ИСТИНА

Introduction Rapid and reliable tumor tissue identification during surgical operations is a challenging problem especially in neurosurgery, where the tissue is formless and precision of tumor/normal tissue border determination is extremely important. Recently we presented a tissue profiling method based on a combination of electrospray ionization and liquid extraction of phospholipids directly from tumor tissue, which allowed to obtain a mass spectrometric profile in less than a minute. For rapid tumor type identification we developed a method based on a search through a reference database containing mass spectra of samples characterized by histopathological methods. In order to validate the results of tissue profiling we identified the compounds forming the molecular profiles by ultrahigh resolution methods allowing fine isotopic structure analysis. Methods Tumor samples were collected from dissected tissues (brain tumors) during neurosurgical operations in the N. N. Burdenko Scientific Research Neurosurgery Institute. A special spray-from-tissue ambient ion source was developed for tumor samples profiling. In this source liquid extraction is immediately followed by ionization. For classification of tumor samples by lipid profiles a database filled by the results of investigation from more than 200 tumor samples was created. High resolution mass-spectrometry data was obtained using Thermo LTQ FT Ultra and ultrahigh resolution data was obtained using Bruker Apex Ultra FTICR instrument with a dynamically harmonized cell. Preliminary Data Determination of the fine isotopic structure allows us to prove the identification results of compounds, which form the lipid profiles and are used for identification of tumor samples. It was found that mass spectra of methanol extracts of brain tumor samples are similar to mass spectra of complex mixtures and this became the reason for developing special methods of signal acquisition in FTICR. It was found that signal accumulation could be ineffective because of phase differences in time-domain signals caused by the variability in the amount of ions in the ICR cell during sample measurement. It was demonstrated, that a phase correction procedure applied for time-domain signals could allow us to increase the resolution and dynamic range to a level sufficient for the observation of the fine isotopic structure of phospholipids even when working with extracts of real biological samples. In order to further increase the resolution filter diagonalization methods (FDM) were applied for signal processing Novel Aspect Identification of lipid mixtures extracted from real biological samples by ultrahigh resolution FTICR MS