Temperature Controlled Multi-Wavelength Laser Welding And Heating System

[0001] The present application claims the benefit of priority from U.S. patent application Ser. No. 60/762894 filed Jan. 30, 2006, the contents of which are incorporated herein by reference.

[0002] The present invention relates generally to light source or laser welding, soldering and heating of tissue samples and more particularly to temperature controlled laser welding, soldering and heating systems applied to tissue welding.

[0003] Tissue sample heating and welding by light (e.g. laser) irradiation is known In particular, tissue heating by light irradiation is used in many medical and surgical applications such as laser welding of tissues, laser assisted cartilage reshaping, and in laser hyperthermia procedures. The light energy is absorbed by the tissue and causes local heats These clinical applications are highly dependent on defining and maintaining the optimal conditions of the light source. Irreversible thermal damage to the tissue by direct laser heating and heat transfer is of a particular concern. Therefore, the general objective of laser-tissue interaction is to accurately heat a desired volume with minimal effects in the surroundings. Since the thermal effect is fundamental to the mechanism behind laser tissue interaction, temperature control is essential to achieve a successful clinical procedure.

[0004] Laser welding of tissues is described in a number of references, see e.g. Karen M. McNally-Heintzelman and Ashley J. Welch, “Laser Tissue Welding”, chapter 39 in Biomedical Photonics Handbook, Tuan Vo-Dinh, 2003 and L. S. Bass and M. R. Treat, “Laser Tissue Welding: A Comprehensive Review of Current and Future Clinical Applications”, Lasers in Surgery and Medicine vol. 17, pp.315-349 , 1995. This is an experimental technique for tissue closure that offers many advantages over conventional closure techniques, such as reduced suture and needle trauma, reduced foreign body reaction, better cosmetic appearance, reduce bleeding, immediate water tight closure and shorting operating times.

[0005] Many in-vitro and in-vivo experimental studies were carried out to weld various types of tissues by using different lasers. An exemplary method and system of controlled laser welding of tissue is disclosed in U.S. Pat. No. 5,409,481. A tissue sample is heated controllably while irradiated by one laser source having one wavelength only. A method and system employing a fiber laser device for medical and cosmetic procedures is disclosed in US Patent Application No. 2003/0055413. The wavelength of a tunable laser source is changed and tuned to a desired wavelength and then the tissue is irradiated in this specific wavelength. A method and system employing an active laser gain medium for medical procedures is also disclosed in U.S. Pat. No. 6,162,213. An active gain medium comprising metal vapor is excited to produce a plurality of wavelengths used in a medical procedure.

[0006] Different types of light activated surgical biological adhesives and stents were developed and used to assist the weld procedure and strength, see e.g. U.S. Pat. Nos. 6,607,522, 5,552,452, and 4,6.33,870. It is assumed that the welding is achieved due to thermal restructuring within the tissue collagen, where new bonds and interaction with adjacent proteins are formed and stabilized upon cooling. A narrow margin exists between a successful and unsuccessful weld, since the process is highly dependent on the temperature.

[0007] The temperature of a tissue sample can be determined by measuring the thermal infrared radiation emitted from it, because warm objects emit IR thermal radiation whose intensity is dependent on their surface temperature. The total intensity I, of the radiation emitted from a surface is given by the equation I=εσT⁴, where ε is the emissivity which depends on the sample type and surface quality, σ is the Stefan-Boltzman constant and T is the temperature.

[0008] The wavelength of maximal emission λ_m is related to the heated body temperature T by Wien's displacement Law: λ_mT=2898 μm K. For biological tissue, T is roughly 300K. It follows that the spectral range of interest for such low temperature radiometry is in the middle infrared (mid-IR) in the spectral range 3-30 μm. The infrared emission emitted from a source can be measured by an infrared radiometer and calibrated for determining the temperature of the source. IR radiometers that measure the radiation emitted from a distant source [see edge S. Sade, O. Eyal, V. Scharf and A. Katzir, “Fiberoptic Infrared Radiometer for Accurate Temperature Measurements,” Applied Optics, Vol. 41, no. 10, pp. 1908-1914, 2002] usually consist of three parts: (1) optics to collect the radiation and to focus it on a detector, (2) an infrared detector to convert the radiation to an electric signal, (3) an electronic system for processing the signal.

