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Document Type and Number:
WIPO Patent Application WO/2005/102151
Kind Code:
A sensor (10) is disclosed, which uses a transmission principle beyond RF-signals and which sensor doesn't need an electrical circuitry. The principle is based on indication means, which built by a contrast interface (32) contrasting two mediums and which contrast interface is readable by sound or radiation. Advantageous embodiments of the present inven­tion include an amplification system via micro channels (20) or a micro gear, which transform a change of length with a very high accuracy and resolution. In a further embodiment a compensation of temperature does not influence the measurement of a force.

Application Number:
Publication Date:
November 03, 2005
Filing Date:
April 20, 2005
Export Citation:
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International Classes:
A61B5/00; A61B5/103; G01L7/10; G01L7/20; (IPC1-7): A61B5/00
Foreign References:
Other References:
See also references of EP 1740092A2
Attorney, Agent or Firm:
Kley, Hansjörg (Postfach 22 16 34, München, DE)
Download PDF:
AMENDED CLAIMS [received by the International Bureau on 03 November 2005 (03.11.2005); original claims
1. 15 replaced by amended claims 1. 13] Claims 1 A sensor (10), comprising first means (22, 42) responsive to a physical impact (F, Tl, T2) thereupon by transforming a change of volume due to the physical impact (F, Tl, T2) into a change of length; and indication means (20; 44, 62) coupled to the first means (22, 42), the indication means indicating the magnitude of the physical impact (F, Tl, T2) , characterized in that the indication means (20; 44, 62) are built by a contrast interface (32) contrasting two mediums and which contrast interface (32) is readable by sound.
2. The sensor (10) according to claim 1, wherein one of the two mediums is a liquid (34) and the other one is a gas.
3. The sensor (10) according to one of the claims 1 or 2, wherein the sensor (10) comprises a reservoir (22) and the indication means (20; 44, 62) comprises a channel (20) for receiving liquid (34) from the reservoir (22) urged from the reservoir (22) by the physical impact (F, Tl, T2) .
4. The sensor (10) according to claim 3, wherein the channel is a micro. channels (20) .
5. The sensor (10) according to claim 4, wherein the micro. channel (20) comprises a spiral or a meandric layout.
6. The sensor (10) according to claim 4 or 5, wherein the micro. channel (20) comprises a maximum width of 1 mm, a maximum height of 0.1 mm and a maximum length of 100 mm.
7. The sensor (10) according to one of the claims 4 to 6, wherein micro. channel (20) comprises a minimum width of 0.01 mm, a minimum height of 0.0001 mm and a minimum length of 10 mm.
8. The sensor (10) according to one of the claims 3 to 7, wherein a second reservoir (22) is connected with the channel (20) in order to separate indication means (32) indicating different physical impacts (F, Tl, T2) .
9. The sensor (10) according to claim 8, wherein the channel (20) contains two liquid/air interfaces (32) where the distance (t2) between the two liquid/air interfaces (32) represents the temperature (Tl, T2) of the sensor (10) .
10. The sensor (10) according to claim 7 or 8, wherein the channel (20) contains two liquid/air interfaces (32) where the distance (f) between one liquid/air interfaces (32) and one reservoir (22) represents the strain (F) applied to that reservoir (22) .
11. The sensor (10) according to one of the claims 4 to 9, wherein the reservoir (22) has at least one recesse (18) in order to increase the volume change when a strain (F) is applied on that reservoir (22).
12. The sensor (10) according to one of the claim 1 to 11, wherein the sensor (10) is biocompatible.
13. The sensor (10) according to claim 12, wherein the (10) sensor is biodegradable.
14. 21 Statement under PCT Aricle 19(1) According to the findings in the search report dated 28th October 2005 a new formulated set of claims 1 to 13 is filed. These amended claims 1 to 10 replace the originally filed claims 1 to 15. There is no need to adopt the description or the drawings to the amended claims 1 to 13. Zurich, 01.11.2005 Hansjorg Kley Agent AV 47543 22.
Passive sensor with wireless transmission

The invention relates to a passive sensor with wireless transmission according to the preamble of claim 1.

Most in situ/in vivo sensors for monitoring parameters within the living body require wires in order to facilitate read out and communication with the sensor. While effective, such sen¬ sor arrangements, and especially the wires penetrating the skin, can cause severe patient discomfort, inflammation, and infection. To address these negative effects, wireless sen¬ sors have been introduced.

