IMS analysis of exhaled breath for detection of cancer

Today there is a growing demand for innovative diagnostic technologies in medicine. This is particularly so in the case of cancer, which is one of the leading causes of death in Europe: its diagnosis very often happens late in the course of the disease since available diagnostic methods are not sufficiently sensitive and specific. An early diagnosis of cancer would have a huge impact onto therapy and could significantly improve quality of live for the patient. Recent pilot studies suggest that detection of different kinds of cancer is possible by means of exhaled air analysis in early stages of the disease. The present project is focused on analysis of exhaled breath by ion mobility spectrometry and the development of the respective database of compounds for the diagnosis of early stages of lung cancer and carcinomas of the upper aero-digestive tracts. Detection of such carcinomas is particularly promising due to the specific anatomical location of cancer cells. The selected analytical technique, namely ion mobility spectrometry (IMS) in combination with a multicapillary column (MCC), allows a sensitive detection of volatile substances directly in air at atmospheric pressure and is therefore suitable for exhaled breath analysis. IMS results will be validated by the following mass spectrometric techniques: proton transfer reaction mass spectrometry (PTR-MS), selected ion flow tube mass spectrometry (SIFT-MS), and gas chromatography with mass spectrometric detection (GC-MS) in combination with solid phase microextraction (SPME). The main advantage of MCC-IMS is its very high sensitivity, making on-line breath sampling and analysis (without any sample preparation steps) possible. Calibration measurements for different compounds with respect to IMS combined with specific multicapillary columns will result in specific retention times and ion mobility (i.e., information on peak location in this two-dimensional setting) for each volatile compound. The respective database will contain such information for the relevant compounds detected in patients with lung cancer or carcinomas of the upper aero-digestive tract. The patient documentation will be done by a questionnaire (stored in hardcopy and electronically), the cancer staging, medication, ICT-code etc. are carefully documented. Medical expertise comes from Primarius Dr. H. Denz (Head of Oncology Dep. at LKH Natters), Prof. M. Fiegl (conducting the "TYROL Small Cell Lung Cancer Study" incorporating more than 1400 lung cancer patients), Prof. W. Hilbe and Prof. G. Gastl. Another advantage of the MCC-IMS combination is the short analysis time, which is less then 10 minutes and so can lead to a higher number of examined patients. The IMS-instrument is relatively small and can be transported easily. Hence IMS is applicable for in-situ analysis at hospitals and medical practices. We expect an early diagnosis of carcinomas of the upper aero-digestive tract to be possible and aim for a monitoring of the disease during clinical treatment (operation, chemotherapy, radiotherapy).