Patent Publication Number: US-11393670-B2

Title: MALDI mass spectrometer and storage medium recording program for MALDI mass spectrometer

Description:
TECHNICAL FIELD 
     The present invention relates to a MALDI mass spectrometer using an ion source employing matrix assisted laser desorption/ionization (MALDI) as well as a storage medium recording a computer program for a MALDI mass spectrometer. 
     BACKGROUND ART 
     In a MALDI mass spectrometer, a sample prepared by mixing a specimen to be analyzed with an ionization-assisting agent called the matrix is irradiated with laser light for a short period of time to turn the components of the specimen in the sample into ions while vaporizing those components. The ions derived from the components of the specimen in this manner are subsequently introduced, for example, into an ion trap mass separator or time-of-flight mass separator in the MALDI mass spectrometer to separate those ions according to their mass-to-charge ratios m/z and individually detect the separated ions. 
     The ion source in a MALDI mass spectrometer normally includes a plate-shaped metallic sample plate, which has a plurality of wells formed on its top surface, allowing one sample to be prepared in each well. The most basic method for preparing a sample includes the steps of dropping a mixed liquid of a solution of the specimen to be analyzed and a matrix solution into a well of a sample plate, and drying that liquid. As another sample preparation method, the step of mixing the solution of the specimen with the matrix solution may be performed on a well of the sample plate. 
     A sample prepared in this manner is not always formed at the center of the well, which has a circular shape as viewed from above. In some cases, the sample may be formed at a position that is within the well yet displaced from the center. Furthermore, even when the sample is formed at or near the center of the well, the optimum measurement point (“sweet spot”) at which the most satisfactory signal (normally, the highest level of signal intensity) is obtained by irradiation with laser light is not always at the center of the well since the distribution of the matrix crystal is non-uniform. To deal with such a situation, in an analysis using a MALDI mass spectrometer, an operator often performs necessary tasks, such as the determination of the point that should be irradiated with laser light while visually observing the location of the sample formed on the sample plate or distribution of the matrix crystal. 
     In order to facilitate the task of determining the laser irradiation point, a MALDI mass spectrometer described in Patent Literature 1 illuminates the sample plate with light within an ultraviolet wavelength region and detects the reflected light from the top surface of the sample plate to create an observation image of the sample plate and display it on a screen of a display unit. When a matrix that absorbs light within the ultraviolet wavelength region is used, the method can produce an observation image which clearly shows the sites where the matrix is distributed. This image allows for an effortless check of the position of the adhered sample on the sample plate, state of distribution of the matrix and other related conditions. 
     CITATION LIST 
     Patent Literature 
     Patent Literature 1: JP 2018-36100 A 
     Non Patent Literature 
     Non Patent Literature 1: “MALDImini™-1 Digital Ion Trap Mass Spectrometer”, disclosed on Shimadzu Corporation&#39;s website, [accessed on Jan. 14, 2020] 
     SUMMARY OF INVENTION 
     Technical Problem 
     However, depending on the kind of matrix, state of the mixture of the matrix and the specimen or other relevant factors, illuminating the sample plate with visible light rather than ultraviolet light may make it easier to check the state of adhesion of the sample. Furthermore, some operators may be accustomed to watching an observation image obtained by illuminating the sample plate with visible light, in which case using such a type of image may allow for a more appropriate judgment. Additionally, two or more kinds of samples respectively prepared using different kinds of matrices may be present in the plurality of wells provided on one sample plate, in which case the check of the state of adhesion of the sample may be satisfactorily performed for only some of the samples by the conventional MALDI mass spectrometer mentioned earlier 
     The present invention has been developed in view of such problems. Its objective is to provide a MALDI mass spectrometer which allows an operator to properly check the state of adhesion of the sample, state of distribution of the matrix and other related conditions, as well as a storage medium recording a computer program for such a MALDI mass spectrometer. 
     Solution to Problem 
     One mode of the MALDI mass spectrometer according to the present invention developed for solving the previously described problem is a MALDI mass spectrometer configured to irradiate a sample on a sample plate with laser light to ionize a component in the sample and perform a mass spectrometric analysis of the component, the MALDI mass spectrometer including: 
     a plurality of light source units each of which is configured to emit a beam of light with a different wavelength region; 
     an illumination light switching section configured to selectively cast one of the beams of light emitted from the plurality of light source units, onto the sample plate as illumination light; and 
     an imaging section configured to acquire an optical image of the sample plate formed by the illumination light, the imaging section being common to the plurality of light source units. 
     One mode of the storage medium recording a program for a MALDI mass spectrometer according to the present invention developed for solving the previously described problem is a computer readable storage medium recording a computer program to be used for a MALDI mass spectrometer configured to irradiate a sample on a sample plate with laser light to ionize a component in the sample and perform a mass spectrometric analysis of the component, the MALDI mass spectrometer further configured to selectively cast one of a plurality of beams of light emitted from a plurality of light source units each of which is configured to emit a beam of light with a different wavelength region, onto the sample plate as illumination light, and acquire, with an imaging section, an optical image of the sample plate formed by the illumination light, and the computer program configured to make a computer function as: 
     a display-processing functional section configured to display, on a screen of the same display unit, a plurality of observation images acquired for the sample plate in which one of the observation images is displayed as a real-time image continuously updated with the passage of time and another one of the observation images is displayed as a snap image which is a still image acquired at a predetermined point in time; and 
     an illumination-light-switching control functional section configured to control a switching operation of the illumination light so that a beam of light emitted from a specific light source unit among the plurality of light source units is cast onto the sample plate as the illumination light when the real-time image is being updated, and a beam of light emitted from a light source unit different from the specific light source unit among the plurality of light source units is cast onto the sample plate as the illumination light at the predetermined point in time specified for acquiring the snap image. 
