Abstract:
A system and method for preparing and dispensing fluid mixtures is provided. Fluid wells are positioned below a plurality of fluid dispensing devices, such as syringes configured to dispense fluid into the individual fluid wells. The fluid dispensing devices are configured to be positionable relative the fluid wells to enable different fluid dispensers to be sequentially positionable over a particular fluid well. A controller controls the relative movement between fluid wells and the fluid dispensing devices. In a preferred embodiment, the controller selectively moves multi-well vessels in one direction and moves the fluid dispensing devices in a second direction so that when directed by the controller, a selected fluid dispensing device is enabled to deposit a determined quantity of a fluid into a selected individual well of the multi-well vessels.

Description:
FIELD OF THE INVENTION  
         [0001]    The present invention relates to the field of fluid dispensing systems. In particular, the present invention relates to an automated and robotic system for providing repeatable, high throughput dispensing of a plurality of fluids.  
         BACKGROUND OF THE INVENTION  
         [0002]    Fluid dispensing systems are useful in a variety of areas, including the area of preparing fluid mixture samples to be screened for identification of a fluid mixture capable of crystallizing a protein that is, in turn, studied with x-rays to determine its function and the function of the gene encoding it.  
           [0003]    With the identification of the more than 31,000 genes of the human genome, the determination of each gene&#39;s role in the functioning of the human body has become of paramount importance. Genes generally function to produce at least one protein, and thus the functions of numerous proteins produced by genes also are studied. Ascertaining protein structure can be an important step in understanding the function of that protein.  
           [0004]    One technique for ascertaining a protein&#39;s structure is to obtain high-quality x-rays of the protein&#39;s crystalline structure. To do so, a preliminary step is crystallizing the protein. One technique for protein crystallization involves crystallizing the protein in a fluid mixture formulated to provide a stable crystal structure for that particular protein. Growing protein crystals using such a technique, however, can be difficult and very time consuming. Each new protein crystallization typically requires a unique concentration and mixture of fluids for crystal growth. It can be necessary to screen a protein sample against hundreds or even thousands of available fluid mixtures in order to determine a proper fluid mixture that will crystallize a single protein. For example, finding the proper fluid mixture may require varying the composition of the mixture using a multidimensional array of variables, such as different salt and buffer fluids, different concentrations and pH values for each fluid, and different atmospheric conditions.  
           [0005]    Screens for suitable protein crystallization conditions are currently conducted manually using skilled technicians. Performing each screen can be a labor intensive process in part because the different fluids into which the proteins are deposited must themselves be deposited in very small amounts into very small fluid reservoirs. The physical act of dispensing such small amounts into such small fluid reservoirs is itself a time consuming and inaccurate process. In addition, the amount of protein available for each individual screen is often limited, and screening fluids used in each screen are typically measured in microliters. This requires a high level of precision and accuracy that can be difficult even for skilled technicians. Reliability and repeatability of each screen is integral to the precision and accuracy of each screen. Accordingly, there exists a need to automate the screening process, and to increase the level of precision, accuracy and repeatability of the process.  
           [0006]    Conventional crystallization techniques may require that each protein to be crystallized is screened against numerous different fluid mixtures (typically hundreds, or many thousand) in order to find a proper composition that provides stable crystallization conditions for the particular protein in question. In a manual screening process, a technician is primarily responsible for measuring, mixing, and dispensing each unique fluid mixture. Such a manual process is time consuming and expensive, and therefore the variations of fluid mixtures are often limited because of time constraints in the screening process. Unfortunately, by reducing the granularity of the screen, a less than optimum fluid mixture will likely be selected. Further, such a manual screening process is highly susceptible to human mathematical and measurement errors in fluid preparation. In such a manner, the screen may produce erroneous, unreliable, or unrepeatable results.  
           [0007]    Yet another problem associated with screening crystallization conditions is that many of the known buffer fluids, and other fluids used in the screens tend to be highly volatile. These volatile fluids can evaporate or change in character over time. Therefore, it can be difficult to manually prepare a screen having a large number of individual tests because of the time required to deposit the fluids into each well. As the different fluids are deposited in each well, the volatile fluids can evaporate or otherwise change composition, rendering the particular screen inaccurate.  
           [0008]    Therefore, there exists a need for a fluid dispensing system that can quickly and repeatedly perform the multiple fluid depositing steps required for large numbers of screens or other types of precise, highly repeated, fluid handling processes.  
