Patent Publication Number: US-8117929-B2

Title: Control of the positional relationship between a sample collection instrument and a surface to be analyzed during a sampling procedure using a laser sensor

Description:
This invention was made with Government support under Contract No. DE-AC05-00OR22725 awarded by the U.S. Department of Energy to UT-Battelle, LLC, and the Government has certain rights to the invention. 
    
    
     BACKGROUND OF THE INVENTION 
     This invention relates generally to sampling means and methods and relates, more particularly, to the means and methods for obtaining samples from areas, or spots, on a surface to be analyzed. 
     The sampling collection techniques with which this invention is concerned involve the positioning of a collection instrument or other sample collection device in relatively close proximity to a surface to be analyzed, or sampled, for purposes of gathering an amount (e.g. ions) of the surface for analysis. An example of one such collection technique is used in conjunction with desorption electrospray ionization (DESI) mass spectrometry, but other techniques, such as may involve desorption atmospheric pressure chemical ionization (DAPCI) or matrix-assisted laser desorption/ionization (MALDI), are applicable here as well. In any of such techniques, it is desirable that the collection instrument be maintained at a predetermined, or desired, distance from the surface to be sampled for optimum collection results and to reduce the likelihood that the collection results will be misinterpreted when subsequently analyzed. 
     Furthermore, there exists some sample-collecting processes which involves a self-aspirating emitter through which an agent is delivered to the surface during the sample-collection process in a spray plume. Such an emitter is commonly fixed in position relative to the sample collection instrument, or device, so that the spray plume is directed toward the surface at a predetermined, or fixed, angle of incidence so that the delivered spray plume is intended to strike the surface to be sampled at a predetermined location for effecting the movement of an amount of the surface to be sampled toward the collection instrument. In other words, there is a desirable spatial assignment which exists between the emitter, the collection instrument and the surface to be analyzed so that if the surface is not accurately positioned in a location (e.g. within a predetermined plane) in which the surface is intended to be positioned, poor collection results are likely to be obtained. 
     To obviate the need for an operator to make manual adjustments to the distance between the sample collection instrument and the surface during the course of a sample collection process, it would be desirable to provide a system and method for accurately controlling the sample collection device-to-surface distance during a sample collection process. 
     Accordingly, it is an object of the present invention to provide a system and method for automatically controlling the distance between a sample collection instrument, or device, and the surface to be analyzed, or sampled, with the instrument which utilizes a laser sensor for monitoring the actual collection instrument-to-surface distance during the sampling procedure. 
     Another object of the present invention is to provide such a system and method wherein the collection instrument-to-surface distance is continually monitored throughout the sampling procedure and adjusted, as necessary, so that the collection instrument-to-surface distance is maintained at an optimal spacing. 
     Yet another object of the present invention is to provide such a system which reduces the likelihood that the results of the sample collection process will be misinterpreted when analyzed. 
     A further object of the present invention is to provide such a system which, when used in conjunction with sample-collecting operations which utilize an emitter which is directed at a predetermined angle toward the sample helps to maintain the proper spatial assignment between the emitter, the collection instrument and the surface to be analyzed during a sample collecting process. 
     Yet another object of the present invention is to provide such a system which is uncomplicated in structure, yet effective in operation. 
     SUMMARY OF THE INVENTION 
     This invention resides in a sampling system and method for collecting samples from a surface to be analyzed. 
     The sampling system includes a sample collection instrument through which a sample is collected from a surface to be analyzed and means for moving the collection instrument and the surface toward and away from one another and wherein there exists a desired positional relationship between the collection instrument and the surface for sample collecting purposes. The system also includes distance-measuring means including a laser sensor arranged in a fixed positional relationship relative to the collection instrument for generating a signal which corresponds to the actual distance between the laser sensor and the surface and wherein there exists a target distance between the laser sensor and the surface when the collection instrument and the surface are arranged in the desired positional relationship for sample collecting purposes. 
     In addition, the system includes means for receiving the signal which corresponds to the actual distance between the laser sensor and the surface and comparison means for comparing the actual distance between the laser sensor and the surface to the target distance between the laser sensor and the surface and for initiating the movement of the laser sensor and the surface toward or away from one another when the difference between the actual distance between the laser sensor and the surface and the target distance is outside of a predetermined range so that by moving the surface and the collection instrument toward or away from one another, the actual distance between the laser sensor and the surface approaches the target distance. 