     Advantageous Effects of Invention 
     In one mode of the MALDI mass spectrometer according to the present invention, the switching of the illumination light by the illumination light switching section may be performed by turn-on and turn-off operations through the drive control of the light source units. Another possibility is to maintain all light source units in the ON state and select the illumination light to be allowed to reach the sample plate, for example, by switching or blocking an optical path using a mirror, shutter or other optical elements. 
     The previously described mode of the MALDI mass spectrometer according to the present invention can acquire, for example, two observation images of the same sample plate, with one image showing the sample plate illuminated with light within the visible wavelength region and the other image showing the sample plate illuminated with light within the ultraviolet wavelength region, and simultaneously display both images or selectively display one of those images. Thus, the previously described mode of the MALDI mass spectrometer according to the present invention can more properly show the user the position of the sample formed on the sample plate, state of distribution of the matrix and other related conditions, thereby allowing the user to easily locate, for example, a sweet spot at which a high level signal intensity can be obtained in the sample. 
     The previously described mode of the storage medium recording a program for a MALDI mass spectrometer according to the present invention enables a computer to simultaneously display, on the screen of the display unit, two observation images of the same sample plate including, for example, one image showing the sample plate illuminated with light within the visible wavelength region and the other image showing the sample plate illuminated with light within the ultraviolet wavelength region. One of the observation images is a real-time image, in which the imaging range on the sample plate changes its position in real time when the position of the sample plate is changed. This allows the user to visually check the observation image of each of the samples at different positions on the sample plate or each of the different sites in the same sample. The other observation image is a snap image, which allows the user to visually check the observation image reflecting the state of a sample on the sample plate observed at the predetermined point in time, despite the change in the position of the sample plate. Thus, by using the previously described mode of the storage medium recording a program for a MALDI mass spectrometer according to the present invention, the user can more properly and efficiently check the position of the sample formed on the sample plate, state of distribution of the matrix, and other related conditions even in the case where, for example, the kind of matrix used for the preparation of the sample changes from one well to another on the sample plate. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         FIG. 1  is a configuration diagram showing the main components of a MALDI-MS system as one embodiment of the present invention. 
         FIG. 2  is a model diagram showing a situation in which the top surface of a sample plate is being imaged in the MALDI-MS system according to the present embodiment. 
         FIG. 3  is a schematic timing chart showing the on/off operation of light sources and an imaging operation in the MALDI-MS system according to the present embodiment. 
         FIGS. 4A and 4B  show one example of a visible-light image and an ultraviolet-light image in the MALDI-MS system according to the present embodiment. 
         FIGS. 5A and 5B  show one example of the transition between two observation images in the MALDI-MS system according to the present embodiment. 
         FIGS. 6A and 6B  show another example of the transition between two observation images in the MALDI-MS system according to the present embodiment. 
         FIGS. 7A and 7B  show still another example of the transition between two observation images in the MALDI-MS system according to the present embodiment. 
         FIGS. 8A and 8B  show still another example of the transition between two observation images in the MALDI-MS system according to the present embodiment. 
         FIGS. 9A and 9B  show still another example of the transition between two observation images in the MALDI-MS system according to the present embodiment. 
     
    
    
     DESCRIPTION OF EMBODIMENTS 
     A MALDI-MS system, which is one embodiment of the MALDI mass spectrometer according to the present invention, is hereinafter described with reference to the attached drawings. 
       FIG. 1  is a configuration diagram showing the main components of the MALDI-MS system according to the present embodiment. This MALDI-MS system is a system using a MALDI ion source as the ion source and an ion trap mass separator as the mass separator, as disclosed in Non Patent Literature 1. 
     As shown in  FIG. 1 , a box-shaped vacuum chamber  10  evacuated by a vacuum pump  11  contains a sample stage  14 , on which a sample plate  15  is to be placed, as well as an extraction electrode  17 , quadrupole deflector  18 , ion trap  20  and detector  26 . A transparent window  100  is provided in the wall (ceiling) of the vacuum chamber  10  directly above the sample stage  14 . A laser emitter  12 , half mirror  13  and visible light camera  32  are arranged in an area above the top wall of the vacuum chamber  10 . Three axes X, Y and Z orthogonal to each other are defined as shown in  FIG. 1  for convenience of the indication of the positional relationship of those components. The X-Y plane is normally a plane parallel to the installation surface of the system. The surface on which the sample plate  15  is to be placed in the sample stage  14  is also parallel to the X-Y plane. 