         SUMMARY OF THE INVENTION  
         [0009]    The present invention alleviates to a great extent the disadvantages of the known protein crystallization and screening techniques by providing an automated system and method of performing multiple fluid depositing steps for high throughput processing protein screening and crystallization.  
           [0010]    Briefly, in a preferred embodiment, fluid wells are positioned below a plurality of fluid dispensing devices. For example, syringes may be configured to dispense fluid into the individual fluid wells. The fluid dispensing devices are configured to be positionable relative the fluid wells. This enables different fluid dispensers to be sequentially positionable over a particular fluid well. A controller preferably controls the relative movement between the fluid wells and the fluid dispensing devices. It is preferred that the controller include software that allows operator flexibility in determining the relative movement between the fluid wells and the fluid dispensing devices.  
           [0011]    In operation, the controller selectively operates a multi-well vessel transport in one direction and moves the fluid dispensing devices in a second direction. When directed by the controller, a selected fluid dispensing device deposits a determined quantity of a fluid into a selected individual well of the appropriate multi-well vessel.  
           [0012]    It is preferred that a plurality of multi-well vessels and fluid dispensing devices be arranged to work in close association with each other so that an increase in throughput is achieved. Accompanying the increase in throughput is an increase in reliability and repeatability, and a decrease in the time associated with fluid deposition. The increased throughput substantially eliminates the conventional problem of having the character of the deposited fluids change as a result of volatility.  
           [0013]    In one aspect the present invention features an apparatus for automatically preparing mixtures of fluids in a plurality (e.g., 96, 384, or 1536) of wells of a multi-well holder. The apparatus includes a plurality of fluid dispensing devices capable of being sequentially positioned above the wells. Each fluid dispensing device is capable of dispensing a fluid into a well when the well is positioned below the fluid dispensing device. The apparatus also includes a controller that controls dispensation of the fluid from the fluid dispensing devices and the relative movement between the fluid dispensing devices and the wells.  
           [0014]    In preferred embodiments, the plurality of tubes are configured so that 1, 2, 3, 4, 5, 6, 7 or 8 multi-well holders can be beneath the plurality of tubes at the same time. Preferably, the plurality of tubes are configured so that the dispensing mechanisms can deliver the material to 1, 2, 3, 4, 5, 6, 7 or 8 multi-well holders at the same time. The plurality of tubes may be configured so that all of the dispensing mechanisms can deliver the material at the same time. In one preferred embodiment, the moving element has a length of at least n multi-well plates, wherein n is the number of multi-well plates, wherein each multi-well plate has m wells, wherein m is the number of wells, wherein the apparatus processes a multi-well plate every m dispensings even though the muti-well plate is in the apparatus for n times m dispensings. For example, the moving element has a length of at least five multi-well plates, wherein each multi-well plate has 96 wells, wherein the apparatus processes a multi-well plate every 96 dispensings, even though the multi-well plate is in the apparatus for 480 dispensings. The dispensor controller preferably directs the delivery of the material from each fluid container to each multi-well plate, for example the dispenser controller may direct the delivery of the material from each of at least eight fluid containers to each of at least five multi-well plates.  
           [0015]    In another aspect, the invention features a system for efficiently loading mother liquors in a plurality of multi-well sample plates for a course screen, the plurality of sample plates arranged with corresponding columns aligned, the system including: (a) a plate arranging area configured to receive the plurality of sample plates; (b) a plurality of fluid containers, each fluid container holding a predetermined mother liquor mixture; (c) a plurality of syringes arranged in an array, the array, each syringe being in fluid communication with an associated one of the fluid containers; (d) a drive mechanism constructed to sequentially position the syringes in the array directly over each column of wells in the sample plate; (e) a dispensing mechanism associated with each syringe; and (f) a fluid controller communicating to the dispensing mechanism; wherein the fluid controller directs the dispensing mechanisms to deliver a quantity of each associated mother liquor into each sample well in a column before the drive mechanism moves the syringe array to a next column.  
