Mihaela Balu Beckman Laser Institute and Medical Clinic, University of California, Irvine 1002 Health Sciences Rd., Irvine, CA, 92612 Tel: (949) 201 5537, e-mail: mbalu@uci.edu EDUCATION Ph.D., Optics, August 2006 College of Optics & Photonics: CREOL, University of Central Florida, Orlando, FL Major: Nonlinear Optics Dissertation: “Experimental Techniques for Nonlinear Material Characterization: A Nonlinear Spectrometer Using a White-Light Continuum Z-scan” (advisor: Prof. Eric W. Van Stryland) M.S., Optics, May 2002 College of Optics & Photonics: CREOL, University of Central Florida, Orlando, FL Major: Nonlinear Optics M.S., Physics, June 1999 University of Bucharest, Bucharest, ROMANIA Major: Physics Minor: Optics B.S., Physics, June 1998 University of Bucharest, Bucharest, ROMANIA Major: Physics Minor: Optics RESEARCH INTERESTS Ø Ø Investigate, develop and optimize laser-based optical imaging instruments/techniques for biomedical and clinical imaging. Advance and apply multiphoton microscopy for non-invasive skin imaging WORK EXPERIENCE Beckman Laser Institute and Medical Clinic, University of California, Irvine Research Scientist (Prof. Bruce Tromberg’s group) Beckman Laser Institute and Medical Clinic, University of California, Irvine Post-doctoral Researcher (Prof. Bruce Tromberg’s group) Newport Corporation, Irvine, CA Intern (Technology and Application Center) College of Optics & Photonics: CREOL, University of Central Florida Research Associate College of Optics & Photonics: CREOL, University of Central Florida Graduate Research Assistant National Institute for Lasers, Plasma, and Radiation Physics, Bucharest, ROMANIA Scientific Researcher Aug 2011 - present Feb 2007 - Aug 2011 May 2007- Aug 2007 Aug 2006 - Feb 2007 Aug 2000 - Aug 2006 Sept 1998 - Aug 2000 RESEARCH EXPERIENCE Research Scientist, Beckman Laser Institute, University of California, Irvine, CA • Apply multiphoton microscopy for non-invasive in-vivo and ex-vivo imaging of human skin (lesions such as benign melanocytic nevi, nevi with irregular shape and pigment distribution suspected of melanoma and skin tumors such as basal cell carcinoma) identifying sensitivity and specificity diagnosis criteria for melanoma and non-melanoma skin cancer - collaborative project with Dr. Kristen Kelly, Dr. Christopher Zachary and Dr. Ronald Harris, Dermatology Department, University of California, Irvine. • Involved in writing the human protocols for the skin imaging studies • Optimize the TPEF/SHG/CARS optical imaging platform by adding a stimulated-Raman scattering (SRS) detection channel for obtaining background-free chemical information about materials - collaborative project with Prof. Eric Potma, Department of Chemistry, University of California, Irvine. • Employ the TPEF/SHG/CARS optical imaging platform to study intramyocellular fat storage in a mouse model of valosincontaining protein (VCP) related diseases such as frontotemporal dementia and Paget disease - collaborative project with Prof. Virginia Kimonis, Division of Genetics & Metabolism, University of California, Irvine and Prof. Eric Potma, Department of Chemistry, University of California, Irvine. Post-doctoral researcher, Beckman Laser Institute, University of California, Irvine, CA Conducted research on nonlinear optical microscopy techniques (two-photon microscopy, second harmonic generation microscopy, coherent anti-Stokes Raman scattering microscopy) for biomedical applications • Analysis of the effect of excitation wavelength on penetration depth in multiphoton microscopy (MPM) imaging for medical diagnosis - collaborative project with Newport Corporation, Irvine, CA (work summarized in a manuscript published in Journal of Biomedical Optics