A TECHNICAL SEMINAR REPORT ON IMPLANTABLE ELECTRONICS

Submitted in partial fulfillment of the requirement for the award of degree of

BACHELOR OF TECHNOLOGY IN ELECTRONICS & INSTRUMENTATION ENGINEERING.

Submitted by

G.HARI KRISHNA

(08C01A1017)

(SCIENT INSTITUTE OF ENGINEERING & TECHNOLOGY, IBRAHIMPATNAM) EMBEDIES THE WORK DONE BY THEM UNDER MY SUPERVISION

HEAD OF DEPARTMENT (EIE)

INDEX

1. ABSTRACT 2. INTRODUCTION 3. SILK TECHNOLOGY 4. FLEXIBLE ELECTRONICS 5. POWER SOURCES

6.

ADVANTAGES AND DISADVANTAGES

7. APPLICATIONS 8. CONCLUSION 9. REFERENCES

1. ABSTRACT

Many existing and envisioned classes of implantable biomedical devices require high performance electronics sensors. An approach that avoids some of the longer term challenges in biocompatibility involves a construction in which some parts or all of the system resorbs in the body over time. This paper describes strategies for integrating single crystalline silicon electronics, where the silicon is in the form of nanomembranes, onto water soluble and biocompatible silk substrates. Electrical, bending, water dissolution and animal toxicity studies suggest that this approach might provide many opportunities for future biomedical devices and clinical applications

The important distinction is that, with medical implants today, the active electrical components that communicate with the body are located in a sealed box and connected with a single wire per sensor. This severely limits the number of sensors that can be implanted in the body. Integrating active electronics on sheets of silk or plastic makes it possible to multiplex the outputs of different sensors, meaning you can put hundreds, or even thousands, of contacts on a sheet. The combination of silicon electronics, based on nanomembranes of silicon, with biodegradable thin film substrates of silk protein, yield a flexible system and device that is largely resorbable in the body

2. INTRODUCTION
By combining silk and electronics, fields like cardiology and neurology may be

transformed over the next decade, by enabling ultra high resolution electrical and chemical interaction with three dimensional biological surfaces. It could also mean that virtually all problems associated with the immune system reacting against the implant are eliminated and that is because much of the implanted systems dissolve almost completely over time. Arrays of transistors have already been demonstrated working on thin films of silk and, instead of the electronics systems being enclosed to protect them from the body, there is no need for protection; the silk enables the electronics to conform to biological tissue. The silk dissolves over time and because the circuits are so thin, just nanometers thick, they cause no irritation. One potential application is detecting harmful bacteria in food. A silk optic material would have a pattern of nanoscale peaks and troughs, with each trough containing a substance that reacted to the bacteria. If the bacteria were present, the troughs would fill, and like a butterfly wing when its structure is altered, change colour, revealing the presence of bacteria. To create the silk electronic implants, silicon transistors about 1mm long and 250nm thick are transferred to the surface of a thin film of silk. The silk holds each device in place, even after the array is implanted into a living body and wetted with saline. The silk is very thin and flexible, enabling it to conform to the tissue surface. In a paper published in the journal Applied Physics Letters (5, 133701, 2009), the researchers say devices can be implanted in animals with no adverse effects and the performance of the transistors on silk inside the body doesn't suffer.

The combination of silicon electronics, based on nanomembranes of silicon, with biodegradable thin film substrates of silk protein, yield a flexible system and device that is

largely resorbable in the body. The use of silicon provides high performance, good reliability, and robust operation. Silk is attractive, compared to other biodegradable polymers because of its robust mechanical properties, the ability to tailor the dissolution, and/or biodegradation rates from hours to years, the formation of non inflammatory amino acid degradation products, and the option to prepare the materials at ambient conditions to preserve sensitive electronic functions. The important distinction is that, with medical implants today, the active electrical components that communicate with the body are located in a sealed box and connected with a single wire per sensor. This severely limits the number of sensors that can be implanted in the body. Integrating active electronics on sheets of silk or plastic makes it possible to multiplex the outputs of different sensors, meaning you can put hundreds, or even thousands, of contacts on a sheet.

In the brain, many procedures today rely on electrodes that have not changed much the tissue/electrode interface has hardly altered in 40 years. Now, the new implants hold out the prospect of mapping at very high resolution, down to groups of cells, and then all the way up to much bigger regions, making it possible to localize things like the networks that cause epilepsy. Another possibility is that the implants could be wrapped around depth electrodes and inserted into the brain to stimulate regions responsible for diseases like Parkinson's. Arrays of silk electrodes could conform to the brain's structure and thereby reach otherwise inaccessible areas. It would be nice to see the sophistication of clinical devices start to catch up with the sophistication of our basic science, and this technology could really close that gap.

