Abstract:
A microarrayer for spotting solution onto slides in an automated microarray dispensing device. Elements of the present invention include: at least one dispense head for spotting the slides, at least one light source capable of illuminating the slides, at least one camera operating in conjunction with the at least one light source. The at least one camera is capable of acquiring and transmitting slide image data to a computer. The computer is programmed to receive the slide image data and analyze it. The computer will then generate post analysis data based on the analysis of the slide image data. The post analysis data is available for improving the spotting of the solution onto the slides. In a preferred embodiment, the slide image data includes information relating to slide alignment, information relating to spot quality, and slide identification information. In a preferred embodiment, the analysis of the information relating to slide alignment enables the computer to make automatic adjustments to the relative positions of the at least one dispense head and the slides to increase the accuracy of the spotting. In a preferred embodiment, the analysis of the information relating to spot quality identifies a spot as pass or fail. An operator is then able to rework the spot. In a preferred embodiment, the analysis of the slide identification information enables the computer to track each slide.

Description:
The present invention relates to automated microarray dispensing devices, more specifically it relates to automated microarray dispensing devices with automated quality inspection capability. 
     BACKGROUND OF THE INVENTION 
     Microarrays, also known as biochips, have recently become important in the study of genomics. The use of a microarray involves laying down an ordered array of genetic elements onto a solid substrate such as a slide. Depending on the application, a microarray may consist of genomic DNA, reverse-transcribed cDNA, or smaller chains of oligonucleotides as well as any preparatory substrates. The microarray is useful because it allows genetic analysis to take place on a massively parallel scale, wherein thousands of genes and markers can be scored in one experiment. 
     A microarrayer, also known as a DNA array printer, is a high-capacity system used to print a microarray onto slides. Typically, a microarrayer is a specially built robotic platform designed to transfer solutions from the well of some type of microplate onto another surface for analysis. This process of depositing the liquid spot onto the slide is known as “spotting”. 
     Recently, microarrayers have become extremely popular in laboratories because they add to the efficient productivity of the laboratory to be able to print samples onto slides accurately and rapidly. Affymetrix, Inc., with offices in Santa Clara, Calif., makes an automated arrayer called the 417 ARRAYER (Part No. 0-0001 and Part No. 0-0009). BioRobotics, with offices in Boston, Mass., produces two versions of an automated arrayer called the MICROGRID and MICROGRID II. GeneMachines, with offices in Menlo Park, Calif., makes an arrayer called the OMNIGRID (Model No. OGR-02). Packard Instrument Company with offices in Meriden, Conn. makes an automated arrayer called the BIOCHIP ARRAYER. 
     Although there are some differences between each of the above listed microarrayers, they are all similar in that they each spot microarrays in an automated fashion. However, there are significant problems with the prior art devices that detracts from their efficient operation. 
     A first problem arises due to the fact that as blank slides are cycled through prior art microarrayers, they can become askew or positioned improperly underneath dispensing tips. This problem results in spots being positioned improperly on the slides. A second problem can arise even if the slide is positioned correctly under the dispensing tips. It is possible for the spot to be deposited in the correct position, but be of poor quality and therefore useless as far as experimentation purposes. 
     Up to now, the only way to deal with these problems was to have a human operator visually monitor and inspect the microarrayer during its operation or inspect the samples after they come off the machine. This solution is an unacceptable waste of human effort. The BIOCHIP ARRAYER made by Packard Instrument Company has attempted to deal with the problem of monitoring the spotting process. However, it has only limited verification functionality with its integrated camera. This means that it verifies whether or not a spot has been dispensed, without any quality inspection to analyze whether that spot was good or bad. 
     What is needed is a better microarrayer with automated quality inspection capability. 
     SUMMARY OF THE INVENTION 
     The present invention provides a microarrayer for spotting solution onto slides in an automated microarray dispensing device. Elements of the present invention include at least one dispense head for spotting the slides, at least one light source capable of illuminating the slides, at least one camera operating in conjunction with the at least one light source. The at least one camera is capable of acquiring and transmitting slide image data to a computer. The computer is programmed to receive the slide image and analyze it. The computer will then generate post analysis data based on the analysis of the slide image data. The post analysis data is available for improving the spotting of the solution onto the slides. In a preferred embodiment, the slide image data includes information relating to slide alignment, information relating to spot quality, and slide identification information. In a preferred embodiment, the analysis of the information relating to slide alignment enables the computer to make automatic adjustments to the relative positions of the at least one dispense head and the slides to increase the accuracy of the spotting. In a preferred embodiment, the analysis of the information relating to spot quality identifies a spot as pass or fail. An operator is then able to rework the spot. In a preferred embodiment, the analysis of the slide identification information enables the computer to track each slide. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 shows the major components of a preferred embodiment of the present invention. 