Letters). • Design of an optical multi-dimensional imaging system based on principles of nonlinear light interactions with tissues. This system integrates three imaging techniques to better assess a biological tissue and its content. The system simultaneously detects the nonlinear signals generated through two-photon excited fluorescence (TPEF), second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) - collaborative project with Prof. Eric Potma, Department of Chemistry, University of California, Irvine. • Design and development of a fiber-based CARS hand-held probe to be used for non-invasive in vivo imaging (work summarized in a manuscript published in Optics Express) - collaborative project with Prof. Eric Potma, Department of Chemistry, University of California, Irvine and Prof. Zhongping Chen, Biomedical Engineering Department, University of California, Irvine. Research Associate, College of Optics & Photonics: CREOL&FPCE, University of Central Florida, Orlando, Fl Maintained and improved the White Light Continuum Z-scan nonlinear spectrometer performance Graduate Research Assistant, College of Optics & Photonics: CREOL&FPCE, University of Central Florida, Orlando, Fl Operated and conducted research in Ultrafast Nonlinear Spectroscopy Laboratory • • • • Generation and characterization of femtosecond white light continuum (WLC) in water, barium fluoride crystal, noble gases and gas-filled hollow fibers Optimization of the WLC spectral broadening by temporally shaping the pulse Development of a nonlinear spectrometer using a WLC Z-scan for nonlinear material characterization (the spectrometer can measure simultaneously nonlinear absorption and nonlinear refraction over a broad spectrum of wavelengths) Characterization of nonlinear materials’ (semiconductors, organics) properties using pump-probe (white light continuum as probe), two photon fluorescence and Z-scan/WLC Z-scan techniques Scientific Researcher, National Institute for Lasers, Plasma, and Radiation Physics, Bucharest, ROMANIA Operated research in Laser Photochemistry Laboratory • Performed experiments for the synthesis of iron oxide nanoparticles using the laser pyrolysis method in the gas phase TEACHING Lectures and presentations on “Interaction of Light with Matter” and “Optical Microscopy” at Beckman Laser Institute, University of California, Irvine (2008-2010) SKILLS Research: Optical design of experiments, optical alignment, design and development of optical instrumentation, nonlinear material characterization, ultrafast laser based optical microscopy, confocal microscopy, multiphoton microscopy, biomedical imaging, coherent anti-Stokes Raman scattering (CARS) microscopy, optical coherence tomography (OCT), optical fiber handling, optical endoscopy Instrumentation: • • • • • • • • MPTflex, multiphoton clinical tomograph Confocal Laser Scanning Biological Microscope (Olympus) META 510, Confocal Laser Scanning Biological Microscope (Zeiss) CPA 2010 regenerative amplified kHz Ti:Sapphire femtosecond laser system (Clark-MXR, Inc.) TOPAS & TOPAS-white Vis/NIR Optical Parametric Generator/Amplifier (Light Conversion) Optical Parametric Oscillator OPAL (Spectra-Physics) MIRA 900 Mode-locked Ti:Sapphire femtosecond oscillator laser system (Coherent, Inc.) Solid-state picosecond oscillator laser system with synchronization module (High-Q Laser) Software: IPLab, ImageJ (image processing), OSLO, ZEMAX (optical design), SolidWorks, Mathcad, Matlab, Mathematica, Visual BASIC EXTRACURRICULAR ACTIVITIES: 12/08-12/09 Vice president of the UC Irvine Chapter of Optical Society of America (OSA) - planned and organized a series of seminars and lectures by renowned scientists in the Optics & Photonics field - involved in