Abstract:
An apparatus for opening and closing a container having a slidable shutter closure moving past the apparatus includes: a rotatable shaft having an axis perpendicular to the direction of travel of the slidable shutter, the shaft being biased against rotation in either direction; a driver for bidirectionally moving the shaft from a position away from the container to a position in the vicinity of the container for opening and closing; and an extension extending outwardly from the rotatable shaft along at least a portion of the shaft into a line of travel, whereby the extension is adapted to engage the shutter closure of the container and move the shutter closure from an open position to a closed position or from a closed position to an open position. A reagent source for an automated analyzer includes: a reagent source which includes a container having a shutter closure which slides between an open and closed position; an apparatus for opening and closing the container. The apparatus includes: a rotatable shaft having an axis perpendicular to the direction of travel of the slidable shutter, the shaft being biased against rotation in either direction; a driver for bidirectionally moving the shaft from a position away from the container to a position in the vicinity of the container for opening and closing; and an extension extending outwardly from the rotatable shaft along at least a portion of the shaft, whereby the extension is located to engage the shutter closure of the container as the container is transported past the extension; and a bidirectional conveyor for transporting the container into engagement with and past the apparatus for opening and closing.

Description:
BACKGROUND OF THE INVENTION 
     The present invention relates to opening and closing a container having a slidable shutter type closure. In particular, the present invention relates to opening and closing a reagent pack on an automated analyzer. 
     Known diagnostic analyzers include immunodiagnostic and clinical chemistry analyzers such as the Vitros® ECi immunodiagnostic analyzer, sold by Ortho-Clinical Diagnostics, Inc. These types of analyzers include a source of reagents for carrying out various tests. Most often, the reagents are stored in containers having removable closures, which are opened and closed each time the reagent is accessed to limit evaporation and provide on-analyzer storage stability. For example, a reagent pack container as shown in  FIG. 1  is used on the Vitros® ECi immunodiagnostic analyzer, sold by Ortho-Clinical Diagnostics, Inc. The shutter closure on the container shown in  FIG. 1  is opened and closed by an opener that is positioned over the shutter closure. In operation, the opener lowers over the shutter, engages the shutter and rotates to open the container. This type of opener is described in “Service Manual for the Vitros ECi Immunodiagnostic System—Reagent Supply,” Publication No. SM3354-6, published Apr. 5, 2001 by Ortho-Clinical Diagnostics, Inc., which is incorporated by reference in its entirety. In addition to having a relatively complex design, this type of opener requires the reagent pack container to be moved into position and come to a complete stop. The opener then engages the stopped reagent pack to open the pack. The pack is then rotated to a reagent metering station where reagent is aspirated using a reagent aspirate probe. The reagent pack is then rotated back to the opener, where the opener engages the shutter closure and closes the reagent pack. 
     In diagnostic analyzers, the throughput of an analyzer, i.e., the number of tests performed per hour, provides an important competitive advantage. However, the analyzer is only as fast as its slowest system. For example, if an incubator of an analyzer can process 180 tests/hr, but the reagent supply can only supply reagent for 90 tests/hr, then the system will necessarily be limited to 90 tests/hr. 
     With the known opener described above, the speed of accessing the reagents is limited (and thus the throughput of the analyzer is limited) due to requirement that the reagent pack be stopped to in order for the opener to engage the shutter opener/closure. Amongst other factors, such as the necessity to wash reagent metering probes, etc., the slow opening of a reagent pack contributes to the overall slowness of reagent metering. For example, the current process used to open and close these packs takes 8 seconds. In the current system using non-disposable reagent metering, the 8-second pack open/close time is not significant because it is done while the reagent-metering probe is being washed. With the disposable tip reagent-metering system being advantageous, the probe wash is eliminated which eliminates the available time to open and close the pack without causing a delay in assay processing. With the disposable tip reagent metering system, the pack opening and closing becomes the roadblock to improved throughput. 
     Other known openers include those described in U.S. Pat. Nos. 5,167,172 and 4,762,029 for opening and closing containers. 
     None of the known art described above, adequately addresses resolving the problems described above, in particular, of opening and closing containers in a relatively simple, efficient and quick manner. For the foregoing reasons, there is a need for a container opener that is relatively simple, efficient and can quickly open and close a container. 
     SUMMARY OF THE INVENTION 
     The present invention is directed to a method that solves the foregoing problems of reducing the time to open and close a container. 