The implants are now being tested in animals and proof of principle has already been demonstrated. Also, MC10, a start up based in Boston, has been formed to commercialize the technology. In July last year, MC10 formed a licensing agreement with the University of Illinois at Urbana-Champaign relating to stretchable silicon technology and the University of Pennsylvania relating to medical applications of this technology. As well as the medical uses described above, MC10 says there are other potential applications, such as stretchable sensor tapes for industrial and healthcare applications, including robotics and ultrathin, lightweight wearable health monitors, and bio inspired 'electronic eye' cameras, providing the basis for ultra compact, high performance imaging systems such as extremely thin mobile phones and lightweight satellites. Also, since these devices can be made with micron thickness and are foldable and rollable, they can be introduced into body with minimal invasiveness, a major benefit.

Silk allows you to have a little bit of a stiff backing to get them into where you want, and then it dissolves away, Think of it as sinking into the wrinkles of the brain, or conforming to the walls of the bladder, or wrapping around nerves. Of course, these are active devices that also offer potentially far greater resolution then has been possible previously. It will be possible to put a device inside someone and take a reading from it just by holding an inductor coil over the skin. Also, there are ways to implant a device that chemicals would bind to, so this could be used to

monitor the region for any molecules that might signal the return of a cancer, for example. One potential application is detecting harmful bacteria in food. A silk optic material would have a pattern of nanoscale peaks and troughs, with each trough containing a substance that reacted to the bacteria. If the bacteria were present, the troughs would fill, and like a butterfly wing when its structure is altered, change color, revealing the presence of bacteria. Medical monitoring is another possibility. A specific case would be monitoring glucose concentration using a silk based photonic monitoring system implanted under the skin that stays there for maybe a month, and would change color depending on what was happening. The optical properties change depending on the biological activity of what is inside the optical material, Components like enzymes or proteins could be mixed in with the liquid silk solution and used as biological markers for oxygen or pH levels. When the components are added to the silk as it is drying, the silk locks the component into its structure and, within the hardened element, the enzyme or protein retains its function. Silk has already been used a lot for tissue engineering applications it's an FDA approved material and there are several companies purifying silk fibers to make them physiologically acceptable. These are being woven into substitutes for ligaments. Silk is a material that interfaces extremely well with the body, causing no immune problems, which is almost unique. You can interface with planar electronic technology, and this gives you lots of control. It's also very green, basically requiring water based processing at room temperature, and it is of course already a commodity, because of the textile industry. It has a spectacular confluence of properties. Other biopolymers are very good at doing specific things but it's like everything comes together with silk.

The Bluetooth based devices could be implanted permanently beneath the skin. Made from flexible silicon and silicone, the devices would be inserted through a small incision and unfurled beneath the skin. Two small tubes might be attached to a blood supply, feeding a coin sized fuel cell which converts glucose and oxygen in the bloodstream into electricity needed to power the device. The surface of the implant, a touch screen control that faces the underside of the skin, is covered with a matrix of field producing pixels that active a matching matrix of pixels tattooed on the skin above the implant. Rather than use ink, tiny clusters of microscopic spheres would be injected into the skin; each sphere filled with a field sensitive material that changes from clear to black when a field in the matrix is turned on. Implanted medical devices could communicate wirelessly with the outside world, as well as with other devices implanted in the same body. Because it is always present and always on, the device could monitors for blood disorders continually, alerting the person of a health problem.

3. SILK TECHNOLOGY
The silk used here is made by boiling the silk worm cocoons and purified it to get this master ingredient. The water based solution of this silk is called as FIBROIN. This liquid can be molded into a wide variety of optical devices such as lens, prism, mirrors e.g. Silk allows you to have a little bit of a stiff backing to get them into where you want, and then it dissolves away, Think of it as sinking into the wrinkles of the brain, or conforming to the walls of the bladder, or wrapping around nerves. Of course, these are active devices that also offer potentially far greater resolution then has been possible previously.

