Abstract:
A biochemical analyzer adapted to automatically perform calibration and quality control protocols using shuttles adapted to remove calibration and quality control solution vials from a loading tray and to inventory said solution vials on board the biochemical analyzer in a calibration and quality control solution server. In addition, the analyzer is adapted to automatically penetrate the closure covering the opening of the calibration and quality control solution vials, aspirate an amount of solution therefrom and dispense said solution into a test cuvette, thereby eliminating the previous need for operator intervention.

Description:
FIELD OF THE INVENTION  
       [0001]     The present invention relates to an apparatus for automatically analyzing a patient&#39;s biological fluids such as urine, blood serum, plasma, cerebrospinal fluid and the like. More particularly, the present invention relates to a method for automating the processes involved in performing quality control procedures within an automated biochemical analyzer adapted for analyzing biological fluids.  
       BACKGROUND OF THE INVENTION  
       [0002]     An increasing number of analytical assays related to patient diagnosis and therapy can be performed by automated biochemical analyzers using a sample of a patient&#39;s infections, bodily fluids or abscesses. Generally, such biochemical analyzers employ a combination of analyte specific chemical reagents and reaction monitoring means to assay or determine the presence or concentration of a specific substance or analyte within a liquid sample suspected of containing that particular analyte. Patient samples are typically placed in tube-like vials, extracted from the vials, combined with various reagents in special reaction cuvettes, incubated, and analyzed to aid in treatment of the patient. In typical clinical biochemical analyzers, one or more assay reagents are added at separate times to a liquid sample, the sample-reagent solution is mixed and incubated within a reaction cuvette. Analytical measurements using a beam of interrogating radiation interacting with the sample-reagent solution, for example turbidimetric or fluorometric or absorption readings or the like, are made to ascertain end-point or rate values from which the amount of analyte may be determined.  
         [0003]     Automated biochemical analyzers are well known and almost universally employ some sort of a calibration curve that relates analyte concentration within a carefully prepared solution having a known analyte concentration against the signal generated by the reaction monitoring means in response to the presence of the analyte. Such solutions are called “calibrators” or “calibration solutions” or “standard solutions” and are contained in tube-like vials closed with a stopper of some sort. It is regular practice within the biochemical analytical industry to establish a full calibration curve for a chemical analyzer by using multiple calibration solutions which have been carefully prepared with known, predetermined varying concentrations of analyte. These calibration solutions are assayed one or more times and the resulting reaction signals are plotted versus their respective known analyte concentrations. A continuous calibration curve is then produced using any of several mathematical techniques chosen to produce an accurate replication of the relationship between a reaction signal and the analyte concentration. The shape of the calibration curve is affected by a complex interaction between reagents, analyte and the analyzer&#39;s electromechanical design. Thus, even if the theoretical analyte-reagent reaction is known, it is generally necessary to employ mathematical techniques to obtain an acceptable calibration curve. The range of analyte concentrations used in establishing a full calibration curve is typically chosen to extend below and beyond the range of analyte concentrations expected to be found within biological samples like blood, serum, plasma, urine and the like. Herein, the term “calibration solution” also encompasses so-called “quality control” solutions typically having a zero-level and a high-level of analyte used to confirm proper analyzer operation but not to calibrate same.  
         [0004]     Due to increasing pressures on clinical laboratories to reduce cost-per-reportable result, there continues to be a need for improvements in the overall cost performance of automated biochemical analyzers. In particular, the necessity for operator involvement in conducting routine analyzer calibration protocols needs to be minimized in order to reduce overall operating expenses. A positive contributor to minimizing operator involvement is the ability to automatically provide a continuous supply of calibration solutions as required to perform a wide range of analyzer calibration protocols.  
         [0005]     Problematically, current procedures employed in the industry for calibrating an analyzer require an operator to retrieve vial containing the requisite calibration solutions from a refrigerated area, open the closed vial or the like, typically by unscrewing a cap or removing a stopper, aspirating a portion of the calibration solution, possibly preparing diluted solutions to provide a range of analyte concentrations, and dispensing some or all of several calibration solutions into a test cuvette. In certain instances, calibration solutions have an undesirably short useful life time during which the solution remains stable and thus are supplied in a more stable powdered form rather than in a less stable liquid form. Prior to being used, a vial containing a powdered or lyophilized calibration solution is opened by an operator, rehydrated using a precise amount of distilled or de-ionized water, the vial is re-closed, shaken to dissolve all lyophilized calibrator before aspirating a portion of the calibration solution. The contents of the test cuvette are then assayed by the analyzer and the results used to either confirm that the analyzer is in proper calibration condition or the results may be used to adjust the analyzer&#39;s calibration curves to achieve a proper calibration condition.  