     The method of the invention includes the steps carried out by the system of the invention. In particular, such steps include the generating of a signal with the distance-measuring means which corresponds to the actual distance between the laser sensor and the surface and determining the actual distance between the laser sensor and the surface from the signal generated by the distance-generating means. Then, the actual distance between the laser sensor and the surface is compared to the target distance, and movement of the surface and the laser sensor toward or away from one another is initiated when the difference between the actual distance between the laser sensor and the surface and the target distance is outside of a predetermined range so that by moving the surface and the laser sensor toward or away from one another, the actual distance approaches the desired target distance. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic view of the system  20  within with features of the present invention are incorporated. 
         FIG. 2  is a perspective view of selected components of the  FIG. 1  system drawn to a slightly larger scale. 
         FIG. 3  is a view of the surface to be analyzed and various components of the  FIG. 1  system as seen from above in  FIG. 2 . 
         FIG. 4   a  is a view illustrating schematically an exemplary positional relationship between the laser sensor, the sample collection instrument and the surface of the  FIG. 1  system seen generally from the front. 
         FIG. 4   b  is a view as seen generally from the right side in  FIG. 4   a.    
         FIG. 5   a  is a view illustrating schematically an exemplary relationship between the components of the  FIG. 4   a  view when positioned in an optimum relationship for sample collecting purposes. 
         FIG. 5   b  is a view similar to that of  FIG. 5   a  except that the components are positioned in one non-optimal relationship for sampling collecting purposes. 
         FIG. 5   c  is a view similar to that of  FIG. 5   a  except that the components are positioned in another non-optimal relationship for sample collecting purposes. 
         FIGS. 6   a  and  6   b  are views illustrating schematically the path of the tip of the sample capillary tube relative to the surface of the  FIG. 1  system during a continuous re-optimization of the capillary tube-to-surface distance. 
         FIG. 7  is a view similar to that of  FIG. 5   a  except that the surface is canted with respect to the horizontal. 
         FIG. 8  is a view similar to that of  FIG. 7  illustrating schematically an exemplary relationship between components of an alternative system within which the present invention is embodied and wherein such components includes two laser sensors. 
     
    
    
     DETAILED DESCRIPTION OF AN ILLUSTRATIVE EMBODIMENT 
     Turning now to the drawings in greater detail and considering first  FIG. 1 , there is schematically illustrated an example of an embodiment, generally indicated  20 , of a desorption electrospray (DESI) system within which features of the present invention are embodied for purposes of obtaining samples from at least one spot, or area, of a surface  22  (embodying a surface to be sampled) for subsequent analysis. Although the surface  22  to be sampled can, for example, be an array whose samples are desired to be analyzed with a mass spectrometer  32 , the system  20  can be used to sample any of a number of surfaces of interest. Accordingly, the principles of the invention can be variously applied. 
     Furthermore and although the depicted system  20  is described herein in connection with desorption electrospray ionization (DESI), the principles of the invention described herein are applicable as well to other surface sampling techniques, such as desorption atmospheric pressure chemical ionization (DAPCI) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. 
     The system  20  of the depicted example includes a collection instrument in the form of a sampling probe  24  (and an associated DESI emitter  25 ) comprising a capillary tube  23  which terminates at a tip  26  which is positionable adjacent the surface  22 . During a sampling process, for example, a predetermined agent is directed from a syringe pump  37  and onto the surface  22  to be sampled through the emitter  25 , and an amount of the sample (e.g. ions of the sample) is conducted by way of a vacuum (and/or an electric field), away from the remainder of the surface  22  through the capillary tube  23  for purposes of analyzing the collected sample. 
     With reference to  FIGS. 1 and 2  and to enable samples to be collected from any spot along the surface  22 , the collection tube  23 , along with its tip  26 , is supported in a fixed, stationary condition, and the surface  22  to be sampled is supported upon a support plate  27  for movement relative to the collection tube  23  along the indicated X-Y coordinate axes, i.e. within the plane of the support plate  27 , and toward and away from the tip  26  of the collection tube  23  along the indicated Z-coordinate axis. The support plate  27  of the depicted system can take the form, for example, of a thin-layer chromatography (TLC) plate upon which an amount of material desired to be analyzed is positioned. It follows that for purposes of discussion herein, the surface  22  is supported by the support plate  27  within an X-Y plane (which corresponds generally to a horizontal plane), and the Z-axis is perpendicular to the X-Y plane. 