Silk fibroin, derived from Bombyx mori cocoons, is a widely used and studied protein polymer for biomaterial applications. Silk fibroin has remarkable mechanical properties when formed into different materials, demonstrates biocompatibility, has controllable degradation rates from hours to years and can be chemically modified to alter surface properties or to immobilize growth factors. A variety of aqueous or organic solvent-processing methods can be used to generate silk biomaterials for a range of applications. In this protocol, we include methods to extract silk from B. mori cocoons to fabricate hydro gels, tubes, sponges, composites, fibers, microspheres and thin films. These materials can be used directly as biomaterials for implants, as scaffolding in tissue engineering and in vitro disease models, as well as for drug delivery.

Fibroin is a type of protein created by Bombyx mori (silkworms) in the production of silk. Silk emitted by the silkworm consists of two main proteins, sericin and fibroin, fibroin being the structural center of the silk, and sericin being the sticky material surrounding it.

Primary structure of fibroin, (Gly-Ser-Gly-Ala-Gly-Ala)n

The fibroin protein consists of layers of antiparallel beta sheets. Its structure mainly consists of the recurrent amino acid sequence (Gly-Ser-Gly-Ala-Gly-Ala)n. The high glycine (and, to a lesser extent, alanine) content allows for tight packing of the sheets, which contributes to silk's rigid structure that can't be stretched (tensile strength). A combination of stiffness and toughness make it a material with applications in several areas, including biomedicine and textile manufacture. Fibroin is known to arrange itself in three structures, called silk I, II, and III. Silk I is the natural form of fibroin, as emitted from the Bombyx mori silk glands. Silk II refers to the arrangement of fibroin molecules in spun silk, which has greater strength and is often used in various commercial applications. Silk III is a newly discovered structure of fibroin.[1] Silk III is formed principally in solutions of fibroin at an interface (i.e. air-water interface, water-oil interface, etc.).

2.1 SILK SOLUTION PREPARATION Silk solution is nothing but fibroin. It is prepared by boiling these silk cocoons and isolating fibroin protein from the solution. This solution is dialyzed and aqueous pure silk solution is taken.

Additional filtering and addition of bio-dopants, enzymes, proteins to the purified silk solution forms a bio active silk solution called OPTICAL GRADE silk solution.

This optical grade silk solution is used to develop wide variety of optical devices such as lenses, prism, and mirrors e.g.

4. Flexible electronics
Flexible substrates are often an interesting alternative for replacing the rigid printed circuit boards (PBC) because of their light weight and flexibility. In many cases, flexible substrates have a higher mechanical reliability than the counterpart rigid boards due to their inherent ability to deform which can reduce the inplane stresses generated during the different thermal processing steps. In order to achieve this flexibility, thinned dies in the order of 1030 lm are embedded in the inner layers of the flexible boards. One of the most common integration approaches consist in connecting, with flip chip technology, the dies to the circuit printed wires. However, some known issues from this approach are the impossibility of testing the dies before embedding, the high precision requirements for the placement of the bare die and the need for very fine pitch flexible printed circuit compatible with the pad pitch of the embedded chip. Another approach is to place the die in an interposer that allows, among other advantages, the possibility to test the chip before embedding and provides a fan out, eliminating in this way the need of high density PCBs and the high precision placement. This novel packaging concept, named Ultra Thin Chip Package (UTCP), is based on the concept of embedding ultra thin chips, with thicknesses below 30 lm, in between two layers of polyimide, resulting in a chip package with a total thickness of only 5060 lm. This package can be assembled on PCB or flex, or can be embedded in a stack of PCB layers.

The basic principle of stretchable electronics is to interconnect rigid or flexible interposers, containing the electronic components, by means of elastic electrical conductors. In order to protect the circuit from environmental factors and to provide a mechanical stability, the interposers and the interconnections are embedded into an elastic polymer. Even though stretchable electronic technology is not as mature as the flexible circuit technology, many different concepts have been proposed in recent years, covering a wide range of applications with dimensions of only few hundreds of microns to some tens of centimeters. Each technology presents some advantages and disadvantages among each other, and the choice of the technology depends largely on its final application. One concept consists in depositing a thin metal film in a pre-stretched substrate. It is reported that once the substrate is released, the metal will deform out-of-plane forming a controlled buckled structure. Even though this unique design offers a controllable stretchability without losing electrical performance, it is limited to relatively small circuits and deformation of only a few percent.