       SUMMARY OF THE INVENTION  
       [0006]     The object of the present invention is to provide a random access biochemical analyzer adapted to determine when and which calibration solutions need to be evaluated by the analyzer and to automatically perform calibration and quality control protocols and make adjustments as required to maintain the analyzer in a proper and accurate analyzing condition. A calibration solution vial supply system important to the present invention employs container shuttles adapted to remove calibration solution vials from a loading tray and to inventory said solution vials on board the biochemical analyzer in a calibration solution server. In addition, the analyzer is adapted to automatically penetrate the closure covering the opening of the calibration solution vials, aspirate an amount of solution and dispense said solution into a test cuvette, thereby eliminating the previous need for operator intervention. This system thus provides a random access calibration solution supply system with the flexibility to position a large number of different calibration solution containers at aspiration locations by moving calibration solution vials between a calibration solution vial loading tray, at least one calibration solution vial server, and at least one calibration solution aspiration location. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0007]     The invention will be more fully understood from the following detailed description thereof taken in connection with the accompanying drawings which form a part of this application and in which:  
         [0008]      FIG. 1  is a schematic plan view of an automated analyzer adapted to perform the present invention;  
         [0009]      FIG. 2  is an enlarged schematic plan view of a portion of the analyzer of  FIG. 1 ;  
         [0010]      FIG. 3  is a perspective elevation view of an automated aliquot vessel array storage and handling unit of the analyzer of  FIG. 1 ;  
         [0011]      FIG. 4  is perspective elevation view of an aliquot vessel array useful in the analyzer of  FIG. 1 ;  
         [0012]      FIG. 5  is a perspective view of a multi-compartment elongate reagent cartridges calibration and control solution vial carrier useful in the analyzer of  FIG. 1 ;  
         [0013]      FIG. 5A  is a perspective view of a calibration and control solution vial carrier useful in the analyzer of  FIG. 1 ;  
         [0014]      FIG. 5B  is a top plan view of the calibration and control solutions vial carrier of  FIG. 5A ;  
         [0015]      FIG. 6  is a top plan view of a calibration solution vial management system useful in performing the present invention;  
         [0016]      FIG. 7  is a perspective view of a single, bi-directional linear shuttle useful in performing the present invention;  
         [0017]      FIG. 8  is a schematic view of a calibration solution aspiration and dispense system useful in performing the present invention; and,  
         [0018]      FIG. 9  is a schematic view of the calibration solution aspiration and dispense system of  FIG. 8  engaged with calibration and control solution vial carrier of  FIG. 5A . 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0019]      FIG. 1 , taken with  FIG. 2 , shows schematically the elements of an automatic chemical analyzer  10  in which the present invention may be advantageously practiced, analyzer  10  comprising a reaction carousel  12  supporting an outer cuvette carousel  14  having cuvette ports  20  formed therein and an inner cuvette carousel  16  having vessel ports  22  formed therein, the outer cuvette carousel  14  and inner cuvette carousel  16  being separated by a open groove  18 . Cuvette ports  20  are adapted to receive a plurality of reaction cuvettes  24  that contain various reagents and sample liquids for conventional clinical and immunoassay assays while vessel ports  22  are adapted to receive a plurality of reaction vessels  25  that contain specialized reagents for ultra-high sensitivity luminescent immunoassays. Reaction carousel  12  is rotatable using stepwise or cyclic movements in a constant direction, the movements being separated by a constant dwell time during which carousel  12  is maintained stationary and computer controlled assay operational devices  13 , such as sensors, reagent add stations, mixing stations and the like, operate as needed on an assay mixture contained within a cuvette  24 .  
         [0020]     Analyzer  10  is controlled by software executed by the computer  15  based on computer programs written in a machine language like that used on the Dimension® clinical chemistry analyzer sold by Dade Behring Inc, of Deerfield, Ill., and widely used by those skilled in the art of computer-based electromechanical control programming. Computer  15  also executes application software programs for performing assays conducted by various analyzing means  17  within analyzer  10 .  
