Patent Publication Number: US-2019167915-A1

Title: Topical cooling device

Description:
This application claims priority under 35 U.S.C. § 119(e) to U.S. provisional application Ser. No. 62/595,195, filed on Dec. 6, 2017, which is hereby incorporated by reference in its entirety. 
    
    
     FIELD OF THE INVENTION 
     The present invention is directed to a device for cooling, desensitizing, and/or numbing the surface of the skin. A device is disclosed for desensitizing, cooling, and/or numbing a target area of the skin prior to an injection by a medical device such as a needle or cannula. 
     BACKGROUND 
     Insulin and other injectable medications are commonly delivered by drug delivery pens, whereby a disposable pen needle hub is attached to the pen to facilitate drug container access and allow fluid to pass from the container through the needle into the patient. 
     The use of pen needles and other delivery devices, such as syringes, that include a needle or cannula can cause pain and discomfort to the patient. Various methods have been proposed to reduce the pain and discomfort to the user, such as by contacting the injection target site with ice or a cold object. While these methods can provide some relief, there is a need for improved devices and methods for reducing the pain and discomfort to the skin of the patient during an injection by a needle or cannula. 
     Various pen needle delivery devices are known in the art for dispensing the substance to the patient. The delivery devices often use a disposable needle hub having a cannula or needle extending from a patient end of the hub for inserting into the patient. A non-patient end of the hub is coupled to the pen delivery device for delivering the substance to the patient. 
     The needle hub assembly is often packaged in a container containing several loose needle hubs. A needle hub is selected from the package and attached to the pen needle delivery device for injecting the patient and then removed to be discarded. The needle hub package includes an outer cover that encloses the needle hub and a removable seal that is peeled from the outer cover to open the cavity so that the needle hub can be removed. The needle hub can have threaded non-patient end that is threaded onto the delivery device. The delivery device with the attached needle hub is then removed from the outer cover. An inner needle shield is attached to the needle hub to cover the cannula until the device is ready for use. The shield is removed to expose the cannula for use to deliver the substance to the patient. After use, the needle hub can be inserted back into the outer cover to enclose the exposed cannula. The pen delivery device is separated from the needle hub leaving the needle hub within the outer cover. 
     Existing pen needle assemblies are disclosed in U.S. Patent Application Publication Nos. 2006/0229562 to Marsh et al. and 2007/0149924 to R. Marsh, the entire contents of both of which are hereby incorporated by reference. 
     Although the prior devices have been suitable for the intended use, there is a continuing need in the industry for improved devices for use a pen needle and delivery devices. 
     SUMMARY 
     A cooling device is provided for contacting and cooling the surface of the skin to provide a desensitizing and numbing effect on the surface of the skin prior to injection or penetration of the skin by a delivery device. The cooling device is able to cool the surface of the skin to a sufficiently low temperature to provide a desensitizing and numbing effect prior to penetration by a medical device, such as a needle or cannula to reduce the pain and/or discomfort associated with the insertion of a needle or cannula. The cooling device is configured to contact and conform to the surface of the skin and cool a delivery target area on the skin where the target area is pierced by a needle, cannula or other medical device. The cooling device reduces the temperature of the skin in the target area to numb or desensitize the target area without freezing or damaging the skin in the target area. 
     The cooling device can be included with a kit, package, or assembly that includes an injection delivery device, such as a pen needle, infusion pump, or other injection apparatus that includes a cannula or needle. The cooling device has a contact area with a size and dimension for providing a desensitizing and numbing effect on the target area of the surface of the skin of the patient to reduce the discomfort associated with the penetration of the needle or cannula. 
     The cooling device in one embodiment includes an internal cavity containing a refrigerant medium, cooling material, or cooling composition, such as a refrigerant gel, that can be cooled or frozen prior to use and can be stored in a cool or frozen state for an extended period of time. The device has at least one contact surface that can be positioned against and directly contacting the target area of the skin of the patient to desensitize and cool the surface of the skin and provide the desensitizing, cooling, and numbing effect. 
     The refrigerant medium can cool the surface of the skin to a temperature of 0-15° C. and typically about 2-10° C. The cooling device cools the target area of the skin to a temperature to provide a numbing effect that does not cause injury or extreme discomfort to the skin. 