     The emitter  25  is fixed in position with respect to the capillary tube  23  and is arranged in a pre-set relationship with respect to the surface  22  so that a jet (gas or liquid) dispensed thereon impinges upon the surface  22  at a predetermined angle of incidence. It therefore follows that there exists a desired relationship, or spatial assignment, between the capillary tube  23 , the emitter  25  and the surface  22  for optimum sample collection results. 
     The support plate  27  is, in turn, supportedly mounted upon the movable support arm  36  of an XYZ stage  28  ( FIG. 1 ), for movement of the support plate  27 , and the surface  22  supported thereby, along the indicated X, Y and Z coordinate directions. The XYZ stage  28  is appropriately wired to a joystick control unit  29  which is, in turn, connected to a first control computer  30  for receiving command signals therefrom so that during a sampling process performed with the system  20 , samples can be taken from any desired spot (i.e. any desired X-Y coordinate location) along the surface  22  or along any desired lane (i.e. along an X or Y-coordinate path) across the surface  22  as the surface  22  is moved within the X-Y plane beneath the collection tube tip  26 . For example, there is illustrated in  FIG. 3  a view of the emitter  25  and capillary tube  23  arranged in position above the surface  22  for collecting samples from the surface  22  as the surface  22  is indexed beneath the capillary tube tip  26  and moved in sequence along a plurality of Y-coordinate lanes, or paths, indicated by the arrows  18 . The characteristics of such relative movements of the surface  22  and the capillary tube  23 , such as the sweep speeds and the identity of the X-Y locations at which the collection tube  23  is desired to be positioned in registry with the surface  22  can be input into the computer  30 , for example, by way of a computer keyboard  31  or pre-programmed within the memory  33  of the computer  30 . 
     Although a description of the internal components of the XYZ stage  28  is not believed to be necessary, suffice it to say that the X and Y-coordinate position of the support surface  27  (and surface  22 ) relative to the collection tube tip  26  is controlled through the appropriate actuation of, for example, a pair of reversible servomotors (not shown) mounted internally of the XYZ stage  28 , while the Z-coordinate position of the support surface  27  (and surface  22 ) relative to the collection tube tip  26  is controlled through the appropriate actuation of, for example, a reversible stepping motor (not shown) mounted internally of the XYZ stage  28 . Therefore, by appropriately energizing the X and Y-coordinate servomotors, the surface  22  can be positioned so that the tip  26  of the collection tube  23  can be positioned in registry with any spot within the X-Y coordinate plane of the surface  22 , and by appropriately energizing the Z-axis stepping motor, the surface  22  can be moved toward or away from the collection tube tip  26 . 
     With reference still to  FIG. 1 , the system  20  of the depicted example further includes a mass spectrometer  32  which is connected to the collection tube  23  for accepting samples conducted thereto for purposes of analysis, and there is associated with the mass spectrometer  32  a second control computer  34  for controlling the operation and functions of the mass spectrometer  32 . An example of a mass spectrometer suitable for use with the depicted system  20  as the mass spectrometer  32  is available from MDS SCIEX of Concord, Ontario, Canada, under the trade designation 4000 Qtrap. Although two separate computers  30  and  34  are utilized within the depicted system  20  for controlling the various operations of the system components (including the mass spectrometer  32 ), all of the operations performed within the system  20  can, in the interests of the present invention, be controlled with a single computer or, in the alternative, be controlled through an appropriate software component loaded within the mass spectrometer software package. In this latter example, a single software package would control the XYZ staging, calculations (described herein) undertaken during the monitoring of the capillary tube-to-surface distance and the mass spectrometric detection. 
     It is a feature of the depicted system  20  that it includes distance-measuring means, generally indicated  40 , for monitoring and controlling the spaced distance (i.e. the distance as measured along the indicated Z-coordinate axis) between the tip  26  of the collection tube  23  and the surface  22 . Within the depicted system  20 , the distance-measuring means  40  includes a laser sensor  42  supported directly above (i.e. along the Z-coordinate axis) the surface  22 . If desired, a closed circuit color camera  44  can be supported above the  22  for collecting images during a sample-collection operation, and a video (e.g. a television) monitor  46  can be connected to the camera  44  for receiving and displaying the images collected by the camera  44 . The monitor  46  is, in turn, connected to the first control computer  30  (by way of a video capture device  50 ) for conducting signals to the computer  30  which correspond to the images taken by the camera  44 . These camera-generated images can be used by an operator to visually monitor and record events during the sample collection process. 