     The quadrupole deflector  18  is composed of four rod electrodes extending in the Y-axis direction. Direct voltages are respectively applied from a power source (not shown) to the rod electrodes to form a deflecting electric field which bends the direction of travel of the ions within the space surrounded by those rod electrodes. The ion trap  20  has the configuration of a three-dimensional quadrupole including a substantially ring-shaped electrode  21  as well as a pair of end-cap electrodes  22  and  24  facing each other across the ring electrode  21 . An ion injection hole  23  is formed in the entrance end-cap electrode  22  located on the side facing the quadrupole deflector  18 , while an ion ejection hole  25  is formed in the exit end-cap electrode  24 . Predetermined voltages are applied from a power source (not shown) to the ring electrode  21  as well as the end-cap electrodes  22  and  24 , respectively, whereby ions can be captured within the space surrounded by those electrodes or ejected from the same space to the outside through the ion ejection hole  25 . 
     The sample stage  14  is movable in the two axial directions of the X and Y axes by a stage driver  16  including a motor. A visible light source  30   a  and ultraviolet light source  30   b  for illuminating the top surface of the sample plate  15  are provided within the space between the sample stage  14  and the extraction electrode  17 . An illumination driver  31  is provided for turning on the two light sources  30   a  and  30   b.    
     The control-and-processing unit  40  includes, as its functional blocks, an analysis controller  41 , observation image acquisition controller  42 , acquired image processor  43 , display processor  44 , data processor  45 , input/output processor  45  and other necessary components. An input unit  47  and a display unit  48  serving as a user interface are connected to the control-and-processing unit  40 . 
     The analysis controller  41  acts as the main controller which operates related sections for executing an analysis. The observation image acquisition controller  42  controls related sections for displaying an observation image of the top surface of the sample plate  15 , as will be described later. The acquired image processor  43  processes image data obtained from the visible light camera  32  to create an observation image. The input/output processor  46  is responsible for the input/output operation using the input unit  47  and the display unit  48 . The display processor  44  creates information to be displayed on the screen of the display unit  48 , and displays the information via the input/output processor  46 . The data processor  45  receives detection data from the detector  26  and processes the data for specific purposes, such as the creation of a mass spectrum. 
     In normal cases, the control-and-processing unit  40  is actually a personal computer, workstation or similar type of computer, with the aforementioned functional blocks and other components embodied by executing, on the computer, dedicated software (computer program) installed on the same computer. In that case, the input unit  47  includes a keyboard and a pointing device provided for the computer, while the display unit  48  includes a display monitor. The aforementioned computer program can be offered to users in the form of a non-transitory storage medium recording the program, such as a CD-ROM, DVD-ROM, memory card, or USB memory (dongle). It may also be offered to users in the form of data transferred through the Internet or similar communication networks. 
     An operation for performing a mass spectrometric analysis on samples formed on the sample plate  15  in the MALDI-MS system according to the present embodiment is hereinafter schematically described. 
     As shown in  FIG. 2 , the plate-shaped sample plate  15  made of metal (normally, stainless steel) has a top surface on which a plurality of wells  151 , each of which has a circular shape as viewed from above, are formed. One sample  152 , which is a mixture of a specimen and a matrix, is formed within each well  151 . There is no specific limitation on the method for preparing the samples  152 . 
     With the sample plate  15  placed on the sample stage  14  and the vacuum chamber  10  evacuated with the vacuum pump  11 , the laser emitter  12  under the control of the analysis controller  41  generates laser light in a pulsed form. The laser light is reflected by the half mirror  13  and passes through the window  100 , to be delivered to a sample on the sample plate  15  in a substantially perpendicular direction. As noted earlier, the sample stage  14  can be moved in the X and Y directions by the stage driver  16 . By this movement, the point of irradiation with the laser light can be adjusted. 
     Upon being irradiated with the laser light for ionization, the components of the specimen in the sample are ionized. The thereby produced ions are extracted from the vicinity of the sample plate  15  by the electric field created by the extraction electrode  17 , and travel in a roughly Z-axis direction to arrive at the quadrupole deflector  18 . The ions have their traveling path bent by approximately 90 degrees due to the deflecting electric field created by the quadrupole deflector  18 , and travel in a roughly X-axis direction. The ions subsequently pass through the ion injection hole  23  and enters the ion trap  20 , to be captured by an electric field created by a radio-frequency voltage applied to the ring electrode  21 . 
     Ions generated from a sample by a single laser-light irradiation are temporarily captured within the ion trap  20 , and subsequently ejected through the ion ejection hole  25  in ascending or descending order of their mass-to-charge ratio by an electric field created by the voltages applied to the end-cap electrodes  22  and  24 . For the ejection of the ions from the ion trap  20 , the technique of resonant excitation in which an ion having a specific mass-to-charge ratio is made to significantly oscillate can be used. 
     The detector  26  sequentially detects the ions ejected from the ion trap  20  and produces a detection signal corresponding to the amount of ions it has received. The data processor  45  receives this detection signal, converts it into digital data, and creates a mass spectrum representing the relationship between mass-to-charge ratio and signal intensity. It should be noted that the MALDI method normally has a comparatively large variation in the amount of ions generated by a single laser-light irradiation. Therefore, in order to improve the accuracy and sensitivity of the analysis, the same sample is irradiated with the laser light multiple times, and the mass spectrum data acquired for each laser-light irradiation are accumulated to obtain a final mass spectrum which is less affected by the variation in the amount of generated ions and other unfavorable factors. 