other activities organized by the UC Irvine OSA Chapter: Art in Science contest, new member recruitment, outreach activities 12/08-12/11 Volunteer in activities organized by the Optical Society of Southern California (OSSC): Family Day, Optricks Day including hands-on science activities for kids at all ages. AWARDS • • • • • • • Merit Scholarship, Bucharest University, 1993-1998 CREOL Fellowship, University of Central Florida, 2000-2005 New Focus Travel Grant; New Focus, 2004 Graduate Student Travel Grant, University of Central Florida, 2004, 2005 SPIE student travel grant, SPIE, 2005 UCF Graduate Studies Fellowship, Summer 2006 Certificate of Appreciation - College of Optics & Photonics: CREOL&FPCE- 2006 AFFILIATIONS • • • • • Skin Disease Oriented Team (Chao Family Comprehensive Cancer Center, UCI) member – 2012 - present SPIE member - The International Society for Optical Engineering; 2000-2006 OSA member - Optical Society of America; 2001-2010 APS&DLS member - American Physical Society & Division of Laser Science; 2004 -2006 IEEE member - Institute of Electrical and Electronics Engineers; 2004 -2006 PUBLICATIONS Peer-reviewed academic journals 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. Balu M, Zachary CB, Harris RM, Krasieva TB, Koenig K, Tromberg BJ, Kelly MK. In Vivo Multiphoton Microscopy of Basal Cell Carcinoma. JAMA Dermatology 2015; published online first April 24, 2015 Balu M, Kelly MK, Zachary CB, Harris RM, Krasieva TB, Koenig K, Durkin AJ, Tromberg, BJ. Distinguishing between benign and malignant melanocytic nevi by in vivo multiphoton microscopy. Cancer Research 2014; 74(10), 2688-97 Mittal R, Balu M, Wilder-Smith P, Potma EO. Achromatic miniature lens system for coherent Raman scattering microscopy. Biomed Opt Express, 2013; 4(10):2196-206 Mittal R, Balu M, Krasieva T, Potma EO, Elkeeb L, Zachary CB, Wilder-Smith P. Evaluation of stimulated Raman scattering microscopy for identifying squamous cell carcinoma in human skin. Laser Surg Med. 2013; 45(8): 496-502 Balu M, Mazhar A, Hayakawa C, Mittal R, Krasieva TB, Koenig K, Venugopalan V, Tromberg BJ. In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin. Biophysical Journal, 2012; 104(1): 258-67 Krasieva TB, Stringari C, Liu F, Sun CH, Kong Y, Balu M, Meyskens FL, Gratton E, Tromberg BJ. Two-photon excited fluorescence lifetime imaging (FLIM) and spectroscopy of melanins in-vitro and in-vivo, Journal Biomed Opt. 2013; 18(3): 031107 Getmanenko YA, Hales JM, Balu M, Fu J, Zojer E, Kwon O, et al. Characterization of a dipolar chromophore with thirdharmonic generation applications in the near-IR. J Mater Chem. 2012;22(10):4371-82. Balu M, Liu GJ, Chen ZP, Tromberg BJ, Potma EO. Fiber delivered probe for efficient CARS imaging of tissues. Opt Express. 2010;18(3):2380-8. Balu M, Baldacchini T, Carter J, Krasieva TB, Zadoyan R, Tromberg BJ. Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media. J Biomed Opt. 2009;14(1):010508. Balu M, Padilha LA, Hagan DJ, Van Stryland EW, Yao S, Belfield K, et al. Broadband Z-scan characterization using a highspectral-irradiance, high-quality supercontinuum. J Opt Soc Am B. 2008;25(2):159-65. Balu M, Hales J, Hagan DJ, Van Stryland EW. Dispersion of nonlinear refraction and two-photon absorption using a white-light continuum Z-scan. Opt Express. 2005;13(10):3594-9. Schafer KJ, Hales JM, Balu M, Belfield KD, Van Stryland EW, Hagan DJ. Two-photon absorption cross-sections of common photoinitiators. J Photoch Photobio A. 2004;162(2-3):497-502. doi: Doi 10.1016/S1010-6030(03)00394-0. Hernandez FE, Belfield KD, Cohanoschi I, Balu M, Schafer KJ. Three- and four-photon absorption of a multiphoton absorbing fluorescent probe. Appl Optics. 