     Furthermore, the system  20  is provided with a webcam  48  having lens which is directed generally toward the collection tube  23  and surface  22  and which is connected to the computer  30  for providing an operator with a wide-angle view of the capillary tube  23  and the surface  22 . The images collected by the webcam  48  are viewable upon a display screen, indicated  52 , associated with the first control computer  30  by an operator to facilitate the initial positioning of the surface  22  relative to the capillary tube  23  in preparation of a sample-collection operation. 
     An example of a closed circuit camera suitable for use as the camera  44  is available from Panasonic Matsushita Electric Corporation under the trade designation Panasonic GP-KR222, and the camera  44  is provided with a zoom lens, such as is available from Thales Optem Inc. of Fairport, N.Y. under the trade designation Optem 70 XL. An example of a video capture device suitable for use as the video capture device  50  is available under the trade designation Belkin USB VideoBus II from Belkin Corp. of Compton, Calif., and an example of a webcam which is suitable for use as the webcam  48  is available under the trade designation Creative Notebook Webcam from W. Creative Labs Inc., of Milpitas, Calif. 
     The operation of the system  20  and its distance measuring means  40  can be better understood through a description of the system operation wherein through its use of the distance-measuring means  40 , the system  20  monitors the real-time measurement of the distance between the collection tube  23  and the surface  22  to be sampled and thereafter initiates adjustments, as needed, to the actual capillary tube-to-surface distance by way of the computer  30  and the XYZ stage  28  so that the optimum, or desired, capillary tube-to-surface distance (as measured along the Z-axis) is maintained throughout a sampling process, even though the surface  22  might be shifted along the X or Y coordinate axes for purposes of collecting a sample from other spots along the surface  22  or from along different lanes across the surface  22 . 
     At the outset of one embodiment of a sample-collecting operation performed with the system  20 , the tip  26  of the capillary tube  23  is positioned (during a set-up phase of the operation) at a desired capillary tube-to-surface distance which corresponds to an optimal, or desired, distance between the capillary tube  23  and the surface  22  for purposes of collecting a sample therefrom, and this optimal distance is determined (by way of the techniques described herein) and stored within the memory  33  of the first control computer  30 . Such a positioning of the surface  22  in such a desired relationship with the capillary tube  23  is effected through appropriate (e.g. manual) manipulation of the joystick control unit  29  of the XYZ stage  28  and is monitored visually by an operator as he watches the TV monitor  46  during this set-up phase of the operation. Once the surface  22  has been positioned in its desired positional relationship with the capillary tube  23 , signals which correspond to this initial (and actual) distance between the laser sensor  42  and the surface  22  are generated by the distance-measuring means  40  and sent to the computer  30  for storage (i.e. in its memory) and later use. 
     It will be understood that the aforementioned manual set-up of the capillary tube tip  26  at such a desired capillary tube-to-surface distance may not be necessary in a fully automated operation. For example, the XYZ stage  28  may not require re-adjustment between sucessive sample-collecting operations. Thus, for a second, or subsequent, sample collecting operation involving a similarly-mounted surface, appropriate commands can be initiated at the computer  30  to initiate a sample collecting operation without the need for a repeated set-up of the capillary tube-to-surface distance at optimal conditions. 
     As mentioned earlier and as illustrated in  FIGS. 4   a  and  4   b , the laser sensor  42  of the distance-measuring means  40  is disposed directly above the surface  22 . For measurement-determining purposes, the laser sensor  42  can be directed toward the surface  22  or toward a location on the (upper) surface of the support plate  27  situated alongside the support  22 . Accordingly and as used herein, the phrase laser sensor-to-surface distance, indicated d POS/LS  in  FIGS. 4   a  and  4   b , can be interpreted as being the actual distance between the laser sensor and the surface or the actual distance between the laser sensor and a location on the (upper) surface of the support plate  27  upon which the surface  22  is supported and wherein such location is disposed beside the surface  22 . 
     The use of laser sensors, like the laser sensor  42  of the distance-measuring means  40 , for measuring the distance from a laser sensor to an object are known so that a detailed description of the operation and structural details of a laser sensor are not believed to be necessary. Suffice it to say that common laser sensors used for measurement purposes emit a laser beam toward an object, and a beam, in turn, is reflected from the object back toward the sensor. The reflected beam is sensed by the laser sensor, and the period required for the laser beam to make the round trip is detected. The distance between the laser sensor and the object is subsequently calculated as being equal to one-half of the time elapsed (during the round trip of the laser beam) multiplied by the velocity of the laser beam. 
