Abstract:
Generally described herein are apparatus, systems and methods related to a mechanical interlock joint geometry for various components and joining of components thereby creating a reliable seal against fluid leaks that is resistant at typical pressures experienced when the components are implanted into a human body. Furthermore, the seal may be enhanced when a fluid pressure exerted inside the components is increased (e.g., from 1 to 10 psi).

Description:
FIELD 
       [0001]    The present invention generally relates to medical systems, devices and uses thereof for treating obesity and/or obesity-related diseases. More specifically, the present invention relates to a mechanical interlock joint geometry for connecting two components. 
       BACKGROUND 
       [0002]    Adjustable gastric banding apparatus have provided an effective and substantially less invasive alternative to gastric bypass surgery and other conventional surgical weight loss procedures. Despite the positive outcomes of invasive weight loss procedures, such as gastric bypass surgery, it has been recognized that sustained weight loss can be achieved through a laparoscopically-placed gastric band, for example, the LAP-BAND® (Allergan, Inc., Irvine, Calif.) gastric band or the LAP-BAND APO (Allergan, Inc., Irvine, Calif.) gastric band. Generally, gastric bands are placed about the cardia, or upper portion, of a patient&#39;s stomach forming a stoma that restricts the food&#39;s passage into a lower portion of the stomach. When the stoma is of an appropriate size that is restricted by a gastric band, food held in the upper portion of the stomach may provide a feeling of satiety or fullness that discourages overeating. Unlike gastric bypass procedures, gastric band apparatus are reversible and require no permanent modification to the gastrointestinal tract. An example of a gastric banding system is disclosed in Roslin, et al., U.S. Patent Pub. No. 2006/0235448, the entire disclosure of which is incorporated herein by this specific reference. 
         [0003]    These gastric banding systems may include components such as a gastric band, an access port, fluid reservoirs and tubing to connect the various aforementioned components. Typically, these implantable components can contain or carry fluid at pressures up to about 12 psi, and are constructed out of special grades of silicone rubber for biocompatibility reasons. Metal or plastic barbed connectors are used to connect these implantable components to one another or to the tubing. These barbed connectors function well with rubber parts of higher durometer (e.g., 70 Shore A durometer or higher) but suffer from a low “pull-out” force resulting in slippage and separation of the rubber part from the barbed connected for lower durometer rubber components. This connection issue has traditionally been addressed by a number of techniques such as using an adhesive to secure the joint, overmolding the rubber on top of the hard connector to create a stronger rubber-to-connector bond, using a screw geometry or a barbed connector against the high durometer rubber, or compression fitting. 
         [0004]    However such approaches have various drawbacks. For example, using an adhesive is undesirable due to the difficulties in controlling the amount delivered and the degree of cure for proper strength. Moreover, the adhesive might not be biocompatible. 
         [0005]    Employing overmolding is also problematic as it is expensive and requires a metal insert which may agitate the surrounding internal organs of the patient. 
         [0006]    Adding a screw geometry increases the cost of the system and fails to guarantee a fluid-tight seal under pressure. In addition, the rubber requires higher durometer materials due to the required structural rigidity. 
         [0007]    Using a barbed connector also adds cost and complexity, in addition to the above-discussed agitation possibility of internal organs due to the rigidity of the materials. Furthermore, the barbed connector may still be limited for use with only high durometer rubbers since the rubber-connector contact might not generate enough resistance against a pull-out force when using a softer rubber. Fatigue-stresses at the rubber-connector junction would also remain an issue under this approach. 
         [0008]    Compression fittings are bulky, expensive and hard to attach during a laproscopic surgical procedure. 
         [0009]    Fusco, U.S. Patent Pub. No. 2009/0220176, discloses an application for filling polyethylene bags for the food industry, which is tangentially related in that it is also geared towards sealing. However, the system of Fusco as illustrated in  FIG. 1  does not appear usable in a human body. Furthermore, the system of Fusco is structurally and functionally different than the present invention. 
         [0010]    As a result, none of these options are particularly attractive in effectively connecting two rubber components. 
         [0011]    Accordingly, what is needed is a connection technique that creates a reliable seal against fluid leaks at typical pressures appropriate for implantation into a human body. 