         [0021]     Temperature-controlled storage areas or servers  26 ,  27  and  28  inventory a plurality of multi-compartment elongate reagent cartridges  30  like that illustrated in  FIG. 5  containing reagents in wells  32  as necessary to perform a given assay like described in co-pending application Ser. No. 09/949,132 assigned to the assignee of the present invention. Reagent cartridges  30  are equipped with a sensor mechanism  31  for automatically determining whenever a reagent container  30  is initially placed onto analyzer  10  whether reagent container  30  is new and unused or whether the reagent container  30  has been previously used. Server  26  also inventories calibration solution vial carriers  30 A like seen in  FIGS. 5A and 5B  having calibration or quality control solutions in vials  30 V to be used in calibration procedures by analyzer  10  in accord with the present invention. As described later in conjunction with  FIG. 6 , server  26  comprises a first carousel  26 A in which reagent cartridges  30  and vial carriers  30 A may be inventoried until translated to second carousel  26 B for access by an aspiration and dispense arm  60 .  FIG. 6  shows an advantageous embodiment in which carousel  26 A and carousel  26 B are circular and concentric, the first carousel  26 A being inwards of the second carousel  26 B. Reagent containers  30  and vial carriers  30 A may be loaded by an operator by placing such containers  30  or carriers  30 A into a loading tray  29  adapted to automatically translate containers  30  and carriers  30 A to a shuttling position described later.  
         [0022]     A key factor in maintaining an optimum assay throughput within analyzer  10  is the ability to timely resupply reagent containers  30  into servers  26 ,  27  and  28  before the reagents contained therein become exhausted. Similarly important is the ability to timely resupply calibration solutions in vials  30 V into server  26  before the solutions contained therein become exhausted so that calibration and control procedures may be conducted as required, whether this be based on the basis of time between calibrations or number of assays performed since an immediately previous calibration or number of assay results outside normal ranges, or changes in the performance of the analyzer. This challenge may be met by timely equipping analyzer  10  with additional requisite calibration solutions used in calibration and control procedures before they become exhausted, thereby maintaining assay throughput of analyzer  10  uninterrupted.  
         [0023]     In order to maintain continuity of assay throughput, and as taught by the present invention, computer  15  is programmed to track reagent and assay chemical solution consumption along with time, and date of consumption of all reagents consumed out of each reagent container  30  and calibration solutions consumed out of each vial container  30 A on a per reagent container, per calibration vial container, per quality control container, per assay, and per calibration basis, for specifically defined time periods. Using this consumption data, time, and current inventory data of already on-board reagent containers  30  and calibration vials  30 V within storage areas  26 , computer  15  is programmed to make an inventory demand analysis for specifically defined time periods so as to determine future assay inventory demands for the specifically defined time periods and display or issue to an operator a list of all of the reagent containers  30  and calibration vials  30 V that will be needed in the future in a timely manner prior to the actual need of said reagent container  30  and calibration vials  30 V. In some instances, reagents in reagent container  30  must be hydrated or diluted prior to use and such a time factor must also be included in the inventory demand analysis. Addition of said reagent containers  30  and calibration vial carriers  30 A by an operator insures sufficient reagent and calibration solution supply to continuously meet future needs of analyzer  10  so that analyzer  10  is maintained in proper operating condition.  
         [0024]     It should be appreciated by the reader that making a calibration solution inventory demand analysis for specifically defined time periods, as opposed to using an inventory demand analysis averaged over specifically defined time periods, is a key factor in practicing the present invention. What has been discovered is that the assay demand load pattern and thus the demand pattern for routine calibration and quality control protocols, for example on a Monday, may be very different from the demand pattern, for example on a Thursday. Further, it has been discovered that the demand load pattern, for example on a given day of the week, is most likely going to be very similar to the demand load pattern on the previous several same day of the week. The basis for a specifically defined demand pattern is due to several factors among which are a range of social practices, for example, sporting events typically being on weekends and/or increased social events at holidays and the like. In addition, for reasons of efficiency, some clinical laboratories schedule select assays, for example, PSA tests, on a certain day near middle of the week, and some out-patient tests, for example glucose, are scheduled earlier in the week. Finally, certain surgeons schedule select types of surgery early in the week and other types of surgery near the end of the week, resulting in different daily patterns of pre-operation patient assays. Further contributing to the demand pattern is the fact that different laboratories have different assay demand patterns, depending, for example, upon whether the laboratory serves an urban community where trauma is more likely than in a rural community, upon whether the laboratory serves a medical research university, upon whether the laboratory serves a specialized hospital like a pediatric hospital, and the like.  