[0009] Only a few optical fibers are transparent in the IR range. Optical fibers made of silver halides are among the best candidates for that purpose. They are highly transparent in the mid-infrared, in the spectral range 3-30 μm, with losses of about 0.2 dB/m at 10.6 μm, IR radiometers which use optical fibers to collect and deliver the radiation to the detector are called IR fiber optic radiometers [see e.g, A. Zur and A. Katzir, “Use of infrared fibers for low temperature radiometric measurements”, Applied Physics Letters, vol. 48, p.449, 1986]. Such a radiometer has an advantage relative to other instruments used to measure temperature, such as thermocouples; the measurement can be done in an electromagnetic environment, in situation in which there is no clear line of sight to the measured sample, and in endoscopic procedures.

[0010] The IR detectors used in the radiometers may be thermal detectors, such as pyroelectric, thermosensitive and thermopile devices, many of whom operate at room temperature, or photonic (i.e. quantum, photoconductive or photovoltaic) detectors such as MCT (HgCdTe) or InSb, which are cooled by liquid nitrogen or thermoelectrically.

[0011] Some prior art tissue heating and/or welding methods are disadvantageous in that the tissue sample is irradiated by only one laser source having only one wavelengths. Other prior art methods do not control and monitor the temperature of the tissue sample or do not irradiate the tissue sample simultaneously with several light sources, each having a different wavelength. Consequently, the upper layers of the tissue sample are being heated and a temperature gradient is formed inside the tissue, preventing tissue welding inside the tissue and/or causing thermal irreversible damage to the tissue.

[0012] There is therefore a widely recognized need for, and it would be highly advantageous to have a welding, soldering and heating system and method in which a sample such as a tissue sample is simultaneously irradiated by a plurality of light sources, preferably lasers, each having different wavelength, while measuring the temperature of the tissue sample, to controllably heat the tissue sample and which temperature is monitored in real time using an IR radiometry subsystem that provides respective IR radiation inputs to control the lasers.

[0013] We propose and demonstrate, for the first time, a temperature controlled welding, soldering and heating system which uses simultaneously a plurality of light sources, preferably lasers, each having a different wavelength, imposed to irradiate a tissue sample In a preferred embodiment the sample is a tissue sample. However, in a general sense, the present invention is equally applicable to other types of solid samples such as plastic, metal and semi-conductor samples. The advantage of such a system is as follows: a better control of the heated tissue sample can be achieved by using several lasers simultaneously and by providing a closed loop temperature control. Such a temperature controlled multi-laser system is essential for a better heating and welding of biological tissues. For biological tissues the absorption length, and therefore the heated region, is wavelength-dependent and changes according to the tissue type and structure. Therefore by using simultaneously more than one laser wavelength, one can achieve uniformity of the heated region and thus obtain uniform temperature profile inside the tissue. This will enable welding of deep layers of tissues such as deep cuts, skin implants and welding of blood vessels. This can not be done using only one laser having one wavelength or a tunable laser, because of temperature gradients which are formed in the tissue. In order to achieve the temperature uniformity, parameters such as wavelengths, powers, temporal and spatial modulation of the different lasers need to be chosen to fit the tissue type and medical procedure. The light sources should be closely monitored and controlled. This can be achieved by measuring the temperature of the tissue sample, preferably by IR radiometry, which provides inputs to the control system. Moreover, by implementing multi-band IR radiometry, the temperature measurement is immune to emissivity changes of the tissue sample during the irradiation (e.g., the loss of water in the tissue). By irradiating simultaneously the tissue sample by plurality of lasers undesired effects, such as peripheral thermal damage, can be reduced or omitted. Moreover, the multi wavelength system can be tailored to fit any type of biological glue, light-sensitive dyed tissue or cooling liquids.

