Abstract:
Embodiments relate to needled fluid transfer adaptors, and related methods and systems for transferring fluid samples between fluid vessels having sealing means.

Description:
SUMMARY 
       [0001]    In general, this disclosure describes techniques for transferring fluid samples between fluid containment vessels or fluid containing components. Techniques further describe the labeling and handling of sample vessels. In particular, this disclosure describes techniques for transferring or aliquoting medical samples from a sample vessel to one or more aliquot vessels. It should be noted that although the techniques of this disclosure are described with respect to examples for aliquoting medical samples in clinical laboratories, the techniques described herein are generally applicable to the transfer of any manner of fluid samples in laboratory settings or otherwise. 
         [0002]    According to one example of the disclosure, an aliquot transfer sample tube adaptor comprises a body having a first end and a second with an axial internal bore running therebetween, a support means intermediate the first end and the second end defining a first receiving cavity and a second receiving cavity, and a needle substantially axially oriented within the internal bore and maintained in position by the support means comprising a first tip intermediate the body first end and the support means and a second tip intermediate the body second end and the support means. In some other embodiments, the needle further comprises at least two apertures on opposing sides of the support means and exposing a lumen internally disposed along a length of the needle. In some embodiments, the adaptor further comprises a needle sheath. In other embodiments, at least one of the needle first tip and needle second tip extend beyond the body first end and body second end, respectively. 
         [0003]    According to another example of the disclosure, an aliquot transfer sample tube adaptor as described above can include apertures variously positioned throughout the needle, such as proximate each needle tip. In other examples, the needle may comprise one or more apertures clustered near the support means on one or both sides of the needle. In certain embodiments, one aperture is located proximate to each needle tip, and a radial aperture cluster is located proximate the support means on one needle side. In other embodiments, one or more needle apertures are sized to prevent particulate from passing therethrough. 
         [0004]    According to another example of the disclosure, a sample transfer system comprises an aliquot transfer sample tube adaptor comprising a body having a first end and a second with an axial internal bore running therebetween, a support means intermediate the first end and the second end defining a first receiving cavity and a second receiving cavity, and a needle substantially axially oriented within the internal bore and maintained in position by the support means, the needle having a first tip intermediate the body first end and the support means, and a second tip intermediate the body second end and the support means; and a plurality of vessels each having a sealing means actuable by a tip of the adaptor needle when positioned within a receiving cavity of the adaptor, and one or more of a plurality of vessels may be sequentially coupled via the sample vessel adaptor creating fluid communication therebetween. In some other embodiments the needle further comprises at least two apertures on opposing sides of the support means and exposing a lumen internally disposed along a length of the needle. In some embodiments of the sample transfer system, the sealing means of one or more of a plurality of vessels or tubes comprises a pierceable membrane. 
         [0005]    According to another example of the disclosure, a method for transferring samples comprises providing a sample vessel adaptor comprising: a body having a first end and a second end with an axial internal bore running therebetween; a support means intermediate the first end and the second end defining a first receiving cavity and a second receiving cavity; and a needle substantially axially oriented within the internal bore and maintained in position by the support means, having a first tip intermediate the body first end and the support means, and a second tip intermediate the body second end and the support means; positioning a sample vessel within the first receiving cavity of the adaptor thereby causing the first needle tip to actuate the sealing means of the sample vessel from a sealed position to an unsealed position; and positioning an aliquot vessel within the second receiving cavity of the adaptor thereby causing the second needle tip to actuate the sealing means of the aliquot vessel; wherein fluid communication is established from the sample vessel to the aliquot vessel and fluid is transferred therebetween. In some other embodiments the needle further comprises at least one aperture on each opposing side of the support means and exposing a lumen internally disposed along a length of the needle. In some other embodiments, fluid communication between the sample vessel and the aliquot vessel is established via the needle lumen. In some embodiments, the sealing means of one or more of the aliquot vessel or sample vessel comprises a pierceable membrane. In still other embodiments, the methods for transferring samples further comprise inverting a coupled adaptor, sample vessel, and aliquot vessel to aid fluid flow into the aliquot vessel. In certain embodiments, the methods for transferring samples further comprise adding a separating gel to the sample tube to separate fluid components. 
