Louisiana State University LSU Digital Commons LSU Doctoral Dissertations Graduate School 2012 Infrared laser ablation for biological mass spectrometry Fan Huang Louisiana State University and Agricultural and Mechanical College, [email protected] Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_dissertations Part of the Chemistry Commons Recommended Citation Huang, Fan, "Infrared laser ablation for biological mass spectrometry" (2012). LSU Doctoral Dissertations. 2235. https://digitalcommons.lsu.edu/gradschool_dissertations/2235 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Doctoral Dissertations by an authorized graduate school editor of LSU Digital Commons. For more information, please [email protected]. INFRARED LASER ABLATION FOR BIOLOGICAL MASS SPECTROMETRY A Dissertation Submitted to the Graduate Faculty of the Louisiana State University Agricultural and Mechanical College in partial fulfillment of the requirements for the degree of Doctor of Philosophy in The Department of Chemistry by Fan Huang B. S., Peking University, China, 2000 M. S., University of Science and Technology of China, 2005 May 2012 ACKNOWLEDGEMENTS This dissertation could not have been completed without the help and support of many people that I truly thank, from the bottom of my heart: To my dear wife Tingting Jia, I am so blessed to have met you, and I cannot imagine the world without you. To my mom Yufang Liu and my dad Zhenjia Huang, you have always believed in me and given me your endless love and support. You are the greatest parents in the world. To my advisor Professor Kermit Murray, I am very grateful for your invaluable guidance and encouragement throughout my Ph.D program studies. You are deeply appreciated. I am also thankful to my committee members, Professor Bin Chen, Professor Jayne Garno, Professor Megan Macnaughtan, and Professor Ernest Mendrela, for your time and helpful advice. Special thanks to Dr. Azeem Hasan for allowing me to work in the mass spectrometry facility and giving me help. To the Murray Research Group both past and present: Mark, Damien, Jae-Kuk, John, Jerrell, Jianan, Xing, Jeonghoon, Jaye, Lancia, Udaya, Nicole, Thabiso, Xin, Sung-gun, Jon, Salla, Pratap, Yonathan, and Chinthaka. You are like brothers and sisters to me here at LSU. I will always remember the time we spent together in the lab, and I sincerely wish you all a great future. Special gratitude goes to post-doctoral researcher Yohannes who taught me how to use the trap instrument, Xing who taught me how to use the infrared lasers, and Zhe from the Mathematics Department at LSU who helped me with MATLAB calculations. Finally, I want to thank all my family and friends, especially those of you in my hometown of Beijing, China. You all have given me much help and support. I will always miss you. ii TABLE OF CONTENTS ACKNOWLEDGEMENTS ......................................................................................................... ii LIST OF TABLES .........................................................................................................................v LIST OF FIGURES ..................................................................................................................... vi LIST OF ABBREVIATIONS ................................................................................................... viii ABSTRACT .................................................................................................................................. xi CHAPTER 1. INTRODUCTION .................................................................................................1 1.1. Mass Spectrometry ................................................................................................................4 1.1.1. Electrospray Ionization .................................................................................................11 1.1.2. Matrix-assisted Laser Desorption Electrospray Ionization ..........................................14 1.2. Fundamentals of Laser Desorption and Ablation ................................................................15 1.3. Research Objectives .............................................................................................................22 CHAPTER 2. EXPERIMENTAL ..............................................................................................24 2.1. Time-of-flight Mass Spectrometry ......................................................................................24 2.2. IR/UV Two-laser MALDI TOF Mass Spectrometer ...........................................................26 2.3. Three-dimensional Quadrupole Ion Trap ............................................................................29 2.4. Continuous Flow IR MALDESI Mass Spectrometry ..........................................................31 2.5. Reagents and Standards .......................................................................................................37 CHAPTER 3. MATRIX-ASSISTED LASER DESORPTION IONIZATION OF INFRARED LASER ABLATED PARTICLES ........................................................................38 3.1. Introduction ..........................................................................................................................38 3.2. Experimental ........................................................................................................................40 3.3. Results and Discussion ........................................................................................................42 3.4. Summary ..............................................................................................................................49 CHAPTER 4. CONTINUOUS FLOW INFRARED MATRIX-ASSISTED LASER DESORPTION ELECTROSPRAY IONIZATION MASS SPECTROMETRY ..................51 4.1. Introduction ..........................................................................................................................52 4.2. Experimental ........................................................................................................................55 4.3. Results and Discussion ........................................................................................................57 4.4. Summary ..............................................................................................................................68 CHAPTER 5. FINITE ELEMENT SIMULATION OF INFRARED LASER ABLATION OF GLYCEROL ..........................................................................................................................69 5.1. Introduction ..........................................................................................................................69 5.2. Ablation Model ....................................................................................................................72 5.3. Results and Discussion ........................................................................................................74 5.4. Summary ..............................................................................................................................84 iii CHAPTER 6. CONCLUSIONS AND FUTURE DIRECTIONS ............................................86 REFERENCES .............................................................................................................................91 APPENDIX A. MATLAB PROGRAM FOR CALCULATING ABLATED SAMPLE VOLUME....................................................................................................................................105 APPENDIX B. LETTERS OF PERMISSION ........................................................................109 VITA............................................................................................................................................128 iv LIST OF TABLES Table 1-1 Commonly used UV MALDI matrices ...........................................................................8 v LIST OF FIGURES Figure 1-1 Schematic diagram of MALDI ......................................................................................7 Figure 1-2 Schematic diagram of ESI ...........................................................................................12 Figure 1-3 Schematic diagram of IR-MALDESI ..........................................................................15 Figure 1-4 Phase diagram near the critical point indicating normal heating and superheating ....18 Figure 2-1 Schematic layout of the IR/UV two-laser matrix-assist laser desorption ionization linear time-of flight mass spectrometer .........................................................................................26 Figure 2-2 Block diagram of the OPO laser .................................................................................28 Figure 2-3 Schematic diagram of the IR/UV two-laser arrangement ...........................................29 Figure 2-4 Cross-section view of an ion trap mass analyzer ........................................................31 Figure 2-5 Schematic of the Hitachi M8000 3DQ ion trap mass spectrometer ............................32 Figure 2-6 Schematic (top) and photograph (bottom) of the CF IR MALDESI MS interface showing the nanospray source, capillary, liquid sample bead, and mass spectrometer orifice .....34 Figure 2-7 Optical layout diagram of the OPO laser ....................................................................35