     One aspect of the invention is directed to an apparatus for opening and closing a container having a slidable shutter closure moving past the apparatus. The apparatus includes: a rotatable shaft having an axis perpendicular to the direction of travel of the slidable shutter, the shaft being biased against rotation in either direction; a driver for bidirectionally moving the shaft from a position away from the container to a position in the vicinity of the container for opening and closing; and an extension extending outwardly from the rotatable shaft along at least a portion of the shaft into a line of travel, whereby the extension is adapted to engage the shutter closure of the container and move the shutter closure from an open position to a closed position or from a closed position to an open position. 
     Another aspect of the invention provides a reagent source for an automated analyzer which includes: a reagent source which comprises a container having a shutter closure which slides between an open and closed position; an apparatus for opening and closing the container. The apparatus includes: a rotatable shaft having an axis perpendicular to the direction of travel of the slidable shutter, the shaft being biased against rotation in either direction; a driver for bidirectionally moving the shaft from a position away from the container to a position in the vicinity of the container for opening and closing; and an extension extending outwardly from the rotatable shaft along at least a portion of the shaft, whereby the extension is located to engage the shutter closure of the container as the container is transported past the extension; and a bidirectional conveyor for transporting the container into engagement with and past the apparatus for opening and closing. 
     Yet another aspect of the invention provides an automated analyzer, which includes: a sample supply source; a sample metering station; a reaction vessel; a reagent source as described above; and a measuring instrument for measuring a property of the sample. 
     Still another aspect of the invention provides a combination container and container opener, which includes: a container having a slidable shutter closure; an apparatus for opening and closing the container. The apparatus includes: a retractable rotatable shaft having an axis perpendicular to the direction of travel of the slidable shutter, the shaft being biased against rotation in either direction; and an extension extending outwardly from the rotatable shaft along at least a portion of the shaft, whereby the extension is adapted to engage the shutter closure of the container. 
     Yet another aspect of the invention provides a method for opening or closing a container, which includes: providing a container having a shutter closure in a closed position slidable to an open position or in an open position slidable to a closed position; providing an apparatus for opening and closing the container, the apparatus includes: a rotatable shaft having an axis perpendicular to the direction of travel of the slidable shutter, the shaft being biased against rotation in either direction; a driver for bidirectionally moving the shaft from a position away from the container to a position in the vicinity of the container for opening and closing; and an extension extending outwardly from the rotatable shaft along at least a portion of the shaft into the line of travel of the conveyor at a neutral position; transporting the container in a first direction toward the apparatus; engaging the extension with the shutter closure as the container moves past the apparatus, whereby the extension forces the closure to slide from a closed to an open position or from an open position to a closed position. 
     Further objects, features and advantages of the present invention will be apparent to those skilled in the art from detailed consideration of the preferred embodiments that follow. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a perspective view of a reagent pack container known in the art. 
         FIG. 2  is a top schematic view of a reagent pack and opener according to a preferred embodiment of the present invention. 
         FIG. 3  is a side cross sectional view of the opener according to a preferred embodiment of the present invention. 
         FIG. 4  is a perspective view of a reagent storage unit usable with the present invention, showing a carousel for rotating the reagent packs. 
         FIG. 5  is a perspective view of a diagnostic analyzer usable with the present invention. 
     
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
     The present invention includes an opener which has a simplified design for quick and dependable opening of a container which has a slidable shutter closure, such as that shown in  FIG. 1 . The simplified design is provided is by using the motion of the container to provide the necessary force to open or close the container, depending on its position. 
     Broadly, the opener includes a rotatable and axially translatable shaft. The axis of the shaft is approximately perpendicular to the direction of travel of the shutter opening. In most cases, this will be perpendicular to the direction of travel of the container. Attached to or extending from at least a portion of the shaft, preferably the end of the shaft closest to the container, is an extension which engages the shutter closure and provides the force necessary to open and/or close the shutter closure. The extension can be fashioned as a paddle or a fin and be a relatively flat extension having a relatively large surface area to engage the shutter closure. 