[0014] A system of the present invention includes a plurality of optical light sources each having a different wavelength, which irradiate and heat simultaneously a tissue sample. In one embodiment of the present invention, the system includes an IR radiometer for monitoring the IR radiation emitted from the tissue sample during the heating and for providing respective IR radiation inputs for closed loop control of the plurality of light sources. In some embodiments, the light sources are lasers. In some embodiments, the system may be used for tissue welding. In other embodiments, the system may be used for tissue soldering. In some embodiments, the system includes a single optical port to convey the light source radiation to and the thermal radiation from the tissue sample. In other embodiments, the system includes two ports, one for conveying the light source radiation to the tissue sample and the other for conveying the thermal radiation from the tissue sample. The heated tissue sample emits thermal IR radiation, whose intensity is determined by the temperature of the tissue sample. In some embodiments, the emitted IR radiation can be measured by the IR radiometer in a single spectral band. In other embodiments, the emitted IR radiation can be measured in a plurality of spectral bands. A computer program or similar analyzing means uses the signal to determine the temperature of the tissue sample and to control each of the light sources so that a desirable surface temperature and temperature depth profile is obtained.

[0015] According to the present invention there is provided a system for non-contact welding, soldering and heating of a tissue sample including a plurality of light sources each having a different wavelength, the sources operative to simultaneously irradiate the tissue sample thereby causing heating and an IR radiometry subsystem for monitoring the IR radiation emitted from the tissue sample during the heating and for providing respective IR radiation inputs for control of each of the light sources.

[0016] According to one feature in the system of the present invention, the light sources include lasers.

[0017] According to yet another feature of the present invention, the system further comprising a control unit coupled to both the IR radiometry subsystem and the laser sources and operative to provide the control of each laser source based on the radiation inputs.

[0018] According to yet another feature of the present invention, the irradiation by the light sources and the thermal radiation from the tissue sample are conducted through a single port.

[0019] According to yet another feature of the present invention, the irradiation by the light sources and the thermal radiation from the tissue sample are conducted through separate ports.

[0020] According to yet another feature of the present invention, the single port includes an optical fiber.

[0021] According to yet another feature of the present invention, the separate ports include separate optical fibers.

[0022] According to yet another feature of the present invention, the lasers are selected from the group consisting of a pulsed laser, a continuous wave gas laser, a solid-state laser, a semiconductor laser and a combination thereof.

[0023] According to yet another feature of the present invention, the IR radiometry subsystem includes an IR detector selected from the group consisting of a thermal detector and a photonic detector.

[0024] According to yet another feature of the present invention, the IR radiometry subsystem further includes an IR-transparent optical fiber for coupling the IR detector to the tissue sample along an optical path.

[0025] According to the present invention there is provided a non-contact welding, soldering and heating system including a plurality of light sources for simultaneously and controllably irradiating and heating a tissue sample, an infrared detector for monitoring IR radiation emitted from the tissue sample during the heating in at least one spectral band and for providing respective IR radiation inputs and a controller for controlling each of the light sources based on the IR radiation inputs, thereby facilitating the controllable heating of the tissue sample.

[0026] According to the present invention there is provided a method for controllably welding, soldering and heating of a tissue sample including the steps of: irradiating and heating the tissue sample simultaneously using a plurality of light sources, measuring the temperature of the tissue sample using an IR radiometer in at least one spectral band to provided real-time temperature inputs and controlling each of the light sources based on real-time temperature inputs provided by the IR radiometer, thereby providing a controlled tissue sample temperature.

[0027] According to a feature in the method of the present invention, the step of irradiating and heating is preceded by a step of adding a substance to better control the heating and to achieve better welding results, the substance selected from the group consisting of a biological glue, a light-sensitive dyed tissue, a cell and a cooling liquid.

[0028] According to one feature in the method of the present invention, the step of irradiating and heating includes irradiating and heating with lasers.

[0029] According to another feature in the method of the present invention, the step of controlling the light sources is done by a controller coupled to both the IR radiometer and the light sources and operative to provide the control of each light source based on the radiation inputs.

[0030] According to yet another feature in the method of the present invention, the irradiation by the light sources and the thermal radiation from the tissue sample is conducted through a conduit selected from the group consisting of a single port and a plurality of separate ports.

[0031] According to yet another feature in the method of the present invention, the single port includes an optical fiber.

[0032] According to yet another feature in the method of the present invention, the separate ports include separate optical fibers.

[0033] According to yet another feature in the method of the present invention, the lasers are selected from the group consisting of a pulsed laser, a continuous wave gas laser, a solid-state laser, a semiconductor laser and a combination thereof.

[0034] According to yet another feature in the method of the present invention, the IR radiometer includes an IR detector selected from the group consisting of a thermal detector and a photonic detector.