The principle of a wireless sensor system is shown in figure 1. Such sensors 10, e.g. strain sensors, are placed in a living body 2. The skin is symbolically shown with a line and denoted by the reference numeral 1. The strain sensor 10 is interrogated via a request signal 15 sent out from a trans¬ mitter/receiver/evaluation unit 16. The unit 16 receives a response signal 17 in order to derive the actual size of the strain.

In wireless sensor systems the sensor unit itself can be de¬ signed active, semi-passive or passive: • Whereas «active» means that the sensor unit consists of active circuits powered by an on board power supply (e.g. battery) . • «Semi-passive» sensor units consist of active circuits which are powered by inductive coupling or an RF signal from the request unit. • «Passive» devices don't have active circuits and employ a distortion of the received request signal as response signal.

Sensor-systems, e.g. for mechanical axial strains, are re¬ ported in-various publications for medical [1, 2] and non¬ medical applications [2-5] . So far only inductor/capacitor circuit (LC) resonators have been described as passive sensor devices in medical appli¬ cations performing over a range of several millimeters [1, 2] .

Brief discussion of available wireless sensor systems

1. LC resonator sensor [1,2] The sensor principle is a LC resonator sensor. Compressive strain changes the actual cross-section of the solenoid or the gap distance of the capacitor, thus changing its induc¬ tance or capacity respectively.

2. Surface acoustic wave sensor SAW [3,4] A passive acoustic sensor principle, like a surface acoustic wave device SAW, re-transmits a linearly distorted version of the radio request signal: a RF interrogation signal is re¬ ceived by the interdigital transducer, e.g. a piezoelectric material, and transformed into a surface wave, which is affected by changes in the surface properties. The surface wave is reflected and then reconverted into an electrical signal and transmitted by the antenna.

3. Magneto-elastic sensor [5] The magneto-elastic sensor mechanically deforms when subjec¬ ted to a magnetic field impulse, launching elastic waves within the sensor the magnitude of which is greatest at the mechanical resonant frequency. Through the inverse magneto- elastic effect, the vibration of the sensor generates a time varying magnetic flux, which can be measured wireless with a set of pick-up coils. In addition, the mechanical vibrations also generate an acoustic wave that can be detected with a microphone. The inverse relation between the length, modulus, or mass of the sensor vibrating in its basal plane and the longitudinal resonance frequency allows the determination of various parameters on a sub-micro scale, e.g. strain, mass loads, liquid viscosity, or temperature. Magneto-elastic sensors are typically made of amorphous ferromagnetic metallic glasses such as Fe4ONi38Mo4B18 or Fe8B13-5Si3-5C2 , which generally miss biocompatibility.

Materials for sensors in medical applications When used for medical applications, like in situ/in vivo monitoring of strains occurring along a bone of the human skeleton, a strain sensor should fulfil several requirements to minimize the impact on the patient. These requirements are first of all biocompatibility or biocompatibility and bio- degradability, which are related to the micro-design of the sensor and the choice of materials. Most of the materials used for the state-of-the art techniques, however, are not biocompatible or biodegradable and a potential system would have to be encapsulated.

Recently a new class of highly biocompatible or biocompati- bility and biodegradability polymeric materials has emerged [7-9] . These materials already had great impact on medical applications like artificial hip joints, biodegradable implants, which provide secure initial fixation strength while allowing degradation and replacement by the host tissue, or biodegradable drug delivery systems.

Sensor design / micro-structuring To provide for maximum biocompatibility when used as medical implant, micro-design of the sensor is preferred, which in- eludes material characterization and micro-structuring of the materials. Usually microfabrication uses photolithographic technologies , which are restricted to photosensitive mate¬ rials only. Biocompatible/-degradable polymers are usually not photosensitive, hence, non-photolithographic technologies like microprinting, replica molding, microembossing, or microcutting are preferred and have been demonstrated for thermoplastic polymers as fabrication method for generating sub-micrometer features [10-15] . Thermoplastic polymers include the class of amorphous and semi-cristalline polymeric solids, which soften when heated above the glass transition temperature (amorphous polymers) or melting temperature (semi-cristalline polymers) .