         [0025]     On a regular basis, for example daily, as taught by the present invention, the calibration and quality control solution consumption data is also transmitted to an external computer system located within a Laboratory Information System (LIS) or Hospital Information System (HIS) or to a Manufacturer Information System (MIS) remotely at the manufacturer of calibration and quality control vials  30 A. The external computer systems use the consumption data to determine the need for re-order of vials  30 V in a timely manner so as to ensure that the calibration solutions in vials  30 V are available in local inventory for future use. In a preferred embodiment of the present invention, the vial  30 V consumption data are used by the manufacturer of calibration vials  30 V and compared to the manufacture&#39;s shipment data to determine re-order quantities. The manufacturer automatically ships additional calibration vials  30 V to the location of analyzer  10  as needed to ensure a continuous supply at that location.  
         [0026]     A bi-directional incoming and outgoing sample tube transport system  34  having input lane  36 A and output lane  36 B shown as open arrows transports incoming individual sample tubes  40  containing liquid specimens to be tested and mounted in sample tube racks  42  beneath a liquid sampling aliquotter  38  using a magnetic drive system like described in U.S. Pat. No. 6,571,934 assigned to the assignee of the present invention. Liquid specimens contained in sample tubes  40  are identified by reading bar coded indicia placed thereon using a conventional bar code reader to determine, among other items, a patient&#39;s identity, the tests to be performed, if a sample aliquot is to be retained within analyzer  10  and if so, for what period of time. It is also common practice to place bar coded indicia on sample tube racks  42  and employ a large number of bar code readers installed throughout analyzer  10  to ascertain, control and track the location of sample tubes  40  and racks  42 .  
         [0027]     After a volume of sample fluid is aspirated from all sample fluid tubes  40  on a rack  42  and dispensed into aliquot vessels  44 V by sampling aliquotter  38 , a rack  42  may be held in a buffer zone until a successful assay result is obtained. Regardless of whether sample fluid racks  42  are held in the sampling zone or buffer zone, shuttle mechanism  43  associated with the buffer zone positions the sample fluid rack  42  onto output lane  36 B. Output lane  36 B, taken with the magnetic drive system, moves racks  42  containing sample fluid tubes  40  toward the end of the output lane  36 B to a frontal area of analyzer  10  which is readily accessible to an operator so that racks  42  may be conveniently unloaded from analyzer  10 .  
         [0028]     Liquid specimens contained in sample fluid tubes  40  are identified by reading bar coded indicia placed thereon using a conventional bar code reader to determine, among other items, a patient&#39;s identity, the tests to be performed, if a sample fluid aliquot is to be retained within analyzer  10  and if so, for what period of time. It is also common practice to place bar coded indicia on sample fluid tube racks  42  and employ a large number of bar code readers installed throughout analyzer  10  to ascertain, control and track the location of sample fluid tubes  40  and sample fluid tube racks  42 .  
         [0029]     Aliquot vessel array transport system  50  seen in  FIG. 6  comprises an aliquot vessel array storage and dispense module  51  and a number of linear drive motors  52  adapted to bi-directionally translate aliquot vessel arrays  44  within a number of aliquot vessel array tracks  57  below a sample fluid aspiration and dispense arm  54  located proximate reaction carousel  12 , as seen in  FIG. 1 . Sample fluid aspiration and dispense arm  54  is controlled by computer  15  and is adapted to aspirate a controlled amount of sample fluid from individual vessels  44 V positioned at a sampling location within a track  53  using a conventional liquid probe  54 P and then liquid probe  54 P is shuttled to a dispensing location where an appropriate amount of aspirated sample fluid is dispensed into one or more cuvettes  24  in cuvette ports  20  for testing by analyzer  10 . After sample fluid has been dispensed into reaction cuvettes  24 , conventional transfer means move aliquot vessel arrays  44  as required between aliquot vessel array transport system  50 , environmental chamber  48  and a disposal area, not shown.  