     FIG. 2 shows slides fifty slides located on  5  locating plates after the slides have been spotted. 
     FIGS. 3-32 illustrate the sequence of operation of a preferred embodiment of the present invention. 
     FIG. 33 shows the major components of a preferred embodiment of the present invention. 
     FIG. 34A shows the rework dispense head in the up position. 
     FIG. 34B shows the rework dispense head in the down position. 
     FIG. 34C shows a slide with a 2D bar code. 
     FIGS. 35A and 35B shows dispense tips attached to dispense heads. 
     FIG. 36 shows a preferred embodiment of the present invention mounted on a vibration isolated base. 
     FIG. 37 shows the major components of a preferred embodiment of the present invention. 
     FIGS. 38A and 38B show a flowchart for the programming of a preferred embodiment of the present invention. 
     FIGS. 39A and 39B show the reworking of a slide for a preferred embodiment of the present invention. 
     FIG. 40 shows another preferred embodiment of the present invention. 
     FIG. 41 shows another preferred embodiment of the present invention. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     A detailed description of a preferred embodiment of the present invention can be described by reference to FIGS. 1-38B. During the operation of the present invention, solution from reservoir plate  5  is automatically deposited onto an array of fifty blank slides  4 A 1 - 4 E 10  located on locating plates  4 A- 4 E (see FIG.  1 ). An operator is able to select via a computer interface whether dispense tip  42  (located underneath dispense head  40 ) or a 4×6 array of dispense tips  7  (located underneath dispense head  6 ) will be used to make the deposits onto slides  4 A 1 - 4 E 10 . In the preferred embodiment, dispense tips  7  and  42  are quill type dispense tips. Locating plates  4 A- 4 E are mounted on linear actuator  15  so that they can move along the x-axis. Linear actuator  26  is mounted on linear actuator  21  so that linear actuator  26  can move along the y-axis. Dispense heads  6  and  40  are mounted on linear actuator  26  so that they can move along the z-axis. Camera  12  with strobe light  13  is focused so as to permit recording of the deposition process and functions to permit verification of slide identification information and to permit verification of proper deposition of solution on the slides. Periodically, during the cycle, the dispense tips are cleaned in sonic cleaner  9 , rinsed in rinse fountain  10 , and then dried in vacuum manifold  11 . After the solution has been deposited onto the slides, the operator can retrieve locating plates  4 A- 4 E containing slides  4 A 1 - 4 E 10  from the position shown in FIG.  2 . 
     Sequence of Operation of a Preferred Embodiment 
     FIGS. 3-32 illustrate the sequence of operation of a preferred embodiment of the present invention. 
     In a preferred embodiment of the present invention, the operation of the components is controlled by PC control system  300 , as shown in FIG.  37 . FIGS. 38A-38E show a flowchart representing preferred programming of PC. control system  300  and corresponds to the sequence illustrated in FIGS. 3-32. 
     As shown in FIG. 3, an operator places five locating plates  4 A- 4 E each having ten clean, blank slides  4 A 1 - 4 E 10  on platform  2 . In a preferred embodiment of the present invention, slides  4 A 1 - 4 E 10  are made by Sequonem with offices in San Diego, Calif. A preferred slide is shown in FIG.  16 B. It has ninety-six etched dispense positions  60  and has its own unique  2 D bar code  65  for identification purposes. 
     As shown in FIG. 4, linear actuator  15  moves platform  2  so that slide  4 A 1  is underneath the dispense head  6 . Dispense head  6  is positioned directly above slide  4 A 1 . Using camera  12  and the strobe light  13 , an image is acquired of slide  4 A 1 . The camera reads the bar code and inspects the positioning and alignment of slide  4 A 1  on locating plate  3 A. The software then analyzes the position data and stores the information. The information stored and will be used later to adjust the positions of slide  4 A 1  and dispense head  6  to ensure accurate placement of the solution on the slide. 