High density stretchable interposers have been developed in IMEC. This technology consists in embedding a thin silicon die (below 20 lm) and the metal interconnections in a stretchable polymer. All operations, except dies transfer, are done in a wafer-level packaging process manner, allowing fast processing of a large number of dies, minimizing costs and time. Thanks to its ease of application, the metallization can be designed with complex geometries allowing some degree of stretchability. Fig. 6 depicts an example of a thin embedded die and the metal interconnections before and after releasing from the wafer. As stretchable substrate, a photo sensitive spin on silicone, WL5150, has been used because of its high elasticity and low

induced stresses from the relatively low Youngs modulus (<160 MPa) and large elongation to break (_37%). The temperature stability of the material up to 300 _C allows for further assembly while remaining under CMOS compatible process temperature (<400 _C). To allow stretchability of the package, metal interconnections have to be stretchable as well. We therefore use a specific design of metal lines with a kind of sinusoidal shape allowing to stretch them such as a 2D spring. In this design, pitch on the die is 100 lm (80 lm pads) are fanned-out to a 400 lm pitch (300 lm pads). This large pitch is compatible with stretchable board

technologies. The dimensions on this design are typical for standard targeted applications. In this activity, extensive FEM simulations are carried out in order to maximize stretchability of the overall embedded subsystem in general and of the metal interconnect in particular. As the required stretchability of these interposers will not exceed 10%, a horseshoe design is not necessary. Fig. 7 illustrate a comparison of the permanent deformation of the copper between straight lines and the meandered lines. Due to the symmetry, only half of the structure has to be modeled, with a symmetry plane applied in the left side of the model. In the right side, a uniform displacement is applied, giving a total deformation in the package of 5%. As the rigid silicon chip does not elongate, the effective stretch in the copper meanders is 8.7%. As it can be seen in Fig. 7, the meandered lines are more reliable than straight lines because of the lower plastic strain. Even though there is a reduction in the plastic strain of the meander line compared to the straight lines, the plastic strain is concentrated in specific zones of the curve, therefore further optimization of the transition zone from rigid (silicon die) to stretchable (copper meanders) need to be investigated. Further improvements have been observed by reducing the copper track width In order to keep a low electrical resistance and increase, at the same time, the stretchability of the meanders, multiple copper meanders, parallel to each other are designed as shown in Figs. In the

case of multiple metal conductors forming a single line, electrical bridges are placed between the tracks in the regions where the lowest deformation is observed (Fig. 8). These bridges help to keep the continuity of the lines after failing in a specific region In other words, if a metal track fails, only one section of the line is lost (between two bridges) in electrical connection instead of the failure of the whole track. This redundancy helps to increase the reliability of the system. Metal conductors are by nature only elastic for a few percent before break, therefore the design of the metal meanders is a dominant factor to give stretchability to a non-stretchable material. FEM has been widely used to characterize the shape of the conductors in order to allow high deformations without permanent damage. Based on these results, a horseshoe metal track

shape is proposed. In this design, the stresses are distributed in a wider region instead of concentrated in the apex of the curve. The damage in the metal is significantly reduced by applying narrow metallization schemes and low elastic modulus of the substrate. Fig. 9 shows an example of a horseshoe design. The metal used for the interconnections is copper, with a Youngs modulus of 117 GPa. The substrate is a silicone, modeled as a NeoHokean material with C10 = 0.157 MPa. After deforming the system 30%, the maximum plastic strain in the copper is only 4.83%. The deformation of the interconnection lines can be different when several meanders are close to each other, or depending on the position of the lines. An example of this phenomenon is shown in Fig. 10. A total nominal deformation of 25% is applied in a uniaxial manner. In the entire test sample we can observe three regions of interest: the clamping zone, where no in-plane deformation is applied; a transition zone, following the rigid clamp, where a

complex deformation is presented, and a stable and homogeneous region where all the meanders deform in the same mode. From the reliability point of view, the transition zone is the critical region; because of the different deformation modes are observed and the maximum elongation of the meanders is observed. As no contraction is allowed in the Y direction, the substrate and copper meanders in this region are deformed as a planar extension test and shows slightly higher damage when compared to the uniaxial tensile test. Moreover, the outermost meanders are bended and stretched at the same time, while the center meanders are only stretched. This means that the total deformation of the outermost copper meanders is higher (lower reliability) than the deformation of the central meanders. This effect is illustrated in Fig. In some applications, where high density interconnections and low stretchability are required, the horseshoe design is not longer a suitable design. Due to the shape of the horseshoe, it is not possible to stack parallel lines; therefore the minimum pitch is governed by the amplitude of the meander. For those applications a pattern with a zigzag structure is designed as shown in Fig. This design, as the horseshoe, presents the characteristic that its electrical resistance is independent on the elongation before metal rupture. Stretchability beyond 40% has been demonstrated with this design .

