,

junior .Net developer, service architect for Pharmacokinetic modeling application.

Nadherna, Martina (274martina@gmail.com) - Czech Republic. Ph.D. , Junior Scientist

with background of analytical chemistry and electrochemistry.

May 2014

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TABLE OF CONTENTS

ABSTRACT………………………………………………………………………………………………………… 3

INTRODUCTION……………………………………………………………………………………………….. 4

LITERATURE REVIEW……………………………………………………………………………………….. 4

THE SENSE OF HUMAN HEARING……………………………………………………….. 4

STRUCTURE AND FUNCTION OF THE COCHLEA………………………………….. 4

DAMAGES TO THE SENSE OF HEARING……………………………………………….. 5

EXISTING COCHLEAR IMPLANTS………………………………………………………….. 5

THE ATP MOLECULE……………………………………………………………………………. 6

PROJECT GOAL…………………………………………………………………………………………………. 6

PROJECT DESCRIPTION…………………………………………………………………………….………. 6

ATP AS POWER SOURCE………………………………………………………………………. 7

IMPLANT MATERIALS AND TOXICITY ISSUES………………………….…… ………. 7

OVERALL DESIGN…………………………………………………………………………………..…………. 8

METHOD FOR FABRICATION…………………………………………………………………….………. 8

ACOUSTIC CHAMBER MODULE…………………………………………………...………. 8

ATP POWER SUPPLY MODULE……………………………………………………. ………. 9

TRANSDUCER CELL…………………………………………………………………..….………. 9

CHARACTERIZATION AND APPLICATION……………………………………………….... ………. 10

CONCLUSIONS AND RECOMMENDATIONS………………………………………..…….………. 10

REFERENCES…………………………………………………………………………………………….………. 10

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ABSTRACT

This project presents an artificial cochlear implant that is powered by ATP energy and

implemented by nano-technological means. Implementation of such implant with nano-technology

allows improvement of the hearing quality, resolution and a very small overall size and a single unit

system compared to similar existing conventional cochlear implants. Powering the implant with ATP

energy eliminates the need for external power source and turns the implant into a fully autonomous

functional implant.

INTRODUCTION

Human hearing is one of the human senses that allow reception of acoustic waves. The ear is

responsible to receive the wave and to transmit it to the human brain via the nervous system. As

every physical system, the hearing sense is exposed to the environment dangers and may be

damaged. One way to treat damages to the hearing sense is by using implants that provide an

alternative to the original hearing organs and allow people to hear.

Before medicine and technology could allow incorporation of a cochlear implant into a

human body, people used external hearing aids; first of them was the very simple hearing aid "Ear

Trumpet" that was invented in the 17th century. Later, in the 19th century, the "Akouphone" was

invented; it was able to transmit electrical signals and to amplify weak signals. In the beginning of the

20th century, The "Vactuphone", was able also to turn speech into the electrical signals was, in

addition, a portable hearing aid. In 1952, the company Zenith came with the first "all-transistor"

hearing aid, and only 6 years later, in 1958, the invention of an integrated circuit ended using

transmitters. In the 1960s we see the beginning of using digital hearing aids - Bell Telephone

Laboratories with their mainframe computer. Creation of a microprocessor and development of the

multi-channel amplitude compression in 1970s opened the possibilities of miniaturization of hearing

aids. In 1980s, the people could finally use the first real-time, all-digital hearing aid containing digital

array processor and minicomputer, consisted of a FM radio transmitter and a receiver [1a]. In 1977,

joint teams from England, Austria, Spain, Switzerland and Western Germany started their program

for developing cochlear implants. In the same year, Dr. Clark and Dr. Tong published their implant,

from which is the present cochlea neuroprosthesis developed. Nowadays the cochlea implant are

fabricated by companies Advanced Bionics (USA), Cochlear (Australia), MED-EL (Austria), Philips

Hearing Implants (Belgium) [1b].

This project presents how nanotechnology can improve the quality of existing hearing aids,

and specifically cochlear implants, for people with damaged sense of hearing.

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LITERATURE REVIEW

THE SENSE OF HUMAN HEARING [2]: Human

sense of hearing is divided into three main units:

external ear, middle ear and inner ear as shown in

Figure 1. The external ear functions as an antenna

and the receiver of the acoustic signal. The function

of the middle ear is to perform impedance matching

between the external ear and between the inner ear.