         [0006]    The details of one or more examples are set forth in the accompanying drawings and the description below. Other features, objects, and advantages will be apparent from the description and drawings, and from the claims. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0007]      FIG. 1A  illustrates a perspective view of an aliquot transfer sample tube adaptor, according to one or more techniques of this disclosure. 
           [0008]      FIG. 1B  illustrates a cross-sectional view of an aliquot transfer sample tube adaptor positioned to mate with a fluid vessel having a pierceable top, according to one or more techniques of this disclosure. 
           [0009]      FIG. 2A  illustrates a perspective view of an aliquot transfer sample tube adaptor needle having multiple apertures, according to one or more techniques of this disclosure. 
           [0010]      FIG. 2B  illustrates a perspective view of an aliquot transfer sample tube adaptor having a plurality of various needle apertures, according to one or more techniques of this disclosure. 
           [0011]      FIG. 3A  illustrates a perspective view of an aliquot transfer sample tube adaptor comprising a needle sheath, according to one or more techniques of this disclosure. 
           [0012]      FIG. 3B  illustrates a cross-sectional view of an aliquot transfer sample tube adaptor comprising a needle sheath, according to one or more techniques of this disclosure. 
           [0013]      FIG. 4A  illustrates a perspective view of a bodiless aliquot transfer sample tube adaptor, according to one or more techniques of this disclosure. 
           [0014]      FIG. 4B  illustrates a perspective view of a bodiless aliquot transfer sample tube adaptor comprising a needle sheath, according to one or more techniques of this disclosure. 
           [0015]      FIG. 5A  illustrates a flow diagram of using an aliquot transfer sample tube adaptor to transfer a sample between a plurality of sample vessels, according to one or more techniques of this disclosure. 
           [0016]      FIG. 6A and 6B  illustrate a cross-sectional view of an aliquot transfer sample tube adaptor mated with two fluid vessels having pierceable caps, according to one or more techniques of this disclosure, wherein the needle is enlarged for the purposes of demonstration. 
           [0017]      FIG. 7A  illustrates a cross-sectional view of a sample vessel containing a fluid sample and a separating gel, according to one or more techniques of this disclosure. 
           [0018]      FIG. 7B  illustrates a cross-sectional view of a sample vessel containing a fluid sample separated into its components by a separating gel, according to one or more techniques of this disclosure. 
           [0019]      FIG. 7C  illustrates a cross-sectional view of a sample vessel containing a fluid sample and a separating gel mated with an aliquot transfer sample tube adaptor and a fluid vessel, according to one or more techniques of this disclosure. 
           [0020]      FIG. 8A  illustrates a device comprising needleless access port, according to one or more techniques of this disclosure. 
           [0021]      FIG. 8B  illustrates a luer-locking adaptor with a springed actuator, according to one or more techniques of this disclosure. 
           [0022]      FIG. 8C  illustrates a device comprising needleless access port mated with a luer-locking adaptor with a springed actuator, according to one or more techniques of this disclosure. 
           [0023]      FIG. 9  illustrates a cross-sectional view of an aliquot transfer sample tube adaptor mated with two fluid vessels having pierceable caps, according to one or more techniques of this disclosure. 
       
    
    
     DETAILED DESCRIPTION 
       [0024]    Diagnostic laboratories play a major role in medicine today. Physicians are heavily dependent of laboratory test results for their clinical decisions. Laboratories have implemented quality control and quality management procedures to ensure the quality of lab results. One focus of efforts to prevent diagnostic errors involves pre-analytic steps. Laboratory test results are heavily affected by the quality of the samples which are impacted by pre-analytical steps. Generally, pre-analytical steps include patient identification and preparation, proper sample collection, accurate labeling of collected samples and transportation of sample to the lab. Correct labeling of patient samples is very crucial and any mistake can have significant medical, social and legal consequences. Mid-size or large clinical laboratories receive hundreds to thousands of patient samples every day for analysis. For a lean process and for better efficiency, many labs have created a specimen processing area which receives all patient samples, processes them and send them to the appropriate laboratory sections for testing. 
