Abstract:
An apparatus and method for aligning a laser beam in an ion source. A mounting member has a first end, a second end, and an axis. An awl is positioned on the axis and operably connected to the first end. A biasing member is arranged to urge the awl along the axis when the apparatus is mounted on the ion source to create a mark for aligning the laser beam.

Description:
BACKGROUND 
     When analyzing samples with an analytical instrument, such as a mass spectrometer that has a matrix assisted laser desorption/ionization (MALDI) ion source, the samples are commonly mixed into in a UV absorbing matrix material and then deposited on a sample plate where the sample and matrix co-crystallize upon drying. A focused pulse of UV energy from a laser beam is directed at the sample, and the UV energy ionizes the sample, which is then passed from the ion source to the analytical instrument through a small orifice such as that defined by a capillary tube. For accurate analysis, the laser beam spot must impinge the plate in a location coinciding with the center axis of the orifice opening of the instrument. Any deviation (even as low as a few hundred microns) from this location of impingement is detrimental to the sensitivity of the spectrometer. 
     Alignment is commonly attempted using a video camera to image the laser beam spot and the proximal end of the orifice opening. Due to a parallax effect, however, it can be difficult to accurately align the laser beam spot. 
     SUMMARY 
     In general terms, the present invention relates to a laser alignment tool for forming a dimple to mark the proper location for a laser beam to strike a target in an ion source. 
     One aspect of the invention provides a method of aligning a laser beam for an ion source. The method comprises forming a mark on a target plate for carrying a sample, the mark being axially aligned with a orifice between an ion source and an analytical instrument; projecting a laser beam onto the target plate forming a UV absorbing matrix material mixed with a sample of molecules for analysis laser spot; and if the laser spot is not aligned with the mark, aligning the laser spot to substantially coincide with the mark. 
     Another aspect of the invention provides a method of aligning a laser beam for an ion source. The method comprises biasing an awl toward a matrix-assisted laser desorption/ionization (MALDI) plate, the awl being axially aligned with an orifice between an ion source and an analytical instrument; pressing the awl against a protective cover mounted on the MALDI plate; forming a mark on the protective cover, the mark opposing the orifice; projecting a laser beam onto the MALDI plate forming a laser spot; if the laser spot is not aligned with the mark, aligning the laser spot to substantially coincide with the mark; and removing the protective covering from the MALDI plate upon the laser spot substantially coinciding with the mark. 
     Yet another aspect of the invention provides an apparatus for aligning a laser beam in an ion source. The apparatus comprises a mounting member having a first end, a second end, and an axis. An awl is positioned on the axis and operably connected to the first end. A biasing member is arranged to urge the awl along the axis when the apparatus is mounted on the ion source. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A  is an axonometric projection of the laser alignment tool. 
         FIG. 1B  is a cross-sectional view of the laser alignment tool illustrated in  FIG. 1A , taken along line  1 B- 1 B. 
         FIG. 1C  is a partial view of an awl on the laser alignment tool illustrated in circle  1 C of  FIG. 1   
         FIG. 2  is a top plan cross-sectional view of a Matrix Assisted Laser Desorption/Ionization (MALDI) ion source in which the laser alignment tool can be used, including a capillary assembly in cross-section. 
         FIG. 3  is a top plan cross-sectional view of the MALDI ion source illustrated in  FIG. 2 , including the mounted laser alignment tool illustrated in  FIGS. 1A and 1B , with the housing in an open position, including a top plan view of a capillary assembly. 
         FIG. 4  is a top plan cross-sectional view of a MALDI Source as illustrated in  FIG. 2 , including the mounted laser alignment tool, with the housing in a closed position, including a top plan view of a capillary assembly. 
         FIG. 5A  is a target plate with a protective covering attached. 
         FIG. 5B  is a target plate with a mark on the protective covering and a laser beam spot. 
         FIG. 6  is an axonometric projection of the laser alignment tool being inserted into a heating sleeve (and over the end of a capillary extension). 