Impedance matching causes the acoustic energy to

be transferred in maximal efficiency to the inner ear

and very low amount (zero in the ideal case) of this energy reflected back. To emphasize, impedance

matching is required because the acoustic energy transferred from one medium, the air, to another,

a liquid, which is found within the inner ear. The

function of the inner ear is to transfer the different

frequencies within the acoustic signal to the

cochlear nerve.

STRUCTURE AND FUNCTION OF THE

COCHLEA [2,3]: The cochlea is a fluid filled tube in

the shape of a spiral with 2.5 turns as shown in

Figure 2A, which contains the organ of Corti. The

basilar membrane, located within the Organ of Corti,

performs the main task of converting the

mechanical sound energy to nerve impulses as it

resonates in a frequency dependent position along

its length as shown in Figure 2B. Along the whole

cochlear tunnel hair-cells sense the local vibration

and translate the local vibration into a flow of

potassium ions (K+); the ions are found initially

within the cochlear tunnel as shown in Figure 3.

Next, the ions flow into a local nerve cell and stimulate it. The stimulation signal is then transferred

to the brain via the auditory nervous system and the brain become aware to the acoustic signal that

entered the ear.

External

ear

Middle

ear

Inner ear

Figure 1: Structure of the human ear [2a] External ear, middle ear and inner ear

Figure 2: (A) Internal ear [2b]

(B) Frequency filtering domains [3a]

(A)

(B)

Base

Apex

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The ear has somewhere around 15-thousand nerve endings connected to the

roughly 1500 inner hair cells along the approximate 3.5 cm of the basilar

membrane. Each inner hair cell has about 10 connected nerve fibers, and very

few nerves connect to more than one hair cell. The nominal frequency

response is logarithmic with displacement along the cochlea where the highest

frequencies are detected at the entrance to the cochlea, and the lowest are

detected at the “far” end. The frequency vs distance has been experimentally

mapped in humans and is characterized by the Greenwood Function

[Hz], where x is the nominal distance in mm from the

Apex. A plot of the Greenwood function is shown in Figure 4.

DAMAGES TO THE SENSE OF HEARING: Damages caused to the human

hearing system may be divided to the following categories: (1) Damage of

the external ear (2) Damage of the middle ear, (3) Damage of the inner ear,

(4) Damage of the auditory nervous system, and (5) Damage of the auditory

units within the brain. The damages above sorted by their severity, the

higher the number the severe the damage. Damages of 1st level are handled

by cosmetic surgeries, implantation of artificial cosmetic bio-implants etc.

Damages of 2nd level are handled by 3D printing technologies that make

artificial and bio-compatible implants of the malleus and the incus (the 2 main parts of the middle

ear). Damages of 3rd level are handled by inserting cochlear implants. Damages of 4th level and above

cannot be handled using existing technologies. In our project we

will focus on damages of the 3rd level.

EXISTING COCHLEAR IMPLANTS [3]: Cochlear implants had

been under development for more than half a century and many

successful results were achieved [3]. All known cochlear implants

include at least 2 units: the external unit and the internal unit as

shown in Figure 5. The external unit includes the power source, the

microphone, the electrical nerve drivers and the digital signal

processor. The internal unit is an array of electrodes that are

connected to the cochlear nerves on one side and to the external

unit from the other side. The internal unit is the auditory nerve

interface.

Figure 3: Hair cell [4]

(A)

(B)

Figure 5: Existing cochlear implants (A) External unit inserted surgically behind the ear [3b] (B) Internal unit inserted surgically into the cochlea [3a]

Figure 4: Plot of the Greenwood function

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THE ATP MOLECULE [5,6,7]: The ATP (Adenosine-Tri-Phosphate) is an important nucleotide in

the human body. It consists of a base called adenine, sugar ribose and three phosphate groups [5].

ATP contains macroergic bounds [6]. It is a bound

evolving a large amount of energy during the

hydrolysis, more than 25 [kJ/mol]. For the hydrolysis

of ATP to ADP (Adenosine-Di-Phosphate) and

phosphate the released energy equals 29.7 [kJ/mol],

the energy storage and release depicted in Figure 6.