2004;43(28):5394-8. Balu M, Hales J, Hagan DJ, Van Stryland EW. White-light continuum Z-scan technique for nonlinear materials characterization. Opt Express. 2004;12(16):3820-6. Martelli S, Mancini A, Giorgi R, Alexandrescu R, Cojocaru S, Crunteanu A, Voicu I, Balu M, Morjan I. Production of iron-oxide nanoparticles by laser-induced pyrolysis of gaseous precursors. Appl Surf Sci. 2000;154:353-9. Proceedings 16. Mihaela Balu ; Kristen M. Kelly ; Christopher B. Zachary ; Ronald M. Harris ; Tatiana B. Krasieva ; Karsten König ; Bruce J. Tromberg; Clinical studies of pigmented lesions in human skin by using a multiphoton tomograph Proc. SPIE 8588, Multiphoton Microscopy in the Biomedical Sciences XIII, 858812 17. Krasieva TB, Stringari C, Liu F, Sun CH, Kong Y, Balu M, Meyskens FL, Gratton E, Tromberg BJ. Two-photon excited fluorescence spectroscopy and imaging of melanin in-vitro and in-vivo Proc. SPIE 8226, Multiphoton Microscopy in the Biomedical Sciences XII, 82262S-82262S-7 2010 18. Balu M, Liu G, Chen Z, Tromberg BJ, Potma EO. Scheme for efficient fiber-based CARS probe. Proc. SPIE 7569, Multiphoton Microscopy in the Biomedical Sciences X, 75693A 2010 19. Balu M, Hagan DJ, Van Stryland EW. “High Spectral Irradiance White-Light Continuum Z-scan” Ultrafast Phenomena XV: Proceedings of the 15th International Conference, Pacific Grove, CA, 2007 Springer Magazines 20. Mihaela Balu, Joel Hales, David J. Hagan, Eric W. Van Stryland, “Nonlinear spectrometer using a white-light continuum Zscan”, Optics and Photonics News (Magazine of Optical Society of America), 16, Issue 12, 28 (December 2005) Patents Zhongping Chen, Gangjun Liu, Mihaela Balu, Bruce J. Tromberg, Eric O. Potma, “System and Method for Efficient Coherence Anti-Stokes Raman Scattering Endoscopic and Intravascular Imaging and Multimodal Imaging “ (US8582096 B2) CONFERENCE PRESENTATIONS 1. Mihaela Balu, Christopher Zachary, Ronald Harris, Tatiana B. Krasieva, Karsten Koenig, Bruce J. Tromberg, Kristen M. Kelly, “In vivo multiphoton microscopy imaging of basal cell carcinoma”, Photonics West, SPIE San Francisco, CA, February 2015oral presentation (invited) 2. Mihaela Balu, Christopher Zachary, Ronald Harris, Tatiana B. Krasieva, Karsten Koenig, Bruce J. Tromberg, Kristen M. Kelly “Pilot study on in vivo multiphoton microscopy imaging of basal cell carcinoma”, ASLMS Annual Conference, Kissimmee, FL, April 2015- oral presentation 3. Mihaela Balu, Rolf Saager, Viera Crosignani, Ata Sharif, Kristen M. Kelly, Anthony J. Durkin, Bruce J. Tromberg “Quantification of melanin in vivo at microscopic and mesoscopic spatial scales”, Lasers in Medicine & Biology Gordon Conference, Holderness, NH, July 2014- poster presentation 4. Mihaela Balu, Christopher Zachary, Ronald Harris, Tatiana B. Krasieva, Karsten Koenig, Anthony J. Durkin, Kristen M. Kelly, Bruce J. Tromberg “Optical markers that distinguish benign and melanocytic nevi in vivo: a multiphoton microscopy study”, ASLMS Annual Conference, Phoenix, AZ, April 2014- oral presentation 5. Mihaela Balu, Kristen M. Kelly, Christopher Zachary, Ronald Harris, Tatiana B. Krasieva, Karsten Koenig, Bruce J. Tromberg, “Origins of contrast in multiphoton microscopy imaging of melanoma”, Photonics West, SPIE San Francisco, CA, February 2014- oral presentation (invited) 6. Mihaela Balu, Kristen M. Kelly, Christopher Zachary, Ronald Harris, Tatiana B. Krasieva, Martin Weinigel, Karsten Koenig, Bruce J. Tromberg, “In-vivo multiphoton microscopy: potential for non-invasive early diagnosis of pigmented lesions”, ASLMS Annual Conference, Boston, MA, April 2013- oral presentation 7. Mihaela Balu, Kristen M. Kelly, Christopher Zachary, Ronald Harris, Tatiana B. Krasieva, Karsten Koenig, Bruce J. Tromberg, “Clinical Studies of