[0035] For a better understanding of the present invention and to show more clearly how it could be applied, reference will now be made, by way of example only, to the accompanying drawings in which:

[0036] FIG. 1 (A-B) is a schematic diagram of a laser heating and welding temperature controlled system of the present invention in two configurations of conveying the radiation to and from the tissue sample: (A) one port system, and (B) two port system;

[0037] FIG. 2 shows schematically the advantage of using a two wavelength laser welding system over a one wavelength laser welding system;

[0038] FIG. 3 shows a schematic example of multi-wavelength laser welding temperature controlled fiber optic system utilizing CO₂ gas laser and a GaAs diode laser;

[0039] FIG. 4 shows a schematic of the synchronization between the lasers irradiation and the thermal measurement;

[0040] FIG. 5 shows the temperature control result of a biological tissue irradiated by multi-wavelength laser welding temperature controlled fiber optic system utilizing CO₂ gas laser and a GaAs diode laser.

[0041] The present invention discloses, in various embodiments, a novel temperature controlled multi-wavelength laser heating and welding system, in which a plurality of different wavelength light sources simultaneously irradiate the tissue sample and in which radiometry is used to measure the temperature of the tissue sample to provide closed loop control of the heating. The radiometric measurements may be performed in several spectral bands. In one embodiment, the system is based on all-fiber technology and on diode lasers.

[0042] This enables the system to be reliable, compact, rigid and portable, allowing the system to be commercialized for many medical procedures.

[0043] FIG. 1A shows schematically a first embodiment of a laser welding system 100 of the present invention. System 100 comprises a plurality of laser sources (in this case, three sources numbered 104, 106 and 108) disposed to irradiate tissue sample 102 simultaneously at different wavelengths λ₁,λ₂,λ₃. Laser sources 104, 106 and 108 may be pulsed lasers, continuous wave gas lasers, solid-state lasers, semiconductor lasers and a combination thereof In this embodiment, the irradiation occurs through a single port 110 and an optical coupling medium 112. Each of the laser sources 104, 106 and 108 is preferably controlled by a personal computer (PC) 114 through a control loop 116. Other types of controllers capable of control and analysis functions may also be used. Preferably system 100 further comprises a radiometry subsystem 118 disposed to monitor and measure thermal radiation 120 emitted from heated tissue sample 102. Preferably, in this embodiment, radiation 120 is conveyed to subsystem 118 through the same single port 110 and optical coupling medium 112 as the laser radiation. In other words, in this embodiment single port 110 conveys simultaneously two types of radiation: laser radiation of the laser sources and thermal radiation from the heated tissue sample In one embodiment, optical coupling medium 112 is a wave-guide, i.e., an optical fiber. In other embodiments, optical coupling medium 112 may be a refractive element, such as tens or prism, or a reflective element such as a mirror.

[0044] Subsystem 118 preferably includes an IR detector in optical communication along an optical path with optical coupling medium 112. Subsystem 118 can measure the IR thermal radiation in one wavelength, two wavelengths or several wavelengths by using filters, a grating, an acousto-optical filter or any other optical element for filtering wavelength [see e.g., S. Sade and A. Katzir, “Spectral Emissivity and Temperature Measurements of Selective Bodies using Multi-band Fiber Optic Radiometry”, Journal of Applied Physics, 96, 3507 (2004)]. Subsystem 118 converts the IR radiation into an electrical, signal which is read by PC 114, which in turn uses it as an input to control lasers sources 104, 106 and 108.

[0045] FIG.1B shows schematically a second embodiment of a laser welding system 100′ of the present invention. In contrast with system 100, system 100′ uses two separate ports 122 and 124, one for conveying radiation to and the other for receiving radiation from tissue sample 102 Port 122 is used to convey the multiple laser radiation to tissue sample 102 and port 124 is used to convey the thermal radiation emitted from tissue sample 102 to IR detector subsystem 118. It is to be understood that in this embodiment, each port is used to convey a different type of radiation independently of the other port. Except for the separate ports, system 100′ includes the same elements as system 100.

[0046] The advantage of such systems 100 and 100′ is as follows. By using several lasers simultaneously, a user can achieve novel and better control over the heating of tissue sample 102. Such improved control is essential for welding and/or heating biological tissues. It is well known that for such tissue samples the absorption length, and therefore the heated region, is wavelength dependent and changes according to the tissue type and structure. In addition, the beams of the different wavelengths can be shaped and/or manipulated in different ways, for example, be focused to a different spot size.