     After camera  12  has acquired the image of slide  4 A 1 , linear actuator  26  is moved via linear actuator  21  to the position shown in FIG. 5 so that dispense head  6  is directly above slide  4 A 2 . Using camera  12  and the strobe light  13 , an image is acquired of slide  4 A 2 . As with slide  4 A 1 , camera reads the bar code and inspects the positioning and alignment of slide  4 A 2  on locating plate  4 A. The software then analyzes the position data and stores the information. The information stored and will be used later to adjust the positions of slide  4 A 2  and dispense head  6  to ensure accurate placement of the solution on the slide. 
     Linear actuator  26  is then moved via linear actuator  21  to the position shown in FIG. 6 so that dispense head  6  is directly above sonic cleaner  9 . 
     As shown in FIG. 7, mounting plate  25  moves downward via linear actuator  26  so that dispense tips  7  are dipped in sonic cleaner  9  for a programmable time period while the cleaner is turned on. When finished, mounting plate  25  moves upward as shown in FIG.  8 . 
     Then, as shown in FIG. 9, platform  31  moves to the left via pneumatic slide  30 , thereby moving rinse fountain  10  and vacuum manifold  11  to the left. Linear actuator  26  is moved via linear actuator  21  back so that it is directly above rinse fountain  10 . 
     As shown in FIG. 10, mounting plate  25  moves downward via linear actuator  26  so that tips  7  are dipped in rinse fountain  10  for a programmable time period while the fountain is turned on. 
     After rinsing, mounting plate  25  moves upward via linear actuator  26 , as shown in FIG.  11 . Platform  31  moves to the right via pneumatic slide  30 , thereby moving rinse fountain  10  and vacuum manifold  11  to the right. 
     As shown in FIG. 12, dispense tips  7  are then lowered into the vacuum manifold  11  via linear actuator  26  and the vacuum is turned on for a programmable time period, thereby drying dispense tips  7 . This cleaning cycle can be set by the user, via the computer interface, to be repeated as many times as necessary. 
     Mounting plate  25  is then raised via linear actuator  26  as shown in FIG.  13 . Linear actuator  26  is then moved via linear actuator  21  so that dispense head  6  is directly above reservoir plate  5 , as shown in FIG.  14 . 
     Mounting plate  25  is then lowered via linear actuator  26  so that tips  7  are dipped into the solution contained in reservoir plate  5 , as shown in FIG.  15 . While in reservoir plate  5 , dispense tips  7  pick up some of the solution to be dispensed. 
     Linear actuator  26  then moves to the first dispense position shown in FIG. 16A so that dispense head  6  is above slide  4 A 1 . Based on the earlier positioning data regarding slide  4 A 1  (see discussion of FIG.  4 ), linear actuator  21  makes minute positioning adjustments to linear actuator  26  and linear actuator  15  makes minute positioning adjustments to platform  2  in order to accurately position dispense head  6  over slide  4 A 1  at the first dispense position. 
     FIG. 16B shows a top view of a blank slide  4 A 1 . In this preferred embodiment, slide  4 A 1  has  96  positions  60  arranged in an 8×12 array. At each position  60 , slide  4 A 1  is etched so as to be better able to retain a drop of solution deposited at the spot. 
     Dispense head  6  is then lowered via linear actuator  26  so that tips  7  are in contact with slide  4 A 1  at the first dispense position, as shown in FIG.  17 A. As tips  7  contact slide  4 A 1 , spots  62  are placed on slide  4 A 1  via surface tension, as shown in FIG.  17 B. 
     Dispense head  6  is raised via linear actuator  26 , as shown in FIG.  18 . Based on the earlier positioning data regarding slide  4 A 1 , linear actuator  21  makes minute positioning adjustments to linear actuator  26  and linear actuator  15  makes minute positioning adjustments to platform  2  in order to accurately position dispense head  6  over slide  4 A 1  at the second dispense position. 
     Dispense head  6  is then lowered via linear actuator  26  so that tips  7  are in contact with slide  4 A 1  at the second dispense position, as shown in FIG.  19 A. As tips  7  contact slide  4 A 1 , more spots  62  are added to slide  4 A 1 , as shown in FIG.  19 B. 
     Dispense head  6  is raised via linear actuator  26 , as shown in FIG.  20 . Based on the earlier positioning data regarding slide  4 A 1 , linear actuator  21  makes minute positioning adjustments to linear actuator  26  and linear actuator  15  makes minute positioning adjustments to platform  2  in order to accurately position dispense head  6  over slide  4 A 1  at the third dispense position. 
