The organic contamination has been recently considered as the most important problem for the photolithography world in the semiconductor industry, especially when the photolithographic methods moved from 130 nm node to 32 nm node. One of the most common organic compounds found in photolithography areas of the clean room is Trimethylsilanol (TMS), which can adsorb on the optical lenses forming a thin molecular layer, hence causing damages. Salt crystal formation is another potential threat for the optical devices. In the clean rooms, this salt is produced by a light-induced reaction between ammonia and an acid. In the context of semiconductor industry, the involved acid is usually the acetic acid produced by hydrolysis from propylene glycol methyl ether acetate (PGMEA), a commonly used organic compound in the photolithography. Here, we present an innovative analytical method using a state-of-the-art proton-transfer reaction-time-of-flight-mass spectrometer (PTR-ToF-MS) for on-line and continuous survey of volatile organic compounds (VOCs) with an emphasis on TMS and PGMEA. The effect of relative humidity on the detection and fragmentation of these organic compounds was assessed. The new analytical method is operated in a real life clean room environment and the results were compared with those obtained with off-line measurements using automated thermal desorber-gas chromatography-mass spectrometry (ATD-GC-MS) as reference method. The contamination sources were detected and identified, which is of paramount importance for the microelectronic fabrication plant. The trapping efficiency of the chemical filters used for AMCs filtration in the photolithography zone was determined. (C) 2015 Elsevier B.V. All rights reserved.