I prepare to analyze oligonucleotides' fragments (4-12 nt) by MALDI TOF/TOFMS. I used trihydroxyacetophenone as matrix and the concentration of sample was approximately 5 ng/ul. The performance of Mass spectra using linear and reflector mode were ok, but the only thing I observed in LIFT mode (CID or LID) was some weak signal look like noies. Should I prepare sample with higher concentration? Could you give me some suggestion about how to improve the resolution of MALDI TOF/TOFMS LIFT mode.
Thank you very much.
Unfortunately no first-hand-experience with LIFT for this application, but in general you should be able to get at least something in a PSD experiment at these levels
Which instrument are you using? Sensitivity will depend on this. Also, are your precursor ion selection and other LIFT conditions properly tuned, i.e. do they work on standards (which are usually peptides) of a similar m/z? Also: Have you tried other matrices especially for the bigger oligos, e.g. 3-HPA?
Sorry for just asking back, but maybe some of these point you in the right direction.
I suggest to use 3-HPA (3-hydroxypicolinic acid) as matrix as THAP is normally used for glycans in MALDI
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