         [0025]    The usual process after the receipt of sample include logging the sample into the laboratory information system (LIS), if the sample comes with a lab requisition form and if it has not already been ordered by health care provider through a computer system. Most laboratory analyzers cannot read the original label on the patient&#39;s sample. Sample processing sections usually create a new label that includes bar coded patient identifiers and test codes that allow automated analyzers in the lab to read the label, to perform the ordered test and to send the result to an electronic medical record. Manual transfer and labeling of these samples pose significant medical, social, and legal consequences. The techniques described herein reduce the risk of contamination of samples, minimize biohazard exposure to laboratory technicians, decrease turn-around time for aliquoting and running the assay, and eliminate some or all human error inherent with manual sample transfer procedures. 
         [0026]    As used herein, “fluid” may refer to liquids, homogenous or heterogeneous solutions, colloids, suspensions, gases, gas-infused liquids, or other applicable species as may be determined by one of skill in the art after review of this disclosure. Particularly, “fluid” may refer to medical fluids, such as urine, amniotic fluid, CSF, serums, pericardial fluid, abscess aspirate, whole blood, serum, plasma or other blood products or other bodily fluids. 
         [0027]      FIG. 1A  illustrates a perspective view of an aliquot transfer sample tube adaptor  100  comprising a body  105 , a first end  106 , a second end  107 , a support means  110 , a first receiving cavity  111 , a second receiving cavity  112 , a needle  115 , a first needle tip  116 , a second needle tip  117 , and a lumen  125 .  FIG. 1B  further illustrates a cross-sectional view of an aliquot transfer sample tube adaptor  100  comprising a body  107 , a support means  110 , a needle  115 , a first needle tip  116 , a second needle tip  117 , a tip-to-tip needle length  118 , a needle first length  119 , a needle second length  120 , and a middle needle length  121 . Fluid vessel  600  is positioned to mate with tube adaptor  100  and comprises a body  607 , a cap  605 , and a pierceable membrane  615 . Tube adaptor  100  optionally comprises an exterior or interior edge or lip (not shown), or other means, which secures the adaptor to the tube or tubes. 
         [0028]    Tube adaptor  100  is capable of receiving fluid vessel  600  in first receiving cavity  111 , wherein needle tip  116  can pierce membrane  615  and establish fluid communication between body  607  and needle lumen  125 . The membrane creates a fluid-tight or substantially fluid-tight seal around the needle. Membranes are fashioned from any suitable material, such as elastomeric or polymeric materials, such that a liquid-tight seal is created upon removal of a needle. Needle tips  116  and  117  can be diagonal or flat, as respectively shown, or shaped in other various manners. Factors for needle tip shape can depend on needle diameter, needle wall thickness, needle material, membrane material to be pierced, or other factors as can be determined by one of skill in the art after careful review of this disclosure. Body  105  can be constructed of rigid, semi-rigid, or flexible materials, depending on the desired use. For example, a rigid or semi-rigid body can be used to hold a mated fluid vessel in place. In other examples, a lip or an edge would be located on the interior of body  105 , for the purpose of securing the adaptor to the tube or tubes. In other examples, a more flexible body may be used as a safety precaution against fluid spray during mating or un-mating of a tube adaptor with one or more fluid vessels. 
         [0029]      FIG. 2A  illustrates a perspective view of an aliquot transfer sample tube adaptor  200  needle  115  having multiple apertures shown in relation to a support means  110  and comprising a first tip  116 , a lumen  125 , a needle tip aperture  126 , a plurality of radial apertures  127 , and a radial aperture cluster region  128 .  FIG. 2B  illustrates a perspective view of an aliquot transfer sample tube adaptor  201  having a plurality of various needle apertures, comprising a support means  110 , a needle  115 , a first needle end  216 , a second needle end  217 , a lumen  125 , a needle tip aperture  126 , a plurality of radial apertures  127 , and a capped needle end  129 . Some advantages of various numbers and positions of needle apertures will be discussed below. 
         [0030]      FIG. 3A  illustrates a perspective view of an aliquot transfer sample tube adaptor  301 , comprising a body  107 , a support means  110 , a needle  115 , and a needle sheath  130 , according to one or more techniques of this disclosure.  FIG. 3B  also illustrates a cross-sectional view of the aliquot transfer sample tube adaptor  301 , additionally showing a lumen  125 . A needle sheath  130  can aid in keeping a needle sterile before use, and provide a degree of protection by isolating the needle tip. 