Wireless sensors however, were not initially designed for implantation within the human body as the required components are or may be electronic and toxic.

The present invention therefore addresses the problem of creating a wireless passive sensor, which uses a transmission principle beyond RF-signals and which doesn't need any electrical circuitry. The latter provides the option to built the sensor entirely from biodegradable materials. Furthermore it is an object of the present invention to create a sensor, which detects a certain parameter, e.g. a change in length or temperature, with a high accuracy as well as high resolution.

These objectives are solved by a sensor according to the features specified in claim 1.

Advantageous configurations and applications of the invention are specified in further claims.

Objectives and advantages of the present invention as well as the preferred embodiments include the following: • to provide a sensor which may be used within the body and communicated with from outside the body; • to create a signal amplification system which may be used with a variety of signal generating means, within the body, the amplification system being detectable from out¬ side the body; • to create an individual sensor and/or amplification system made of bio-compatible and/or bio-degradable materials so as to facilitate a reduction in the number of required surgeries; • to set out a method for using the above mentioned invention; and • to implement the aforementioned using low cost materials so as to facilitate mass production and disposability.

A preferred task of the wireless in situ passive strain sensor (acronym: WIPSS) is to detect in situ/in vivo mechani¬ cal strains via a low-cost, implantable, biocompatible and biodegradable, micro-designed, wireless and passive sensor unit.

The concept of the sensor unit is to transmit small relative strains, typically occurring in the human body of the order 0.00001 to 0.001 according to the indications in [6], via an amplifycation system into a signal which can be detected through human tissue by available ultrasound or other imaging technologies via radiation.

The strain sensor according to the present invention requires no power supply and may be composed of biocompatible or bio¬ compatible and biodegradable materials thereby obviating the need.for surgical removal. The sensor unit may have a micro design so that it may be implemented in a variety of uses. One use is on a bone wherein the sensor is directly connected to the bone via known surgical techniques such as gluing. The micro-size facilitates localized positioning. The use of biocompatible or biocompatible and biodegradable materials causes low costs and facilitates disposability and mass pro¬ duction.

Biocompatible and biodegradable materials are known in the art and may be used as a base material for the present in¬ vention. Such materials include DEGRAPOL, polyglcolide, poly- lactide, poly(£-caprolactone) , poKlactide co-glycolide) , and other materials as set out in the article Middleton et al.. Biocompatible materials include: Polyvinylchloride, Polyethylene, Polymethylmethacrylate, Polyamides and the like. Reference is made to [16] an [17] . In addition, the materials used for the components of the present invention may comprise all materials, such as polymers, but not limited to, biocompatible or biocompatible and biodegradable mate- rials, that are capable of transfering stress into strain and therefore into a change in volume of the sensor's body.

The amplification unit is readable from outside the body by conventional ultrasound techniques. Other reading techniques may be used as known to one skilled in the art as radiation e.g. in the visible or near visible range. Ultrasound, as is known, reads through human tissue and can «see» liquid gas and solid gas interfaces. The liquids may also be biode¬ gradable and biocompatible as per the discussion above. Liquid is also included in the sensing unit such that de¬ formation of the sensing unit urges the liquid, along a track in the amplification unit, the track being imageable from outside the body. Alternatively, micro-gear systems may be used with a gas bubble at a lever's end for an indicator. The lever may pivot in response to deformation, the mechanical force of which is directly transmitted to the lever. The mechanical force may originate from a sensor unit wall. Accordingly, more than one lever responding to more than one wall may be used. Additionally more than one bubble may be employed.

The imaging may be a pixel maze of 100 pixels. The amplifica¬ tion unit may include micro-channels, also called micro- tubes, for the liquid to flow in. The actual layout and design of the micro-channels is a design choice dependent upon application.

The invention will become apparent upon consideration of the following detailed description of specific embodiments thereof with a reference to a drawing in which: Figure 1 principle of a wireless sensor system according to the state of the art; Figure 2a, 2b, 2c principle of the signal amplification according to two embodiments of the present invention; Figure 3 another embodiment of a mechanical strain ampli- fication; Figure 4 an embodiment of a hydro-mechanical strain amplification; Figure 5a, 5b a further embodiment of a hydro-mechanical strain amplification sensing or compensation effects of temperature.