         [0030]     A number of aspiration and dispense arms  60 ,  61  and  62  comprising conventional liquid probes,  60 P,  61 P and  62 P, respectively, are independently mounted and translatable between servers  26 ,  27  and  28 , respectively and outer cuvette carousel  14 . Probes  60 P,  61 P and  62 P comprise conventional mechanisms for aspirating reagents required to conduct specified assays at a reagenting location from wells  32  in an appropriate reagent cartridge  30 , the probes  60 P,  61 P and  62 P subsequently being shuttled to a dispensing location where reagent are dispensed into cuvettes  24  contained in cuvette ports  20  in outer cuvette carousel  14 . A number of reagent cartridges  30  are inventoried in controlled environmental conditions inside servers  26 ,  27  and  28 . In like manner, a number of calibration solution vials  30 V are inventoried in controlled environmental conditions inside server  26 , and may be accessed by aspiration and dispense arm  60  as required to conduct calibration and quality control protocols as required to maintain analyzer  10  in proper operating condition. A key factor in maintaining high assay throughput of analyzer  10  is the capability to inventory a large variety of vials  30 V having the requisite calibration and control solutions to perform a large number of calibration and quality control protocols inside reagent storage area  26 A and  26 B and to then quickly transfer random ones of these vials to aspiration and dispense locations for access by probe  60 P.  
         [0031]      FIG. 6 , taken with  FIG. 7 , illustrates a single, bi-directional linear shuttle  72  adapted to remove vial carriers  30 A from loading tray  29  having a motorized rake  73  that automatically locates vial carriers  30 A at a loading position beneath shuttle  72 . Vials  30 V are identified by the type of calibration and control solution contained therein using conventional barcode-like indicia and a bar-code-reader  41  proximate loading tray  29  and are closed with a septum  32 S. Computer  15  is programmed to track the location of each and every vial  30 V carried in vial carrier  30 A as the carrier is transported within analyzer  10 . In the instance that reagent container shuttle  72  is transferring a single vial carrier  30 A, as seen in  FIG. 7 , shuttle  72  comprises an automated tensioner  72 G like described in co-pending U.S. Pat. Ser. No. 10/623,311 and assigned to the assignee of the present invention and designed to compensate for changes in length a shuttling drivebelt  72 B may experience during use or for changes in tension the drivebelt  72 B may experience during abrupt reversals of direction so that vial carriers  30 A may be precisely positioned at their intended location as the drivebelt  72 B wears. In use of tensioner  72 G, a motor  72 M is controlled by computer  15  to circulate drivebelt  72 B in clockwise and counter-clockwise directions in order to position vial carriers  30 A within slots in carousel  26 . In  FIG. 7 , drivebelt  72 B has vial carrier  30 A attached thereto by means of edge guides  72 C so that vial carrier  30 A containing vials  30 V of calibration or quality control liquids may be shuttled bi-directionally along the direction indicated by the double-headed arrow. Shuttle  72  is thereby adapted to dispose a vial carrier  30 A into slots within server  26  and to dispose such vial carriers  30 A into either of two concentric carousels  26 A and  26 B within server  26 . Shuttle  72  is also adapted to move vial carriers  30 A between the two concentric carousels  26 A and  26 B. As indicated by the double-headed arc-shaped arrows, carousel  26 A may be rotated in both directions so as to place any particular one of the vial carriers  30 A disposed thereon beneath reagent aspiration arm  60 .  
         [0032]     Reagent container shuttles  27 S and  28 S in  FIG. 6  are similar in design to carrier shuttle  72  seen in  FIG. 7 . Reagent aspiration arms  60 ,  61  and  62  are shown in dashed lines to indicate that they are positioned above the surfaces of reagent containers  30  inventoried in carousel  26 B, and reagent container trays  27 T and  28 T, respectively. From this description, it is clear that shuttle  72  may also move reagent containers  30  between reagent container loading tray  29 , reagent container trays  27 T and  28 T, and carousels  26 A and  26 B; in addition shuttles  27 S and  28 S may move reagent containers  30  in reagent container trays  27 T and  28 T to appropriate aspiration locations (or to a loading location beneath shuttle  72 ) and reagent carousels  26 A and  26 B may place any reagent container  30  beneath reagent aspiration arm  60 , providing a random access reagent supply system.  
         [0033]     Aspiration and dispense arm  60  and probe  60 P useful in performing the present invention may be seen in  FIG. 8  as comprising a Horizontal Drive component  60 H, a Vertical Drive component  60 V, a Wash Module component  60 W, and a Wash Manifold component  60 M having the primary functions described in Table 1. Horizontal Drive component  60 H and Vertical Drive component  60 V are typically computer controlled stepper motors or linear actuators and are controlled by computer  15  for providing precisely controlled movements of the Horizontal Drive component  60 H and Vertical Drive component  60 V.  