     
    
    
     DETAILED DESCRIPTION 
     Various embodiments of the present invention will be described in detail with reference to the drawings, wherein like reference numerals represent like parts and assemblies throughout the several views. Reference to various embodiments does not limit the scope of the invention, which is limited only by the scope of the claims attached hereto. Additionally, any examples set forth in this specification are not intended to be limiting and merely set forth some of the many possible embodiments for the claimed invention. 
     Referring to  FIGS. 1A and 1B , one possible embodiment of a laser alignment tool  100  provides a fixture for marking the location at which a laser beam should strike a target plate. The laser alignment tool  100  includes a mounting member  104  that has a generally tubular wall  103 , defining a cavity  109  sized to receive a mounting structure such as a capillary extension tube as described below, and a central axis  116 . A first or distal end  105  of the tubular member  104  is open to the cavity  109  for receiving the capillary extension tube into the cavity  109 . A second or proximal end  107  of the tubular member  104  has a wall  111  that extends radially from and is orthogonal to the axis  116 . 
     The shape and dimensions of this inner cavity  109  can vary depending on the shape of the capillary extension tube that it receives. Additionally, the shape and dimensions of the inner cavity  109  are established so that the capillary tube  128  will gently slide into the inner cavity  109  but the laser alignment tool  100  will not become skewed or otherwise move radially with respect to an axis of the capillary tube. At least one hole  112 ,  114  is defined in the tubular member  104 . The holes  112 ,  114  extend between and open to the inner cavity  109  and the outer surface  115  of the tubular member  104  so that a cleaning solvent can flow through the cavity  109  to clean the inner surfaces  117  of the laser alignment tool  100 . 
     An awl  106  projects from the wall at the proximal end  107  of the tubular member  104 . The awl  106  has a point  113  that is positioned on the axis  116 . In one possible embodiment, the awl  106  is formed with a right circular cone in which oppositely disposed segments on the conical walls that extend to the vertex are at 90° relative to one another. The awl  106  can include any structure that has a point capable of leaving a mark when pressed against a surface. 
     Although a certain configuration of the awl  106  is described, other embodiments include awls that have shapes other than a right circular cone or other than a cone. Other possible embodiments could also include structures to support the point of the awl on the axis other than the radial wall and other than a structure that completely closes off the cavity at the proximal end  107 . 
     A first flange  110  is positioned at the first or distal end  105  of the tubular member  104  and extends radially from the outer surface  115 . A second flange  108  is positioned at the second or proximal end  107  of the tubular member extends radially from the outer surface  115 . A spring  102  extends around the outer surface  115  of the tubular member  104  and is seated between and is held in positioned by the first  110  and second  108  flanges. During manufacturing the proximal end of the spring  102  is fitted over the first flange  110  and then twisted around the first flange  110  in a screw-like manner until it is completely seated between the first and second flanges  110  and  108 . 
     In the exemplary embodiment, the laser alignment tool  100  is formed with a material that is easily cleaned and is hard enough that the awl  106  will leave a mark when pressed against a surface. One possible example of a material that can be used to form the laser alignment tool  100  is stainless steel, which is hardened by a heat treatment process. In other possible embodiments, the awl  106  and the other portions of the laser alignment tool  100  are made from different types of material. 
     Referring to  FIG. 2 , one possible application for the laser alignment tool  100  is an atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) ion source  119  for instrumentation  146  such as a mass spectrometer. An example of an ion source with which the laser alignment tool can be used is the atmospheric pressure ion source identified by model no. G1974A PDF-MALDI, which is commercially available from Agilent Technologies, Inc. having its principal place of business in Palo Alto, Calif. The ion source  119  includes a housing  123  that can open to provide access to interior components. In one possible embodiment, the housing  123  has target side or portion  132  and an instrument side or portion  130 . The target side  132  is slidably mounted on rails  154   a  and  154   b  that allow it to be axially slid into and out of sealing engagement with the instrument side  130  of the housing  119 . A latch  125  is attached to the target  132  and instrument  130  sides of the housing  119 . The latch  125  secures the housing in a closed position so that the two portions of the housing remain in a stationary position with respect to one another and so that the interior cavity  127  of the housing  119  remains closed and sealed, or isolated, from the exterior environment. 