The principle of the strain amplification according to the following depicted embodiment is show in figure 2a and figure 2b for a sensing unit 10. A reservoir 22 contains an incom¬ pressible liquid 34. The reservoir 22 has an opening to a micro tube 20. Under a force F, see fig. 2b, the volume of the reservoir will be decreased and there will be a corres¬ ponding change of the position of an liquid/gas interface. Figure 2c shows a similar embodiment of a sensing unit 10 with a reservoir 22. Recesses 18 enhance the decrease of the volume, when a force F is applied to the side walls, this kind of recesses are also called accordion principle.

An concrete embodiment of the invention is shown in figure 4. A sensing unit 10 comprises a liquid containing reservoir 22. The reservoir 22 may comprise biocompatible and/or biode¬ gradable polymers such discussed above. Other polymers may be used or substituted provided that they are bio-compatible and/or biodegradable.

The size and shape of the reservoir 22 is dependent upon ap¬ plication with other designs than the one depicted available to one skilled in the art. As depicted, the reservoirs 22 compress a substantial square-like structure having an upper and lower surface with a side length of about 5mm. The reser¬ voir 22 is three dimensional with a width of about 2 mm. The reservoir materials must be biocompatible, with the following mechanical properties. The reservoir mechanical properties should not be to stiff and be easily coupled to the bone. The sensing unit may be transparent or opaque.

A micro-channel 20 connects the reservoir 22 with a display unit 30. The channel 20 may have a variable length depending upon the location of the display unit 30. Accordingly, the display unit could be placed directly on the sensing unit 30, or remote from the reservoir 22. The latter could be pre¬ ferable for applications several centimeters inside the body, where it might be preferable for the display unit 30 to be placed substantially below the skin. Likewise, depending upon application, the channel 20 may be several millimeters, centimeters and so forth without limit but for the physical properties of the components. The material for the channel 30 may be the same as the reservoir 22 or at least within the same family of materials.

The display unit 30 may comprise the same material or at least same family of materials as the sensing unit 10. The display unit 30 comprises a housing having a micro-channel path 20 running therein. The path design is a matter of design choice provided that the resolution of the outer body sensing device is able to resolve locations along the path. As shown in figure 4, a spiral layout of the channel 20 is provided. Other layouts as e.g. a meandric layout are also applicable. State of the art microstructing fabrication tech¬ niques such as photo and non-photolithography or soft photo- lithography may be used to fabricate the path. The micro- channel 20 is fabricated so as to accommodate liquid 34 from the reservoir 22 therein and therethrough. As shown in the figure, gradations 26 are included on the surface of the dis¬ play unit 30. While such may be part of the fabrication pro- cess, as depicted, such are the result of imaging techniques to be discussed below. The reservoir 22 is liquid tight during sensor operation and include liquid therein. The actual amount of liquid as well as the liquid itself is a matter of design choice, provided the composition and amount do not rise to the level of toxicity. Preferably, the liquid is biocompatible or biocompatible and biodegradable.

In operation, e.g. as strain sensor, the sensing unit 10 is positioned at a location where the force F is of interest. One location of operation is within the human body, including attachment directly to or within a bone. Because of the presence of the micro-channel 20, the display unit 30 may be remotely located from the sensing unit 10. Accordingly, the sensing unit 10 is placed and arranged such that forces F cause at least one wall of the sensing unit to deform. The deformation in turn forces a comparably equal amount of liquid from the reservoir 22. The liquid is received via micro-channel 20. Accordingly, the liquid forced from reser¬ voir 22 by the wall deformation directly increases the amount of liquid located in the micro-channel 20 and display channel 20 thereby pushing the forward liquid/gas interface 32 fur- ther along path. As the volume or amount of liquid 34 in the display channel 20 increases, more and more of the channel 20 becomes occupied such that the location of the end point 32 of the liquid within the display channel 20 is an indication of the amount of deformation occurring at the reservoir 22 and accordingly, the amount of stress F present in the area surrounding the reservoir 22.

Imaging means, such as ultrasound waves reflected by the liquid/gas interface 32 may be used from outside the body to detect the location of the liquid end point. Imaging techniques may be used to apply a grid like image over the path such that units of measurements and readable displays may result.