In the body cells ATP has the ability to transfer the

functional groups, especially the phosphate group, so

the ATP represent so called pool of macroergic

phosphate, which is a storage system for chemical energy. Each transfer of the phosphate group is

catalysed by the enzymes called ATPases. Enzymes are the biomolecules, highly selective catalysts,

and are responsible for the character and the rate of chemical reactions and control most of the

biochemical processes in the living body [6,7]. The ATP can be synthesized in the body from the

starting component: ADP and inorganic phosphate during an

aerobic phosphorylation with help of the enzymes. Transport

in the cells is a vector process, it means it is going against the

concentration gradient. This requires a supply of chemical

energy, which can be e.g. the cleavage of ATP.

PROJECT GOAL

Design of an autonomous ATP powered, single unit

cochlear implant. The implant will be designed as a flexible rod shaped unit to allow surgical

implantation within the cochlea as shown in Figure 7, this way it will be interfaced to the auditory

nervous system of the patient. Furthermore, the implant will be attached to a nearby blood channel

that will supply the required ATP molecules.

PROJECT DESCRIPTION

The purpose of our sensor is to duplicate the basilar membrane’s excitation of the individual

auditory neurons at the inner hair cell interface. We will postulate that the mechanical resonant

function of the basilar membrane will still be operational, and we will use that selective resonance to

excite the appropriate nerve endings via our nano ear sensor. The basic geometry of the cochlea sets

the length of the sensor at 35 mm to physically mate with the basilar membrane and auditory nerves

– allowing ample room for an entire array of sensor cells. The sensor will be comprised of a linear

Energy

P

P

Energy

Figure 6: ADP to ATP and ATP to ADP cycle ATP to ADP conversion release energy ADP to ATP conversion require energy

Figure 7: Single unit ATP powered nano based cochlear implant Before implantation on left (black flexible rod) After implantation on right (within the cochlea)

Blood line

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array of CNT FETs. Nominally one per nerve, or about 15,000 –

giving spacing of 2.3 µm per array element. This easily allows

for multiple cell redundancy and will allow the use of relatively

large scale traditional photolithographic processing.

ATP AS POWER SOURCE: The system Na+/K+/ATP as a

voltage source was already demonstrated by Huang [8] and is shown in Figure 8. We will use same

principles and use the ATP as a power source for our sensor. Transportation of the sodium and

potassium ions from one side of the membrane to another requires the energy as in the human cell

process. In this project we will use the pump as it was already suggested in the work of Huang et al.

[8]. The transistor with using ATP was published also by Freeman et al. [9] In the body, the

concentration of Na+ and K+ ions on the opposite

sides is different, and the pump working against the

concentration gradient as well. So for this process

certain energy is needed. For both cases the energy

from the ATP cleavage is used and the enzyme

Na+/K+/ATPase is involved for the acceleration of the

process.

IMPLANT MATERIALS AND TOXICITY ISSUES:

The whole unit case will be made of PDMS

(PolyDiMethylSiloxan). PDMS is a polymer on silicon

base. It is optically clear, inert and nonflammable. It

belongs to viscoelastomers - depending on

temperature and flow time acts like a viscous liquid or elastic solid. Solid PDMS is hydrophobic, so it

means that it will not allow water to swell the material [10a]. It is widely used in biological and non-

biological application because of its biocompatibility, low toxicity and chemical inertness [10b].

Carbon nanotubes exist in two forms: single-wall and multi-wall nanotubes. Both forms are already

widely used in biotechnological applications. Due to that a lot of interest was put on their toxicity. In

the range of the commonly used concentration (10-150 μg/ml) of ultrapure dispersible CNT they do

not have any toxicity and according to the study [11a], they are suitable for an extensive use on

biomedical applications. According to the review [11b] of carbon nanotube toxicity their risk is the

risk of their inhalation, mainly if they are chronically inhaled. In this case single wall nanotubes can

be more dangerous than quartz. To improve the biocompatibility the functionalization of CNT can be

done [12]. Nevertheless the problem in toxicity in vivo lies on the dispersion of CNT [13]. In our

sensor we do not have any dispersed CNT so this risk is minimal. For the electrodes in our sensor two

Figure 8: ATP used as voltage source within a CNT based FET [8]

Figure 9: General structure of the cochlear implant. Functional domains on left. Modular units on right

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metals were suggested - silver and gold. Pure silver is not toxic.