     In one embodiment, the cooling device includes a container having an open end and an internal cavity and a thermally transmitting member forming a closure for closing the open end of the container. A refrigerant medium, cooling liquid or cooling composition is contained in the cavity of the container and in contact with an inner surface of the closure. The thermally transmitting member is made of a heat transmitting or thermally conducting material that enables the refrigerant medium to cool the skin that contacts the thermally transmitting member to a temperature of about 2° C. to 10° C. Refrigerant medium in one embodiment is in direct contact with an inner surface of the heat transmitting material. 
     The cooling device in one embodiment is sufficiently small to be stored in the pocket or package of the injection device. In one embodiment, the cooling device has a generally cylindrical shape with a length of about 2-3 inches and diameter of about 0.5 to 1 inch. The thermally transmitting member has a sink contact area with a diameter of about 0.5 to 1 inch. 
     The container of the cooling device can be made of a thermally insulating material and constructed to maintain the refrigerant medium in a frozen, cooled, or chilled state for an extended period of time. The container can be made of thermally insulating plastic material or metal that can include at least one thermally insulating layer made of an insulating material. The insulating material can be closed cell foam or open cell foam, such as a polyurethane or polystyrene. 
     In one embodiment, the container has an inner wall and an outer wall defining a cavity between the inner and outer walls. An insulating material, such as polymer foam, can be injected and/or molded between the inner and outer walls to provide the insulating properties of the container. In other embodiments, the cavity between the inner and outer walls can be filled with an insulating gas or air. In further embodiments, the cavity between the inner and outer walls can under a vacuum or reduced pressure to reduce the heat transmission between the inner and outer walls. The surface of the inner wall and the outer wall can include a heat reflective surface, film, or coating to inhibit the transmission of radiant heat into or out of the container. 
     In another embodiment, the cooling device includes a thermally insulating container with an open end and an internal cavity. A closure for the container can be a bulb-like member forming a bladder containing a refrigerant medium within the cavity of the container where a portion of the bladder is accessible through the open end of the container. The refrigerant medium or cooling composition in one embodiment can be a refrigerant liquid such as a hypertonic aqueous solution that can be frozen and provide a cooling effect for an extended period of time. The bladder can be made of a flexible polymer that is able to contain the refrigerant medium for repeated freezing and thawing cycles. The bladder can have a thickness sufficient to contain the refrigerant medium and provide sufficient heat transmission to cool the skin of a patient on contact with the surface of the bladder. The bladder can be made of a polymer, such as polyurethane, that can remain flexible at temperatures below 10° C. and typically below 0° C. 
     The refrigerant medium can be a suitable liquid or gel that can be frozen and reused to provide a cooling, freezing, and desensitizing effect when contacting the skin to reduce the pain and discomfort during an injection. The refrigerant medium can be a gel or liquid. The refrigerant medium can be an aqueous mixture of propylene glycol, hydroxyethylcellulose, sodium polyacrylate, silica gel and the like. In other embodiments, the refrigerant medium can be an aqueous solution of sodium chloride and/or calcium chloride. 
     The bladder in one embodiment is received within the cavity of the thermally insulated container with an end portion projecting from the open end of the container a distance for contacting the skin of the patient during use. An insulating lid can be coupled to the open end of the container. The bladder can occupy substantially the entire internal volume of the container. In one embodiment, an air gap can be provided in a portion of the cavity of the container to accommodate for expansion during freezing of the refrigerant medium, 
     In another embodiment, the container includes a side wall, a bottom wall, an open top end, and closure member coupled to the container to close the open top end of the container. The container encloses a refrigerant medium that can be frozen and stored in a frozen state for an extended period of time. The closure member can be a flexible polymer that is able to cool the skin when the closure contacts the skin of the patient. 
     The objects, advantages, and salient features of the invention will become apparent from the following detailed description, which, taken in conjunction with the annexed drawings, discloses exemplary embodiments of the invention. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The above benefits and other advantages of the various embodiments of the present invention will be more apparent from the following detailed description of exemplary embodiments of the present invention and from the accompanying figures, in which: 
         FIG. 1  is a side view of a container and lid in one embodiment; 
         FIG. 2  is a side view of  FIG. 1  showing the lid separated from the container; 
         FIG. 3  is a cross-sectional view of the container of  FIG. 1 ; 
         FIG. 4  is a cross-sectional view of the container in another embodiment; 
         FIG. 5  is a cross-sectional view of the container and lid in a further embodiment showing the insulating space between an inner and outer wall of the container; 
         FIG. 6  is a cross-sectional view of the container in another embodiment; 
         FIG. 7  is a cross-sectional view of the container in a further embodiment; 
         FIG. 8  is cross-sectional view of the container in another embodiment; 
         FIG. 9  is a cross-sectional view of the container in a further embodiment; and 
         FIG. 10  is a cross-sectional view of the container of  FIG. 9  showing the bladder in the extended position. 