In a second embodiment, as shown in figure 3, the display unit may not be remotely located from the sensing unit 10. Herein, direct mechanical coupling between sensing unit 10 and display unit 30 are used with the walls of the sensing unit 10 also defining the outer boundaries of the display unit 30. Other relations between sensing and display unit walls may be employed without departing from the spirit of the invention. The sensing unit 10 is depicted as a square having substantially equal-length sides. Other geometrical shapes may be employed, as would be envisioned by one skilled in the art, as may be required for example upon application. For example, with some applications a trapezoidal or trian- gular shape may be substituted. Returning to figure 3, a micro rod 44 is mechanically connected to a side wall 54. The micro rod 44 is so arranged so as to displace with displace¬ ment of side wall 54. For purposes of clarify, only one micro rod affixed to a single wall is shown. An additional number of gear rods 44 attached to the same or other side walls may be used depending upon application. The additional gear rods 44 facilitate stress detection from other directions. The display unit 30 comprises a surface bordered by the sensing unit walls. Located on the display unit is a rotating gear 62. The rotating gear 62 is depicted as a full circle, although, semi-circles and other geometrical designs com¬ prising one or more gears which convert the lateral displace¬ ment of the gear rod 44 into a circular displacement may be employed. Rotating gear 62 includes teeth 56, sized and spaced so as to mechanically cooperate with the micro gear teeth 56 such that lateral displacement of the micro gear 44 is mechanically converted into rotational displacement by the cooperation of the two gears teeth 56. Affixed to rotating gear 62 is a display arm 66. Display arm 66 is arranged to rotate with the rotating gear 62 and may further be affixed to a midpoint or pivot of the rotating gear 62. At the .other end of the arm is a display. As depicted, the display is an encased gas bubble, that is a liquid/gas interface 32. Other displays may be used provided they are non-toxic, biocom- patible or biocompatible and biodegradable and detectable by non-evasive means from outside the body. As in known in the art, ultra-sound detected the interface of liquid and gas 32 thereby making the displacement of display visible from out¬ side the body. The side walls may have a length of 6 milli¬ meters and the display a width of 0.4 millimeters. The sensing unit walls 54 are elastic and comprised of the same materials as those employed above with the first embodiment.

Known ultrasound imaging techniques may be employed to detect the location and displacement on a display 30. The mapable display includes radial gradations 26 which may be used to determine rotational displacement of the display. Should the sensor wall 54 deformation be converted into another mechani¬ cal displacement, appropriate mapping would be used to detect the respective display.

Figure 5a shows an embodiment based on the principle accor¬ ding to the figures 2a, 2b or 2c. Two reservoirs 22 each containing an incompressible liquid are coupled via a chan¬ nel. Assumed is no strain nor force on neither reservoir 22, but this embodiment is exposed in an environment of a tem- perature Tl. By changing the temperature Tl the distance tl between the two liquid/air interfaces 32 changes accordingly, that is an increase of temperature leads to a decrease of the distance tl and vice-versa. This principle serves as a base for a thermometer. The location of the said liquid/air inter- face 32 either - one or both - will be detected with radia¬ tion. The location of the center of the two liquid/air inter¬ faces 32 remains unchanged during a change of temperature. The before mentioned location is represented by a distance fθ.

According to figure 5b a strain F acts on the left reservoir 22 causing a decrease of its volume. The liquid/air interface moves to the right. The distance f of the middle of said liquid/air interface represents a measure for the strain F acting on the left reservoir 22. Furthermore the embodiment according to figure 5b is exposed in an environment of a tem¬ perature T2 > Tl. Since the right hand reservoir 22 is also exposed to the same temperature T2, the influence of tempera¬ ture is separated, only the distance t2 changes according to the change of temperature but not the distance f.

The present sensing unit 10 may be used with other display or amplification units and viceversa.