     Dispense head  6  is then lowered via linear actuator  26  so that tips  7  are in contact with slide  4 A 1  at the third dispense position, as shown in FIG.  21 A. As tips  7  contact slide  4 A 1 , more liquid spots  62  are added to slide  4 A 1 , as shown in FIG.  21 B. 
     Dispense head  6  is raised via linear actuator  26 , as shown in FIG.  22 . Based on the earlier positioning data regarding slide  4 A 1 , linear actuator  21  makes minute positioning adjustments to linear actuator  26  and linear actuator  15  makes minute positioning adjustments to platform  2  in order to accurately position dispense head  6  over slide  4 A 1  at the fourth dispense position. 
     Dispense head  6  is then lowered via linear actuator  26  so that tips  7  are in contact with slide  4 A 1  at the fourth dispense position, as shown in FIG.  23 A. As tips  7  contact slide  4 A 1 , more liquid spots  62  are added to slide  4 A 1 , as shown in FIG.  23 B. 
     Dispense head  6  is raised via linear actuator  26 , as shown in FIG.  24 . Camera  12  and strobe  13  scans slide  4 A 1  and acquires images and inspects for spot quality. It is at this point that PC control system  300  (FIG. 37) identifies slide  4 A 1  as pass or fail. (Preferred computer controlled techniques for making this determination are discussed in a following section.) 
     As shown in FIG. 25, based on the earlier positioning data regarding slide  4 A 2  (see discussion regarding FIG.  5 ), linear actuator  21  makes positioning adjustments to linear actuator  26  and linear actuator  15  makes positioning adjustments to platform  2  in order to accurately position dispense head  6  over slide  4 A 2  at the first dispense position for slide  4 A 2 . 
     The four-stage liquid dispense cycle (explained above with respect to slide  4 A 1  in discussion regarding FIGS. 17A-24) is repeated so that at the end of the four-stage cycle, slide  4 A 2  contains spots  62 , as shown in FIG.  26 B. At the end of the four stage cycle, dispense head  6  is raised via linear actuator  26 , as shown in FIG.  26 A. Camera  12  and strobe  13  scans slide  4 A 2  and acquires images and inspects for spot quality. It is at this point that the control system identifies slide  4 A 2  as pass or fail. 
     As shown in FIG. 27, linear actuator  21  moves linear actuator  26  so that dispense head  6  is above slide  4 A 3 . 
     The sequence outlined in the discussion regarding slides  4 A 1  and  4 A 2  (depicted in FIGS. 4-26) is repeated with regards to slides  4 A 3  and  4 A 4 . To summarize, by utilizing light provided by strobe  13 , camera  12  will first record the positions of slides  4 A 3  and  4 A 4 . Then, dispense tips  7  are dipped in sonic cleaner  9 . Dispense tips  7  are then rinsed in rinse fountain  10 . Then, dispense tips  7  are dried in vacuum manifold  11 . This cycle is repeated as needed. Then, liquid is picked up by dispense tips  7  when dispense tips  7  are lowered into reservoir plate  5 . Then, liquid is spotted onto slide  4 A 3  by dispense tips  7  in a four-stage liquid dispense cycle. Likewise, liquid is spotted onto slide  4 A 4  in a four-stage liquid dispense cycle so that liquid has been spotted on both slides, as shown in FIGS. 28B and 28C. 
     The process is then repeated for the remaining six slides  4 A 5 - 4 A 10  until all the slides on locator plate  4 A have been spotted, as shown in FIG.  29 . 
     Linear actuator  15  then moves platform  2  so that slide  4 B 1  of locator plate  4 B is underneath dispense head  6 , as shown in FIG.  30 . 
     In a similar fashion, dispense tips  7  continue to spot all ten slides on locator plates  4 B- 4 E, until the last slide  4 E 10  has been spotted, as shown in FIG.  31 . 
     After slide  4 E 10  has been spotted and camera  12  and strobe  13  has scanned slide  4 E 10  for spot quality, linear actuator  15  moves platform  2  to the position shown in FIG. 32 so an operator can remove locator plates  4 A- 4 E. 
     Computer Controlled Pass-Fail Determination Technique 
     The computer controlled pass-fail determination technique determines individual spots as pass or fail based on several criteria. For each slide, the camera system scans a region to look for a spot. In a preferred embodiment the criteria that are applied to that inspection region are spot presence, spot size in area, spot location, and spot geometry. Additional criteria can be added through software configuration. Each of the criteria can have upper and lower limits designated which define the acceptable values for that particular criteria. 