     
    
    
     Throughout the drawings, like reference numbers will be understood to refer to like parts, components, and structures. 
     DETAILED DESCRIPTION OF THE EXEMPLARY EMBODIMENTS 
     Reference to embodiments of the present invention are illustrated in the accompanying drawings, wherein like reference numerals refer to like elements throughout. The embodiments described herein exemplify, but do not limit, the present invention by referring to the drawings. The exemplary embodiments are presented in separate descriptions, although the individual features and construction of these embodiments can be combined in any number of ways to meet the therapeutic needs of the user. The embodiments and/or elements can be combined with one another to form various additional embodiments not specifically disclosed, as long as the embodiments do not contradict one another. 
     It will be understood by one skilled in the art that this disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The embodiments herein are capable of of being modified, practiced or carried out in various ways. It will be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Unless limited otherwise, the terms “connected,” “coupled,” and “mounted,” and variations thereof herein are used broadly and encompass direct and indirect connections, couplings, and mountings. In addition, the terms “connected” and “coupled” and variations thereof are not limited to physical or mechanical connections or couplings. Further, terms such as up, down, bottom, and top are relative, and are employed to aid illustration, but are not limiting. 
     A cooling device is provided for cooling the surface of the skin of a patient to provide a temporary desensitizing or numbing effect to the skin immediately or shortly before the insertion of a needle, cannula or other medical device into the skin. The cooing device can be used alone or in combination with a delivery device such as a kit, package, or assembly. 
     The cooling device is primarily intended for use with a medical device, such as a delivery device, where a needle or cannula of the delivery device penetrates the skin for delivery of a substance, such as a pharmaceutical, or for withdrawing a fluid from the patient. Examples of a delivery device can include a pen needle, infusion pump, syringe, patch pump, lancet, catheter, or other injection or delivery device. The cooling device is also suitable for use in intravenous drug delivery devices and phlebotomy applications. The medical device can also be a catheter, central line ports, sub-surface ports that can be accessed for drug delivery, such as in chemotherapy applications. The delivery device in one embodiment is a pen needle commonly used delivery of insulin where it is necessary for the patient to introduce the needle into the skin to a controlled depth for the insulin delivery. 
     The cooling device contains a refrigerant medium or cooling medium that is re-usable for multiple uses. In one embodiment, the cooling device includes a refrigerant medium where the device can be placed in a freezer to freeze the refrigerant medium until ready for use. As used herein, a freezer refers to a device or apparatus that cools below 20° C. and is able to cool the refrigerant medium below the freezing point of the refrigerant medium. The cooling device is able to keep the refrigerant medium in a frozen, cold, or chilled state for several hours to provide a useful life to the device. The cooling device in one embodiment is able to maintain the cold temperature for 6 to 8 hours during normal use. The refrigerant medium can be cooled to a temperature of a standard freezer to a temperature at or below −20° C. The cooling device is sufficiently insulated to maintain the temperature of the refrigerant medium at or below about 5° C. and preferably at or below about 2° C. for 6-8 hours when stored at room temperature. 
     In one embodiment, the cooling device has a sufficiently small size that the device is able to fit within the pocket of the user or can be retained within the package or container that stores the pen needle and supplies until ready for use. The cooling device in one embodiment can have a substantially cylindrical shape with a length of about 2-3 inches and a width or diameter of about 0.5 to 1 inch although other sizes and dimensions can be used as needed. 