     With reference to  FIG. 5   a , there is depicted a typical relationship between the laser sensor  42 , the capillary tube  26  and the surface  22  of the depicted system  20  when the positional relationship (i.e. the distance) between the capillary tube  23  and the surface  22  is optimum for sample collecting purposes. More specifically, the surface  22  is situated generally in the X-Y plane, the capillary tube  23  is disposed immediately above the surface  22  and the laser sensor  42  is disposed on the side of the capillary tube  23  opposite the surface  22 . 
     Furthermore, the laser sensor  42  is fixed in relationship to the capillary tube  26 . In other words, the Z-coordinate distance as measured between the laser sensor  42  and the capillary tube  23 , indicated d SC/LS  in  FIGS. 4   a ,  4   b  and  5   a , should be constant throughout a sample collecting operation even though the surface  22  may be raised or lowered (by way of the XYZ stage  28 ) during the operation. If it is therefore desired to determine the actual distance between the capillary tube  23  and the surface  22  once the distance between the laser sensor  42  and the capillary tube  23  (indicated d SC/LS  in  FIGS. 4   a ,  4   b  and  5   a ) and the thickness of the capillary tube  23  are known, the distance between the capillary tube  23  and the surface  22  can be calculated by subtracting the thickness of the capillary tube  23  from the distance between the laser sensor  42  and the surface  22  (d POS/LS ). 
     Once the actual distance between the laser sensor  42  and the surface  22  during this set-up stage (i.e. when the capillary tube-to-surface distance is set to its optimum) is determined, this laser source-to-surface distance is stored in the computer  30  and designated, for present purposes, as the target laser sensor-to-surface distance which is desired to be maintained throughout the sample collection process. In other words, once the target laser source-to-surface distance is stored within the computer  30 , the sampling process can be initiated by moving the surface  22  relative to the capillary tube  23  along the X-Y plane for the purpose of collecting samples from desired locations on, or along desired lanes across, the surface  22 . During the sampling process, the actual distance between the laser sensor  42  and the surface  22  is periodically measured with the distance-measuring means  40 , and each measured actual laser sensor-to-surface distance is subsequently compared to the target laser sensor-to-surface distance, and adjustments are made, if necessary, to maintain the actual laser sensor-to-surface distance close to the target laser sensor-to-surface distance. 
     It will be understood that for comparison purposes, the computer  30  (i.e. the memory  30  thereof) is preprogrammed with information relating to acceptable distance (i.e. tolerance) limits relative to the target distance. In other words, if it is determined that the actual laser sensor-to-surface distance differs from the target laser sensor-to-surface distance by an amount which is outside of these tolerance limits, commands are sent to the XYZ stage  28  to initiate Z-axis adjustments between the capillary tube  23  and the surface  22  to bring the actual distance back in line with (i.e. within the tolerance limits of) the target laser source-to-surface distance. It follows that such preset tolerance limits correspond to a predetermined range within which the actual laser source-to-surface distance can be close enough (e.g. within +3 μm) to the desired target laser source-to-surface distance that no additional movement of the surface  22  toward or away from the capillary tube  23  is necessary. 
     With reference to  FIGS. 5   b  and  5   b , there are depicted exemplary relationships between the laser sensor  42 , the capillary tube  23  and the surface  22  when the capillary tube-to-surface distance is not optimum for sample collecting purposes. By comparison and as mentioned earlier, the capillary tube-to-surface distance in the component relationship depicted in the  FIG. 5   a  view is taken to be optimum for sample collecting purposes, and accordingly the laser sensor-to-surface distance in this  FIG. 5   a  relationship is determined during the set-up phase of the sample collecting operations. However, in the  FIG. 5   b  example, the laser sensor-to-surface distance (d POS/LS ) is greater than the laser sensor-to-surface distance determined in the set-up phase—thus indicating that a wider-than-desired gap has developed between the capillary tube  23  and the surface  22 . If the determined laser sensor-to-surface distance of the  FIG. 5   b  example is outside of the pre-set tolerance limits, then the computer  30  will initiate appropriate commands to move (by way of the XYZ stage  28 ) the surface  22  toward the capillary tube  23  so that the actual laser sensor-to-surface distance moves closer to the target laser sensor-to-surface distance (e.g. the laser sensor-to-surface distance determined during the set-up phase of the operation). 