     Any value that falls outside of the limits for any criteria qualifies that spot and slide as failed. The actual inspection values are determined by analyzing the grayscale intensity of each pixel. The total number of pixels falling above and below a threshold are tallied to give values for each of the inspection criteria. 
     Rework Capability 
     As explained above, after each slide has been spotted, camera  12  and strobe  13  scans the slide and acquires images and inspects for spot quality. It is at this point that the control system identifies the slide as pass or fail. In a preferred embodiment of the present invention, an operator monitoring the spotting process via monitor  305  (FIG. 37) has the option of correcting a slide that has failed. 
     For example, FIG. 29 shows locating plate  4 A after all slides  4 A 1 - 4 A 10  have been spotted. At this point, an operator can scan locating plate  4 A. A good plate shows up green as in all slides pass. A plate with at least one bad spot on one of the slides shows up red. The user can then zoom in on the bad slide and the good and bad spots show up green and red respectively as pass or fail. From there, the user can decide whether or not to rework the bad spots. 
     FIGS. 39A and 39B show where an operator has decided to rework slide  4 A 6  that has a spot that has failed quality inspection. Dispense head  40  is lowered via pneumatic slide  41  so that dispense tip  42  is lower than dispense tips  7 . Solution from reservoir plate  5  is then deposited on the slide at the location of the failed spot. If there are other spots that failed, the operator can likewise rework those spots in a similar fashion. 
     Although in the description given above regarding the rework process, the operator reworked failed slides after locating plate  4 A had been entirely spotted, it is also possible to rework failed slides at other stages during the spotting process. For example, it may be desirable to wait until all slides  4 A 1 - 4 E 10  on plates  4 A- 4 E have been spotted (FIG. 31) before reworking them. This allows an operator to be free to do other activities while the initial spotting is taking place. Then, after all slides have been spotted, he can come back and do all the reworking at one sitting. 
     Alternatively, it may be desirable to rework each slide immediately after it has been spotted, as shown in FIG.  24 . 
     Automatic Rework Capability 
     The previous section described a preferred embodiment where an operator can decide whether or not to rework a spot based on a computer determination of pass or fail. In another preferred embodiment the rework decision is made automatically by the computer based on whether or not the spot has passed or failed. In this preferred embodiment, the computer makes a determination whether or not a spot has passed or failed using the computer controlled pass-fail determination technique earlier described. If, based on its analysis, the computer determines that the spot has failed, the computer will automatically take steps to rework the spot. For example, dispense tip  42  will extract solution from reservoir plate  5 . Then, the computer will lower dispense head  40  via pneumatic slide  41  so that dispense tip  42  is lower than dispense tips  7 , as shown in FIGS. 39A and 39B. Solution from reservoir plate  5  will then deposited on the slide at the location of the failed spot. 
     Components of a Preferred Embodiment of the Present Invention Three Axis Robotic Positioning Stage 
     In a preferred embodiment, linear actuators  26 ,  21  and  15  are industrial grade precision ground ball screw linear actuators, as shown in FIG.  33 . These linear actuators are manufactured by Parker Automation (Model #s:404XR and 406XR series). They are each controlled by a smart servomotor (SmartMotor, Model #2320 VRE, manufactured by Animatics, with offices in Santa Clara Calif.), which is a fully self-contained closed loop servo system. Each of these smart servomotors contains the motor, encoder, amplifier, and controller all in one small package mounted to the linear actuator. Linear actuator  15  (the x-axis positioning device) has an overall travel distance of 600 mm with an accuracy within +/−0.032 micrometers Linear actuator  21  (the y-axis positioning device) has an overall travel distance of 400 mm with an accuracy within +/−0.032 micrometers. Linear actuator  26  (the z-axis positioning device) has an overall travel distance of 100 mm with an accuracy within +/−micrometers. In this preferred embodiment, this extreme accuracy is needed to accommodate very small spot size and spacing between spots. The linear actuators have pitches of 5 mm per revoloution giving a positioning accuracy of 0.032×10 −6  meters. 