                   TABLE 1                       Module   Primary Functions                   Horizontal Drive   Position the Vertical Drive 60V over vials 30V       60H   containing calibration or quality control           liquids and carried in a vial carrier 30A and           over cuvettes 24 carried in ports 20 in           carousel 14.       Vertical Drive   Drive probe 60P through the septum 30S of a       60V   vial 30V.       Wash Module   Remove contamination from probe 60P with       60W   liquid cleansing solutions       Wash Manifold   Connect probe 60P to Pump Module 60P       60M       Probe 60P   Aspirate and dispense calibration or quality           control liquids and sample fluids                  
 
         [0034]      FIG. 9  shows probe  60 P as a conventional hollow, liquid-carrying bore having conventionally defined interior and exterior surfaces and supported by Wash Manifold  60 M, the Wash Manifold  60 M being connected by a hollow air tube  70  to a three-way valve  71 . Probe  60 P preferably has a tapered point designed to reduce friction when inserted through septum  30 S and may be connected to Wash Manifold  60 M using any of several screw-like connectors, not shown, or alternately, permanently welded thereto. Valve  71  is operable to optionally connect air tube  70  to (1) a vent valve  73  connected to an atmospheric vent tube  74  and an air supply  75 , or to (2) a piston-type syringe pump  76  by a hollow air tube  77 . A conventional air pressure measuring transducer  78  is connected to air tube  77  between pump  76  and valve  71  by a hollow air tube  79 .  
         [0035]      FIG. 9  illustrates probe  60 P having punctured septum  30 S of a vial  30 V and positioned within a calibration or quality control liquid contained therein. Level sensing means, for example using well known capacitive signals, are may be advantageously employed in order to ensure that probe  60 P is in fluid communication with the liquid. Piston  76  is activated and the distance it is moved is controlled by computer  15  so that a controlled volume of calibration or quality control liquid is withdrawn or aspirated into probe  60 P. During this process, valve  71  is closed to vent tube  72 , but is open to air tube  77  and air tube  70 . Valve  71  is operable to optionally connect air tube  70  to a vent valve  73  connected to an atmospheric vent tube  74 . After aspiration of calibration or quality control liquid from vial  30 V is completed, Wash Manifold  60 M is raised by Vertical Drive  60 V and positioned by Horizontal Drive  60 H so that probe  60 P may dispense calibration or quality control liquid into a cuvette  24  carried in port  20  in carousel  14 .  FIG. 9  also shows Wash Manifold  60 W as comprising a flush valve  82  connected to Wash Manifold  60 W by a hollow liquid carrying tube  81 . Flush valve  82  is operable to connect liquid carrying tube  81  to a pressurized rinse water source  84  by a hollow liquid tube  83 .  
         [0036]     From this description, it is clear to one skilled in the art that the capabilities of shuttle  72  to move vial carriers  30 A between loading tray  29  and servers  26 A and  26 B, taken in combination with the capabilities of carousels  26 A and  26 B to place any vial carrier  30 A beneath aspiration arm  60 , and the capabilities of aspiration and dispense arm  60  and probe  60 P to access liquid solutions from closed vials  30 V provide a random access vial carrier  30 A supply system with the flexibility to deliver a large number of different calibration solutions into cuvettes  24  as needed to automatically perform calibration protocols and make adjustments as required to maintain the analyzer in a proper and accurate analyzing condition without need for operator intervention.  
         [0037]     It should be readily understood by those persons skilled in the art that the present invention is susceptible of a broad utility and application. Many embodiments and adaptations of the present invention other than those herein described, as well as many variations, modifications and equivalent arrangements will be apparent from or reasonably suggested by the present invention and the foregoing description thereof, without departing from the substance or scope of the present invention.  
         [0038]     Accordingly, while the present invention has been described herein in detail in relation to specific embodiments, it is to be understood that this disclosure is only illustrative and exemplary of the present invention and is made merely for purposes of providing a full and enabling disclosure of the invention. The foregoing disclosure is not intended or to be construed to limit the present invention or otherwise to exclude any such other embodiments, adaptations, variations, modifications and equivalent arrangements, the present invention being limited only by the claims appended hereto and the equivalents thereof.