However it can be oxidized to silver salts or silver oxide [14], which are

nephrotoxic and hepatotoxic. A chronic exposition to the silver

compounds leads to argyria [15,16]. Pure gold would be more suitable

material, because of its stability in the environment. Gold can be

oxidized only under extreme conditions to gold(I) and gold(III) salts,

which are irritant and caustic [15], but the conditions for oxidizing are

not reached in the human body.

OVERALL DESIGN

The whole implant case will be made of PDMS because of its

flexible and inert nature. The shape of the implant will be cylindrical

rod with a diameter of 0.3-1mm. The implant will include the acoustic

resonance chamber, where the mechanical vibrations will be sorted or

filtered to the different geometrical regions depending on their

frequency. Next, the vibrations will be translated to electrical signal by

the transducers array. The transducers array will then stimulate the

local nerve. The transducers array will be interfaced to the cochlear

nervous system with the electrodes array. The functional domains of the

implant are shown in Figure 9. The implant will be powered by ATP

power supply module that is colored with a red color. The ATP power will

be connected to a nearby bloodstream to receive ATP molecules and

return used ADP and other products to the bloodstream. 3D renderings

of the acoustic chamber and the ATP power supply shown in Figure 11.

METHOD FOR FABRICATION

The implant will be divided to three modules and each module

will be fabricated separately. The three modules are the acoustic

chamber, the ATP power supply, and the transducers array as shown in

Figure 9.

ACOUSTIC CHAMBER MODULE: The acoustic chamber module

will be made of 5 PDMS layers as shown in Figure 10 (TOP). Each layer

will be created from a Silicon negative template to which we inject the

PDMS material and wait until it dries. The process is similar to that used Figure 11: 3D Structures TOP – Acoustic chamber

BOTTOM - ATP power supply

Figure 10: (TOP) PDMS layers of the acoustic chamber (BOTTOM) PDMS layers of the ATP power supply

Layers ordered by ABC where A is the bottom layer

CNT flexible conducting thin film

PDMS

Ionic pumps array on a lipid film

Legend

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in reference [17]. Since layer A is same as E and layer B is same as D, we have effectively only 3 layers

to fabricate using the Si negative. All the layers will be glued up together to form the whole

functional module. After the module will get its final form it will be filled

with a liquid to achieve same viscosity as in the real cochlea to allow

frequency selectivity within the module.

ATP POWER SUPPLY MODULE: The ATP power supply module will

be made of 5 PDMS layers and 2 thin film conductive CNT film as used in

the artificial skin [18]. Layer D of the module is a unique PDMS layer that

will embed a lipid bilayer with biological ion pumps as demonstrated by

Huang et al. [8]. When the blood will flow into the module the ion pumps

will assure charge gradient along the whole lipid film. The latter will result

in a voltage potential of few hundreds millivolts, which is enough to

stimulate the auditory nervous system. The two conductive CNT film will

allow the flow of the electrical current and power the whole system.

TRANSDUCER CELL: The artificial ear sensor will use an array formed from a few thousand of

the following sensor: The basic sensor cell is composed of several components, all fabricated on a

common Si substrate: (a) CNT “wiggler” rod to mechanically couple the vibrations to the FET gate. (b)

A FET transistor, who’s gate is sensitive to the movement of the “wiggler”. (c) A low pass RC filter (~5

mS) to integrate the high frequency input down to a slower signal suitable to stimulate the nerve

cells. (d) The binding structure (spike) where the individual nerve will be attached. The key principle

in this design is to use the CNT to emulate the ear’s stereocilia that sway with the varying sound

pressures. In this design, the CNT modulates the gate structure of the FET, thus controlling its

conductivity. The CNT is ideal to replace the 10 nm diameter stereocilia in this application because of

its strength, durability, and high aspect ratio. The typical movements are in the order of just a few

molecular diameters. The low pass filter is necessary to “slow down” the output of the FET, since the

nerves have relatively slow activation time compared to the frequencies of the sound. The diode

may well not be required since we DO want the output to decay with no input – this will take some

experimental design. Given the typical geometry of the ear that the grid array must attach to, the

nominal size of the sensor cell should be 2µm or less. This 2000 nm allows ample space to fit the

individual cells. The capacitor and the nerve spike will be the largest components since the current

and voltage levels are quite low. Several details will need to be worked out, including the time

constant required to properly drive the nerves and the optimal length of the CNT. This simple

structure will be easy to fabricate as an array by simple, large geometry CMOS photolithographic

processes. The design of the transducer cell is shown in Figure 12.

