Method for the detection of incorrect deposition on a MALDI sample support
The invention relates to a method for the detection of incorrect deposition on a MALDI sample support with several separate sample sites, where after the preparation on the sample support, an area located between two sample sites is sampled with a desorption laser, and a signal of an ion detector in a mass spectrometer is acquired in temporal relation to the sampling. The signal is examined for the presence of a signal which indicates incorrect deposition. An advantage of the method is particularly that it can be carried out using a MALDI ion source and a connected mass analyzer, and that it requires little procedural effort.
1. A method for the detection of an incorrect deposition on a MALDI sample support which has several separate sample sites, wherein during or after the preparation on the sample support, an area located between two sample sites is sampled with a desorption laser, and a signal of an ion detector in a mass spectrometer is acquired in temporal relation to the sampling, and the signal is examined for the presence of a signal shape which indicates incorrect deposition.
2. The method according to claim 1 , where the signal recorded by the ion detector has a mass-independent intensity value, and the signal shape indicating incorrect deposition is an intensity value which is above an intensity threshold essentially determined by noise.
3. The method according to claim 1 , where the signal recorded by the ion detector is a mass-resolved mass spectrum, and the signal shape indicating incorrect deposition is an ion signature in the mass spectrum which deviates from a predetermined reference signature.
4. The method according to claim 3 , where the presence of MALDI matrix ions in a mass-resolved mass spectrum is defined as an indication of incorrect deposition.
5. The method according to claim 3 , where the areas between sample sites are coated with a substance which has a characteristic ion signature, and a difference between the characteristic ion signature and the ion signature in the mass-resolved mass spectrum is defined as an indication of incorrect deposition.
6. The method according to claim 5 , where the substance exhibiting a characteristic ion signature is a matrix substance which differs from the matrix substance used for preparing samples on the sample support.
7. The method according to claim 1 , where the adjacent sample sites are digitally or electronically labeled when a signal shape indicating incorrect deposition is detected from an area between these sample sites.
8. The method according to claim 1 , where an area around a sample site is sampled along the whole of its periphery with the desorption laser and examined for incorrect depositions before the sample site is investigated analytically.
9. The method according to claim 1 , where a selected point on an area between two adjacent sample sites is sampled with the desorption laser and examined for incorrect depositions.
10. The method according to claim 1 , where a positioning device aligns the sample support and a light beam guide of the desorption laser with respect to each other in such a way that the desorption laser can target an area between sample sites.
11. The method according to claim 1 , where a repetition rate of the desorption laser is one to ten kilohertz.
12. A method for the mass-spectrometric detection of analyte molecules ionized with the aid of MALDI, comprising:
providing a sample support having several separate sample sites and being prepared with samples;
directing a desorption laser at different sample sites in succession and activating it in order to ionize and detect any analyte molecule(s) prepared there; and
sampling an area around a next sample site to be bombarded with the desorption laser in order to deduce the presence of contamination from a signal of an ion detector in a mass analyzer, which is interrogated in temporal relation to the sampling.
13. The method according to claim 1 , where the mass spectrometer is a time-of-flight mass spectrometer.
14. The method according to claim 6 , where the matrix substance used for preparing samples and the substance exhibiting the characteristic ion signature are two different materials, one being sinapic acid and the other being cyano-4-hydroxycinnamic acid.
15. The method according to claim 9 , where the point is located where four sample sites are diagonally closest.
16. The method according to claim 1 , where a user is alerted via an acoustic, optical or other type of alarm signal while the method is still being carried out, when a positive indication of contamination is found.
17. The method according to claim 1 , where there is no need to use additional optical imaging apparatus for the incorrect deposition to be detected.
18. The method according to claim 10 , where the positioning device comprises at least one of an XY stage and tilting (micro)mirrors.
19. The method according to claim 1 , where the desorption laser is a solid state laser.
20. The method according to claim 1 , where the sample support has one of 96, 384, and 1536 sample sites.