     Linear actuator  15  controls the positioning of platform  2  containing slides  4 A 1 - 4 E 10  along the x-axis of motion making all slides presentable to the dispense head  6 . Linear actuator  21  controls the positioning of the dispense head along the y-axis of motion making all slides  4 A 1 - 4 E 10 , sonic cleaner  9 , rinse fountain  10 , vacuum manifold  11 , and reservoir plate  5  presentable to dispense head  6 . Linear actuator  26  controls the positioning of dispense head  6  along the z-axis of motion allowing dispense head  6  to be lowered to and raised from all slides  4 A 1 - 4 E 10 , sonic cleaner  9 , rinse fountain  10 , vacuum manifold  11 , and reservoir plate  5 . 
     Cleaning Station 
     Cleaning station  33  consists of sonic cleaner  9 , rinsing fountain  10 , and a drying vacuum manifold  11 . In a preferred embodiment, sonic cleaner  9  is an ultrasonic cleaner manufactured by Prosonic, Inc. (part no. E0028). Sonic cleaner  9  can contain either a cleaning solution or simply purified water. Dispense tips  7  are dipped in the sonic cleaner  9 , where the ultra sonic oscillations of the cleaning solution clean the tips. 
     Rinsing fountain  10  and the vacuum manifold  11  are placed on a pneumatic slide  30 . Pneumatic slide  30  is used to select which operation is to be performed, rinsing or drying. The reason for this slide is so that both operations can be performed at a single position along the y-axis. This allows for both operations without having to increase the overall travel of linear actuator  26  along the y-axis. 
     Rinsing fountain  10  pumps in purified water and drains it out to a waste bin. Dispense tips  7  are dipped in this purified water to rinse away any debris or cleaning solution that may remain on the tips after cleaning. 
     Drying vacuum manifold  11  is a block with an array of holes in it that match the array of dispense tips  7 . The tips are inserted into the block, each of these holes are connected to a manifold which is connected to a vacuum generator and air supply. The vacuum pulls away any remaining liquid or debris left on the dispense tips after rinsing. 
     Dispense Head Assemblies 
     As shown in FIG. 35B, dispense head  6  is a 4×6 grid Micro Quill Holder (part no. 11946-0) made by Major Precision of Arizona. A 4×6 array of primary dispense tips  7  are held in dispense head  6 . As shown in FIG. 35A, dispense head  40  is a Micro Quill Holder also made by Major Precision. Dispense tip  42  is held in dispense head  40 . Dispense tips  7  and  42  are spring loaded within the dispense heads  6  and  40 . 
     As shown in FIGS. 1,  34 A and  34 B, dispense head  6  is rigidly mounted to mounting plate  25 , whereas dispense head  40  is mounted to pneumatic slide  41  (manufactured by Robohand, Inc., with offices in Montroe, Conn., part no. MPS1-2). Mounting plate  25  is capable of moving up and down along the z-axis via linear actuator  26 . Furthermore, dispense head  40  is capable of independent additional movement up and down along the z-axis via pneumatic slide  41 , as shown in FIGS. 34A-34B. 
     During normal operation, such as that depicted in the sequence illustrated in FIGS. 3-32, dispense head  6  is used to spot slides  4 A 1 - 4 E 10 . For example, FIG. 34C shows a front view of dispense tips  7  in contact with slide  4 A 1 . Dispense tips  7  will be used to spot slide  4 A 1  at positions  60 , as shown in FIG.  34 C. Note that when dispense head  6  has been selected, dispense head  40  is raised via pneumatic slide  41  so that dispense tips  42  do not interfere with the spotting process. 
     If, however, the operator wishes to spot slide  4 A 1  at positions  61  (FIG.  34 C), dispense head  40  will be lowered via pneumatic slide  41  so that dispense tips  42  are in contact with slide  4 A 1  and dispense tips  7  are out of the way, as shown in FIG.  34 B. 
     Camera and Lighting 
     In a preferred embodiment, camera  12  and strobe  13  are mounted to the side of linear actuator  26  as shown in FIG.  1 . Camera  12  is a self-contained camera with image processing and Ethernet capabilities manufactured by DVT Corporation with offices in Norcross, Ga. (series 600 model). Using light provided by strobe  13 , camera  12  can snap pictures while in dynamic motion, process the image for results, pass the results off to the PC control system, and prepare for the next image acquisition. The camera uses a 55 mm Telecentric lens which provides the proper field of view and magnification for reading of 2D bar code  62  (FIG. 34C) and for image inspection. Strobe light  13  is preferably Model DL2449, manufactured by Advanced Illumination, with offices in Rochester, Vt. In the preferred embodiment, the image acquisition time is ˜40 ms and the image processing time is ˜50 ms. The system can also be equipped with a flouresence device along with the camera for further genomic expression analysis. 