       SUMMARY 
       [0012]    Generally described herein are apparatus, systems and methods related to a mechanical interlock joint geometry for various components and joining of components thereby creating a reliable seal against fluid leaks resistant at typical pressures experienced when the components are implanted into a human body. Furthermore, the seal may be enhanced when a pressure is increased (e.g., from 1 to 10 psi). In other words, fluid pressure may even increase the seal contact pressure. 
         [0013]    In one embodiment, provided is a gastric banding system for the treatment of obesity. The gastric banding system includes a gastric band having an inflatable portion and a ring, a first tube having a first end and a second end, the first end of the first tube connected to the inflatable portion, a fluid reservoir including two halves and a first interlock, the first half having a first ball and a first flange, and the second half defining a first ball receiving cavity for receiving the first ball, and further defining a first flange receiving cavity for receiving the first flange, wherein the two halves of the fluid reservoir form the first interlock when the first ball receiving cavity receives the first ball, and when the first flange receiving cavity receives the first flange, the fluid reservoir further having a first end and a second end, the first end of the fluid reservoir connected to the second end of the first tube, a second tube having a first end and a second end, the first end of the second tube connected to the second end of the fluid reservoir, and an access port connected to the second end of the second tube. 
         [0014]    In one embodiment, provided is a fluid reservoir for carrying fluid within a gastric banding system for the treatment of obesity. The gastric banding system includes a first half of the fluid reservoir and a second half of the fluid reservoir. The first half of the fluid reservoir may include a first connector for fluidly connecting the fluid reservoir to an inflatable portion of a gastric band, a first housing coupled to the connector, the first housing defining a first sub-reservoir, the first housing tapering to a first flat joining surface, a ball and flange coupled to the first flat joining surface, the ball and flange defining a second sub-reservoir. The second half of the fluid reservoir may include a second connector for fluidly connecting the fluid reservoir to an access port, a second housing coupled to the second connector, the second housing defining a third sub-reservoir, the second housing tapering to a second flat joining surface, the second housing further defining a ball receiving cavity for receiving the ball and a flange receiving cavity for receiving the flange to interlock the first half of the fluid reservoir with the second half of the fluid reservoir. 
         [0015]    In one embodiment, provided is a tube-to-tube apparatus for establishing a fluid path between a first tube and a second tube to allow the tubes to carry fluid within a gastric banding system for the treatment of obesity. The apparatus includes a first sleeve and a second sleeve. The first sleeve may include a first end overmolding the first tube, an intermediate portion coupled to the first end, the intermediate portion defining a first sub-reservoir and having a first flat joining surface, a second end having a ball and flange, the second end protruding from the first flat joining surface and defining a second sub-reservoir fluidly coupled to the first sub-reservoir. The second sleeve may be interlocked to the first sleeve and may include a first end of the second sleeve overmolding the second tube, an intermediate portion coupled to the first end of the second sleeve, the intermediate portion defining a third sub-reservoir and having a second flat joining surface, and a second end of the second sleeve defining a ball receiving cavity for receiving the ball and a flange receiving cavity for receiving the flange to interlock the first sleeve with the second sleeve. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0016]    The features, obstacles, and advantages of the present invention will become more apparent from the detailed description set forth below when taken in conjunction with the drawings, wherein: 
           [0017]      FIG. 1  illustrates a prior art self-sealing container. 
           [0018]      FIG. 2  illustrates a gastric banding system including various components according to an embodiment of the present invention. 
           [0019]      FIG. 3A  illustrates a fluid reservoir according to an embodiment of the present invention. 
           [0020]      FIG. 3B  illustrates a cross-sectional view of the fluid reservoir of  FIG. 3A  according to an embodiment of the present invention. 
           [0021]      FIG. 3C  illustrates a finite element analysis model of the fluid reservoir of  FIG. 3A  according to an embodiment of the present invention. 
           [0022]      FIG. 3D  illustrates the structure of a first half of the fluid reservoir of  FIG. 3A  according to an embodiment of the present invention. 
           [0023]      FIG. 3E  illustrates the structure of a second half of the fluid reservoir of  FIG. 3A  according to an embodiment of the present invention. 
           [0024]      FIG. 4A  illustrates a tubing according to an embodiment of the present invention. 
