Among post-genome studies, proteomics studies with comprehensive analyses of genome-produced proteins are intensively conducted, where the proteomics studies include researches of the developments, functions and structures of the proteins. Proteins exhibit their functions through interactions with other molecules (such as other proteins or nucleic acids) with noncovalent bonds (such as hydrogen bonds, ionic bonds and hydrophobic interactions) in almost all vital activities including cell proliferation, differentiation and apoptosis. Thus, in order to reveal the functions of every protein, it is important to know with which molecules the protein reacts.
Owing to the conspicuous progress in mass spectrometers in recent years, mass analysis has become an indispensable method of identifying and analyzing the structures of bio-molecules such as proteins and nucleic acids. In the mass analyses of such bio-molecules, MALDI-TOFMS (Matrix Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry) and FAB-MS (Fast Atom Bombardment-Mass Spectrometry) are quite effective. In the MALDI method, a sample to be analyzed is mixed with a material called matrix which possesses photon absorbing capability, and a series of pulse lasers are irradiated onto the sample-matrix mixture. The matrix quickly absorbs the laser energy, is heated instantaneously, and is vaporized, in the course of which the sample in the matrix is desorbed and ionized. That is, in the MALDI method, the sample indirectly receives the energy which the matrix has received from the laser pulses. Thus the MALDI method is categorized as one of the soft ionizing methods, so that a large molecule can be analyzed without breaking or fragmenting it. Usually, the nitrogen laser of 337 nm wavelength, and matrix substances that absorb such laser are used in the MALDI method.
Both MALDI-TOFMS and FAB-MS are effective in analyzing refractory substances, but MALDI-TOFMS has an advantage over FAB-MS in that it can ionize hydrophilic large molecules. So the MALDI-TOFMS is useful in measuring the molecular mass of proteins and peptides. However, it has a shortcoming that low polarity molecules are hardly ionized, because such molecules have a low hydrophilic affinity with the matrix of MALDI, and thus are difficult to be hydrogenated. On the other hand, in the FAB-MS, glycerin-like viscous matrix is used, and such viscous matrix can trap low polarity molecules, hydrogenate them and easily ionize them.
As described above, both MALDI-TOFMS and FAB-MS have respective advantages and disadvantages. If, then, the MALDI-TOFMS can ionize low polarity molecules having the molecular mass of 3000 or larger, which is out of the analyzable range of FAB-MS, the mass analyses of large molecules will have a wide range of applications.
In the protein-protein complex or protein-nucleic acid complex (which are collectively referred to as “protein complexes” hereinafter), the protein-protein or the protein-nucleic acid is bonded weakly with the noncovalent bond. So the protein complexes break at the bond when they are ionized with the conventional MALDI method using, for example, a nitrogen laser, and it is impossible to ionize the complexes as a whole (Japanese Unexamined Patent Publication No. 2004-037128, [0009]-[0011]).
Further, in the MALDI method, the sample does not need to absorb the laser light directly, which enables ionization of a wide variety of samples. However, it is impossible to selectively ionize a specific component or specific kind of molecules (e.g., a DNA or a peptide) of the sample. When a specific kind (target kind) of molecules is to be ionized, it is necessary to irradiate a laser having the wavelength proper to the target kind and give the energy directly to the molecule, rather than indirectly via the matrix. But, up to now, there has been no such mass spectrometer that can change the wavelength of laser irradiated to the sample depending on the target molecule. Thus it is impossible to separately ionize plural kinds of molecules contained in protein complexes.