Quantum Enhanced Microscopy, Equs Annual Workshop, Noosa, AUS, December 2016 - Poster Accompanied by Abstract
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QUANTUM ENHANCED MICROSCOPY Catxere Andrade Casacio B.Sc., B.Eng., M.Sc. A thesis submitted for the degree of Doctor of Philosophy at The University of Queensland in 2020 School of Mathematics and Physics, ARC Centre of Excellence for Engineered Quantum Systems (EQUS) Abstract In optical microscopy, as in any biological measurement performed with light, there is a compromise between increasing power to improve resolution and decreasing power to prevent photodamage to the biological structure. Quantum optics allows this compromise to be overcome, enabling improved precision without increased illumination intensity. This thesis demonstrates, for the first time, absolute quantum advantage in microscopy, with a specific focus on Stimulated Raman Scattering (SRS) microscopy. SRS microscopy is a powerful tool widely used in many fields, especially in biomedical sciences. It uses a two-photon process where the light is downshifted in frequency by being absorbed and subsequently inelastically scattered by the intrinsic molecular vibrations in the sample. Each element or molecule has a different response, allowing selective imaging of biological systems. SRS microscopy is particularly useful because it is label-free (no addition of dyes, beads or any implanted tracer), meaning that imaging contrast is achieved without modification of, or interference with, the specimen. Here I present our newly built state-of-the-art shot-noise limited SRS microscope. I also characterize the Raman microscope, describe the developped imaging system and show SRS spectroscopy and imaging of both polystyrene beads and living yeast cells. The quantisation of light introduces a fundamental uncertainty, or quantum noise, in both the amplitude and phase quadratures of an optical field. A squeezed state of light is a state of the optical field where the uncertainty of one of these quadratures is reduced below the quantum noise. Therefore, it provides an approach to reduce the noise level below this quantum noise limit and consequently increases measured signal-to-noise ratio. Here I describe the concepts involved in this technique and present our newly built light squeezer. I characterize the squeezing and show up to -1.3 dB of noise floor reduction for a 6 picosecond pulsed laser, which is the pulse duration that maximises the Raman interaction. In this thesis we apply squeezed states of light in SRS, developping a quantum-enhanced micro- scope. Our SRS Raman intensity noise is DI=I ≈ 10−7 and the measured quantum efficiency of the built photodiode is h = 72%. In this proof of principle we show a reduction of the noise floor of at least 13% below the quantum noise limit for Raman imaging of polystyrene beads and living yeast cells. This enhancement allowed us to resolve the cell membrane where with conventional microscope would be unresolvable. It also allowed sub-micron spatial resolution. The improved image contrast and reduced imaging time, while avoiding photodamage in the sample, surpasses the current state-of-the-art Raman microscopes and opens opportunities for new discoveries in biophysics. Declaration by author This thesis is composed of my original work, and contains no material previously published or written by another person except where due reference has been made in the text. I have clearly stated the contribution by others to jointly-authored works that I have included in my thesis. I have clearly stated the contribution of others to my thesis as a whole, including statistical assistance, survey design, data analysis, significant technical procedures, professional editorial advice, financial support and any other original research work used or reported in my thesis. The content of my thesis is the result of work I have carried out since the commencement of my higher degree by research candidature and does not include a substantial part of work that has been submitted to qualify for the award of any other degree or diploma in any university or other tertiary institution. I have clearly stated which parts of my thesis, if any, have been submitted to qualify for another award. I acknowledge that an electronic copy of my thesis must be lodged with the University Library and, subject to the policy and procedures of The University of Queensland, the thesis be made available for research and study in accordance with the Copyright Act 1968 unless a period of embargo has been approved by the Dean of the Graduate School. I acknowledge that copyright of all material contained in my thesis resides with the copyright holder(s) of that material. Where appropriate I have obtained copyright permission from the copyright holder to reproduce material in this thesis and have sought permission from co-authors for any jointly authored works included in the thesis. Catxere A. Casacio COVID-19 This thesis was completed during the 2020 worldwide corona-virus pandemic. Despite the resulting disruption to work locations, health, routines, and reduction in working time, the thesis was completed on schedule, with no additional allowances or any adjustment to the pre-pandemic deadlines. Publications during candidature Conference abstracts 1. C. A. Casacio et al., Quantum enhanced non linear microscopy, 23nd Australian Institute of Physics Congress (AIP), Perth, AUS, December 2018 - oral presentation accompanied by abstract. 