           [0025]      FIG. 4B  illustrates a cross-sectional view of the tubing of  FIG. 4A  according to an embodiment of the present invention. 
           [0026]      FIG. 4C  illustrates a close-up view of a portion of the tubing of  FIG. 4A  according to an embodiment of the present invention. 
           [0027]      FIG. 5A  illustrates a fluid reservoir connected to tubing on both ends according to an embodiment of the present invention. 
           [0028]      FIG. 5B  illustrates a cross-sectional view of the fluid reservoir-tubing system of  FIG. 5A  according to an embodiment of the present invention. 
           [0029]      FIG. 5C  illustrates a close-up view of a portion of the reservoir-tubing system of  FIG. 5A  according to an embodiment of the present invention. 
           [0030]      FIG. 6  illustrates a fluid reservoir having a trapezoidal-shaped element according to an embodiment of the present invention. 
           [0031]      FIG. 7  illustrates a fluid reservoir having a triangular-shaped element according to an embodiment of the present invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0032]    Apparatuses, systems and/or methods that implement the embodiments of the various features of the present invention will now be described with reference to the drawings. The drawings and the associated descriptions are provided to illustrate some embodiments of the present invention and not to limit the scope of the present invention. Throughout the drawings, reference numbers are re-used to indicate correspondence between referenced elements. 
         [0033]    While described generally herein with components of a gastric banding system, one of ordinary skill in the art will understand that the concepts are applicable to any scenario where sealing against leaks may be advantageous and is not meant to be limited to the scope of gastric banding systems. 
         [0034]    The present invention generally provides mechanical interlock joint geometry for creating a reliable seal against fluid leaks at a range of pressures. Furthermore, the seal may be enhanced when a pressure is increased (e.g., from 1 to 10 psi). That is, fluid pressure may increase the seal contact pressure. 
         [0035]    One embodiment of the components of the gastric banding system  200  is illustrated in  FIG. 2  and comprises a gastric band  205  coupled to a subcutaneous injection port  235  via a first tubing  202 , a reservoir  203  and a second tubing  204 . The gastric band  205  comprises a circular ring  207  and an inflatable portion  210  disposed on the inside of the ring  207 . The inflatable portion  210  separates the patient&#39;s stomach from the ring  207  when the gastric band  205  is implanted around the esophageal-gastric junction of the patient&#39;s stomach. The ring  207  provides structure and support to the inflatable portion  210 , and facilitates implanting the gastric band  205  around the patient&#39;s stomach. 
         [0036]    The access port  235  may be sutured onto the rectus muscle sheath or any other conveniently accessible muscle. The rectus muscle sheath provides a secure surface on which to attach the access port  235  under a layer of fat that separates the patient&#39;s skin from the muscle. 
         [0037]    The inflatable portion  210  may be filled and drained with a fluid via the reservoir  203 . For example, the second tubing  204  may be connected to the subcutaneous access port  235  for filling and draining the inflatable portion  210  via subcutaneous injections. When more fluid is introduced in the inflatable portion  210 , the constriction around the stomach generally becomes tighter. Correspondingly, when less fluid is present, the constriction loosens and/or opens up. 
         [0038]    The fluids used within the gastric band  205  may include any fluid that is biocompatible and incompressible. The fluid has no adverse effect on the patient in the unlikely event that a leak emanates from the system. The fluid can simply be water or any biocompatible polymer oil such as caster oil. In an example embodiment, the fluid is saline, a drug, and/or combinations thereof. 
         [0039]    Certain components (e.g., the first tubing  202 , the reservoir  203  and the second tubing  204 , etc.), including their structure and the joining to adjacent components thereof will now be described. 
         [0040]      FIG. 3A  illustrates a fluid reservoir  303 , which may be the reservoir  203  of  FIG. 2 , with other components of the gastric banding system removed for clarity. While described with respect to the gastric banding system, the assembly of the fluid reservoir  303  may be used in any implantable apparatus including obesity-controlling products. Here, the fluid reservoir  303  may include two halves, a male half  310  and a female half  315 . The two halves  310  and  315  may be molded separately and then pushed or pressed together to create the fluid-tight fluid reservoir  303 . No adhesive, external rings, clamps or other devices are necessary. In this example, the two halves  310  and  315  may be constructed out of silicone rubber of Shore A durometer of  50  or greater and may be molded over a pair of standard metal connectors  320  and  325 , as the fluid reservoir  303  can be connected to an extruded tube. The metal connectors  320  and  325  may serve as an interface for transferring fluid into and out of the fluid reservoir  303 . 
