All rights reserved.iv DEDICATION I dedicate this dissertation to my family, especially to my mom and dad whom many years ago left their mother country with two pairs of empty hands, and brought their children to the land of opportunities. It is because of them that today I have the chance to study and follow my dreams. I could not be where I am today without their love, hard work, support, and sacrifice.They are my existence and my success will forever be theirs.I would like to dedicate this work to all the friends in my personal and professional network, who have always welcomed me with their kind word, kind thought, and kind heart. Last but not least, I dedicate this dissertation to my special friend Michael, who has been by my side throughout the hardest years, to whom I can share my true emotions especially in the down times. His unconditional love, support, trust, and confidence in me has helped and will continue to help me overcome many tough waves in life. Today, over 15,000 Ion Mobility Spectrometry (IMS) analyzers are employed at worldwide security checkpoints to detect explosives and illicit drugs. Current portal IMS instruments and other electronic nose technologies detect explosives and drugs by analyzing samples containing the headspace air and loose particles residing on a surface. Canines can outperform these systems at sampling and detecting the low vapor pressure explosives and drugs, such as RDX, PETN, cocaine, and MDMA, because these biological detectors target the volatile signature compounds available in the headspace rather than the non-volatile parent compounds of explosives and drugs.In this dissertation research volatile signature compounds available in the headspace over explosive and drug samples were detected using SPME as a headspace sampling tool coupled to an IMS analyzer. A Genetic Algorithm (GA) technique was developed to optimize the operating conditions of a commercial IMS (GE Itemizer 2), leading to the successful detection of plastic explosives (Detasheet, Semtex H, and C-4) and illicit drugs (cocaine, MDMA, and marijuana).Short sampling times (between 10 sec to 5 min) were adequate to extract and preconcentrate sufficient analytes (> 20 ng) representing the volatile signatures in the headspace of a 15 mL glass vial or a quart-sized can containing ≤ 1 g of the bulk explosive or drug.vii Furthermore, a research grade IMS with flexibility for changing operating conditions and physical configurations was designed and fabricated to accommodate future research into different analytes or physical configurations. The design and construction of the FIU-IMS were facilitated by computer modeling and simulation of ion's behavior within an IMS. The simulation method developed uses SIMION/SDS and was evaluated with experimental data collected using a commercial IMS (PCP Phemto Chem 110). The FIU-IMS instrument has comparable performance to the GE Itemizer 2 (average resolving power of 14, resolution of 3 between two drugs and two explosives, and LODs range from 0.7 to 9 ng).The results ...