     Similarly, in the  FIG. 5   c  example, the laser sensor-to-surface distance (d POS/LS ) is less than the desired laser sensor-to-surface distance determined in the set-up phase—thus indicating that a smaller-than-desired gap has developed between the capillary tube  23  and the surface  22 . In fact, such a determination could indicate that the capillary tube  23  has been bent upwardly by the surface  22 . If the determined laser sensor-to-surface distance of the  FIG. 5   c  example is outside the pre-set tolerance limits, then the computer  30  will initiate appropriate commands to move (by way of the XYZ stage  28 ) the surface away from the capillary tube  23  so that the actual laser sensor-to-surface distance moves closer to the target laser sensor-to-surface distance (i.e. the laser sensor-to-surface distance determined during the set-up phase of the operation). 
     It can therefore be seen that in accordance with an embodiment of the present invention, the control of the actual capillary tube-to-surface distance during a sample collecting process is comprised of a series of steps. Firstly and in preparation of a sample collection operation performed with the system  20 , an operator adjusts the Z-axis position of the surface  22  until the surface  22  is positioned in relatively close proximity to the tip  26  of the capillary tube  23  so that the capillary tube tip-to-surface distance is optimum for sample collection purposes. During this set-up stage, the relative position between the surface  22  and the capillary tube tip  26  can be visually monitored by the operator who watches the images obtained through the webcam  48  and displayed upon the computer display screen  52 . It will be understood, however, and as mentioned earlier, this initial set-up stage can be omitted in a fully automated operation. 
     Once the surface  22  is moved into a desired positional relationship with the capillary tube tip  26  during this set-up stage, the operator enters appropriate commands into the computer  30  through the keyboard  31  thereof so that the initial (and actual) laser sensor-to-surface distance is determined with the distance-measuring means  40 . In this connection, distance-measuring means  40  (by way of the laser sensor  42 ) is used to measure the actual laser sensor-to-surface distance, and a signal which corresponds to the measured distance is conducted from the distance-measuring means  40  to the computer  30 . This initial laser sensor-to-surface distance is stored within the computer memory  30  and designated, for present purposes, as the target laser sensor-to-surface distance to which subsequently-determined actual laser sensor-to-surface distances are ultimately compared. 
     When a sample collection process is subsequently undertaken, periodic measurements of the actual laser sensor-to-surface distances are taken with the distance-measuring means  40 . Electrical signals corresponding to these measured distances are immediately transmitted to the computer  30  for comparison to the target laser sensor-to-surface distance. Such periodic measurements can be taken at preselected and regularly-spaced intervals of time (e.g. every one-half second), and the time interval between which these actual laser sensor-to-surface distances are taken can be preprogrammed into, or selected at, the computer  30 . 
     As far as the analysis of the collected samples are concerned, the samples collected from the surface  22  through the collection tube  23  are conducted to the mass spectrometer  32  and are analyzed thereat in a manner known in the art. If desired, a second control computer  34  (introduced earlier and shown in  FIG. 1 ), having a display screen  38  and a keyboard  39 , can be connected to the mass spectrometer  32  for controlling its operations. In other words, the keyboard  39  can be used for entering commands into the computer  34  and thereby controlling the operation and data collection of the mass spectrometer  32 . 
     It is common that during a sample-collecting operation performed with the system  20 , the surface  22  is moved relative to the capillary tube  23  within the X-Y plane so that the tip  26  of the capillary tube  23  samples the surface  22  as the surface  22  sweeps beneath the probe  24 . For this purpose and by way of example, the computer  30  can be pre-programmed to either index the surface  22  within the X-Y plane so that alternative locations, or spots, can be positioned in sample-collecting registry with the capillary tube tip  26  for obtaining samples at the alternative locations or to move the surface  22  along an X or Y coordinate axis so that the surface  22  is sampled with the capillary tube  23  along a selected lane (such as the paths  18  of  FIG. 3 ) across the surface  22 . 