     When not engaged with the closure the extension is in a neutral position. However, since the shaft is rotatable, the extension is capable of being moved away from the neutral position when it is engaged with the closure. To return the extension to the neutral position, a biasing force, for example, provided by dual acting torsion springs, is provided which applies a force against the extension when the extension is away from the neutral position. This ensures that the extension is returned to its proper neutral position each time after engagement to provide proper alignment for engagement with the next container closure. Of course, since the apparatus is capable of opening and closing, it is necessary that the extension be moved or deflected in both directions and that the biasing force can return it to the neutral position from either deflected position. 
     As described above, the shaft is axially translatable. That is, it can be moved along the length of its axis. In those preferred embodiments, the extension can be moved away from the shutter closure of the container, when it is desired to not open the container. The shaft can be moved axially or translated by any suitable force, such as provided by a solenoid, a servo motor or pneumatic or hydraulic actuation systems. 
     The opener can be used with any suitable container having a closure that can be engaged with the extension, and which opens or closes by interaction of the extension and closure with the movement of the container providing the opening and closing force. In a preferred embodiment, the closure of the container is a shutter-type closure where the opening of the container is exposed by the closure sliding across the opening. To assist in engagement with the extension, a protrusion is provided that extends from the closure surface. 
     In a preferred embodiment, the container can be a reagent pack as shown in  FIG. 1  and the protrusions are ribs that extend perpendicularly from the shutter closure to provide contact with the extension of the opener. The ribs must be positioned so they will provide sufficient time of contact so that as the container passes past the extension, the ribs will contact the biased extension which will force the slide closure to move either into an open or closed position depending on the direction of travel of the container. 
     In a preferred embodiment, the containers are used to hold reagents on a diagnostic analyzer. The reagent containers can be located and stored on the analyzer, preferably in a refrigerated condition for greater stability. In a preferred embodiment, the containers are located on a carousel that is capable of moving the containers past and into contact with the opener of the present invention, as well as the reagent metering system. Of course, a linear conveying system could also be used. 
     Now reference will be made to the non-limiting preferred embodiments shown in the figures.  FIG. 1  is a known reagent pack container  10  used on diagnostic analyzers such as the Vitros® ECi analyzer described above. As  FIG. 1  shows, the container includes two reagent bottles  11   a  and  11   b  having openings  12   a  and  12   b , respectively. A frame  13   a ,  13   b  and  13   c  are used to contain the reagent bottles and to provide support for the slidable shutter. The vertical support  13   b  can be constructed in a tubular fashion in order to hold reaction wells. A sliding shutter closure  15  is mounted on the top of the reagent pack  10 . In the embodiment according to  FIG. 1 , a single bifurcated slidable shutter having two sections  15   a  and  15   b  is used for each opening  12   a  and  12   b , respectively. The shutter is rotatably anchored to the reagent pack by pin  15   c.    
     A reagent pack according to  FIG. 1  which has been modified along with the opener according to the present invention, is shown in  FIG. 2 .  FIG. 2  is a top view of three side-by-side reagent packs on a carousel tray (not shown in  FIG. 2 ). The reagent packs are similar to those shown in  FIG. 1  and like reference numbers denote like features. One significant difference between the reagent pack in  FIG. 1  and those shown in  FIG. 2  is the addition of additional ribs  17   a  and  17   b . These additional ribs allow the opener(s)  30  shown in the  FIG. 2  embodiment to engage the shutter closure  15 . The original ribs  16   a  and  16   b  are preferably retained to allow the modified reagent pack to be used on diagnostic analyzers that do not include the opener of the present invention. 
     The packs can move in both a clockwise direction B and a counterclockwise direction A as shown by the arrows in  FIG. 2 . Also shown in  FIG. 2  are two openers  30  one each located on both sides of the reagent packs. As shown in  FIG. 3 , the opener includes an axially movable shaft  31  that can be moved in an direction shown by arrow C. The shaft  31  can also rotate about its axis in a direction D as also shown in  FIG. 3 . The opener also includes an extension  32  that extends away from the axis of the shaft. The extension can have any desired shape or configuration as long as it is capable of interacting with the ribs  17   a  and  17   b . Preferably, the extension is in the shape of a paddle or blade, i.e., having a large planar surface area, relative to its thickness. 
     The opener can be mounted above or below the reagent packs as long as the extension  32  can interact with the ribs on the reagent pack. Preferably, it is mounted above the reagent packs. As shown in  FIG. 3 , the opener is mounted above the reagent packs using bracket or journal  40  that can be attached to any suitable part of the analyzer. As explained above, the shaft  31  can be axially translatable by any suitable force described above. In a preferred embodiment, the force can be a stepper motor  34  located at the top of the shaft  31 . The motor is controllable to raise and lower the extension  32  into and out of contact with the reagent packs. This feature is useful when it open and closing of the reagent packs is not necessary, but rotation of the reagent packs past the opener(s) is necessitated. 