     For the previously described analysis, the task of determining the point of irradiation with the laser light in the sample in advance of the analysis is performed by the user (operator) as follows: An observation image showing an enlarged view of a sample on the sample plate  15  is displayed on the screen of the display unit  48 . Watching the observation image, the operator inputs instructions from the input unit  47  to appropriately change the position of the sample stage  14  to ascertain which position in the sample is appropriate for the analysis. In this task, the operator refers to an observation image of the top surface of the sample plate  15  displayed on the screen of the display unit  48 . An operation for displaying this reference image is hereinafter described in detail. 
     The visible light source  30   a  is a visible LED which emits light within the visible wavelength region. The ultraviolet light source  30   b  is an ultraviolet LED which emits light within the ultraviolet wavelength region. In the present example, this LED emits light within an ultraviolet wavelength region centered on 350 nm. Examples of the matrices used for MALDI include DHB (2,5-dihydroxybenzoic acid) and CHCA (α-cyano-4-hydroxycinnamic acid). DHB has the maximum absorption wavelength around 330 nm, while CHCA has the maximum absorption wavelength around 341 nm. The difference between the peak emission wavelength in the emission wavelength distribution of the ultraviolet light source  30   b  and the maximum absorption wavelengths of those matrices is as small as 20 nm. Those wavelength bands overlap each other to a considerable extent. In this manner, the wavelength band of the ultraviolet light source  30   b  is selected so that it will sufficiently overlap the absorption wavelength band of the matrix to be used. 
     As shown in  FIG. 2 , the top surface of the sample plate  15  is illuminated with either visible or ultraviolet light which is cast obliquely from above. For example, when the sample plate  15  is illuminated with the visible light, the light is almost entirely reflected by the top surface of the sample plate  15  inclusive of the samples  152  since the matrix in the samples  152  does not significantly absorb visible light. The reflected light enters the visible light camera  32 . Therefore, with the visible light camera  32 , an observed image can be obtained in which important objects on the top surface of the sample plate  15 , such as the marks indicating the position of the wells  151 , can be satisfactorily observed. 
     On the other hand, when the sample plate  15  is illuminated with the ultraviolet light, the matrix in the samples  152  significantly absorbs ultraviolet light around the specific absorption wavelength band, and emits fluorescent light within the visible wavelength band. Meanwhile, the ultraviolet light hitting the top surface of the sample plate  15  where no sample  152  is present is almost entirely scattered without undergoing absorption. The visible light camera  32 , which is configured to mainly detect visible light, produces an observation image in which the sites where the matrix is present can be brightly seen. Thus, two evidently different observation images are obtained for the same imaging range by using the ultraviolet light and the visible light as the illumination light. 
       FIGS. 4A and 4B  show one example of the visible-light image (an optical image acquired by using the visible light for the illumination) and the ultraviolet-light image (an optical image acquired by using the ultraviolet light for the illumination) corresponding to one well, taken with the visible light camera  32 . In the visible-light image shown in  FIG. 4A , the ring-shaped mark indicating the position of the well is clearly visible, whereas the sample portion is unclear. By contrast, in the ultraviolet-light image shown in  FIG. 4B , the sample portion is clearly visible, in which the sites where the matrix is abundantly present look particularly white. With this image, the state of distribution of the matrix can be satisfactorily recognized. 
     The cross hairs shown in  FIGS. 4A and 4B  are a marker whose point of intersection indicates the point of irradiation with the laser light for ionization. From this marker and the observation images, the operator can recognize the laser irradiation point in the sample at that point in time. 
     In the MALDI-MS system according to the present embodiment, one of the following display modes can be used for displaying observation images on the screen of the display unit  48 . 
     &lt;First Display Mode&gt; 
       FIGS. 5A and 5B  illustrate the transition of the display image in the first display mode. 
     In this display mode, the observation image acquisition controller  42  displays, via the input/output processor  48 , a screen on the display unit  48  which allows users to select either the visible light or ultraviolet light as the illumination light. On this display, the operator selects either the visible light or ultraviolet light. Upon receiving the selecting instruction via the input/output processor  46 , the observation image acquisition controller  42  controls the illumination driver  31  to turn on either the light source  30   a  or  30   b  corresponding to the visible or ultraviolet light selected. Either light source  30   a  or  30   b  is thereby turned on, and the light emitted from the light source illuminates the top surface of the sample plate  15 . 
     The visible light camera  32  acquires an optical image of the top surface of the sample plate  15  through the half mirror  13 , window  100 , and opening of the extraction electrode  17 . The image data acquired with the visible light camera  32  is sent to the acquired image processor  43 , which performs predetermined image processing to create an observation image for display. The display processor  44  shows the created observation image at a predetermined position on the screen of the display unit  48 . Accordingly, if the operator has selected the visible light as the light to be used for illumination, a visible-light image as shown in  FIG. 5A  is displayed. If the operator has selected the ultraviolet light as the light to be used for illumination, an ultraviolet-light image as shown in  FIG. 5B  is displayed.  FIGS. 5A and 5B  are images corresponding to the  FIGS. 4A and 4B  mentioned earlier, for example. 