     Vibration Isolated Base 
     As shown in FIG. 36, vibration isolated base  80  is provided to minimize any possible affects that high frequency environmental vibrations might have on the dispensing process. This base is a pneumatic system which acts as a shock absorber to the system. In a preferred embodiment, the base is manufactured by Newport, Inc. with offices in Irvine, Calif., model #CM-225. 
     PC Based Control System 
     FIG. 37 depicts a block diagram of PC control system  300  and other components of a preferred embodiment of the present invention. PC Control System  300  includes CPU  301  with associated memory (RAM  302  and ROM  303 ). It also includes a touch screen monitor/interface  305  that allows for operator monitoring, intervention and control of the present invention. In the preferred embodiment, the computer system is a PC based computer equipped with an ethernet card and running windows software. The programming is preferably written in VISUAL BASIC. (VISUAL BASIC is a federally registered trademark of Microsoft Corp., a Delaware Corporation) PC Control System  300  is equipped with CMS (Central Monitoring System). The CMS gives PC Control System  300  it&#39;s own IP (Internet Protocol) address and ethernet connectivity. This allows for remote monitoring and control via Intranets as well as Internet provided that the bandwith is available for proper functionality. The software is highly comfigurable to allow increased flexibility for customers with varying slide types, slide sizes, slide orientations, spot size, spot spacing and many other variables. 
     Control of the Components of the Preferred Embodiment of the Present Invention through the PC Control System 
     As previously stated, linear actuators  26 ,  21  and  15  are industrial grade precision ground ball screw linear actuators. As shown in FIG. 37, PC control system  300  sends signals to smart servomotors  26 A,  21 A and  15 A to control linear actuators  26 ,  21  and  15 , respectively. PC control system  300  controls sonic cleaner  9  and rinse fountain  10 . Compressed air source  310  provides compressed air to pneumatic slides  30  and  41  via valves  310  controlled by PC control system  300 . Vacuum generator  320  provides a vacuum to vacuum manifold  11  via valve  317 . As previously explained camera  12  and strobe  13  work in conjunction to provide sensory data to PC control system  300 . This input is used to accurately position the dispense heads over the slides to ensure optimum spotting and to verify the quality of the spotting as “pass” or “fail” using multiple criteria as to placement at intended location as well as spot size (too big or too small). 
     Second Preferred Embodiment of the Present Invention 
     A second preferred embodiment of the present invention is shown in FIG.  41 . In the second preferred embodiment, dispense head  106  is connected via mounting plate  125  to linear actuator  126  so that dispense tips  107  can be raised and lowered along the z-axis into solution in microplate  190 . Camera  112  and strobe  113  are rigidly mounted to the side of linear actuator  126  so that they remain stationary with respect to the side of linear actuator  126  along the z-axis. Linear actuator  126  is mounted to linear actuator  121  so that it can move along the y-axis. 
     Platform  182  is mounted to linear actuator  180  so that it can move along the x-axis. Locating plate  4 A is placed on top of platform  182 . Platform  102  is mounted to linear actuator  115  so that it can move along the x-axis. Microplate  190  is place on top of platform  102 . In this preferred embodiment platform  102  has the capacity to hold ten microplates  190 . 
     Solution in microplate  190  is removed via dispense tips  107 . Linear actuator  126  then moves along the y-axis so that dispense tips  107  are above locating plate  4 A. The solution is then spotted in a fashion similar to that described for the earlier preferred embodiments. Camera  112  with strobe  113  is focused so as to permit recording of the deposition process and functions to permit verification of slide identification information, permit verification of proper deposition of solution on the, slides, and to verify slide alignment. As explained above, slide image data is transferred via camera  112  to a PC control system where the data is analyzed. The results of the analysis are then available for improving the spotting of the solution onto the slides. For example, spots that have failed to meet the threshold limits can be reworked. Also, the computer can automatically make adjustments to the relative positions of the slides and dispense tips based on the slide alignment analysis. Periodically, during the cycle, the dispense tips are cleaned in sonic cleaner  109 , then rinsed in the rinse fountain and dried in vacuum manifold  111 . 