2. C. A. Casacio et al., Velocity measurement in optical tweezers for biology, 3rd Australian and New Zealand Conference on Optics and Photonics (ANZCOP), Queenstown, NZL, December 2017 - poster accompanied by abstract. 3. C. A. Casacio et al., Velocity measurement in optical tweezers for biology, 10th Ions KOALA (Conference on Optics, Atoms and Laser Applications), Brisbane, AUS, November 2017 - oral presentation accompanied by abstract. 4. C. A. Casacio et al., Velocity measurement in optical tweezers for biology, EQuS Annual Workshop, Hunter Valley, AUS, September 2017 - poster accompanied by abstract. 5. C. A. Casacio et al., Quantum enhanced non linear microscopy, Joint 13th Asia Pacific Physics Conference and 22nd Australian Institute of Physics Congress (AIP), Brisbane, AUS, December 2016 - oral presentation accompanied by abstract. 6. C. A. Casacio et al., Quantum Enhanced Microscopy, EQuS Annual Workshop, Noosa, AUS, December 2016 - poster accompanied by abstract. 7. C. A. Casacio et al., Ultra-high Bandwidth Tracking of Micro/Nano Particles in Fluid, EQuS Optomechanics Incubator, Brisbane, AUS, December 2016 - poster accompanied by abstract. 8. C. A. Casacio et al., Quantum Enhanced Microscopy, EQuS Optomechanics Incubator, Brisbane, AUS, December 2016 - poster accompanied by abstract. 9. C. A. Casacio et al., Quantum Enhanced Microscopy, Gordon Research Conference: Lasers in Medicine and Biology, West Dover, USA, July 2016 - poster accompanied by abstract. Publications included in this thesis 1. [1] Catxere A. Casacio, Lars S. Madsen, Alex Terrasson, Muhammad Waleed, Kai Barnscheidt, Boris Hage, Michael A. Taylor, and Warwick P. Bowen, Quantum correlations overcome the photo- damage limits of light microscopy, under review; preprint available at ArXiv:2004.00178. Contributor Statement of contribution % C. Casacio data collection 80 data analysis 75 experiment design 25 experiment construction 80 microscope design and construction 5 detector design and construction 5 text writing 20 L. Madsen data collection 5 experiment design 25 experiment construction 20 microscope design and construction 5 detector design and construction 5 text writing 20 A. Terrasson data collection 10 data analysis 25 text writing 5 M. Waleed microscope design and construction 90 text writing 5 K. Barnscheidt detector design and construction 40 text writing 5 B. Hage detector design and construction 40 text writing 5 M. Taylor data collection 5 experiment design 25 initial concept 50 text writing 20 W. Bowen experiment design 25 detector design and construction 10 initial concept 50 text writing 20 Contributions by others to the thesis Supervision throughout my candidature Prof Warwick P. Bowen and Dr Lars S. Madsen Assistance with proof-reading and feedback Prof Warwick P. Bowen (Chapters 2, 4 & 5), Prof Jacquiline Romero (Chapters 4 & 5), Dr James Bennett (Chapter 3), Dr Martin Stringer (Chapters 1-6) Thesis examination Dr Costanza Toninelli and Prof Shigeki Takeuchi Contributions to the experimental setup Ulrich Hoff made the platform for the nonlinear crystal, and Alex Terrasson made the code for the microscope scan and post-processed some microscopy images used (both acknowledged throughout the text). All other contributions are as acknowledged in “Publications included in this thesis”. Statement of parts of the thesis submitted to qualify for the award of another degree None. Research involving human or animal subjects No animal or human subjects were involved in this research. Acknowledgments Here I say a true thank you for all your help and support. To my supervisors, Warwick and Lars, who taught me all they could in and out of the laboratory. A Nico pour etreˆ disponible a` m’aider chaque fois que necessaire´ et a` Alex pour arriver au milieu du chaos et des` le debut´ plonger dans les tachesˆ du travail acharne´ - specialement´ pour faire le scan pour que ma these` soit plus el´ egante.´ To James for the physics discussions that always so easily enlightened me. To Kaerin, Alan, Angie, Tara, Erinn and Nonnie, for making (all!) the routine problems to go away and solve administrative and building-related jobs so efficiently. To Rob and Chris for quickly making parts of the lab to work properly. And to Sam for all the 4 years of IT hiccups solved. To Dave and Griffo: you are awesome and your job outstanding! I’ll keep nice memories for playing golf in the mechanic workshop... To Waleed for building such a fine microscope. Dive dive Pakistan! To Boris and Kai for their collaboration on making the high-bandwidth and high-power detector - you saved me so much time that I did not have! And to Ulrich for welcoming me on my PhD with a brand-new home-made squeezing oven. To QOLadies, Beibei, Aswa, Yasmine and Larnii, who cheered my always-surrounded-by-men days with the refreshment of bubble-tea.