     The operator can switch the selection between the visible light and ultraviolet light by using the input unit  47 . According to the switching instruction, the observation image acquisition controller  42  switches the light source that should be turned on. Accordingly, the observation image displayed on the screen of the display unit  48  is also switched between the visible-light and ultraviolet-light images. The observation image displayed in this situation is a real-time image showing a view of the top surface of the sample plate  15  in real time. Therefore, for example, when the operator changes the position of the sample stage  14  in the X-Y plane by an operation using the input unit  47 , the range of the displayed observation image also correspondingly changes its position. In this manner, the operator can select an observation image which is easier for the operator to watch, or one which the operator is accustomed to watching, to determine the point to be irradiated with laser light. 
     &lt;Second Display Mode&gt; 
       FIGS. 6A and 6B  illustrate the transition of the display image in the second display mode which is different from the first display mode. 
     In the present display mode, the observation image acquisition controller  42  controls the illumination driver  31  so that the visible light source  30   a  and the ultraviolet light source  30   b  are alternately turned on at predetermined intervals of time. Accordingly, the light emitted from the visible light source  30   a  and the one emitted from the ultraviolet light source  30   b  alternately illuminate the top surface of the sample plate  15  at predetermined intervals of time. 
     The image data acquired with the visible light camera  32  for the illumination light is sent to and processed by the acquired image processor  43 . The display processor  44  displays the created observation image within the screen of the display unit  48 . Accordingly, a visible-light image as shown in  FIG. 6A  and an ultraviolet-light image as shown in  FIG. 6B  are automatically and alternately displayed on the screen of the display unit  48 . As in the first display mode, the observation image displayed in this manner is a real-time image of the top surface of the sample plate  15 . Therefore, the operator can determine the point to be irradiated with laser light while visually checking both the visible-light and ultraviolet-light images in real time. 
     &lt;Third Display Mode&gt; 
       FIGS. 7A and 7B  illustrate the transition of the display image in the third display mode which is different from the first and second display modes.  FIG. 3  is a schematic timing chart showing the turn-on/off operation of the light sources  30   a  and  30   b  as well as an imaging operation in the third display mode. 
     In the third display mode, as in the second display mode, the observation image acquisition controller  42  controls the illumination driver  31  so that the visible light source  30   a  and the ultraviolet light source  30   b  are alternately turned on at predetermined intervals of time t 1  (see  FIG. 3 ). Accordingly, the light emitted from the visible light source  30   a  and the one emitted from the ultraviolet light source  30   b  alternately illuminate the top surface of the sample plate  15  at predetermined intervals of time t 1 . 
     The image data acquired with the visible light camera  32  for the illumination light is sent to and processed by the acquired image processor  43 . The display processor  44  displays the created observation image within the screen of the display unit  48 . In the third display mode, as shown in  FIGS. 7A and 7B , the display processor  44  displays an image display frame  50  within the screen of the display unit  48 , with the two observation images, i.e., the visible-light and ultraviolet-light images, horizontally arranged. An indicator  51  which turns on and off is provided above each of the visible-light and ultraviolet-light images in the image display frame  50 . 
     As shown in  FIG. 3 , while the visible light is illuminating the top surface of the sample plate  15 , the visible light camera  32  acquires a visible-light image of the top surface of the sample plate  15 . This visible-light image is a real-time image. The display processor  44  displays, in the left area of the image display frame  50 , the visible-light image acquired in real time under illumination with the visible light, as well as turns on the indicator  51  above the same image (see  FIG. 7A ). This indicator  51  shows that the image is the real-time image. 
     After completion of the turn-on period for the visible light source  30   a , the light source that should be turned on is switched from the visible light source  30   a  to the ultraviolet light source  30   b , whereupon the ultraviolet light begins to illuminate the top surface of the sample plate  15 . In this situation, the visible light camera  32  acquires an ultraviolet-light image of the top surface of the sample plate  15  as the real-time image. The display processor  44  displays, in the right area of the image display frame  50 , the ultraviolet-light image acquired in real time under illumination with the ultraviolet light, as well as turns on the indicator  51  above the same image. Meanwhile, the display processor  44  creates a snap image, or a still image, from the visible-light image which has been displayed as the real-time image immediately before the switching of the light source from the visible light source  30   a  to the ultraviolet light source  30   b , and continues displaying the snap image in the left area of the image display frame  50 . Understandably, this snap image displayed in the left area of the image display frame  50  is no longer a real-time image, so that the indicator  51  above the same image is turned off (see  FIG. 7B ). 
     The display processor  44  performs the previously described processing every time the light source that should be turned on is switched from the visible light source  30   a  to the ultraviolet light source  30   b  or vice versa. Accordingly, as shown in  FIGS. 7A and 7B , the real-time image and the snap image are interchanged with each other between the visible-light and ultraviolet-light images every time the light source that should be turned on is switched at regular intervals of time t 1 , with the indicator  51  above the real-time image turned on and the indicator  51  above the snap image turned off. As described earlier, for example, when the operator changes the position of the sample stage  14  in the X-Y plane by an operation using the input unit  47 , the range of the observation image displayed on the real-time image also correspondingly changes, whereas the range of the observation image displayed on the snap image is fixed. 
     The third display mode allows an operator to determine an appropriate point to be irradiated with the laser light while comparing the visible-light and ultraviolet-light images displayed side by side. 
     &lt;Fourth Display Mode&gt; 
       FIGS. 8A and 8B  illustrate the transition of the display image in the fourth display mode which is different from the first through third display modes. 