         [0041]      FIG. 3B  illustrates a cross-sectional view of the fluid reservoir  303  of  FIG. 3A . Here, the two halves  310  and  315  of the fluid reservoir  303  are illustrated to be interlocked via a ball  350  and a flange  355 . That is, when the ball  350  and the flange  355  of the male half  310  are inserted and/or pushed into a ball receiving cavity  360  and a flange receiving cavity  365  of the female half  315 , respectively, the flat, circumferential joining surface  376  and  375  of the male half  310  and the female half  315 , respectively, are brought into contact to create the sealed fluid reservoir  303 . 
         [0042]    While the two halves  310  and  315  are utilized, the fluid reservoir  303  may actually be considered to comprise three sub-reservoirs joined together and in fluid communication. As previously described, the male half  310  of the fluid reservoir  303  defines both the first sub-reservoir  304  and the second sub-reservoir  305 , which in turns leads into the third sub-reservoir  306  defined by the female half  315 . The second sub-reservoir  305  may be proximal to the mating features which interlock to join the male half  310  and the female half  315 . In one embodiment, the second sub-reservoir  305  is formed in the shape of an hour-glass. 
         [0043]    When assembled as shown in  FIG. 3B , pressure introduced by the carrying of fluid within the first, second and third sub-reservoirs  304 ,  305  and  306  promotes the sealing capabilities of the fluid reservoir  303  as a whole. More particularly, as shown in  FIG. 3C , three seals or sealing surfaces  380 ,  385  and  390  are enhanced or provided when the reservoir  303  is filled with fluid. 
         [0044]    The first seal  380 , which occurs between the flange  355  and the flange receiving cavity  365  is enhanced by forces illustrated by arrows  363 ,  368  and  369 . More particularly, the fluid inside the third sub-reservoir  306  causes the force as shown by the arrow  363  to press the flange  355  against a wall of the flange receiving cavity  365  in the direction of arrow  363 . In other words, by employing a flap-shaped geometry with respect to the flange  355 , and having fluid only on one side of the flange  355 , the seal is enhanced. Additionally, fluid inside the first sub-reservoir  304  causes forces in the direction of arrows  369  to further press the flange  355  against the wall of the flange receiving cavity  365 . Furthermore, the forces illustrated by arrows  368  pulls the wall of the flange receiving cavity  365  even more tightly into the flange  355 . In this manner, in addition to initial interference, the seal  380  is greatly enhanced when the reservoir  303  is filled with fluid (which is precisely when the seal  380  is needed to be enhanced to prevent leakage). 
         [0045]    The second seal  385  is caused initially by the interference between the ball  350  and the ball receiving cavity  360 . However, the second seal  385  is enhanced when fluid is present in the second sub-reservoir  305 . The fluid in the second sub-reservoir  305  causes an upward pressure shown by arrow  361  pressing the ball  350  further into the ball receiving cavity  360 . Noticeably, relatively-speaking, the ball receiving cavity  360  displaces less than the ball  350  because fluid in the third sub-reservoir  306  actually causes a slight bulge in the direction of  359  since the wall of the female half  315  is thinner at the location of arrows  359 . In this manner, the fluid within the second and third sub-reservoirs  305  and  306  enhance the seal between the ball  350  and the ball receiving cavity  360 . 
         [0046]    The third seal  390  is caused, in one embodiment, by opposing forces in directions shown by arrows  368  and  369 . In other words, the pressure that tries to pull the male half  310  and the female half  315  of the reservoir  303  apart actually generates a better fluid seal at the joint created by the ball  350  and the ball receiving cavity  360 . Moreover, the force illustrated by arrow  363  exerts and further press the ball  350  into the contacting wall portions of the ball receiving cavity  360 . In addition, the ball  350  creates a wedge effect, which only further assists the sealing process. 