4.1 Reliability and failure analysis

As it was discussed the reliability of the stretchable interconnections depends not only on the constitutive behavior of the substrate and the metal interconnections but also on the mechanical design and the applied deformation. FEM simulations results presented here were done for a specific design and deformation and presented as the maximum plastic strain in the copper. During fatigue cycles, much smaller but periodic, elongations are applied to the circuits producing a fatigue failure of the metals. In order to model the fatigue test and estimate the fatigue lifetime, the stretchable circuit was subjected to cyclic deformations at a specific percentage and a FEM model was used to calculate the accumulated plastic strain per cycle for the same elongation. These kinds of tests were repeated for seven different elongations going from 2.6% to 22%. In this way, we translate the applied strain into a damage criterion (plastic strain). If a new design is created or the thickness of the substrate is modified, we can use the FEM to calculate the plastic strain and therefore estimate the fatigue lifetime. The result of this translation is strain per cycle is the value calculated by FEM, whereas the lifetime is obtained experimentally. An equation based on the CoffinManson law is used to fit the data points into a correlation curve.
depicted graphically in Fig. 13. In this plot, the accumulated plastic

In order to observe the failure mechanism, a home built stage was mounted directly in the SEM in order to monitor in situ the deformation mechanism of the horseshoes shaped metal tracks. The samples were specially designed, with the copper exposed in the surface of the silicone. In

this way, it was possible to take high resolution images of the elastic interconnections at different phases of the deformation. Several observations are done from these images. Firstly, although the copper metal is deposited in-plane, during the deformation, a combined opening of the horseshoe and twisting of the metal is observed giving rise to an out-of-plane deformation of the meander. This mechanism is beneficial for the reliability because it implies a lower induced plastic strain. Secondly, before the final break of the copper track, an interfacial delamination is observed.

5. POWER SOURCES
Currently, the use of implanted medical devices for long-term monitoring of medical conditions presents a challenge in terms of a renewable power source. Such devices need a selfsufficient power source that does not interact with its surroundings, and batteries are impractical due to their need for replacement. Power consumption is said to be so low that no battery will be needed for most applications. The device can harvest energy from ambient sources, via miniaturized solar cells or the movements of its wearer. The human body is an excellent source of thermal as well as mechanical energy. Thermal gradients are present on the surface of the skin and may be used for external skin-mounted sensors. Vibrational energy scavenging is also a viable source of renewable energy and devices powered by the human heartbeat have been created. Electricity to power implanted medical devices can be harvested from the pulse of a blood vessel, a gentle breeze, or the motion from walking. Two small tubes might be attached to a blood supply, feeding a coin sized fuel cell which converts glucose and oxygen in the bloodstream into electricity needed to power the device.

6. ADVANTAGES AND DISADVANTAGES

ADVANTAGES 1. 2. 3. 4. Low power consumption Flexible Almost dissolves in to body Dont cause irritation 5. Water soluble and bio-compatible silk substrate 6. no immune problems

DISADVANTAGES 1. Cost is high. 2. Complex to design. 3. May damage skin or tissue at which it is implanted.

7. APPLICATIONS
1. Monitor chronicle diseases. 2. Photonic tattoo showing blood pressure and sugar levels. 3. To monitor progress after surgery. 4. Electroencephalogram (EEG) measurement. 5. Cardiac implantable electronic devices. 6. detecting harmful bacteria in food 7. Silk based LEDs. 8. stretchable sensor tapes 9. electronic eye cameras 10. Lightweight satellites. 11.extremely thin mobile phones 12.sportswear

8. CONCLUSION
It is believed that in the future many electronic assemblies on rigid substrates will be replaced by mechanically flexible or even stretchable alternatives. The success of flexible and stretchable electronics is based in the broad number of applications where the weight, size, cost and shape among others are an asset. This paper summarizes the ongoing activities for the integration of IC at a wafer level and board level for flexible, stretchable and potentially smaller devices.

9. REFERENCES
http://www.technologyreview.in/biomedicine/25086/ http://www.technologyreview.in/computing/23847/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816979/ http://engineering.illinois.edu/news/2009/11/16/silk-and-silicon-combine-a-new-generationimplantable-biomedical-devices-are-resorba http://www.newelectronics.co.uk/electronics-technology/silicon-gets-silky/22073/