           [0016]    In preferred embodiments the plurality of syringes are configured so that 1, 2, 3, 4, 5, 6, 7 or 8 sample plates can be beneath the plurality of syringes at the same time. The plurality of syringes preferably are configured so that the dispensing mechanisms can deliver the material to 1, 2, 3, 4, 5, 6, 7 or 8 sample plates at the same time. The plurality of syringes may be configured so that all of the dispensing mechanisms can deliver the material at the same time. In one preferred embodiment, the system includes a moving element that has a length of at least n sample plates, wherein n is the number of sample plates, wherein each sample plate has m wells, wherein m is the number of wells, wherein the system processes a sample plate every m dispensings even though the sample plate is in the system for n times m dispensings. For example, the moving element has a length of at least five sample plates, wherein each sample plate has 96 wells, wherein the system processes a sample plate every 96 dispensings, even though the sample plate is in the system for 480 dispensings. The fluid controller preferably directs the delivery of the material from each fluid container to each sample plate, for example, the dispensor controller directs the delivery of the material from each of at least eight fluid containers to each of at least five multi-well plates.  
           [0017]    In another aspect, the present invention provides a method for automatically preparing a mixture in a well of a multi-well holder. The method involves the steps of: (a) moving the multi-well holder so that the well is positioned below a fluid dispensing device; (b) dispensing fluid from the fluid dispensing device into the well; and (c) repeatedly moving the multi-well holder so that the well is positioned below a next fluid dispensing device and dispensing fluid from the next fluid dispensing device into the well until a predetermined mixture is prepared.  
           [0018]    In preferred embodiments, the plurality of syringes are configured so that 1, 2, 3, 4, 5, 6, 7 or 8 multi-well holders can be beneath the plurality of syringes at the same time. The plurality of syringes preferably are configured so that the syringes can deliver the material to 1, 2, 3, 4, 5, 6, 7 or 8 multi-well holders at the same time. The plurality of syringes may be configured so that all of the syringes can deliver the material at the same time. In one preferred embodiment, the sample plates are on a moving element that has a length of at least n sample plates, wherein n is the number of multi-well plates, wherein each multi-well plate has m wells, wherein m is the number of wells, wherein the method processes a multi-well plate every m dispensings even though the method involves n times m dispensings. For example, the sample plates are on a moving element that has a length of at least five multi-well plates, wherein each multi-well plate has 96 wells, wherein the method processes a multi-well plate every 96 dispensings, even though the method involves 480 dispensings. Preferably, a controller directs the delivery of the material from one or more fluid containers to each sample plate. For example, the controller directs the delivery of the material from each of at least eight fluid containers to each of at least five multi-well plates.  
           [0019]    Finally, in another aspect, the present invention provides a syringe array for dispensing liquid into a plurality of multi-well sample plates. The syringe array includes a plurality of N syringes coupled into a linear array. N is a whole number multiple of the number of sample wells in one line of each sample well. Each sample plate includes sample wells organized in a geometric pattern. The line may be a row or a column. By way of example, the number of sample wells in a line may be 12 and N may be 96.  
           [0020]    In preferred embodiments of any of the aspects of the invention described herein, the footprint of the tubes in the column direction (i.e., the column length footprint) of the multi-well holder is at least 5.030, 10.060, 15.090, 20.120, 25.150, 30.180, 35.210, 40.240, or 45.270 inches long.  
           [0021]    It readily will be appreciated that an advantage of the present system is to increase the speed, accuracy and reliability of protein crystallization and processing operations. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0022]    These and other features and advantages of the present invention will be appreciated from review of the following detailed description of the invention, along with the accompanying figures in which like reference numerals refer to like parts throughout.  
         [0023]    [0023]FIG. 1 is an elevation of a fluid dispensing system in accordance with the present invention;  
         [0024]    [0024]FIG. 2 is a perspective view of a plurality of multi-well vessels positioned underneath a tube array in accordance with the present invention;  
         [0025]    [0025]FIG. 3 is an elevation of a tube array and fluid source in accordance with the present invention;  
         [0026]    [0026]FIG. 4 is a plan view of a plurality of tubes positioned adjacent a multi-well vessel in accordance with the present invention;  
         [0027]    [0027]FIG. 5 is a flow-chart illustrating a method for dispensing a plurality of fluids in accordance with the present invention; and  
         [0028]    [0028]FIG. 6 is a plan view of a multi-well vessel positioned underneath a section of a tube array in accordance with the present invention. 
     
    
       [0029]    Some or all of the Figures may be schematic representations for purposes of illustration and do not necessarily depict the actual relative sizes or locations of the elements shown.  
       DETAILED DESCRIPTION OF THE INVENTION  
       [0030]    In the following paragraphs, the present invention will be described in detail by way of example with reference to the drawings. Throughout this description, the preferred embodiments and examples do not limit the scope of the present invention.  