[0047] FIG. 2 describes schematically the advantage of using several wavelengths lasers for welding over a single wavelength laser welding system. In the case of laser welding systems which use only one wavelength 202, heated region 204 which is created by laser λ₁ 206 is not uniform, i.e. a temperature gradient exist between the upper surface and the inner bulk of the tissue sample 102. In the case of laser welding systems which uses more than one wavelength 208 (in this example two wavelengths) and assuming that the penetration depth of laser λ₁ 204 is shorter than the penetration length of laser λ₂ 210, laser λ₁ 204 heats the upper surface and laser λ₂ 210 heats the inner bulk of the tissue sample 102. By simultaneously irradiating the tissue sample with two lasers 204 and 210 we obtain simultaneous heating of the upper surface of tissue sample 102 and the inner bulk of tissue sample 102. We thus achieve a better control of the heated region 212 and parameters such as the heated volume and the uniformity of the heated region 212 can be controlled in a better manner. It is to be understood that this example of using two lasers at two wavelengths is for the purpose of explanation only and that the principle described is the same for using several lasers each radiating at different wavelength.

Temperature Measurement Using the IR Radiometry Sub System 118

[0048] As mentioned, the temperature measurement of the tissue sample 102 is done by subsystem 118 i.e., by radiometric methods. Radiometric methods are based on collecting the infrared radiation emitted from a warm body in a certain spectral band Δλ and determining the temperature T of the body, using the formula I=∫_Λλε(λ)W_bbλ(λ,T)dλ, where I is the radiance, ε is the body emissivity, and W_bbλ is the Planck distribution function [see e.g., M Bass, Handbook of optics, McGraw-Hill, Inc. New-York, 1995, 2nd ed. Chapter 24]. IR radiometers basically consist of an optical part, which collects and delivers the emitted IR radiation from the measured body to an infrared detector. The detector converts the radiation to an electrical signal, which is then, amplified by an electronic circuits. An infrared transmitting fiber can be incorporated in the radiometric system, to collect and deliver the emitted radiation from the measured body to the detector.

[0049] The temperature measurement can be done by any of three methods according to the number of spectral bands in which the IR radiation is measured: (I) Single band method —the radiometer measures the radiation in a single spectral band. The assumption is that the emissivity of the measured body is close to 1 (i.e. blackbody). (II) Dual band method—these radiometers measure the radiation emitted in two different spectral bands. It is assumed that the emissivity is constant (i.e. gray body) in both spectral bands and that the background radiation is low relative to the temperature of the tissue sample. The temperature is calculated from the ratio of the signals obtained for the two bands. (III) Multi-band method [see e.g. S. Sade and A. Katzir, “Spectral Emissivity and Temperature Measurements of Selective Bodies using Multi-band Fiber Optic Radiometry”, Journal of Applied Physics, 96, 3507 (2004)]—these radiometers measure the IR radiation in at least three spectral bands.

[0050] The multi-bald method is based on measuring the emitted radiation from tissue sample 102 at different spectral bands in the mid and far infrared 2-30 μm using multi-band radiometer. Then by solving a set of equations, one can measure simultaneously and in real time the tissue sample temperature and emissivity and the background temperature. For N spectral bands we obtain a set of N equations with M=N+2 unknowns: N unknowns are the N emissivities in the N spectral bands, and two unknowns are the two temperatures T_sample and T_back. The set of equations can be written in a general form:
S(Δλ₁)=A₁×f(T_sample,ε₁^sample,T_back)+B₁(Δλ₁)
S(Δλ₂)=A₂×f(T_sample,ε₂^sample,T_back)+B₂(Δλ₂)
S(Δλ_N)=A_N×f(T_sample,ε_N^sample,T_back)+B_N(Δλ_N)   (1)
Experimentally A_i and B_i can be found via calibration measurements using a blackbody (or a body with a known emissivity). The value of the tissue sample emissivity, temperature and the background temperature is obtained simultaneously from the solution of equation set (1).

A Temperature Controlled Multi Wavelength Laser Welding and Heating System Utilizing CO₂ Gas Laser and a GaAs Diode Laser.