     A capillary assembly  148  is mounted inside the instrument side  130  of the housing  119  and includes a capillary  122 , a capillary extension  128 , and a heating sleeve  120 . The capillary assembly  148  has a center axis  124  defining an ion passage  133  for ions to flow from the housing  119  into the instrument  146 . The capillary  122  passes through the wall  129  of the housing  119  on the instrument portion  130  and defines an orifice  131  that provides a passage for ions to flow from the interior  127  of the housing  119  into the analytical instrument  146 . The capillary  122  extends into the interior volume  127  of the housing  119 . The capillary extension  128  has an opening  126  providing an input to the ion passage  133  defined in the capillary assembly  148 . The capillary extension  128  is axially aligned with the capillary  122  and extends outward from the capillary  122  and into the housing  119 . The tubular heating sleeve  120  surrounds and is concentric to the capillary extension tube  128 . An annular space  135  is defined between the capillary extension  128  and the heating sleeve  120 . 
     Additionally, a collar  121  is positioned on the outer surface of the capillary extension  128 . The cavity  109  defined in the laser alignment tool  100  conforms to the geometry of the outer surface of the capillary extension  128  and the collar  121 . Although a particular structure for a capillary assembly  148  is illustrated in the exemplary embodiment, other embodiments might use different structures for defining a passage for ions to flow into the analytical instrument  146 . 
     A target holder  138  is mounted in the interior  127  of the housing  119  and positioned on the target side  132  of the housing by xy stages  137 . A target plate  136 , which has a front or sample surface  139  and a rear surface  141 , is mounted on the target holder  138 . When mounted on the target holder  138 , the target plate  136  is orthogonal to and directly opposes the opening  126  of the capillary extension  128 . In the exemplary embodiment, the target plate  136  is mounted on the target holder  138  by magnetic force. In other embodiments, alternative mechanisms such as clips are used to mount the target plate  136  to the target holder  138 . In the exemplary embodiment, a UV absorbing matrix material mixed with a sample of molecules for analysis is deposited on the target plate  136 . Although particular structures for a target holder  138  and target plate  136  are illustrated in the exemplary embodiment, other embodiments might use different structures and configurations. 
     The opening  126  to the capillary extension  128  is opposing and spaced from, but proximal to, the target plate  136 . When a laser beam  130 , described herein, strikes the target plate  136 , energy from the laser beam  130  causes the sample mixed in the matrix to ionize and form a gaseous plum at the opening  126  of the capillary extension  128 . A mechanism, such as pressure differential and electrical fields then causes the ions to flow through the ion passage  133  and into the analytical instrument  146  for analysis. 
     A laser assembly  142  is mounted on the sidewall  143  of the instrument side  130  of the housing  119 . The laser assembly  142  includes a laser  145  that orientated to project a laser beam  130  though a lens  152 . In one possible embodiment, the laser  145  is positioned orthogonally to the axis  124  of the capillary assembly  148 . A mirror  144  is then positioned and orientated to reflect the laser beam  130  so that it is directed toward the target plate  136  and to strike the target plate  136  at a point directly opposing the opening  126  of the capillary extension  128 . The mirror  144  is mounted on a bracket  147  to support it in a desired orientation. Although a particular arrangement for the laser assembly  142  is illustrated in the exemplary embodiment, other embodiments might use different structures arrangements for the laser  145  and an associated laser assembly  142 . 
     A video camera  134  is also mounted on a sidewall  149  of the instrument side  130  of the housing  119 . A mirror  151  is mounted on a bracket  153  and is positioned and orientated to reflect and image of at least the portion of the target plate  136  that directly opposes the opening  126  of the capillary extension  128 . The video camera  134  is positioned and orientated so that the reflected image of the target plate  136  in the mirror is within its field of view and an operator monitoring the output of the video camera  134  can view where the laser beam  130  strikes the target plate  136  when the housing  119  is closed and sealed. In one possible embodiment, the video camera  134  is positioned orthogonally to the axis  124  of the capillary assembly  148 , and video camera  134  and the laser assembly  142  are mounted on opposing sidewalls  143  and  149 . Although a particular arrangement and orientation for the video camera  134  is illustrated in the exemplary embodiment, other embodiments might use different arrangements and orientations for the video camera  134  or even different mechanism for viewing the target plate  136  while the laser  145  is projecting a laser beam  130 . 