     As also explained above, while the extension is rotatable in both directions about shaft  31 , it is biased against doing so by the action of a biasing force provided by a dual acting torsion spring  33 . When no force is being applied to the extension, the extension is in a neutral position  32   a  which extends into the path of travel of the reagent pack. When the reagent pack engages the extension, the extension is moved into deflected positions  32   b  or  32   c  shown by phantom lines in  FIG. 2 . After disengagement, the spring  33  biases the extension back into its neutral position. 
       FIG. 4  shows the reagent packs in a reagent storage unit of a clinical analyzer. The reagent packs  10  (slidable shutter closures not shown) are located on a conveyor  50 , which rotates the reagent packs past reagent pack opener(s) (not shown in  FIG. 4 ). 
     In operation, the extension  32  is lowered by servo motor into the line of travel of the reagent packs  10  on conveyor  50 . If the reagent packs are traveling in direction B as shown in  FIG. 2 , rib  16   a  will contact extension  32  in its neutral position  32   a . Upon contact, extension  32  will deflect or move by rotation to towards position  32   b . Due to the biasing force, the shutter opener will also deflect rotating the shutter around pin  15   c . As the conveyor continues to rotate, the extension will then contact rib  17   a , further deflecting the extension towards position  32   b  and further rotating shutter around pin  15   c . After the extension disengages rib  17   b , the extension returns to its neutral position and the shutter opening will be in its open position as shown by reagent pack  10   b . Reagent may then be aspirated from the reagent pack by reagent metering probe  100  described below in connection with  FIG. 5 . 
     Closing the reagent packs will operate in much the same way as opening. When an open pack is transported on conveyor  50  in direction A as shown in  FIG. 2 , the extension in its neutral position  32   a  will contact rib  17   b . As the reagent pack moves, extension  32  is deflected by rotation about shaft  31  towards position  32   c . The shutter opening will also deflect and rotate around pin  15   c  towards a closed position. As the conveyor continues to rotate in direction A, the extension will contact rib  16  further rotating shutter opening towards closed position. Upon disengagement of the extension  32  from ribs  16 , the extension  32  will return to neutral location  32   a.    
       FIG. 5  shows a preferred clinical analyzer that can be used the opener/closer of reagent packs according to one embodiment of the present invention. The type of analyzer is described in more detail in U.S. Ser. No. 09/482,599 filed Jan. 13, 2000, the contents of which are incorporated by reference. As shown in  FIG. 5 , reagent packs  10  are initially external to the system but they are components that are manipulated by the reagent source. Reagent packs  10  are configured to contain the reagents necessary to conduct an assay. Typically, they include one or more antigenic or antisera components used to combine with the analyte and provide adhesion to or with a reaction vessel. 
     The reagent source includes autoload station  110  which shuttles reagent packs to the reagent supply substation  112  by any suitable drive mechanism such as a chain and sprocket, belt and pulley, gear train, linked belt mechanism, a driven series of mechanical links such as pawl links, or the like. The reagent source further includes a reagent supply cooler  120  that cools the interior of the reagent supply substation according to the functional requirements of the reagents (typically, 3-15° C., preferably 4-10° C.). In this way, reagent supply cooler  120  maintains reagents and reaction vessels at the appropriate humidity and temperature. 
     The reagent source further includes a reagent metering arm  145  having a reagent probe  100  movably attached to it. Reagent metering arm  145  is pivotable so that it can position the reagent probe  100  in position to dispense reagent or diluent into a reaction vessel. Reagent probe  100  aspirates, transports, and dispenses reagent and/or diluent into reaction vessel. It is generally configured so that it also moves in a vertical direction to dip into the opened reagent packs  10  and lower itself into the vicinity of the reaction vessel (well). This is accomplished by any of the well known mechanisms for affecting vertical motion such as gear train with step motor, belt and pulley assembly, pneumatic or hydraulic lifts, or the like. A stepper motor with fine steps (at least about 390 steps per cm of vertical motion are desired) connected to a rack and pinion drive is the preferred mechanism for regulating vertical motion. Where pivoting is required, a stepper motor with fine steps is also preferred (generally, at least about 1720 steps per revolution of the shaft used to rotate the probe or probe arm are desired) with the pinion comprising or attached to the outer diameter of the shaft that is rotated. Control of stepper motors, and hence probe and mechanism movement, is accomplished by techniques well known in the art such as those described in U.S. Pat. No. 5,646,049 which is incorporated herein by reference. 