         [0031]    I. A Multi-Fluid Dispensing System  
         [0032]    Referring now to FIG. 1, an apparatus for preparing a fluid mixture is shown. More particularly, the apparatus for preparing a fluid mixture is illustrated as a multi-fluid dispensing system  20 . The multi-fluid dispensing system  20  provides an automated and robotic process for handling, dispensing and storing fluid samples. The fluid samples may be, for example, genetic material, chemicals, or living cells. In one embodiment, the fluids may be “mother liquors” for the growth of protein crystals. Other types of fluids can be employed in the present invention. Although the illustrated examples are used to prepare fluid mixtures for screening protein crystallization mixtures, the apparatus and method for preparing fluid mixtures may be used for other purposes and in other fields.  
         [0033]    The multi-fluid dispensing system  20  comprises a plurality of fluid dispensing tubes  25  mounted in a tube array  23 . The tube array is attached to a tube transport  30 . In one embodiment, 96 tubes  25  are mounted to the tube array  23  in a single row. Different numbers of tubes  25  mounted in a different arrangement on the tube array  23  can be employed. For example, shown in FIG. 4, a plurality of tubes  25  are mounted in a staggered configuration on tube array  23 .  
         [0034]    Referring to FIGS. 2 and 3, tube transport  30  mounts the tube array so that the plurality of tubes are aligned with a conveyor  50 . In a preferred embodiment the conveyor  50  provides for movement of multi-well vessels in the positive X-direction  95 . The tube transport  30  is configured to move the tube array  23  in both the positive and negative Y-direction  100 , which is substantially perpendicular to direction of movement provided by the conveyor  50 . Although the conveyor  50  and the tube transport  30  are configured to provide relative movement between the tubes  25  and the vessels  45 , other arrangements may be used for providing such relative movement. For example, either a conveyor or a tube transport may be individually constructed to provide both X- and Y-axis movement.  
         [0035]    In a preferred embodiment, tube transport  30  communicates with controller  65  and is moved by electric motors, although other types of transport devices can be employed to move tube transport  30 , such as pneumatic, hydraulic or other suitable devices.  
         [0036]    A fluid source  35  comprises a plurality of fluid pumps  37  for pumping fluid to the tubes  25 . The fluid pumps  37  are controlled by a plurality of pump control boxes  39 , which are preferably operated by a controller  65 . The controller  65  may be, for example, a general purpose computing device such as a commonly available PC which has been programmed to perform the steps required by the present invention. The controller  65  is operated through an operator interface  70  such as a touch-activated CRT. Other devices can be used to interface with the controller  65 , such as a keyboard, or voice-activated system. Also, controller  65  may be a dedicated controller circuit or processor configured as an embedded controller, and may be locally present or accessed through a network, such as a local or wide area network.  
         [0037]    In one embodiment, the fluid pumps  37  are solenoid valve dispensers that are connected to the tubes  25 , which are positive displacement syringe pumps. The syringe pumps are configured to dispense very small amounts of fluid. For example, one embodiment of the present invention employs tubes  25  that dispense nanoliters or microliters of fluid, preferably about 1-10 nanoliters or microliters. In a preferred embodiment, the fluid source  35  comprises 96 solenoid valve dispensers each communicating with the 96 tubes  25 .  
         [0038]    When configured for protein crystallization growth, fluid pumps  37  are each coupled to a fluid source, with each fluid source being a “mother liquor” designed to facilitate growth of protein crystals. These mother liquors can be salts, buffers, detergents, organic chemicals, and other suitable fluids. Virtually any fluid can be dispensed by the fluid pumps  37  into tubes  25 .  
         [0039]    Referring to FIGS. 1 and 2, the tube array  23  is arranged to dispense fluid through the tubes  25  into individual wells  40  located in a multi-well plate or vessel  45 . The multi-well plates  45  are dispensed from plate dispensers  55  onto a conveyor  50 . The multi-well plates  45  are carried down the conveyor  50 , and fluid is dispensed into the wells  40 . The plates  45  are collected at the other end of the conveyor by plate receivers  60 . Alternatively, the plates  45  can be delivered to a diving board  62  for delivery to another device or technician for further processing.  