     In the fourth display mode, as in the third display mode, the visible-light and ultraviolet-light images are displayed side by side within an image display frame  60 . However, unlike the third display mode in which the used light source is automatically switched at regular intervals of time, the present mode allows the operator to perform an operation using the input unit  47  to select which of the visible and ultraviolet light sources  30   a  and  30   b  should be used, as in the first display mode. In the present case, as shown in  FIGS. 8A and 8B , radio buttons  61  for selecting the visible or ultraviolet light are provided within the image display frame  60 . By clicking one of those radio buttons  61 , the operator can select the light source to be used. The observation image corresponding to the selected light source will be the real-time image. 
     After the light source to be used has been switched by the operator, for example, from the visible light source  30   a  to the ultraviolet light source  30   b  (from  FIG. 8A  to  FIG. 8B ), the visible light image which was displayed in real time immediately before the switching is maintained on the display as a snap image. Accordingly, after the switching operation, the visible-light image as the snap image and the ultraviolet-light image as the real-time image are displayed side by side within the image display frame  60 . 
     In order to sequentially perform measurements for a plurality of wells  151  on the sample plate  15 , the MALDI-MS system according to the present embodiment is provided with the function of automatically driving the sample stage  14  so that the laser irradiation point will be automatically set at or near the center of the next well  151  in a predetermined order, i.e., so that the next well  151  to be subjected to the measurement will come into the imaging range. When the imaging range has been automatically moved to the next well  15  in this manner, the light source is temporarily switched to the one that is not the selected light source at that point in time, and the observation image of the top surface of the sample plate  15  immediately after the movement is taken as the snap image. When a new snap image has been obtained in this manner, the display processor  44  updates the snap image displayed within the image display frame  60  with the new observation image. Accordingly, for example, even under the condition that the light source currently selected for the illumination is the visible light source  30   a , when the imaging range has automatically been moved to the next well  151 , the ultraviolet-light image, which is currently displayed as the snap image, will be updated with the latest snap image acquired after the movement. This operation prevents the situation in which an image displayed as the snap image shows a well that is not the well which the operator is observing in the real-time image. 
     The fourth display mode allows an operator to select, as the real-time image, an observation image which is easier for the operator to watch, or one which the operator is accustomed to watching, and to determine the laser irradiation point while comparing the visible-light and ultraviolet-light images displayed side by side. 
     The system may be configured so that, when the operator performs an operation for changing the position of the sample stage  14  in order to change the laser irradiation point, the cross-hairs mark indicating the laser irradiation point changes its position on the snap image so that it correctly indicates the laser irradiation point at that point in time, while the imaging range in the snap image remains unchanged. This configuration allows the operator to correctly recognize the laser irradiation point not only on the real-time image but also on the snap image, thereby avoiding a false recognition of the laser irradiation point. 
     &lt;Fifth Display Mode&gt; 
       FIGS. 9A and 9B  illustrate the transition of the display image in the fifth display mode which is different from the first through fourth display modes. 
     In the third and fourth display modes, the visible-light and ultraviolet-light images are displayed at their respectively designated positions within the image display frame. In the fifth display mode, it is the real-time image and the snap image that have their display positions fixed, with the real-time image on the left side and the snap image on the right side within the image display frame  70 . When visible light is selected with a visible/ultraviolet light selection radio buttons  71  as shown in  FIG. 9A , the visible-light image is displayed as the real-time image on the left side, while the ultraviolet-light image is displayed as the snap image on the right side. When ultraviolet light is selected with the visible/ultraviolet light selection radio buttons  71  as shown in  FIG. 9B , the ultraviolet-light image is displayed as the real-time image on the left side, while the visible-light image is displayed as the snap image on the right side. 
     As for the snap image, a real-time image displayed immediately before the switching of the light source, or an image acquired immediately after an automatic movement of the imaging range to the next well, can be used, as in the fourth display mode. 
     The fifth display mode allows an operator to select, as the real-time image, an observation image which is easier for the operator to watch, or one which the operator is accustomed to watching, and to determine an appropriate laser irradiation point by additionally referring to the snap image as needed while continuously watching the real-time image. 
     As in the case of the fourth display mode, the system in the fifth display mode may be configured so that the cross-hairs mark indicating the laser irradiation point changes its position on the snap image so that it correctly indicates the laser irradiation point at that point in time. This configuration allows the operator to correctly recognize the laser irradiation point also on the snap image, thereby avoiding a false recognition of the laser irradiation point. 
     Although the two observation images are horizontally arranged within the image display frame in any of the third through fifth display modes, it is naturally possible to vertically arrange them. It is also possible to superpose the visible-light and ultraviolet-light images on each other on the display, with their relative position adjusted so that the same site on the top surface of the sample plate  15  comes to the same position in both images, instead of arranging them horizontally or vertically. 
     In the MALDI-MS system according to the previously described embodiment, two types of light sources, i.e., the visible and ultraviolet light sources, are used. It is also possible to use three or more light sources. The use of both visible and ultraviolet light sources is not indispensable; it is possible to use two or more types of light sources all of which emit light within the ultraviolet wavelength region, with their wavelength bands shifted from each other (without completely overlapping each other). A light source which emits light within an infrared, near-infrared or other wavelength bands may be used in place of the ultraviolet light source. What wavelength band should be used for the illumination can be determined according to the absorption wavelength band of the used matrix. Accordingly, in the case where a plurality of kinds of matrices are used for the plurality of samples formed on one sample plate  15 , a light source with an appropriate wavelength band should preferably be used for each matrix. 