     With reference to  FIGS. 6   a  and  6   b , there is schematically illustrated the positional relationship between the surface  22  and the capillary tube tip  26  as the surface  22  is passed beneath the capillary tube tip  26  during a sample-collection operation and the movement of the capillary tube tip  26  during a re-optimization of the capillary tube-to-surface position. (Within both  FIGS. 6   a  and  6   b , the surface  22  is depicted at an exaggerated angle with respect to the longitudinal axis of the capillary tube  23  for illustrative purposes.) More specifically and within  FIG. 6   a , the surface  22  and the capillary tube  23  are moved relative to one another during a sample-collection process so that samples are collected from a lane of the surface  22  in the negative (−) X-coordinate direction indicated by the arrow  62 , and within  FIG. 6   b , the surface  22  and the capillary tube  23  are moved relative to one another during a sample-collection process so that samples are collected from a lane of the surface  22  in the positive (+) X-coordinate direction indicated by the arrow  63 . 
     Meanwhile, the dotted lines  64  and  66  depicted in  FIGS. 6   a  and  6   b  indicate the outer boundaries, or preset limits, between which the capillary tube tip  26  should be positioned in order that the optimum, or desired, distance is maintained between the surface  22  and the capillary tube tip  26  for sample collecting purposes. For example and in order to maintain the optimum distance between the capillary tube  26  and the surface  22  at a distance which corresponds to the optimum distance for sample collecting purposes, the capillary tube tip  26  should not be moved closer to the surface  22  (along the Z-axis) than is the line  64  nor should the capillary tube tip  26  be moved further from the surface  22  than is the line  66 . In practice, the spaced-apart distance between the preset limits (as measured along the Z-axis) can be within a few microns, such as about 6 μm, from one another so that the preset limits (corresponding to the dotted lines  64  and  66 ) are each spaced at about 3 μm from the target distance at which the surface  22  is optimally-arranged in relationship to the capillary tube tip  26 . Accordingly and during a sample-collection operation performed with the system  20 , actual laser sensor-to-surface distances are determined at spaced intervals of time, and appropriate signals which correspond to these actual laser sensor-to-surface distances are transmitted to the computer  30 . 
     Each measured actual laser sensor-to-surface distance is then compared, by means of appropriate software  70  ( FIG. 1 ) running in the computer  30 , to the desired target distance between the laser sensor  42  and the surface  22 , which target distance is bounded by the prescribed limit lines  64  and  66  (of  FIG. 6   a  or  6   b ). If the actual laser sensor-to-surface distance is determined to fall within the prescribed limit lines  64  and  66 , no relative movement or adjustment of the surface  22  and the capillary tube tip  26  along the Z-axis is necessary. However, if the actual laser surface-to-surface distance is determined to fall upon or outside of the prescribed limit lines  64  and  66 , relative movement between or an adjustment of the relative position between the surface  22  and the capillary tube tip  26  is necessary to bring the actual laser sensor-to-surface distance back within the prescribed limits corresponding with the limit lines  64  and  66 . Accordingly and during a sample-collection operation as depicted in  FIG. 6   a  in which frequent adjustments of the surface  22  and the capillary tube  23  along the Z-axis must be made as the capillary tube  23  is moved relative to the surface  22  along the negative (−) X-coordinate axis, the path followed by the capillary tube tip  26  relative to the surface  22  can be depicted by the stepped path  68 . 
     By comparison and during a sample-collection operation as depicted in  FIG. 6   b  in which frequent adjustments of the surface  22  and the capillary tube  23  along the Z-axis must be made as the capillary tube  23  is moved relative to the surface  22  along the positive (+) coordinate axis, the path followed by the capillary tube tip  26  relative to the surface  22  can be depicted by the stepped path  69 . 
     As mentioned earlier, by equating the laser sensor-to-support plate to the laser sensor-to-surface (as is the case when the laser sensor  42  is used to measure the distance to a location on the support plate  27  situated alongside the surface  22 , rather than to the surface  22  itself), could be a source for error, especially if the support plate  27  is canted at an appreciable angle with respect to the X-Y plane. However, if in the event that the support plate  27  is canted with respect to the X-Y plane, compensation for such an error can be made. For example, there is shown in  FIG. 7  a laser source-to-surface relationship wherein the surface  22  is canted at an angle of M degrees with respect to the X-Y plane. It can be seen in this  FIG. 7  view that the actual laser sensor-to-surface distance (along the Z-coordinate direction) (i.e. d POS/LS ) would inaccurately represent the Z-axis distance between the capillary tube  23  and the surface  22 . 