         [0031]      FIG. 4A  illustrates a perspective view of a bodiless aliquot transfer sample tube adaptor  400  comprising a support means  410 , a needle  115 , a first needle tip  116 , and a second needle tip  117 .  FIG. 4B  illustrates a perspective view of a bodiless aliquot transfer sample tube adaptor  401 , comprising a needle  115 , a support means  410 , and a needle sheath  130 . These embodiments can be practiced with any other variations as described herein. For example, the bodiless aliquot transfer sample tube adaptors  400  and  401  may have a plurality of tip and/or radial apertures. The bodiless construction can increase versatility of use with variously sized fluid vessels and additionally save on material cost and cost of manufacture. In some embodiments, the bodiless aliquot transfer sample tube adaptor can be coupleable to and/or uncoupleable from a separate body piece. 
         [0032]      FIG. 5A  illustrates a flow diagram of using an aliquot transfer sample tube adaptor to transfer a sample between a plurality of sample vessels, which can describe a partial or complete fluid transfer method  530 . Step A depicts a tube adaptor  100  being positioned to mate with a sample tube  500  containing a liquid sample  510 . Step B depicts the tube adaptor  100  mated to the sample tube  500 . Step C depicts the tube adaptor  100  positioned to mate with an aliquot tube  501 . Step D depicts the tube adaptor  100  mated with the sample tube  500  and an aliquot  501 , wherein fluid communication is established therebetween and the fluid sample  510  is transferred to aliquot tube  501 . Transfer may occur as a result of gravity, pressure differences between sample tube  500  and aliquot tube  501 , or other factors. In some embodiments, sample tubes and/or aliquot tubes can each comprise a plunger-type element at the base to provide positive pressure and/or suction to facilitate fluid transfer. Similarly, vent ports may be used to maintain ambient pressure within the tubes, or manipulate pressure via an external pump or compressor. 
         [0033]    In some embodiments, all fluid is transferred to an aliquot tube. In other embodiments, a portion of the fluid is transferred to an aliquot tube. In some other embodiments, a portion of the fluid is transferred to each of a plurality of aliquot tubes, which can be arranged in a queue. Tube adaptor  100  may be utilized to transfer fluid to, from, and/or between fluid vessels in a queue as described in method  530  of  FIG. 5A , or any other applicable transfer methods described herein or those which one of skill in the art would recognize as applicable after review of this disclosure. 
         [0034]    Transfers can be executed manually by laboratory personnel or by an automated process or machine, including, but not limited to, a Secure Aliquoting Machine (SAM). A SAM may comprise a robotic arm attached to a sensored tip. In some embodiments, sensored tips may be metal or plastic, or a combination thereof. A metal tip can use a probe which is sensitive to electrical resistance, while a plastic tip uses a change in pressure to sense a liquid. Use of an aliquot transfer sample tube adaptor as described herein in addition to or as an alternative to sensored tips can provide increased device efficiency and performance, as significantly reduce device costs. 
         [0035]    For further demonstration of fluid transfer techniques, and others,  FIG. 6A  and  FIG. 6B  illustrate a cross-sectional view of an aliquot transfer sample tube adaptor  100  mated with two fluid vessels  600  and  700 , each having bodies  607  and  707 , respectively, caps  605  and  705 , respectively, with each cap having a pierceable membrane  615  and  715 , respectively. The tube adaptor  100  comprises a body  107 , a support means  110 , and a needle  115  having a first end  116  and a second end  117 . The needle comprises a needle tip aperture  126  and  146  at each of the first end  116  and the second end  117 , respectively, and a cluster of radial apertures  127  located intermediate the support means  110  and the first tip  116 . In addition, one or more, or a cluster of radial apertures  127  can be located intermediate the support means  110  and the second tip  117  (not shown). A tube adaptor  100  is considered to be mated when a needle tip, such as  116  or  117 , pierces the pierceable membrane, such as  615  or  715 , and enters the body of a sample tube, such as  607  or  707 , respectively, thereby creating fluid communication between the body  607  or  707  and the needle lumen  125 . A gap  620  may exist between a tube adaptor  110  support means  110  and a fluid vessel  600  cap  605  or pierceable membrane  615  during mating. 