     In the MALDI-MS system according to the previously described embodiment, the switching of the illumination light to be cast onto the sample plate  15  is achieved by turning on/off the light sources. As another example, the switching of the illumination light to be cast onto the sample plate  15  may be achieved by switching an optical path using a mechanically movable mirror, a shutter, or other types of optical elements. 
     Although an ion trap is used as the mass separator in the MALDI-MS system according to the previously described embodiment, there is actually no limitation on the type of mass separator or method of mass separation as long as the ion source is a MALDI ion source (including an atmospheric pressure MALDI ion source). Accordingly, for example, the present invention can be applied in a MALDI-TOFMS using a time-of-flight mass separator for mass separation. 
     [Various Modes of Invention] 
     A person skilled in the art can understand that the previously described illustrative embodiments are specific examples of the following modes of the present invention. 
     (Clause 1) One mode of the MALDI mass spectrometer according to the present invention is a MALDI mass spectrometer configured to irradiate a sample on a sample plate with laser light to ionize a component in the sample and perform a mass spectrometric analysis of the component, the MALDI mass spectrometer including: 
     a plurality of light source units each of which is configured to emit a beam of light with a different wavelength region; 
     an illumination light switching section configured to selectively cast one of the beams of light emitted from the plurality of light source units, onto the sample plate as illumination light; and 
     an imaging section configured to acquire an optical image of the sample plate formed by the illumination light, the imaging section being common to the plurality of light source units. 
     (Clause 2) In the MALDI mass spectrometer described in Clause 1, one of the plurality of light source units may be configured to emit light within a visible wavelength region. 
     (Clause 3) In the MALDI mass spectrometer described in Clause 1 or 2, one of the plurality of light source units may be configured to emit light within an ultraviolet wavelength region. 
     (Clause 4) In the MALDI mass spectrometer described in Clause 3, the ultraviolet wavelength region may be a region overlapping an absorption wavelength band of a matrix used for preparing the sample. 
     The MALDI mass spectrometer described in any one of Clauses 1-4 can acquire, for example, two observation images of the same sample plate, with one image showing the sample plate illuminated with light within the visible wavelength region and the other image showing the sample plate illuminated with light within the ultraviolet wavelength region, and simultaneously display both images or one of them selectively. Therefore, the device can properly present the user the position of the sample formed on the sample or its state of adhesion, regardless of the kind of matrix used for preparing the sample or the state of the formed sample, thereby allowing the user to locate, for example, a sweet spot at which a high level of signal intensity can be obtained in the sample. 
     (Clause 5) The MALDI mass spectrometer described in one of Clauses 1-4 may further include an input unit configured to allow a user to give an instruction for the switching of the illumination light, where the illumination light switching section is configured to switch the illumination light according to the instruction given through the input unit. 
     The MALDI mass spectrometer described in Clause 5 allows a user to select and display an observation image acquired under illumination which produces an easy-to-watch condition for the user. Accordingly, for example, even an operator who is accustomed to watching images under illumination with visible light can properly determine the laser irradiation point while watching the displayed observation image. 
     (Clause 6) In the MALDI mass spectrometer described in one of Clauses 1-4, the illumination light switching section may be configured to switch the illumination light in order at regular intervals of time. 
     The MALDI mass spectrometer described in Clause 6 can simultaneously or sequentially display observation images acquired under different illuminating conditions, without depending on an instruction or operation by the user. Accordingly, for example, even when it is impossible to previously determine which of the visible and ultraviolet regions is suitable for the illumination, the operator can properly determine the laser irradiation point by watching the displayed observation images. 
     (Clause 7) The MALDI mass spectrometer described in Clause 5 or 6 may further include a display processor configured to display, on a screen of a display unit, an observation image created in real time based on a signal from the imaging section. 
     The MALDI mass spectrometer described in Clause 7 can provide a user with a real-time image acquired under a predetermined type of illumination, such as the visible light or ultraviolet light. 
     (Clause 8) The MALDI mass spectrometer described in Clause 5 or 6 may further include a display processor configured to display, on a screen of a display unit, a plurality of observation images respectively corresponding to the plurality of light source units, based on signals from the imaging section, where one of the observation images corresponds to the illumination light cast onto the sample plate at that point in time and is a real-time image continuously updated with the passage of time, while another one of the observation images is a snap image acquired at a predetermined point in time. 
     (Clause 9) In the MALDI mass spectrometer described in Clause 8, the predetermined point in time may be a point in time immediately before a point in time where the illumination light is switched by the illumination light switching section. 
     In the MALDI mass spectrometer described in Clause 8 or 9, a real-time image and a snap image respectively acquired under illumination light with different wavelength bands can be displayed next to or superimposed on each other. This allows the user to determine an appropriate laser irradiation point by comparing a plurality of observation images or selecting an observation image which is easier for the user to watch. 