List of reference numerals, glossary 1 Skin 2 part of living body 10 Sensing unit, sensor unit, strain sensor 12 Lower surface 14 Lower surface 15 Request signal, power transmission 16 Transmitter/receiver/evaluation unit 17 Response signal 18 recess, indentation 20 indication means; micro channel, micro tube, display channel, channel, tube 22 first means responsive to a physical impact; reservoir 26 gradation 28 surface 30 display unit, display 32 contrast interface; liquid/gas interface, liquid end point 34 incompressible liquid 36 gas, gas 38 outlet into micro-channel 20 40 spiral

42 elastic container

44 indication means; gear rod, micro gear

50 sensing unit

54 side wall

56 teeth 62 indication means, rotating gear

66 display arm, lever

List of used acronyms and symbols F force

f, f0 length representing a force

Tl, T2 temperature

tl, t2 length representing a temperature

WIPSS wireless in situ passive strain sensor


[1] L. Rosengren, P. Rangsten, Y. Backlund, B. Hok, B. Svedbergh, and G. SeIen, "A System for Passive Implantable Pressure Sensors, " Sensors and Actuators a- Physical, vol. 43, pp. 55-58, 1994. [2] J. C. Butler, A. J. Vigliotti, F. W. Verdi, and S. M. Walsh, "Wireless, passive, resonant-circuit, inductively coupled, inductive strain sensor, " Sensors and Actuators a-Physical, vol. 102, pp. 61-66, 2002. [3] W. E. Bulst, G. Fischerauer, and L. Reindl, "State of the art in wireless sensing with surface acoustic waves," Ieee Transactions on Industrial Electronics, vol. 48, pp. 265-271, 2001. [4] A. Pohl, "A review of wireless SAW sensors," Ieee Transactions on Ultrasonics Ferroelectrics and Frequency Control, vol. 47, pp. 317-332, 2000. [5] C. A. Grimes, C. S. Mungle, Z. F. Zeng, M. K. Jain, W. R. Dreschel, M. Paulose, and K. G. Ong, "Wireless magnetoelastic resonance sensors: A critical review," Sensors, vol. 2, pp. 294-313, 2002. [6] D. B. Burr, C. Milgrom, D. Fyhrie, M. Forwood, M. Nyska, A. Finestone, S. Hoshaw, E. Saiag, and A. Siinkin, "In vivo measurement of human tibial strains during vigorous activity," Bone, vol. 18, pp. 405-410, 1996. [7] J. C. Middleton and A. J. Tipton, "Synthetic biodegradable polymers as orthopedic devices," Biomaterials, vol. 21, pp. 2335-2346, 2000. [8] A. Lendlein, P. Neuenschwander, and U. W. Suter, "Tissue-compatible multiblock copolymers for medical applications, controllable in degradation rate and mechanical properties," Macromolecular Chemistry and Physics, vol. 199, pp. 2785-2796, 1998. [9] B. Saad, Y. Kuboki, M. Welti, G. K. Uhlschmid, P. Neuenschwander, and U. W. Suter, "DegraPol-Foam: A degradable and highly porous polyesterurethane foam as a new substrate for bone formation, " Artificial Organs, vol. 24, pp. 939-945, 2000. [10] Y. N. Xia and G. M. Whitesides, "Soft lithography," Annual Review of Materials Science, vol. 28, pp. 153- 184, 1998. [11] N. Stutzmann, T. A. Tervoort, C. W. M. Bastiaansen, K. Feldman, and P. Smith, "Solid-state replication of relief structures in semicrystalline polymers," Advanced Materials, vol. 12, pp. 557-562, 2000. [12] N. Stutzmann, T. A. Tervoort, D. J. Broer, H. Sirringhaus, R. H. Friend, and P. Smith, "Microcutting materials on polymer substrates," Advanced Functional Materials, vol. 12, pp. 105-109, 2002. [13] G. Fichet, N. Stutzmann, B. V. O. Muir, and W. T. S. Huck, "Microembossing of elastomeric triblock copolymers," Advanced Materials, vol. 14, pp. 47-51, 2002. [14] D. K. Armani and C. Liu, "Mircofabrication technology for polycaprolactone, a biodegradable polymer, " Journal of Micromechanics and Microengineering, vol. 10, pp. 80- 84, 2000. [15] D. V. McAllister, P. M. Wang, S. P. Davis, J. H. Park, P. J. Canatella, M. G. Allen, and M. R. Prausnitz, "Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies, " Proceedings of the National Academy of Sciences of the United States of America, vol. 100, pp. 13755-13760, 2003. [16] J. B. Park, J. D. Bronzino: Biomaterials-Principles and Applications. Pp. 55-77. 2003, CRC Press LLC. [17] Shastri V.P. : Non-Degradable Biocompatible Polymers in Medicine: Past, Present and Future Current Pharmaceutical Biotechnology, October 2003, vol. 4, no. 5, pp. 331-337(7) .