     Referring to the drawings, the cooling device  10  includes a container  12  having a side wall  14 , an open end  16 , and a closed bottom end formed by a bottom wall  18 . In the embodiment shown, the container  12  has a substantially cylindrical shape although other shapes can be used. The container  12  is made of a thermally insulating material that is able to withstand repeated freezing and thawing cycles and retain the refrigerant medium in a cooled or frozen state. In one embodiment, the container is made from a plastic material with a sufficient thickness and strength to retain the refrigerant medium in a frozen or cooled state for an extended period of time. The container  12  can be made of polymer foam and can include a heat reflective surface or coating  15  on an inner surface of the container. In the embodiment shown in  FIG. 3 , the heat reflective surface  15  is formed on the bottom wall  18  and the side wall  14 . The outer surface of the container can also include a heat reflective coating  17  to inhibit heat conduction and reflect thermal radiation into or out of the container and the refrigerant medium. 
     In the embodiment shown in  FIGS. 1-3 , the cooling device  10  includes a thermally transmitting member functioning as a closure to enclose a cooling composition referred to as a refrigerant medium  22  within the container  12 . In the embodiment shown, the thermally transmitting member closing the container is an inner container such as a flexible bladder  20  that contains and encloses the refrigerant medium  22 . The bladder  20  forms an enclosure for the refrigerant medium  22  and is positioned within the cavity of the container  12  as shown in  FIG. 2 . The bladder  20  can be made of a flexible polymer that can conform to the inner configuration of the container  12 . The bladder  20  is made of a polymer material that is able to withstand the freezing and thawing of the refrigerant medium and retain the refrigerant medium without leakage during the normal use of the device. In one embodiment, an air gap  24  is provided between the bladder  28  and the bottom wall  18  of the container to allow for expansion of the refrigerant medium during freezing. In other embodiments, an air gap or space can be provided in the bottom portion of the bladder  20  to allow for the expansion of the bladder  20  and the refrigerant medium  22  during freezing as shown in  FIG. 2 . 
     The bladder  20  in one embodiment is flexible to conform to the inner surfaces of the container and to conform to the contour of the skin of the patient when contacted with and pressed against the skin of the patient. In one embodiment, the bladder  20  can be adhesively attached to the walls  14  of the container  12 . The bladder  20  has a thickness to contain the refrigerant medium while allowing sufficient heat transmission through the bladder to cool the skin of the patient. The bladder  20  forms a closed, self-contained unit for the refrigerant medium  22  to reduce the risk of leakage. The bladder is typically a flexible polymeric material. The bladder  20  can be fixed in the cavity of the container or can be removable from the container. 
     The container in the embodiment shown has a substantially cylindrical side wall with an open end complementing the inner dimension of the side wall. The bladder  20  occupies a substantial portion of the inner cavity of the container  12  to maximize the volume of the refrigerant medium  22  relative to the dimensions of the container. The side wall  14  covers and encloses a substantial portion of the bladder  20  to thermally insulate the bladder  20  during handling of the device. 
     II 
     In the embodiment shown, the bladder  20  has an end contact portion  26  forming a skin contact area for contacting the skin of the patient during use. The contact portion  26  of the bladder  20  has a domed shape as shown in  FIG. 2  to provide a skin contact area for contacting the surface of the skin during use. In the embodiment shown, the contact portion  26  projects outwardly from the open end  16  of the container  12  for ease of contacting the skin. In other embodiments, the contact portion  26  of the bladder  20  can be substantially flush with the open top end  16  of the container  12 . The contact portion  26  of the bladder  20  is sufficiently flexible to conform to the surface of the skin when pressed against the skin. In the embodiment shown, the bladder  20  has a substantially uniform wall thickness. In other embodiments, the contact portion can be thinner or thicker than sides and bottom of the bladder to control the heat transfer and cooling effect through the contact portion. 
     A lid  30  is provided to fit onto the open top end  16  of the container  12  to close the container and cover the end contact portion  26  of the bladder  20 . The lid  30  in the embodiment shown has a side wall  32  forming an open end  34  shown in  FIG. 2  with a shape and dimension complementing the shape and dimension of the side wall  14  of the container  12 . An end wall  36  is formed with the side wall  32  as a one piece assembly. The lid  30  can be provided with a thermally reflective inner surface or coating  31  to reduce heat transmission through the lid  30 . In further embodiments, a reflective surface or coating  33  can be provided on an outer surface of the lid. 
     In the embodiment shown, the lid  30  fits over the outer surface of container  12  and is coupled to the container by a friction fit or interference fit. In the embodiment shown, the lid  30  when coupled to the container  12  is spaced a slight distance from the end contact portion  26  of the bladder  20  to inhibit heat transmission through the lid  30  to the bladder  20  and refrigerant medium  22  contained within the bladder  20 . 
