Methods and apparatus for aligning ion optics in a mass spectrometer

A method of calibrating an ion source, the ion source including a sample control system including a sample holder for supporting a sample plate in a sample plane and a laser source having a focal point representing a point at which a beam generated by the laser source intersects the sample plane, the method comprising:

• mounting a sample plate in the sample holder, the sample plate including one or more target regions;
• determining a relationship between a coordinate system of the sample plate and a coordinate system of the sample control system, the relationship being determined at least in part by aligning one or more fiducials relative to a reference point of the sample control system, the fiducials including a first fiducial, a second fiducial disposed at a known displacement from the first fiducial, and a third fiducial, and by defining reference points of the sample plate coordinate system, the determining including:
• generating a first image of the sample plate, the first image including a representation of at least a first fiducial and a second fiducial of the one or more fiducials;
• processing the first image to identify a location of the first fiducial and a location of the second fiducial in the first image;
• aligning the reference point of the sample control system relative to the identified location of the first fiducial and the location of the second fiducial;
• moving the sample plate relative to the reference point;
• generating a second image of the sample plate, the second image including a representation of a third fiducial of the one or more fiducials;
• processing the second image to identify a location of a third fiducial in the second image;
• aligning the reference point of the sample control system relative to the identified location of the third fiducial;
• and
• determining an alignment error of the coordinate systems of the sample control system and the sample plate based at least in part on the moving and alignment of the reference point relative to the identified locations of the first, second, and third fiducials;
• and
• using the determined relationship to align a target region of the sample plate with ion optics of a mass spectrometer for a mass spectrometric analysis.

A computer program product, tangibly embodied on a computer-readable medium, for calibrating an ion source, the ion source including a sample control system including a sample holder for supporting a sample plate in a sample plane, and a laser source having a focal point representing a point at which a beam generated by the laser source intersects the sample plane, the product including instructions operable to cause data processing apparatus to perform operations comprising:

• receiving data indicating that a sample plate is mounted in the sample holder, the sample plate including one or more fiducials defining reference points of a sample plate coordinate system and one or more target regions at one or more predefined locations in the sample plate coordinate system;
• determining a relationship between the coordinate system of the sample plate and a coordinate system of the sample control system, the relationship being determined at least in part by aligning one or more fiducials relative to a reference point of the sample control system using pattern recognition techniques;
• and
• using the determined relationship to align one of the target regions of the sample plate with ion optics of a mass spectrometer for a mass spectrometric analysis.

A computer program product, tangibly embodied on a computer-readable medium, for calibrating an ion source, the ion source including a sample control system including a sample holder for supporting a sample plate in a sample plane and a laser source having a focal point representing a point at which a beam generated by the laser source intersects the sample plane, the product including instructions operable to cause data processing apparatus to perform operations comprising:

• receiving data indicating that a sample plate is mounted in the sample holder, the sample plate including one or more target regions;
• determining a relationship between a coordinate system of the sample plate and a coordinate system of the sample control system, the relationship being determined at least in part by aligning one or more fiducials relative to a reference point of the sample control system, the fiducials including a first fiducial, a second fiducial disposed at a known displacement from the first fiducial, and a third fiducial, and by defining reference points of the sample plate coordinate system, the determining including:
• generating a first image of the sample plate, the first image including a representation of at least a first fiducial and a second fiducial of the one or more fiducials;
• processing the first image to identify a location of the first fiducial and a location of the second fiducial in the first image;
• aligning the reference point of the sample control system relative to the identified location of the first fiducial and the identified location of the second fiducial;
• moving the sample plate relative to the reference point;
• generating a second image of the sample plate, the second image including a representation of a third fiducial of the one or more fiducials;
• processing the second image to identify a location of a third fiducial in the second image;
• aligning the reference point of the sample control system relative to the identified location of the third fiducial;
• and
• determining an alignment error of the coordinate systems of the sample control system and the sample plate based at least in part on the moving and alignment of the reference point relative to the identified locations of the first, second, and third fiducials;
• and
• using the determined relationship to align a target region of the sample plate with ion optics of a mass spectrometer for a mass spectrometric analysis.

A mass spectrometry system, comprising:

• an ion source, the ion source including a sample control system including a sample holder for supporting a sample plate in a sample plane and a laser source having a focal point representing a point at which a beam generated by the laser source intersects the sample plane;
• and
• a processing unit configured to perform operations comprising:
• determining a relationship between a coordinate system of a sample plate mounted in the sample holder and a coordinate system of the sample control system, the relationship being determined at least in part by aligning one or more fiducials relative to a reference point of the sample control system using computer-implemented pattern recognition techniques, the fiducials defining reference points of the sample plate coordinate system;
• and
• using the determined relationship to align a target region of the sample plate with ion optics of a mass spectrometer for a mass spectrometric analysis, the target region at a predefined location in the sample plate coordinate system.

A method of generating ions for mass spectrometry, comprising:

• depositing a sample onto a sample plate to provide one or more target regions in the sample, the sample plate including one or more fiducials defining reference points of a sample plate coordinate system, the one or more target regions at one or more defined locations in the sample plate coordinate system;
• mounting the sample plate in a sample holder of an ion source having a sample control system;
• determining a relationship between the coordinate system of the sample plate and a coordinate system of the sample control system, the relationship being determined at least in part by aligning the one or more fiducials relative to a reference point of the sample control system using computer-implemented pattern recognition techniques;
• using the determined relationship to align one of the target regions of the sample plate with ion optics of a mass spectrometer;
• directing a beam from a laser source to the target location in the sample by directing the beam at a known or determinable displacement from at least one of the fiducials.