Method for loading sample supports for mass spectrometers

• US 5,770,860 A
• Filed: 07/10/1997
• Issued: 06/23/1998
• Est. Priority Date: 07/12/1996
• Status: Expired due to Term

• Current Assignee: Bruker-Franzen Analytik GmbH
• Original Assignee: Bruker-Franzen Analytik GmbH
• Inventors: Franzen, Jochen
• Primary Examiner(s): NGUYEN, KIET TUAN
• Application Number:
  US08/891,362
• Time in Patent Office: 348 Days
• Field of Search: 250/288, 250/288 A
• US Class Current: 250/288
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00364 Pipettes
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01L 2300/0893 having a very large number of wells, microfabricated wells
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 3/50853 with covers or lids
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 2035/00237 Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/1037 Using surface tension, e.g. pins or wires
• CPC Class Codes: G01N 35/1065 Multiple transfer devices
• CPC Class Codes: G01N 35/1072 with provision for selective pipetting of individual channels
• CPC Class Codes: G01N 35/1074 arranged in a two-dimensional array
• CPC Class Codes: H01J 49/0413 for automated handling
• 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

Abstract

A method for rapid loading of large sample supports with a very large number of analyte samples for mass spectrometric analysis using the ionization method of matrix-assisted desorption by laser bombardment (MALDI). The method consists of using microtiter plates already introduced in biochemistry and molecular genetics for parallel processing of a large number of dissolved samples and a multiple pipette unit for simultaneous transfer of sample solution quantities from all reaction wells on a microtiter plate to the sample support, the sample support having at least the same size. By repeated loading with samples from other microtiter plates, spaced between the samples already applied, a very high density of samples can be achieved. Some of these samples can be reserved for a mass spectrometric determination of the sample positioning on the sample support, and the positions of the other samples can then be interpolated.

Claims

1. Method for rapidly loading of a large number of solved samples for mass spectrometric analysis from microtiter plates onto a sample support plate, comprising the steps

(a) using a sample support plate in the size of a microtiter plate, and

(b) transferring amounts of sample solution from microtiter plate wells to the sample support plate simultaneously for a large subset of the samples of the microtiter plate, using a multiple pipette.

2. Method according to claim 1, wherein the sample support plate is already covered with a matrix layer for matrix-assisted laser desorption and ionization (MALDI).

3. Method according to claim 1, wherein a multiple pipette with at least 96 pipette tips is used for the simultaneous transfer of the samples.

4. Method according to claim 3, wherein the multiple pipette has as many individual pipettes as the number of sample wells in the microtiter plate.

5. Method according to claim 3, wherein the multiple pipette consists of a large number of individual stamps, on each of which droplets of the dissolved sample remain hanging and can thus be transferred.

6. Method according to claim 5, wherein sample molecules are attracted and concentrated on the pipette tips using a electrophoresis voltage between the sample solution and the pipette tips, and wherein the sample molecules are transferred from the pipette tips to a MALDI layer by reversing the electrophoresis voltage.

7. Method according to claim 1, wherein the samples for a sample support are taken from several microtiter plates and sample spot arrays from different microtiter plates are interlaced.

8. Method according to claim 7, wherein the samples from different microtiter plates form blocks of sample spots on the sample support plate, and one such block is smaller than the area on the microtiter plate belonging to one reaction well.

9. Method according to claim 8, wherein the samples from 4 microtiter plates with 384 sample wells each are applied in blocks of 2×

2 sample spots with a spacing of about 2 millimeters, so that there are 1,536 sample spots on the sample support plate after loading.

10. Method according to claim 8, wherein the samples from 25 microtiter plates with 384 sample wells each are applied in blocks of 5×

5 sample spots with a spacing of 0.9 millimeters, so that there are 9,600 sample spots on the sample support plate after loading.

11. Method according to claim 8, wherein the samples from 121 microtiter plates with 384 sample wells each are applied in blocks of 11×

11 sample spots with a spacing of 0.4 millimeters, so that there are 46,464 sample spots on the sample support plate after loading.

12. Method according to claim 8, wherein at least one block of samples is used to determine the exact positions of the sample spots relative to the other samples of the block and relative to the sample support plate area after the sample support has been inserted into the mass spectrometer.

13. Method according to claim 12, wherein the four blocks for this determination of the relative positions are located in the corners of the sample support plate.

14. Method according to claim 8, wherein one sample spot each from the blocks consists of a known substance for the purposes of analytical quality assurance.

15. Method according to claim 7, wherein every sample from every microtiter plate is applied by double transfer of the samples from each microtiter plate twice at different positions for purposes of quality assurance using double measurements.