     (Clause 10) One mode of the storage medium recording a program for a MALDI mass spectrometer according to the present invention is a computer readable storage medium recording a computer program to be used for a MALDI mass spectrometer configured to irradiate a sample on a sample plate with laser light to ionize a component in the sample and perform a mass spectrometric analysis of the component, the MALDI mass spectrometer further configured to selectively cast one of a plurality of beams of light emitted from a plurality of light source units each of which is configured to emit a beam of light with a different wavelength region, onto the sample plate as illumination light, and acquire, with an imaging section, an optical image of the sample plate formed by the illumination light, and the computer program configured to make a computer function as: 
     a display-processing functional section configured to display, on a screen of the same display unit, a plurality of observation images acquired for the sample plate in which one of the observation images is displayed as a real-time image continuously updated with the passage of time and another one of the observation images is displayed as a snap image which is a still image acquired at a predetermined point in time; and 
     an illumination-light-switching control functional section configured to control a switching operation of the illumination light so that a beam of light emitted from a specific light source unit among the plurality of light source units is cast onto the sample plate as the illumination light when the real-time image is being updated, and a beam of light emitted from a light source unit different from the specific light source unit among the plurality of light source units is cast onto the sample plate as the illumination light at the predetermined point in time specified for acquiring the snap image. 
     The storage medium recording a program for a MALDI mass spectrometer described in Clause 10 enables a computer to simultaneously display, on the screen of the display unit, two observation images of the same sample plate including, for example, one image showing the sample plate illuminated with visible light and the other image showing the sample plate illuminated with ultraviolet light. One of the observation images is a real-time image, in which the imaging range on the sample plate changes its position in real time when the position of the sample plate is changed. This allows the user to visually check the observation image of each of the samples at different positions on the sample plate or each of the different sites in the same sample. The other observation image is a snap image, which allows the user to visually check the observation image reflecting the state of a sample on the sample plate observed at the predetermined point in time, despite the change in the position of the sample plate. Thus, by using the storage medium recording a program for a MALDI mass spectrometer described in Clause 10, the user can more properly and efficiently check the position of the sample formed on the sample plate, its state of adhesion and other related conditions. 
     (Clause 11) In the storage medium recording a program for a MALDI mass spectrometer described in Clause 10, the illumination-light-switching control functional section may be configured to control the light source units so as to switch the illumination light according to an illumination-switching instruction given through an input unit by a user so that the light source unit corresponding to a selection by the user is used as the specific light source unit whose emission light is cast onto the sample plate as the illumination light, and the display-processing functional section may be configured to display, as the real-time image, an observation image acquired under illumination with the emission light from the specific light source unit. 
     The storage medium recording a program for a MALDI mass spectrometer described in Clause 11 allows the user to select an observation image acquired under illumination which produces an easy-to-watch condition for the user, and display it as the real-time image. Accordingly, for example, an operator who is accustomed to watching images under illumination with visible light can properly determine the laser irradiation point by watching the real-time visible-light image while additionally referring to the ultraviolet-light image taken as a snap image. The user can also appropriately switch the observation image to be displayed as the real-time image according to the kind of matrix, state of distribution of the matrix and other related conditions. 
     (Clause 12) In the storage medium recording a program for a MALDI mass spectrometer described in Clause 10, the illumination-light-switching control functional section may be configured to control the light source units so as to switch the illumination light in order at regular intervals of time, and the display-processing functional section may be configured to display, as the real-time image, an observation image acquired under illumination light which is cast onto the sample plate, and to display, as the snap image, an observation image corresponding to illumination light which is not cast onto the sample plate. 
     By the storage medium recording a program for a MALDI mass spectrometer described in Clause 12, real-time images acquired under different illuminating conditions can be sequentially displayed, without depending on an instruction or operation by the user. Accordingly, for example, even when it is difficult to determine which of the visible and ultraviolet light is suitable for acquiring observation images, the operator can properly determine the laser irradiation point by watching the displayed real-time image and snap image. 
     (Clause 13) In the storage medium recording a program for a MALDI mass spectrometer described in one of Clauses 10-12, the predetermined point in time may be a point in time immediately before a point in time where the illumination light is switched by the illumination-light-switching control functional section. 
     By the storage medium recording a program for a MALDI mass spectrometer described in Clause 13, every time the illumination light is switched, the latest snap image can always be displayed. 
     REFERENCE SIGNS LIST 
     
         
           10  . . . Vacuum Chamber 
           100  . . . Window 
           11  . . . Vacuum Pump 
           12  . . . Laser Emitter 
           13  . . . Half Mirror 
           14  . . . Sample Stage 
           15  . . . Sample Plate 
           151  . . . Well 
           152  . . . Sample 
           16  . . . Stage Driver 
           17  . . . Extraction Electrode 
           18  . . . Quadrupole Deflector 
           20  . . . Ion Trap 
           21  . . . Ring Electrode 
           22  . . . Entrance End-Cap Electrode 
           23  . . . Ion Injection Hole 
           24  . . . Exit End-Cap Electrode 
           25  . . . Ion Ejection Hole 
           26  . . . Detector 
           30   a  . . . Visible Light Source 
           30   b  . . . Ultraviolet Light Source 
           31  . . . Illumination Driver 
           32  . . . Visible-Light Camera 
           40  . . . Control-and-Processing Unit 
           41  . . . Analysis Controller 
           42  . . . Observation Image Acquisition Controller 
           43  . . . Acquired Image Processor 
           44  . . . Display Processor 
           45  . . . Data Processor 
           46  . . . Input/Output Processor 
           47  . . . Input Unit 
           48  . . . Display Unit