     In a system  20  used by applicants, the Y-axis distance between the line of the beam emitted from the laser source  42  and the center of the capillary tube is about 500 μm. Applicants have also found that if, for example, the angle ω (i.e. the angle of tilt of the surface  22 ) is about one degree (which, in practice, is so small that it is hard to adjust manually), then the product of tan(ω) and 500 μm is only about 9 μm. This 9 μm value is an acceptable error and would not likely have a noticable effect on the signal levels sensed across the surface. If, in the event, that such an error is not acceptable, a system can employ two laser sensors to obtain a more accurate representation of the laser sensor-to-surface distance along the Z-axis distance. 
     For example, there is depicted in  FIG. 8  a fragment of a system, generally indicated  120 , including a surface  122 , a capillary tube  123  and a pair of laser sensors  142  and  143  arranged above the capillary tube  123  so as to emit downwardly-directed beams equidistant from and on opposite sides of the capillary tube  123 . An accurate calculation of the laser sensor-to-surface distance can be obtained by averaging the laser sensor-to-surface distances measured by the two laser sensors  142 ,  143 . The value resulting from this calculation can be taken to be representative of the Z-axis distance between the capillary tube  123  and the surface  122  to reduce the likelihood of error resulting from a tilting of the surface  122  with respect to the X-Y plane. 
     It follows from the foregoing that a system  20  and associated method has been described for controlling the capillary tube-to-surface distance during a surface sampling process utilizing a sample collection device. In this connection, the system  20  automates the formulation of real-time re-optimization of the sample collection instrument-to-surface distance using distance measurements obtained with a laser sensor  42 . The distance measurement analysis includes the periodic measurement of the actual distance between the laser sensor  42  and the surface  22  followed by a comparison of each of the measured actual laser sensor-to-surface distances to a target laser sensor-to-surface distance. By comparing the actual laser sensor-to-surface distance to a target laser sensor-to-surface distance (which corresponds to a desired capillary tube-to-surface distance which can, for example, be established during a set-up phase of the procedure, the system  20  can automatically and continuously re-optimize the capillary tube-to-surface distance during the sample collection procedure by adjusting the spaced laser sensor-to-surface distance, as necessary, along the Z-coordinate axis. 
     If desired, the surface  22  can be moved along the X-Y plane (and relative to the capillary tube  23 ) to accommodate the automatic collection of samples with the capillary tube  23  along multiple parallel lanes upon the surface  22  with equal or customized spacing between the lanes. Samples can be collected with the aforedescribed system  20  at constant scan speeds or at customized, or varying, scan speeds. 
     The principle advantages provided by the system  20  and associated method for controlling the capillary tube-to-surface distance throughout a sample-collection process relate to the obviation of any need for operation intervention and manual control of the capillary tube-to-surface distance (i.e. along the Z-coordinate axis) during a sample-collection process. Accordingly, the precision of a sample-collection operation conducted with the system  20  will not be limited by the skill of an operator required to monitor the sample-collection process. Moreover, the system  20  also provides advantages which bear directly upon the accuracy of samples collected with the capillary tube  23 . For example, because the optimum, or desired, capillary tube-to-surface distance is maintained throughout the sample collecting process, the likelihood that the surface  22  would be inaccurately sampled—which could lead to misinterpretation of the collected samples, when analyzed—is substantially reduced. 
     The aforedescribed system  20  and process provide a further advantage in sample collecting equipment which employs componentry, such as the emitter  25  having a spray tip, which are intended to be positioned in a desired spatial relationship, or assignment, with one another. For example, in a sample collection system in which a spray tip and surface to be sampled are typically arranged in a fixed relationship with respect to one another during a sample collection operation, a change in the spray tip-to-surface distance also results in a change in the sampling capillary-to-surface distance by a corresponding amount. However, because the system  20  and process of the present invention helps to maintain a desired capillary tube-to-surface distance during a sample collecting process, the system  20  and process also help to maintain desired spatial relationship between the emitter, the collection tube and the surface to be sampled. 
     It will be understood that numerous modifications and substitutions can be had to the aforedescribed embodiment without departing from the spirit of the invention. For example, although the aforedescribed embodiments have been shown and described wherein the capillary tube  23  is supported in a fixed, stationary condition and the surface  22  is moved relative to the capillary tube  23  along either the X, Y or Z-coordinate directions to position a desired spot or development lane in registry with the capillary tube  23 , alternative embodiments in accordance with the broader aspects of the present invention can involve a surface which is supported in a fixed, stationary condition and a capillary tube, along with the laser sensor fixed in relationship therewith, which is movable relative to the surface along either the X, Y or Z coordinate directions. Accordingly, the aforedescribed embodiments are intended for the purpose of illustration and not as limitation.