     In operation, the reagent probe  100  aspirates and dispenses fluids via connection to a fluidics systems comprised of valves, pumps, tubing, and the like. It is preferably charged by vacuum and can disperse by release of vacuum or by pressurization. 
     Sample supply source loads and meters sample to the appropriate reaction vessels (preferably, wells not shown). It is also capable of providing input to the data processing systems via bar code reader  200  that reads bar codes that may be placed on patient sample vessels such as test tubes and the like. The sample supply source also includes a number of subsystems and components. The sample supply subsystem is one which is comprised of a bar code reader  200  for inputting sample identification data as described above and a sample tray conveyor  205 , one or more sample tray transports  210 , and positioner  215  for moving sample to the sample metering station adjacent to the sample positioner (i.e. the position into which proboscis  230  is lowered, as described below). 
     The sample tray conveyor  205  can be any conveyor system for moving vessels and can employ an electrically or mechanically movable magnetic drive that propels a carousel  220  atop a sample tray transport  210  having a magnetic or ferrous component attractive to the magnetic drive. Alternatively, the sample tray conveyor  205  can comprise a motor driven chain and sprocket mechanism, a driven series of mechanical links such as pawl links, a belt driven system or the like. The preferred sample tray conveyor is an elliptical magnetically driven tracked system. In this system, the sample tray is preferably a carousel  220  that sits atop a transport  210  that has a piece susceptible to magnetic attraction. This enables it to be moved around the ellipse through the rotation of a magnetic field around the perimeter of the elliptical track from a position beneath the sample trays. In this configuration, the outer diameter of the sample tray can be geared so that the tray can be rotated about its own central axis by a geared piece such as positioner  215  adjacent to the bar code reader  200  (or at any other convenient location around the exterior of the elliptical track). 
     The sample metering subsystem aspirates samples and dispenses them into reaction vessels via proboscis  230 . The proboscis and its related metering arm  245  are preferably similar in design to the reagent metering arm  145  described above. Disposable tips (not shown) through which sample can be aspirated and dispensed are preferably fitted on the proboscis and are disposed after use. The tips are preferably conical with the apex of the cone pointed toward down. Appropriate robotic commands are used to position the proboscis over the tips and then temporarily attach the tips via force (injection of the proboscis into the hollow portion of the tip). For convenience, a supply of tips can be maintained on a tip supply carousel (not shown). The tips can likewise be removed by raising the proboscis drive to its top most travel, activating an ejector sleeve (not shown). Generally, disposable tips are comprised of a molded thermoplastic such as polyethylene or polypropylene. Such tips avoid direct and repeated contact of sample and a singular proboscis end. 
     In operation, the sample metering subsystem functions similarly to that of the reagent metering system. Sample, loaded on sample carousel  220  is driven to a location reachable by the proboscis  230 . After having loaded a disposable tip onto the proboscis, the system pivots the proboscis directly overhead a sample vessel. The proboscis is then lowered into a vessel such as a tube on the carousel where it aspirates a quantity of sample sufficient for the assay to be conducted. The proboscis is then pivoted to a position that is overhead a well residing in outer ring (not shown) where the sample is dispensed. It is preferable that the sample is dispensed into the well before reagent has been dispensed into the well. The proboscis can then be used to validate the proper metering of the sample into the well. This is accomplished by fitting the proboscis with a sensor such as an optical sensor on sample metering arm  245 . The sensor (not shown) is in communication with a transducer (not shown) and the data processing system  600 . The sensor preferably detects the level of the sample by pressure differential, through capacitance, or reflected energy as is known in the art. An optical sensor can also be used to home the proboscis to its proper position. After metering and measuring the sample, reagent is preferably dispensed into the well as described above. Mixing of sample and reagent is accomplished by dispensing reagent into the well containing sample with sufficient velocity to give partial mixing. 