         [0040]    Illustrated in FIG. 1, plate dispensers  55  can store a plurality of vessels or plates  45  for dispensing onto conveyor  50 . The plate dispensers  55  communicate with controller  65  to lower vessels  45  by a rack-and-pinion unit (not shown). In a similar arrangement, the plate receivers  60  can hold a plurality of plates or vessels  45 . The vessels  45  are loaded into plate receivers  60  by an arrangement of posts which are rack-and-pinion driven (not shown). Other devices can be used to store and dispense vessels  45 . For example, other robotic or manual arrangements may be employed.  
         [0041]    In one embodiment, the present invention can be configured to dispense a multiplicity of different mother liquor fluid combinations into a plurality of wells located in vessels  45 . In one embodiment, vessel  45  contains a total of 96 wells  40  arranged in eight columns and nine rows, as illustrated in FIGS. 2, 4 and  6 . The twelve rows are parallel to the y-direction  100  and the columns of vessel  45  are parallel to the x-direction  95 . More or fewer wells  40  may be contained in vessel  45 .  
         [0042]    One particular method of dispensing fluids for growing protein crystals employs four vessels  45 , each vessel containing 96 wells  40  for a total of 384 wells. 96 different fluids are dispensed from the 96 tubes  25  mounted on the tube array  23 . The combination of tubes  25  and their corresponding fluids dispense different combinations and concentrations of fluids so that each of the 384 wells contains a unique mixture of fluids. The specific unique mixture in each well is known by the controller and may be used for later process decisions or displayed on the operator interface  70 . In this manner, a screen to determine the best combination and concentration of fluids for growing an optimum protein crystal can be quickly determined.  
         [0043]    In a preferred embodiment, after dispensing the fluids into the 384 wells, protein crystals are grown and selected based on the quality of the crystal according to user-defined criteria. For example, the 16 “best” quality crystals are isolated and the specific combination and concentration of fluids used to grow those crystals are recalled by controller  65  and displayed using operator interface  70 . Preferably, a “fine-screen” test is performed to optimize the concentration and combination of fluids for each of the 16 fluid combinations that resulted in the 16 best crystals.  
         [0044]    During the fine-screen process of this preferred embodiment, 24 variations of each of the 16 fluid combinations are dispensed from the fluid dispensing tubes  25  into new vessel  45  wells  40 . For example, if one of the 16 fluid combinations that resulted in a high-quality protein crystal comprised 5 percent of fluid A and 95 percent of fluid B, the corresponding fine screen would be composed of variations of the fluid combination of 5 percent of fluid A and 95 percent of fluid B. As an example, one of the 24 fine screen variations could be composed of 5.1 percent of fluid A and 94.8 percent of fluid B. Other variations could be 5.2 percent of fluid A and 94.9 percent of fluid B or 4.9 percent of fluid A and 95.1 percent of fluid B. In this manner, an optimized fluid combination and concentration can be determined for growing an optimum protein crystal.  
         [0045]    II. Method for Dispensing Fluids  
         [0046]    Referring to FIGS. 2, 4 and  5 , one method and procedure for dispensing fluids or mother liquors into vessel  45  wells  40  are described. One embodiment of the present invention can dispense a multiplicity of mother liquor combinations and concentrations for later testing. This is useful because a range of fluid combinations and concentrations must be tested to determine which conditions will achieve a suitable protein crystal, since the specific criteria required to achieve a suitable protein crystal has not yet been determined for each protein in the human genome.  
         [0047]    Referring to FIG. 5, in step  200 , a combination of fluids to be dispensed into a vessel  45  well  40  is determined. In step  205 , each of the fluids in the combination is assigned to a respective tube. In step  210 , the vessel  45  well  40  is moved to one of the tubes. The fluid is then dispensed in a specific amount into the vessel  45  well  40  in step  215 . Next, step  220  determines of whether the vessel has received all of the fluids of the specific fluid combination. If all of the required fluids have been dispensed into the vessel  45  well  40 , the process ends. However, if additional fluids must be dispensed into the vessel  45  well  40 , then the vessel  45  well  40  is moved to another tube  25 , in step  210 . Then step  215  and step  220  are performed as discussed, and this process is repeated until all of the necessary fluids have been dispensed into the specific vessel  45  well  40 .  
         [0048]    Referring to FIGS. 2 and 5, another procedure for dispensing mother liquors into specific vessel  45  well  40  will be described. Vessels  45  are placed on conveyor  50 . Each vessel  45  comprises 12 rows  42  and 8 columns  44 . Each well  40  and each vessel  45  has a column  42  height of about 9 millimeters and a row width of about 9 millimeters. Other vessels  45  can be employed having different numbers of wells  40  and different well  40  dimensions.  