Figure 12: Transducer cell (TOP) Layout

(BOTTOM) Electrical scheme

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CHARACTERIZATION AND APPLICATION

Used materials: PDMS, CNT conductive thin film, Gold electrodes, Lipid bi-layer film

No external power supply, ATP driven with flexible electronics

Diameter: 0.3mm to 2mm (depends on patients cochlear geometry)

Length: 20mm to 35mm (depends on patients cochlear geometry)

Spectral resolution: 20KHz/15,000sensors ~ 1.3 Hz/sensor

Nerve driving voltage capability: 100mV to 300mV CONCLUSIONS AND RECOMMENDATIONS

A fully autonomous ATP powered cochlear implant was designed based on nano technology.

The main advantages of the proposed implant are its capability to be driven from ATP molecules, its

small overall size, and that it is a single unit that includes everything required to function

independently. Because of the preliminary character of the design, further studies should be made to

test the chosen materials and their functionality.

Future enhancements of the proposed design could be integration of the unit with external

audio and multimedia devices such as computers, MP3 and DVD players via a wireless link. In such

case the implant will function as remote wireless earphone. Other variant will be the possibility to

turn the implant into a brain-computer interface (BCI) [19] to allow another IO interface for

computers and similar gadgets protected with standards such as HIPAA [20a] or WASC [20b].

Integrating the unit with an external computer will allow preprocessing the raw data and allow online

language translation that will allow people of different cultures and languages to talk to each other.

REFERENCES 1. (a)http://en.wikipedia.org/wiki/History_of_hearing_aids (b)http://en.wikipedia.org/wiki/Cochlear_implant 2. Richard L. Drake, A. Wayne Vogl, Adam W. M. Mitchell, GRAY'S ANATOMY FOR STUDENTS, 2nd ed. 2009 ; (a) Figure 8.107, (b)

Figure 8.119 3. Cila Umat and Rinze Anthony Tange, COCHLEAR IMPLANT RESEARCH UPDATES, InTech 2012 ; (a) Page 8, Figure 2 (b) Page 31,

Figure 8 4. http://labspace.open.ac.uk/mod/resource/view.php?id=415649 5. http://en.wikipedia.org/wiki/Adenosine_triphosphate 6. Karlson P., Zaklady biochemie. Academia Praha 1981 7. http://en.wikipedia.org/wiki/Enzyme 8. Huang S.-Ch. J., Artyukhin A.B. et al., Nanoletters 2010 9. Freeman R., Gill R., Willner I., Chemical Communications 33 (2007) 3450-3452. 2007 10. Nayak T:R., et al., Current Nanoscience 6 (2010) 141-154. 11. (a) http://de.wikipedia.org/wiki/Polydimethylsiloxan (b) Wu Y., Coyer S.R., Ma H., Garcia A.J., Acta Biomaterialia 6 (2010) 2898-

2902. 12. (a) Lam C.-W., et al, Critical Reviews in Toxicology 36 (2006) 189-217. (b) Gulati N., Gupta H., Critical Review in Therapeutical

Drug Carrier Systems 29 (2012) 65-88. 13. Kim, J.S., Song K.S., Lee J.H., Yu I.J., Archives of Toxicology 85 (2011) 1499-1508. 14. Nordberg G.F., Fowler B.A., Nordberg M., Friberg K.: Handbook on the toxicology of metals,Academic Press, 2007, 3rd edition. 15. Tichy M.: Toxikologie pro chemiky (Toxicology for chemist). Karolinum Praha 1998. 16. http://en.wikipedia.org/wiki/Silver (on 8th of May 2014). 17. Haimov Boris et al. The Journal of Physical Chemistry C, 2013 18. Hossam Haick, Introduction to Nano Technology, course book, 2013 19. http://en.wikipedia.org/wiki/Brain%E2%80%93computer_interface#Human_BCI_research 20. (a)http://en.wikipedia.org/wiki/Health_Insurance_Portability_and_Accountability_Act

(b)http://projects.webappsec.org/w/page/13246978/Threat%20Classification

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