     Some assays require dilution of the sample. When this is the case, sample is first metered into a dilution vessel that is preferably substantially similar to the wells previously described except that they are not generally treated with any reagent or other materials to which added reagent will adhere. That is, they are functionally inert within the context of the immunochemical reactions of interest. Proboscis  230  is used to meter the sample as in other assays. 
     In the processing system, reaction wells containing sample, reagent, and (optionally) diluent are mixed with signal reagent and incubated in incubator  300 . Chemiluminescence or other appropriate signal generation of the reaction of sample analyte and reagent(s) is also read in this system. Well wash arm  310  and well wash probe  315  are the principle components of the well wash subsystem whose function is to wash the wells and remove sample and unbound reagent (analyte is bound to the reaction vessel along with reagents that manifest the signal that is read later). The temperature and humidity are controlled within incubator  300  for a time and at a temperature appropriate to the assays being performed. Incubation time can differ from assay to assay and is under the control of the data processing system. 
     Returning to the well wash subsystem, after appropriate incubation, well wash probe  315  (which is preferably similar in design to the reagent probe  100 ) is manipulated so that it aspirates and dispenses sample and unbound reagent out of the reaction wells and then dispenses wash fluid into the wells, aspirates and dispenses again. Thus, to this point within the reaction wells, reagent and analyte have reacted and have been adhered to the well. The well wash arm has removed materials that have not reacted and/or could otherwise interfere with sample reading. 
     It is also possible to configure such an instrument so that the unmeasured materials would adhere to a reaction vessel and the contents of the vessel would be further processed or be subject to some reading. In such a case they would then have to be aspirated and dispensed to another vessel. 
     Upon completion of well washing, the well wash arm  310  articulates movably attached well wash probe  315  to a position to aspirate sample and unbound reagent and dispense wash fluid to the reaction vessel. Generally, wash fluid is dispensed as the well wash probe  315  is lifted out of the reaction vessel. The signal reagent subsystem comprises signal reagent arm  410 , signal reagent probe  400 , signal reagent (packs)  420 , and prime/pump assembly  415  as its major components. Signal reagent probe  400  (which is preferably similar in design to the other probes already described), movably attached to signal reagent arm  410  aspirates, transport, and dispenses signal reagent from signal reagent pack  420  to the wells. Signal reagent arm  410  is fitted to a prime, pump assembly  415  for this purpose. Signal reagent is a composition that contains a component that produces a signal upon combination with the reacted reagent/sample combination (e.g., luminol derivatives). Luminometer  500  is comprised of a fiber optic bundle  510  that communicates with photomultiplier  520  which is in further communication with data processing system  600 . In operation, the fiber optic bundle  510  is positioned over the sample with mixed reagent and, optionally, diluent. Chemiluminescent signals generated by the reacting reagent/sample combination are then transmitted to the photomultiplier that converts the light signal to an electrical signal for processing according to conventional digital techniques. An internal reference (not shown) can be used for calibration of the luminometer  500 . 
     Data processing system  600  is an integrated array of circuitry used to coordinate the function of the systems and subsystems, conduct system diagnostics, calibrate instrumentation, record results, and analyze results. It includes well known processing devices such as microprocessors and may be in electronic communication with any number of external processing systems. For example, it may be linked through a local area network to other analytical instrumentation so that tests are scheduled and results are compiled and reported for a number of different assays, some of which are not conducted on the instrument described here. 
     As described above, the advantages of the present invention as described above are in reducing the time required to open and close reagent packs for clinical analyzers. For example, in some embodiments, nearly all of the approximately 8 seconds needed for opening and closing reagent packs can be eliminated to reduce the reagent dispense timing cycle from 28 seconds to 20 seconds. This creates the potential to significantly increase the throughput speed of an analyzer. In the preferred embodiment described above in connection with the drawings, the reagent packs useable with the opener of the present invention can also be used on analyzers having prior openers, thus backwards compatibility is retained. 
     The opening and closing method according to the present invention can be implemented by a computer program, having computer readable program code, interfacing with the computer controller of the analyzer as is known in the art. 
     It will be apparent to those skilled in the art that various modifications and variations can be made to the compounds, compositions and processes of this invention. Thus, it is intended that the present invention cover such modifications and variations, provided they come within the scope of the appended claims and their equivalents. 
     The disclosure of all publications cited above are expressly incorporated herein by reference in their entireties to the same extent as if each were incorporated by reference individually.