         [0036]      FIG. 6A  indicates the direction of fluid flow  711  a fluid sample  610  transfers from fluid vessel  600  to fluid vessel  700  via the needle lumen  125 . The number and placement of needle apertures can enhance the rate of fluid flow between fluid vessels and/or through a needle lumen, and also allow for more complete transfer of fluid. A needle having only one needle tip aperture, such as  126 , can only transfer an amount of fluid  611  from fluid vessel  600  to fluid vessel  700  without rotating or manipulating the position of the mated elements  100 ,  600 , and  700 . Radial apertures  127  allow for all or substantially all of fluid sample  610  of fluid vessel  600 , e.g., fluid portion  611  and fluid portion  612 , to transfer to fluid vessel  700 . In some embodiments a plurality of radial apertures  127  enhance the speed of fluid transfer and allow for versatility of use with fluid vessels having pierceable membranes of varying thicknesses. 
         [0037]    In some embodiments it may be advantageous to exclude radial apertures, or include radial apertures only on certain portions of a tube adaptor needle.  FIG. 6B  shows an inverted orientation of elements  100 ,  600 , and  700  from that of  6 A after complete transfer of fluid sample  610  between fluid vessel  600  and fluid vessel  700  has been effected. As shown, fluid level  613  is below needle tip  117  and backflow of fluid sample  610  into fluid vessel  600  is not possible in the current orientation. 
         [0038]      FIG. 7A  illustrates a cross-sectional view of a sample vessel  750  containing a fluid sample  710  and a separating gel  713 , wherein sample vessel  750  comprises a cap  755  having an integrated pierceable membrane  765 .  FIG. 7B  illustrates a cross-sectional view of a sample vessel  750  containing a fluid sample  710  separated into its components  711  and  712  by a separating gel  713 . In some embodiments, a separating gel  713  is introduced into the sample tube  750  to separate fluid components before or during fluid transfer. For example, a separating gel may be denser or heavier than blood plasma and lighter or less dense than other cellular components or cellular debris. In some examples the gel  713  may be combined in a sample tube  750 , such as a typical blood collection BD Vacutainer or similar container, with a blood sample  710  and centrifuged to produce a multi-layered fluid arrangement within the tube wherein the blood cellular components  712  are positioned at the bottom of the tube and the gel  713  is positioned above, separating the cellular components  712  from the blood plasma  711  at the top of the arrangement. In other examples, component separation may occur by natural settling or other methods. 
         [0039]    In some embodiments the sample tube  750  position may be manipulated, such as wholly inverted, and the gel will hold a constant position and prevent movement of the blood cellular components. In some embodiments the gel position may change, but a complete or substantially complete isolation of the blood cellular components and blood plasma will be maintained. During a partial or complete inversion of the sample tube, the blood plasma can freely flow to the top or capped end of the tube where it may be extracted using any of the techniques described herein. 
         [0040]      FIG. 7C  illustrates a cross-sectional view of a sample vessel  750  containing a fluid sample separated into components  711  and  712  by a separating gel  713 , the sample vessel  750  being mated with an aliquot transfer sample tube adaptor  201  and a fluid vessel  700 .  FIG. 7C  demonstrates the advantages of the needle  115  aperture configuration of tube adaptor  201  when transfer of fluid portion  711  is desired. Radial apertures  127  create fluid communication with fluid sample  711  and the needle  115  lumen  125  allowing fluid sample portion  711  to transfer into fluid vessel  700 . Separating gel  713  and needle capped end  129  prevent fluid communication between needle lumen  125  and fluid portion  712 . In some embodiments, separating gels comprise a viscosity sufficient to prevent gel flow through needle apertures. Radial aperture cluster region  228  can be designed based on factors such as pierceable membrane  755  thickness, amount of fluid sample, separating gel types, and number and thicknesses of various fluid layers. 
         [0041]    In all embodiments herein, the length of one or both aliquot transfer sample tube adaptor needles can depend on one or more of a variety of factors such as the height of a sample tube, the thickness of a pierceable sample tube cap, the amount of fluid being transferred between one or more tubes or sample vessels, the number and the location of radial apertures desired, or a particular layered fluid arrangement within the sample tube. In certain embodiments, having a plurality of radial apertures on the aliquot transfer sample tube adaptor needle ensures that the maximum amount of serum or plasma or other fluid will be transferred from the tube containing the sample to the aliquot tube, independent of the thickness of the pierceable membrane or tube cap. In some embodiments, needle length is determined independently from or in cooperation with the number and/or position of needle. 
