Method and apparatus for MALDI analysis

• US 6,812,455 B2
• Filed: 04/03/2002
• Issued: 11/02/2004
• Est. Priority Date: 09/19/1996
• Status: Expired due to Fees

• Current Assignee: Agena Bioscience Inc. (Mesa Laboratories Inc.)
• Original Assignee: Sequenom Incorporated (Laboratory Corporation Of America Holdings)
• Inventors: Hillenkamp, Franz, Reuter, Dirk, Higgins, G. Scott, Lough, David M.
• Primary Examiner(s): Berman, Jack
• Application Number:
  US10/117,558
• Publication Number:
  US 20020109085A1
• Time in Patent Office: 944 Days
• Field of Search: 250/288, 250/423.P, 738/648.1
• US Class Current: 250/288
• CPC Class Codes: B01J 2219/00387 Applications using probes
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: H01J 49/0418 for laser desorption, e.g. matrix-assisted laser desorption/ionisation [MALDI] plates or surface enhanced laser desorption/ionisation [SELDI] plates
• CPC Class Codes: H01J 49/164 Laser desorption/ionisation, e.g. matrix-assisted laser desorption/ionisation [MALDI] sample holders H01J49/0418

Abstract

Matrix assisted laser desorption/ionization (MALDI) is performed in a manner that thermalizes large analyte ions in a plume of desorbed material for spectroscopic analysis. The thermalized ions have a low or zero mean velocity and are presented at a well-defined instant in time, reducing artifacts and sharpening the spectral peaks. In one embodiment the light is delivered to a matrix or sample holder having a cover, baffle or compartment. The baffle or compartment impedes or contains a plume of desorbed material and the analyte undergoes collisions to lower its mean velocity and directionality. Thus “thermalized” the analyte ions are passed to a mass analysis instrument.

Claims

1. An apparatus for matrix assisted laser desorption of a large molecule analyte, such apparatus comprising:

a support stage; and

an optical fiber, wherein;

the support stage includes a means for holding a sample on a substrate in a defined region of the stage and is adapted to hold the optical fiber; and

the optical fiber includes a first end adapted to couple to a light source for receiving a light input, and a second end held by said stage in a position to illuminate a spot region on the sample, the stage positioning the second end so that its output beam passes through the substrate to directly illuminate said spot region on the sample with a spot of defined size at a fluence effective to desorb the analyte from the sample.

2. An apparatus of claim 1, comprising a plurality of optical fibers in an array arranged to illuminate an array of separate spot regions of the sample, each fiber being separately actuable to desorb material from a respective spot region of the sample at a distinct time whereby plural samples of desorbed analyte may be provided at successive instants to a common mass analyzer.

3. An apparatus of claim 1, wherein the stage is operative to move the substrate with the sample in at least two lateral dimensions relative to the second end of the optical fiber for aiming at arbitrary locations on the sample to desorb material.