     The container  12  and lid  30  are generally made of a thermally insulating material and constructed to maintain the refrigerant medium in a frozen or cooled state for an extended period of time and preferably up to about 6-8 hours when stored at room temperature. In the embodiment of  FIGS. 1-3 , the container  12  and lid  30  are made of a thermally insulating plastic material and have a thickness constructed to provide the desired insulating properties to maintain the refrigerant medium at a temperature to provide the cooling and desensitizing of the skin of the patient. The side wall  14  of the container  12  has sufficient thermal insulating properties so that handling of the container  12  by the patient reduces heat transmission from the hand of the patient and the outside environment through the side wall to retain the cooling temperature within the container and the refrigerant medium. 
     The refrigerant medium  22  within the container  12  can be a suitable composition that can be frozen by placing in a standard freezer to provide the cooling and desensitizing effect when placed in contact with the skin. In one embodiment, the refrigerant medium can be an aqueous hypertonic solution, such as an aqueous sodium chloride solution that can be placed in a freezer and frozen until ready for use. The refrigerant medium can be an aqueous solution that can include other salts to reduce or lower the freezing point of water. The refrigerant medium can be reused by refreezing the device. 
     The refrigerant medium can alternatively be other solutions or compositions that are able to maintain a frozen state for an extended period of time. Examples of suitable refrigerant medium or cooling medium can be a liquid or gel containing one or more compounds that is able to lower the freezing point of water. The refrigerant medium can be an aqueous mixture that can include hydroxyethylcellulose, sodium acrylate, vinyl coated silica gel, and the like. In other embodiments, the refrigerant medium can be an aqueous solution containing calcium chloride, magnesium chloride, sodium formate, potassium formate, sodium acetate, potassium acetate, propylene glycol, ethyl alcohol, propyl alcohol, sorbitol, glycerol, and mixtures thereof. 
     In another embodiment shown in  FIG. 4 , the container  40  can be made with an inner wall  42  and an outer wall  44  defining a gap  46  between the inner wall  42  and outer wall  44 . The inner surfaces  48  of the inner wall  42  and the inner surface  50  of the outer wall  44  can be provided with a heat reflecting surface, finish, film, or coating  51  to reduce the heat convection through the container walls. The gap  46  between the inner wall  42  and the outer wall  44  can be filled with polymer foam or other insulation material. In the embodiment shown in  FIG. 4 , the gap  46  can be filled with air or inert gas to inhibit heat transmission through the side wall and bottom of the container. In a further embodiment, the gap  46  can be a vacuum or pressure below atmospheric pressure to inhibit the transfer of heat through the wall and bottom of the container. The container  40  includes a bladder  20  and air gap  24  as in the previous embodiment that is received in the cavity of the container  40  to retain a refrigerant medium  22  and provide the contact end portion  26  to cooling skin of the patient. 
     A lid  52  of the container  40  is also constructed with an inner wall  54  and an outer wall  56  to define a gap  58  between the inner wall  54  and outer wall  56 . As with the container  40 , the gap  58  between the inner wall and outer wall can be filled with an insulating gas or air or can be provided with a vacuum or reduced pressure. The inner surfaces  60  of the inner wall  54  and the inner surface  62  of outer wall  56  can be provided with a thermally reflective finish or reflective coating  63 . 
     In the embodiment of  FIG. 5 , the gap  46  of the container  40  and the gap  58  of the lid  52  are filled with an insulating material  64 , such as a foam material. The container of  FIG. 5  is substantially the same as in  FIG. 3  and need not be described in further detail. The bladder  20  is also substantially the same as in the previous embodiment. 
     In a further embodiment shown in  FIG. 6 , the container  12  and the bladder  20  enclose a solid core  66  within the bladder  20  to provide a greater thermal mass for retaining the refrigerant medium at the desired temperature for an extended period of time. In the embodiment shown, the core  66  has a substantially cylindrical shape complementing the shape and dimension of the bladder  20  and the container  12 . The core  66  can be made of a metal such as stainless steel, aluminum or other suitable metal. The metal core  66  can be a solid material that is not reactive with the refrigerant medium. 