     In use, referring to  FIGS. 3 and 6 , the housing  119  is opened by separating the target side  132  from the instrument side  130 . The distal end  105  of the laser alignment tool  100  is then inserted into the annular space  135  between the capillary extension  128  and the heating sleeve  120  so that the spring  102  is seated against the face  118  of the heating sleeve  120 . In this position, the point  113  of the awl  106  is aligned on the axis  124  of the capillary assembly  148 . 
     Referring to  FIGS. 3 and 5   a  an adhesive paper label  156  is placed on the back surface of the target plate  136 , and the target plate  136  is mounted on the target holder  138  so that the front or sample surface  139  is facing the target holder  138 . The paper  156  has UV fluorescence, which provides visibility of the laser beam spot. In an embodiment, the adhesive paper label  156  also has a yellow color. 
     Referring to  FIGS. 4 and 5   b  after the laser alignment tool  100  and target plate  136  with the adhesive paper label  156  are mounted, the housing  119  is closed so that the target side  132  of the housing engages the instrument side  130  of the housing  119 . The point  113  of the awl  106  strikes the paper label  156  and leaves a mark or dimple  160  in the paper  156 . Additionally, the spring  102  is compressed between the flange  108  at the proximal end  107  of the laser alignment tool  100  and the face  118  of the heating sleeve  120 . The spring  102  biases or urges the awl  106  against the paper label  156  and the spring force helps make a visible mark  160  in the adhesive paper label  156 . 
     Other embodiments for forming a mark  160  to align the laser  130  are possible. For example, a mark could be placed directly into the surface  141  of the target plate  136 . In other embodiments, different types of protective coatings other than the label  156  described herein could be used for receiving a dimple  160  by the awl  106 . In yet other embodiment, the mark  160  could be placed on a substitute or dummy target plate or even on the sample surface  139  of the target plate  136  as opposed to the back surface  141 . There are also other possible embodiments for mounting the laser alignment tool  100  in addition to the exemplary embodiment disclosed herein. For example, one embodiment might be configured to fit over the end of the heating sleeve  120 . 
     After forming the dimple  160  in the adhesive paper label  156  and opening the housing  119 , the laser alignment tool  100  is removed from the capillary assembly  148 , and the housing is closed again. The laser  142  is then activated to project a laser beam spot  158  onto the target plate  136 . The position of the laser beam spot  158  is adjusted so that it is centered on the dimple  160 . In one possible embodiment, the position of the laser beam spot  158  is adjusted by laterally adjusting the position of the laser  145  relative to the sidewall  143  of the housing  119 . In another possible embodiment the position of the laser beam spot  158  is adjusted by changing the angular orientation of the laser  130  with respect to the sidewall  143  of the housing  119 . In other possible embodiment the position of the laser beam spot  158  is adjusted by moving the position and orientation of the mirror  144  or by some other mechanism. The laser beam spot  158  is viewed through the video camera  134  while it is being positioned. 
     After the laser  130  is aligned, the housing  119  is opened, the target plate  136  is removed form the target holder  138 , and the adhesive paper label  156  is removed from the target plate  136 . The target plate  136  could be washed with isopropyl alcohol or some other cleaning solvent to remove any residual adhesive. A sample can then be deposited onto the target plate  136  for testing and analysis. 
     The various embodiments described above are provided by way of illustration only and should not be construed to limit the invention. Those skilled in the art will readily recognize various modifications and changes that may be made to the present invention without following the example embodiments and applications illustrated and described herein, and without departing from the true spirit and scope of the present invention, which is set forth in the following claims.