         [0047]    The semi-sphere shaped ball  350  may provide the advantage of easier assembly. However, other shapes are possible, which may provide other advantages. For example, as shown in  FIGS. 6 and 7 , configurations such as trapezoid and/or a triangle are illustrated. 
         [0048]    The configuration of  FIG. 6  illustrates a fluid reservoir  600  having a trapezoid-shaped engaging element  610  in place of the ball-shaped engaging element (e.g., ball  350  of  FIG. 3 ). The trapezoid-shaped engaging element  610  may be formed to include angles  605  in the range of between 92-135 degrees. By having an angle closer to about 92 degrees, the mechanical advantage provided by the wedge effect may be maximized. 
         [0049]    The configuration of  FIG. 7  illustrates a fluid reservoir  700  of yet another shape. Here, the fluid reservoir  700  has a triangular-shaped engaging element  710  in place of the ball-shaped engaging element (e.g., ball  350  of  FIG. 3 ). Similar to the trapezoidal-shaped engaging element  610  of  FIG. 6 , the triangular-shaped engaging element  710  may be formed to include angles  705  in the range of between 92-135 degrees to improve the mechanical advantage and hence, the seal. 
         [0050]    Referring back to the fluid reservoir  303 ,  FIGS. 3D and 3E  illustrate the male half  310  and the female half  315  of the reservoir  303  separated for clarity. As shown in  FIG. 3D , the male half  310  may be molded and may include a “bottle-shaped” housing portion defining the first sub-reservoir  304  outwardly tapering to a flat, circumferential joining surface  370  which is integrated, on the other side, to the ball  350  and flange  355  which not only serves as mating members but defines on its interiors the second sub-reservoir  305 . This male half  310  may be molded out of silicone rubber and may stretch to allow the core of the mold to be pulled out from the larger hole on the connection side. 
         [0051]    The female half  315  of the reservoir  303  illustrated in  FIG. 3E  may include a similar “bottle-shaped” portion defining the third sub-reservoir  306  outwardly tapering to a flat circumferential joining surface  375 , which is of equal diameter to the circumferential joining surface  370  of the male half  310 . The female half  315  may include the female mating members including the ball receiving cavity  360  and the flange receiving cavity  365  hidden from view, and may also be constructed out of silicone rubber or other appropriate materials and may be molded despite undercut features. 
         [0052]    While the above-described mating technique to create an enhanced seal has been discussed thus far in relationship with a fluid reservoir, such embodiments are mere examples and the applicability of the concepts may be applied to other devices or apparatuses including other portions of the gastric banding system. 
         [0053]    For instance, the interlocking geometry may be used to connect two extruded silicone tubes to avoid the usage of barbed or compression fitting. 
         [0054]      FIG. 4A  illustrates how a tube  401  may be connected to another tube  402  using an over-molded sleeve  410 . The extruded tubes  401  and  402  can be as long as desired, but are shown truncated in  FIG. 4A  for clarity. The tube  401 , for example, may be connected to an inflatable portion of a gastric band while the tube  402  may be a connecting tube of a reservoir or an access port. More particularly, the tubes  401  and  402  may be extruded and might not itself incorporate the interlocking geometry. Instead, as shown in the cross-sectional view of  FIG. 4B , the tubes  401  and  402  may be connected to the sleeve  410 , which may comprise a male sleeve  411  and a female sleeve  412 , which are interlocked together via similar geometry as discussed above with respect to the fluid reservoir of  FIG. 3 . Since the sleeve is overmolded on the tubes  401  and  402 , adhesives are not required to attach the tubes  401  and  402  to their respective ends of the sleeve  410 . 
         [0055]    As far as the interlocking geometry is concerned, the proportions may be smaller in the sleeve  410  as compared to the fluid reservoir  303  of  FIG. 3 , but similarly, three sub-reservoirs are established to create the forces that enhance the sealing ability at the interlock. 
         [0056]      FIG. 4C  illustrates a close-up view of the connection between the extruded tube  401  and the male sleeve  411 . The male sleeve  411  may be a single structural component and hollowed out and overmolded on the tube  401  at one end defining the first sub-reservoir  403  and the second sub-reservoir  404 . The first sub-reservoir  403  may lead directly into an opening of the tube  401 . Depending on the size of the first sub-reservoir  403  desired, the portion of the tube  401  that is overmolded by the male sleeve  411  may be configured. In addition, the length of the tube  401  that is overmolded may also impact lateral flexibility, such that more flexibility may be achieved where the overmolded area is minimized. 