[0051] In this example we describe experiments and their results. The experiments were done using an experimental two port temperature controlled multi wavelength laser welding and heating system, such as system 100′.

[0052] FIG. 3 illustrates an experimental system 300 that uses a C0₂ gas laser source 302 and a GaAs diode laser source 304. The two laser sources were used to irradiate simultaneously a biological tissue sample 306. CO₂ laser 302 emitted radiation at a wavelength of 10.6 micron, and was coupled to a silver halide infrared transmitting optical fiber 308. The GaAs laser diode 304 emitted radiation at a wavelength of 0.83 micron, and was coupled to a silica fiber 310. The thermal radiation 312 emitted from the heated tissue sample 306 was collected by a silver halide optical fiber 314 and delivered to an IR radiometer 316. The signal from radiometer 316 is read by a PC 318, which uses it to control the power of the two lasers sources.

[0053] The Optical Penetration Depth, O.P.D., in water is approximately 11 microns for the CO₂ laser and approximately 1 meter for the GaAs diode laser. The O.P.D. of the GaAs laser can be controlled by using indocyanine green at different concentrations. Therefore by simultaneously using both lasers and an adequate concentration of the indocyanine green a versatile light source was formed.

[0054] Radiometer 316 was calibrated and used to measure the surface temperature of the tissue sample 306, and a proportional control algorithm [see e.g., O. Eyal, A. Katzir, “Thermal feedback control technique for transistor—transistor logic triggered CO₂ laser used for irradiation of biological tissue utilizing infrared fiber optic radiometry ,” Applied Optics, Vol.33, No.9, 1994] used in the personal computer 318 were used to control the lasers. Radiometer 316 is based on a pyroelectric detector and has an internal chopper. The chopper and a synchronized electric circuit were used to solve the problem of blinding of the detector by the CO₂ laser light reflected from the tissue sample. The tissue sample is irradiated by a train of laser pulses synchronized to the time intervals when the detector is blocked by the chopper, whose position is detected by an optical gate. This synchronization, shown in FIG. 4, ensures that only thermal radiation can reach the detector, whereas the CO₂ laser radiation reflected from the sample is blocked and cannot interfere with the measured signal. The chopper frequency was adjusted to 8 Hz, and therefore this was also the irradiation frequency of the tissue. The average powers of the CO₂ and GaAs lasers were adjusted to 0.31 Watt and 1.3 Watt, respectively.

[0055] All three optical fibers were held by a mechanical holder 320 3 mm above the tissue sample and were directed to the same point. The diameter of the irradiated spot 322 was approximately 3 mm, for both laser wavelengths, The length of the silver halide fibers 308 and 314 was 1.5 meter, and it had diameter of 0.9 mm, while the length of the silica fiber 310 was 2 meter and it had diameter of 0.6 mm.

Experimental Results

[0056] The experimental results are described in FIG. 5. The tissue sample 306 was dyed with indocyanine green at concentration of approximately 1 mg/ml. It was first irradiated just by the GaAs laser 304 and its temperature was elevated from a room temperature of 30° C. and stabilized to a target temperature of 60±1° C. While GaAs laser 304 was still working, CO₂ laser 302 was set to ON and the tissue temperature was stabilized to a target temperature of 62±1° C. The CO₂ radiation was then stopped and the temperature was stabilized back to the target temperature of 60±1° C. Finally, GaAs laser 304 was stopped and tissue 306 cooled down to its initial room temperature. The temperature profile of the tissue is affected by changes that occur in the tissue structure during the irradiation procedure, and can be better controlled by choosing the right form and parameters for the control algorithm.

[0057] In summary, the present invention discloses a novel system and method for welding, soldering and heating of samples, in particular tissue samples, in which the temperature of the tissue is being measured and monitored using IR radiometry for providing respective inputs for a closed loop control of a plurality of light sources, which in turn irradiate simultaneously the tissue sample. Each light source has a different wavelength, which means that the tissue sample is being irradiated simultaneously by radiation of several wavelengths, giving rise to better control of the heated region and volume making the welding, soldering and heating processes more efficient. Moreover, the temperature measurement can be done in several wavelengths, which makes the temperature measurement more accurate.

[0058] All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.

[0059] While the invention has been described with respect to a limited number of embodiments, it will be appreciated that many variations, modifications and other applications of the invention may be made.