     In one embodiment, the metal core  66  includes a corrosion resistant coating. The core  66  can be contained within the bladder  20  and surrounded by the refrigerant medium  22 . Typically the core  66  is completely surrounded by the refrigerant medium  22 . The core in one embodiment is spaced from the skin contact portion  26  or skin contact surface. 
       FIG. 7  shows an embodiment where the container  40  include a gap  41  or space between the inner wall  42  and the outer wall  44  providing an insulating effect. The solid core  66  is contained within the bladder  20  as in the previous embodiment. 
     The core  66  can have a longitudinal length extending between the open end and the bottom end of the container  12 . In one embodiment, the core  66  can have a length to extend past the open end of the container as shown in  FIG. 6  and  FIG. 7  into the domed shaped end portion of the bladder. Typically the core is spaced from the contact area  26  so that the contact area  26  can bend and conform to the surface of the skin of the patient. The position of the core can be fixed within the bladder by a suitable attachment mechanism. In other embodiments, the core can free floating within the bladder. In other embodiments, the solid core  66  can have a length less than a length of the container to be positioned completely within the container below the open end. In further embodiments, the core can have a hollow cavity  67  as shown in  FIG. 7  and enclose a refrigerant medium that is the same as or different from the refrigerant medium surrounding the core. 
       FIG. 8  shows another embodiment where the container  70  includes a side wall  72 , a bottom wall  74 , and an open top end  76 . A skin contact member  78  forming a closure is attached to the container side wall  72  to enclose the cavity within the container. The refrigerant medium  80  is provided within the cavity and retained by the skin contact member  78 . The container  70  can be made of a thermally insulating material as in the previous embodiments. The closure member  78  seals the container to retain the refrigerant medium  80 . In one embodiment, the closure member  78  is made of a flexible polymer that is in direct contact with the refrigerant medium  80  and is able to cool the skin of the patient on contact with the skin of the patient. The flexible polymer is able to conform to the container of the skin when pressed against a target site. In other embodiments, the closure member  78  can be a rigid material such as plastic or metal. 
     In the embodiments shown, the refrigerant medium is contained within the bladder in a fixed position relative to the container with at least an end portion projecting from the open end of the container. In other embodiments, the bladder and refrigerant medium can be stored completely within the container and advanced to a position where the bladder containing the refrigerant medium can contact the surface of the skin of the patient. 
     An advancing and retracting mechanism  90  can be provided to move the bladder  92  toward the open end  94  of the container  96  and retract the bladder after use. The advancing mechanism can be, for example, a threaded mechanism that moves a plunger-like member and is able to retract the bladder back into the container. In one embodiment shown in  FIGS. 9 and 10 , the mechanism  90  can be manually operated plunger  98  coupled to a piston  100  that can be manipulated by sliding the plunger  98  toward the open end of the container to advance the bladder to a position where the bladder  20  extends from the open end of the container as shown in  FIG. 10 . The skin contact surface of the bladder is exposed to contact the skin of the patient to provide the cooling effect. After use, the bladder can be retracted into the container  96  as shown in  FIG. 9  and covered by a lid  102 . The bladder is typically retracted into the container a distance where the bladder does not contact the lid  102  to reduce the heat transfer from the refrigerant medium through the lid. Other mechanisms can be provided that are able to move the bladder to an operating position. 
     The device is used for the insertion of a medical device into a patient by piercing the skin of the patient and introducing the medical device subcutaneously, intravenously, intradermally, or intramuscularly. The device is particularly suitable in a method for the injection of a medication, such as insulin, into a target area of the skin. The skin contact area of the bladder is pressed against the skin in the target area of the skin for a time sufficient to cooling the skin and numb or desensitize the target area. A medical device, such as a needle or cannula then pierces the skin in the target area and the medication is introduced to the patient or fluid drawn from the patient. 
     The foregoing embodiments and advantages are merely exemplary and are not to be construed as limiting the scope of the present invention. The description of an exemplary embodiment of the present invention is intended to be illustrative, and not to limit the scope of the present invention. Various modifications, alternatives, and variations will be apparent to those of ordinary skill in the art, and are intended to fall within the scope of the invention. It is particularly noted that the features of different embodiments and claims may be combined with each other as long as they do not contradict each other. Accordingly, all such modifications are intended to be included within the scope of this invention as defined in the appended claims and their equivalents.