         [0057]    While not shown, in a similar manner, the female sleeve  412  may also be a single structural component and hollowed out and overmolded on the tube  402  at one end defining the third sub-reservoir  405 . The third sub-reservoir  405  may lead directly into an opening of the tube  402 . Similarly, depending on the size of the third sub-reservoir  405  desired, the portion of the tube  402  that is overmolded by the female sleeve  412  may be configured, which in turn may also impact lateral flexibility. 
         [0058]    Alternatively, or in addition, a tube-to-tube connection may be made without the over-molded sleeves. For example, a first tube may be molded to have the male features (e.g., ball and flange) while a second tube may be molded to have the female features (e.g., ball receiving cavity and the flange receiving cavity). By pressing the male features of the first tube into the female features of the second tube, the two tubes may be joined very similar to the manner described above with respect to fluid reservoir  303 . 
         [0059]      FIG. 5A  illustrates how the concepts of the self-locking and self-sealing mechanical interlocks as applied to a reservoir and the tubing may be applied in combination to eliminate the need for metal or plastic connectors. As shown, three distinct interlocks  510 ,  515  and  520  may be employed to connect a reservoir  503  with a pair of tubes  504  and  505  (one on each side of the reservoir  503 ) to create a self-sealing, self-locking fluid path able to transfer fluid from one end  506  of the first tubing  504  to a distal end  507  of the second tubing  505 . In one embodiment, the end  506  may lead to an inflatable portion of the gastric band, while the other end  507  may lead to an access port. Or, where the reservoir  503  is only attached to the access port, the reservoir  503  may be attached to the tubing on one end (e.g., end  506 ) while closed at the other end. 
         [0060]      FIG. 5B  is a cross-sectional view of the system of  FIG. 5A  illustrating the three interlocked joints  510 ,  515  and  520  functioning in unison to create the self-sealing, self-locking fluid path able to transfer fluid from one end  506  of the first tubing  504  to a distal end  507  of the second tubing  505 . Also shown in this view is how the sleeves  521  and  522  may be overmolded on not only the tube portions  531  and  532 , respectively, but also over the end portions  533  and  534  of the reservoir  503 . 
         [0061]    As an example,  FIG. 5C  illustrates a close-up view of the portion of the sleeve  522  overmolded on the end portion  534  of the reservoir  503 , thus eliminating the need for a connector or an adhesive. 
         [0062]    It should be appreciated that the over-molding and/or the geometrical joint interlocks can be applied to a number of different components not explicitly described herein. Moreover, the geometrical shapes and the number of interlocks utilized to joint together a component or to join one component with another component may also be altered while still being within the spirit and scope of the invention. 
         [0063]    Unless otherwise indicated, all numbers expressing quantities of ingredients, volumes of fluids, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. 
         [0064]    The terms “a,” “an,” “the” and similar referents used in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention. 
         [0065]    Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member may be referred to and claimed individually or in any combination with other members of the group or other elements found herein. It is anticipated that one or more members of a group may be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims. 
         [0066]    Certain embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Of course, variations on these described embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventor expects skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context. 
         [0067]    Furthermore, certain references have been made to patents and printed publications throughout this specification. Each of the above-cited references and printed publications are individually incorporated herein by reference in their entirety. 
         [0068]    Specific embodiments disclosed herein may be further limited in the claims using consisting of or and consisting essentially of language. When used in the claims, whether as filed or added per amendment, the transition term “consisting of” excludes any element, step, or ingredient not specified in the claims. The transition term “consisting essentially of” limits the scope of a claim to the specified materials or steps and those that do not materially affect the basic and novel characteristic(s). Embodiments of the invention so claimed are inherently or expressly described and enabled herein. 
         [0069]    In closing, it is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the present invention. Other modifications that may be employed are within the scope of the invention. Thus, by way of example, but not of limitation, alternative configurations of the present invention may be utilized in accordance with the teachings herein. Accordingly, the present invention is not limited to that precisely as shown and described.