     Operation of the First Preferred Embodiment with the Second Preferred Embodiment The first preferred embodiment (described in the sequence illustrated in FIGS. 3-32) can be used in conjunction with the second preferred embodiment to spot slides. For example as shown in FIG. 32, locating plate  4 A can be removed from the microarrayer via an operator after it has been spotted with a base solution. Locating plate  4 A can be transferred to the microarrayer depicted in FIG.  41 . It can be placed on platform  180 . DNA from microplate  190  can then be spotted on top of the base solution spotted already on slides  4 A 1 - 4 A 10 . 
     Use of the Present Invention with Other Microarrayers 
     Although the present invention was described as being used with the preferred microarrayer depicted in the sequence described by reference to FIGS. 3-32, those of ordinary skill in the art will recognize that it is possible to use camera  12 , strobe  13  and a PC control system in conjunction with a variety of microarrayer designs. For example, in the background section of this application, several microarrayers were mentioned. It would be possible to one of ordinary skill in the art to modify a prior art automatic microarrayer to include camera  12  and strobe  13 . Camera  12  and strobe  13  would then work in conjunction to provide sensory data to PC control system  300 , as described above. Also, as explained above, the input would be used to accurately position the dispense heads over the slides to ensure optimum spotting and to verify the quality of the spotting as “pass” or “fail”. 
     Modification of Rework Dispense Tips 
     The previous embodiments showed one dispense tip  42  extending downward from dispense head  40 . It was explained how the single dispense tip  42  is used for reworking (correcting) defective spots. It is possible, however, to modify dispense head  40  so that multiple dispense tips can extend downward from dispense head  40 . A preferred embodiment is shown in FIG. 40 in which five dispense tips  42 A-E extend down below dispense head  40 . In this preferred embodiment, dispense tips  42 A-E are retractably connected to dispense head  40 . As shown in FIG. 40, dispense tips  42 A-D are retracted inside dispense head  40 . The rightmost dispense tip  42 E is extended below the other dispense tips and is spotting slide  4 A 1 . In a preferred embodiment, dispense tips  42 A-E are mounted to a pneumatic slides  43 . 
     An advantage of this embodiment is that each dispense tip  42  can be configured to dispense a different volume of solution. For example, in a preferred embodiment, dispense tip  42 A would dispense 1 nL of solution, dispense tip  42 B would dispense 2 nL of solution, dispense tip  42 C would dispense 4 nL of solution, dispense tip  42 D would dispense 8 nL of solution, and dispense tip  42 E would dispense 16 nL of solution. 
     After initially spotting the slides as explained above, camera  12  and strobe  13  would work in conjunction to provide sensory data to PC control system  300  reporting the quality of the spots. The spots would then be classified as pass or fail. If a spot has failed, the software in conjunction with PC control system  300  would determine the amount of solution required to correct the failed spot. Then, during the reworking sequence, the dispense tip that dispenses the most correct volume would be extended down from dispense head  40  and the other dispense tips would be retracted upward inside dispense head  40 , as shown in FIG.  40 . 
     While the above description contains many specifications, the reader should not construe these as limitations on the scope of the invention, but merely as exemplifications of preferred embodiments thereof. Those skilled in the art will envision many other possible variations are within its scope. For example, although the above sequence described a dispensing process utilizing slides that have  96  dispense positions, those of ordinary skill in the art will recognize that it is possible to use other slides as well. For example,  384  or  1536  position slides could be used. It is also possible to use a blank microscope slide with no pre-etched dispense positions. Accordingly, the location of the different dispense positions will vary depending on the type of slide being used. The spacing and orientation of the slide can be selected by an operator through the maintenance menu on the computer interface. Also, the previous embodiments disclosed using a strobe light to illuminate the slide below the camera. One of ordinary skill in the art will recognize that it is possible to illuminate the slide with other light sources besides a strobe light. For example, the slide could be illuminated with a camera flash, a constant bright light, or a fluorescence device, such as a fluorescent LED. If a fluorescence device is used to illuminate the slide, those of ordinary skill in the art will recognize that it is possible to add a fluorescent dye to the solution being spotted to achieve more in depth characterizations. For example, by using a fluorescent LED and adding fluorescent dye to the solution, greater volume determination can be achieved based on fluorescent intensity of the spot. Also, in the preferred embodiment, it was mentioned that dispense tips  7  and  42  were quill type dispense tips, it would be obvious to substitute other types of dispense tips. For example, piezo type dispense tips could also be used. Accordingly the reader is requested to determine the scope of the invention by the appended claims and their legal equivalents, and not by the examples which have been given.