         [0049]    After the vessel  45  is placed on the conveyor  50  the conveyor moves the vessel  45  in 9 millimeter increments in the X-direction  95 . Tube array  23  containing 96 tubes  25  is moved by tube transport  30  in the Y-direction  100 . Illustrated in FIG. 6, controller  65  aligns the first tube  25 A of the tube array  23  over a first well  40  in a first row  42 A, first column  44 A. As discussed above and illustrated in FIG. 5, the controller determines whether or not a fluid must be dispensed into that specific vessel  45  well  40 . If the controller orders fluid to be dispensed into that specific well  40 , the fluid is dispensed through the first tube  25 A.  
         [0050]    The tube array  23  is then moved by tube transport  30  over one column (i.e., 9 millimeters). This positions the first tube  25 A over a second well  40  in the first row  42 A, second column  44 B. Again, controller  65  determines whether or not fluid is to be dispensed into the second well  40 . Once the fluid has been dispensed, if necessary, the tube transport  30  moves the tube array  23  a distance of 9 millimeters to the next column  44 C and positions the first tube  25 A over a third well  40 . This process is repeated until the first tube  25 A has been positioned over each well  40  in the first row  42 A of the plate  45 . Conveyor  50  then moves the plate  45  in the X-direction  95  9 millimeters, positioning the first tube  25 A over the first well in the second row  42 B.  
         [0051]    Illustrated in FIG. 6, first tube  25 A coupled to tube array  23  and second tube  25 B also coupled to tube array  23  are positioned over the first well  40  of the first two rows  42 A and  42 B. The procedure described in step  210  of FIG. 5 is now repeated for the first well  40  in row  42 B as well as the first well of row  42 A. Because two tubes  25 A and  25 B are positioned over two wells  40 , two different fluids can be dispensed simultaneously, if necessary, depending upon the combination of fluids to be dispensed into each well  40 . Once the controller has determined if a fluid is to be dispensed into each well and that dispensing has occurred, the tube transport  30  moves the tube array  23  in the Y-direction  100  to position the first tube  25 A and second tube  25 B over the next column  44 B in the plate  45 . The dispensing of fluids then commences if necessary for that well  40 . In this manner, appropriate fluids can be dispensed in the appropriate combination and concentration into each well  40  of each vessel  45 .  
         [0052]    Referring to FIGS. 2 and 4, as the vessels  45  progress down the conveyor  50  and are exposed to more tubes  25  and the tube array  23 , the controller can dispense up to 96 fluids substantially simultaneously if necessary. In this manner, an extremely high throughput of fluid combinations can be achieved in the wells  40  of each vessel  45 . The rate of fluids that can be dispensed by the present invention is unachievable by human technicians and allows any for an extremely high number of combinations of fluids to be dispensed. In addition, each combination and concentration of fluids in each well  40  can be recalled from the operator interface  70 , and can be repeated with repeatable accuracy due to the automated process performed by the present invention.  
         [0053]    The arrangement of tubes need not be in a linear arrangement as illustrated in FIG. 2. For example, shown in FIG. 4, the tubes  25  can be arranged in a staggered configuration or any other suitable configuration.  
         [0054]    Referring to FIG. 4, the tubes  25  can be periodically rinsed and dried so that the concentrations of fluids dispensed through the tubes remain consistent. Tube transport  30  positions the tube array  23  over the tube bath  80  that contains a suitable tube rinse, such as ethanol or ionized water or any other suitable rinsing fluid. The tubes are immersed in the rinse and then the tube array  23  is moved by the tube transport  30  to the tube dryer  85  that is connected to a vacuum source  90 . The tube dryer  85  includes tube holes  87  into which the tubes  25  are inserted by the tube transport  30 . The vacuum source  90  is turned on by the controller  65 , drying the tubes  25 .  
         [0055]    One skilled in the art will appreciate that the present invention can be practiced by other than the preferred embodiments which are presented in this description for purposes of illustration and not of limitation, and the present invention is limited only by the claims that follow. For example, features of the methods and devices described in International Patent Publication WO 00/78445, published Dec. 28, 2000, incorporated herein by reference in its entirety including any drawings or figures, can be used in conjunction with the methods and devices of the present invention. It is noted that equivalents for the particular embodiments discussed in this description may practice the invention as well.