         [0042]    Throughout this disclosure embodiments of aliquot sample transfer tube adaptors may be described as having one or two needles, although the functional difference between either construction should be construed as minimal, as a two needle configuration will comprise two needles in fluid communication unless otherwise indicated. One of skill in the art after review of this disclosure will appreciate the benefits of a one or two needle construction, such as in ease or cost of manufacture, yet will readily appreciate the applicability of either construction for the techniques described herein. 
         [0043]    Further, “needle” as used herein can describe lumenous shafts, or other blunt, sharp, or semi-sharp shafts which can be used to puncture, pierce, penetrate, or otherwise disrupt a seal or enclosure, such as a pierceable membrane. 
         [0044]    “Pierceable membrane” as used herein, should be construed to refer to any element which closes, seals, shuts, or otherwise preserves an opening. Pierceable membranes are able to be pierced by sharp objects, such as needles, without leaking fluid, air, or other material around the pierced area. As provided herein, the pierceable membranes of the techniques described herein are capable of reclosing, resealing, self-healing, rehealing, or reshooting once the sharp object is removed from the pierceable membrane. The pierceable membrane described herein is able to recover the ability to be fully sealed or closed. Further, as provided herein, pierceable membranes are capable of retaining a needle or other object used to puncture the stopper without allowing fluids or materials to leak, seep, pass or flow around the area of the stopper that is retaining the needle or object. 
         [0045]    The pierceable membrane can be made of rubber, latex, polymeric materials, or any suitable bio-compatible material, or a combination thereof. The pierceable stopper is made of one or more materials that are able to be sterilized via medically approved and acceptable means, and able to be pierced or punctured by an object, including but not limited to a sharp object, such as a needle, without leaking, seeping, passing or flowing around the area of the stopper that is retaining the needle or object. The pierceable stopper is self-healing, gas proof, solvent proof, and liquid proof. 
         [0046]    In some embodiments, pierceable membranes can be replaced by, or used in conjunction with, other sealing elements such as check valves, luer locks, or other self-sealing element, or edges, lips or ridges which one of skill in the art would identify as applicable to the techniques described herein after review of this disclosure. These alternative or additional sealing elements can be actuated, unseated, or otherwise removed from a sealing position or condition by a needle, a shaft, or other suitable means. For example, one or more needle tips of an aliquot transfer sample tube adaptor may be used to unseat a check valve from a sealing position. Examples of luer locks or check valves suitable for use with aliquot sample tube adaptors, sample transfer systems and transfer methods provided herein are found in the art, including but not limited to U.S. Pat. No. 5,984,373. 
         [0047]      FIG. 8A  illustrates a device  800  comprising needleless access port  801 , which may be incorporated with one or more techniques of this disclosure. For example, a needle tip of an aliquot transfer sample tube adaptor may be used to unseat or disrupt a sealing position or condition of the needless access port  801  to create fluid communication between the device  800  and the adaptor. 
         [0048]      FIG. 8B  illustrates a luer-locking adaptor with a springed actuator  821 , which may be incorporated with one or more techniques of this disclosure. For example, an aliquot transfer sample tube adaptor may comprise one or a plurality of springed actuators. Actuator  821  can comprise a lumen. Actuator  821  can comprise a one or a plurality of apertures.  FIG. 8C  illustrates device  800  mated with a luer-locking adaptor  820 , which may be incorporated with one or more techniques of this disclosure. 
         [0049]      FIG. 9  illustrates a cross-sectional view of an aliquot transfer sample tube adaptor  100  mated with two fluid vessels  500  and  700 , each having bodies (not enumerated), caps  505  and  705 , respectively, with each cap having a pierceable membrane (not shown). The tube adaptor  100  comprises a body, a support means  110 , and a needle having a first end  116  and a second end  117 . The needle comprises a needle tip aperture at each of the first end  116  and the second end  117 , respectively, and a cluster of radial apertures  127  located intermediate the support means  110  and the first tip  116  and another cluster of radial apertures  127  located intermediate the support means  110  and the second tip  117 . 
         [0050]    All publications, patents, and patent documents are incorporated by reference herein, as though individually incorporated by reference. 
         [0051]    While specific embodiments have been described above with reference to the disclosed embodiments and examples, such embodiments are only illustrative and do not limit the scope of the invention. Changes and modifications can be made in accordance with ordinary skill in the art without departing from the invention in its broader aspects as defined in the following claims.