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  • Picosecond Infrared Lasers (PIRL): Applications in Biodiagnostics and Towards Quantitative Mass

    Spectrometry

    by

    Jing Zou

    A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy

    Department of Physics University of Toronto

    © Copyright by Jing Zou 2016

  • ii

    Picosecond Infrared Lasers (PIRL): Applications in Biodiagnostics

    and Towards Quantitative Mass Spectrometry

    Jing Zou

    Doctor of Philosophy

    Department of Physics

    University of Toronto

    2016

    Abstract

    A new concept based on the Picosecond Infrared Laser (PIRL) has been introduced to selectively

    excite water to directly drive ablation of biological tissue faster than any competing energy

    dissipation process that could damage surrounding tissue. This thesis work showed that this

    mechanism can be exploited for a new form of spatially resolved mass spectrometry with the

    prospect of near instant biodiagnostics with mass spectroscopic sensitivity. The ion source for

    imaging mass spectrometer was based on PIRL ablation with an electrospray pick up source to

    entrain the ablated species. This hybrid Picosecond Infrared Laser Assisted Electrospray

    Ionization (PIR-LAESI) showed a limit of detection of 100 nM and a spatial resolution of ~ 100

    μm, limited only by the current focusing optics. The longitudinal spatial resolution is

    approximately determined by the absorption depth. At the wavelengths of PIRL pulse, the light is

    absorbed within a few microns at the ablation threshold, resulting in removal of ~ 4 μm thick of

    material per pulse, which is the size of a single cell. Most importantly no additional treatment

    was needed as in Matrix Assisted Laser Desorption/Ionization (MALDI). Molecular images

    using PIR-LAESI for both plant and animal tissues could be collected directly and matched to

    optical images of the same region. The image quality was compared to nanosecond LAESI

    versions. Smaller crater size with PIR-LAESI was noted with similar molecular image quality,

  • iii

    indicating PIR-LAESI a more sensitive approach with higher spatial resolution. The question is

    how far the sensitivity can be improved. In principle, single protein detections is possible if there

    is no thermal fragmentation as shown in this work. New direct in vacuum sample presentation to

    mass spectrometry should enable this ultimate limit to single molecular detection, using an

    electric field for ion separation. Molecular dynamics simulation on the ablation process driven by

    PIRL on ionic polymer water solutions revealed the effect of electric field cannot be observed in

    the early stage of plume expansion but that the polymers stay intact with shedding of the water

    solvation layers. These results illustrate that selective excitation of the water provides the desired

    ablation physics.

  • iv

    Acknowledgments

    Proverbs 20:24

    A person’s steps are directed by the LORD.

    Here I am delighted to express my sincere gratitude to the people who helped me to complete

    this thesis. Great thanks firstly to my supervisor, Prof. Dwayne Miller, for his supervision, advice

    and support in every stage of this research. His great patience, passionate motivation and

    encouragement led me through all the frustrations and stresses. He taught me how to think

    critically and independently as a scientist. His generous expression of his excitation and

    happiness in every step I made helped me to establish self-confidence. Dwayne is also very

    active in networking with people from academic, industry and society, which makes me realize

    that science is not only the adventure of scientists themselves but of entire communities.

    I would like to thank my collaborators Dr. Francis Talbot, Dr. Kresimir Franjic and Dr. Arash

    Zarrine-Afsar who went through all the challenges and failures with me. They are the happiest

    scientists that I know and we had a lot of fun in the lab. They passed their expertise (mass

    spectrometry from Francis, laser engineering from Kresimir, biomedical analysis from Arash)

    and all the other technical knowledge to me without any reservation. They taught me the most

    important thing a scientist should know: research is re-search until I find the answer. Francis

    contributed in making the control program for the lasers and translational stages as well as the

    molecular map construction program based on the mass spectrum. Kresimir built the water

    cooling system for the sample plate and Arash supplied animal samples for the tissue imaging

    experiments. Along with this academic support, they were all my advisers and psychological

    counsellors during my Ph.D.

    Many thanks also given to Dr. Alessandra Tata. She did the molecular imaging of the same

    animal samples with other technology for comparison. She also contributed a lot in writing our

    paper.

    Members in the machine shop in Department of Chemistry deserve my thousands of thanks,

    John, Johnny, Dave and Ahmed. The machine shop is the most fabulous one I know. As a

  • v

    student whose Ph.D needed a lot of instrumentation design, I stepped in their office with

    problems from time to time and they always gave me the answer with the parts made in super

    high quality. Without their help, there is no way I could have had a working setup to do the final

    experiments.

    I would also like to express my sincere appreciation to Prof. Leonid Zhigilei and Dr. Chengping

    Wu at the University of Virginia (UVA) for their support in the molecular dynamics simulation.

    They wrote the code and taught me how to modify the code to simulate the system of interest.

    They hosted me warmly during my stay in UVA last summer. We had a very good time together.

    I would also like to thank the members of my committee members, Prof. Claudiu Gradinaru and

    Prof. David McMillen, for their guidance and valuable suggestions during my thesis work. Both

    of them made my very stressful Ph.D days much easier with their kindness and help.

    Almost all of the many current and previous members of Dwayne Miller’s research group have

    helped me by sharing their equipment and skills, and by making the research time enjoyable with

    laughter and good mood/food. I am grateful to all of them with special thanks to Dr. Gustavo

    Moriena for his patience and kindness in giving advice with respect to equipment needs and Dr.

    Etienne Pelletier for his advice in maintaining laser systems in the early stage of this project. A

    very special thanks to Dr. Wesley Robertson of the German branch of the Miller group for his

    constant encouragement in the last two years of my Ph.D and his meaningful advice in my thesis

    content.

    I would also like to give thanks to my families in China and my friends in the Toronto Chinese

    Bible Church. Thanks to my grandfather, Prof. Hualing Zeng in China University of Geosicened

    for his caring and advising in my academic career. Thanks to Pastor Gong Mingpeng and Pastor

    Xu Chunping for their spiritual help in leading me to know our Lord and His unfailing love.

    Thanks to Yali, Lili, Clara, Holly, Lucy, Pauline and Chuling for their spiritual support and

    prayer in my hardest time.

    A special thanks given to my boyfriend Qiaoning Wang. I am so grateful to meet you in my last

    year of my Ph.D. Even if we are across the Pacific Ocean, your love and word are the sweetest

    support in my thesis writing and the rest of my life.

  • vi

    Most of all, I would like to thank my parents who walked with me along the way and have

    always supported my dream. I know being away from you so far and so long brought you a lot of

    worries and pressure especially when my health had some troubles. I know you missed me

    greatly. Your unconditional love is the warmest shelter in my life. This thesis is dedicated to you.

    It is already a long acknowledgment. But in the end, I still want to give the greatest thanks to my

    Heavenly Father. Thanks for your unfailing love to me! Thanks for your guidance in my life!

    Just as it is said in Proverbs 20:24 A person’s steps are directed by the LORD. You loved me and

    directed me before I got to know you. You planted the dream in my heart when I was 16 years

    old ---- contribute my efforts in conquering cancer with laser technology. After so many years

    you led me to this right place, handed me the right project which matches the dream perfectly

    and provided all the support I mentioned above. The firm realization that I am on your path and I

    am in your hands became the final-power to raise me up at moments I wanted to give up. Thanks

    to God!

  • vii

    Table of Contents

    Acknowledgments .......................................................................................................................... iv

    Table of Contents .......................................................................................................................... vii

    List of Tables ...............................................................

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