[diablo]

Hi folks,

anyone familiar with MALDI-TOF MS? - why is linear mode time of flight (TOF) the method of choice for large proteins and not the reflectron mode?

[MOTOBALL]

I would assume that it is connected with the reflectron mode being used to increase the resolution of the MS for accurate mass determination.  Increasing the resolution will allow the separation of the m/z 28.abcde and m/z 28.vwxyz ions of CO and N2, and the accurate mass allows identification as either CO or N2.
Taking -NH2 = 16; O = 16; N = 14; CH2 = 14 etc, a molecule of mass ~400-500 daltons will have about 30 of any one of these units.  There is a relatively limited number of combinations of C, H, N, O etc that will give MW 450, and the mass spectrum will show clearly resolved ions that are present due to isotopic contributions. As a simple example, C2H6 will show
12C.12C.1H.1H.1H.1H.1H.1H    this will be the most intense single
12C.13C...
13C.12C...
13C.13C....
12C.12C.2H.1H.....
12C.13C.2H.1H.....
etc., etc. due to the presence of low-level isotopic contributions, as indicated above.

A large protein, say MW 100,000 daltons will have a frighteningly large number of 12C, 13C, 1H, 2H, 14N, 15N etc combinations (not counting O, P, S atoms).  This results in a molecular ion region that may consist of hundreds/thousands of unresolved peaks present in a "blob" type distribution.

Nothing is therefore gained by using the reflectron mode, and signal intensity may actually be lost.

You should consult the literature available from the manufacturers to check my explanation and to see just about where the mass cutoff is to obtain a well-resolved spectrum of the type described above for C2H6.