Pigmented Lesions in Human Skin by Using a Multiphoton Tomograph”, Photonics West, SPIE San Francisco, CA, February 2013- oral presentation (invited) 8. Mihaela Balu, Kristen M. Kelly, Christopher Zachary, Ronald Harris, Tatiana B. Krasieva, Karsten Koenig, Bruce J. Tromberg, “Application of MPTflex multiphoton tomograph in monitoring of human skin cellular metabolism during hypoxia and in clinical studies on skin cancer imaging”, FLIM, Saarbrucken, Germany June 2012- oral presentation 9. Krasieva TB, Stringari C, Liu F, Sun CH, Kong Y, Balu M, Meyskens FL, Gratton E, Tromberg BJ. Two-photon excited fluorescence spectroscopy and imaging of melanin in-vitro and in-vivo” SPIE Photonics West, San Francisco, CA (January 2012) - poster presentation 10. Mihaela Balu, Gangjun Liu, Zhongping Chen, Bruce J. Tromberg, Eric O. Potma, “Fiber delivered probe for efficient CARS imaging of tissues“ SPIE Photonics West, San Francisco, CA (January 2010) - poster presentation 11. Eric W. Van Stryland, Mihaela Balu, David J. Hagan, Gero Nootz, Scott Webster, Lazaro Padilha, Claudio Cirloganu, Peter Olzsak, Seth Marder, Joe Perry, “White-Light Continuum Z-scan Nonlinear Optical Spectroscopy”, PQE XXXVII (Physics of Quantum Electronics conference), Snowbird, Utah, Jan. 6-10, 2008 - invited talk 12. Lazaro Padilha, Gero Nootz, Mihaela Balu, David J. Hagan, Eric W. Van Stryland, “Nonlinear Refraction of Semiconductor Quantum Dots Using Single Wavelength and White-Light Continuum Z-scan”, Nonlinear Optics (NLO), Kona, Hawaii, July 30August3, 2007 - oral presentation 13. Eric Van Stryland, David Hagan, Mihaela Balu, Jie Fu, Claudiu Cirloganu, Scott Webster, “Measuring the Spectral Dependence of Nonlinear Absorption and Refraction”, Annual Meeting of the American Chemical Society, Polmer Branch, San Francisco, Sept. 2006 - invited talk 14. Mihaela Balu, David J. Hagan, Eric W. Van Stryland, “High Spectral Irradiance White-Light Continuum Z-scan”, International Conference on Ultrafast Phenomena, Pacific Grove, CA, July 31-August 4, 2006 - poster presentation 15. Mihaela Balu, David J. Hagan, Eric W. Van Stryland, “Broadband Z-scan characterization of NLO Materials Using High Energy, High Quality Supercontinuum Generated by Filamentation in Krypton” International Symposium on Materials and Devices for Nonlinear Optics, Dingle, Ireland, June-2006 - oral presentation 16. Mihaela Balu, David J. Hagan, Eric W. Van Stryland, “Spectral Measurement of Nonlinear Absorption and Refraction Using a White-Light Continuum Z-scan”, Frontier in Optics/LS Annual Meeting, Tucson, AZ, October 2005 - oral presentation 17. Mihaela Balu, Joel Hales, David J. Hagan, Eric W. Van Stryland, “Two-Photon Absorption and the Dispersion of Nonlinear Refraction Using a White-Light Continuum Z-scan”, SPIE, San Diego, CA, July 2005 - oral presentation 18. Eric W. Van Stryland, Mihaela Balu, Jie Fu, David J. Hagan, “Degenerate and Nondegenerate Nonlinear Absorption and Refraction”, NOMA, Cetraro, Italy, June 2005 - oral presentation 19. Mihaela Balu, Joel Hales, David J. Hagan, Eric W. Van Stryland, “Two-Photon Absorption and the Dispersion of Nonlinear Refraction Using a White-Light Continuum Z-scan”, CLEO/IQEC, Baltimore, MD, May 2005 - poster presentation 20. Mihaela Balu, Joel Hales, David J. Hagan, Eric W. Van Stryland, “Z-scan using white-light continuum”, OSA Annual Meeting, Rochester, NY, October 2004 - oral presentation 21. Mihaela Balu, Joel Hales, David J. Hagan, Eric W. Van Stryland, “White-light continuum Z-scan technique for nonlinear materials characterization”, Nonlinear Optics (NLO), Kona, Hawaii, August 2004 - oral presentation 22. Mihaela Balu, Joel Hales, David J. Hagan, Eric W. Van Stryland, “White-light continuum Z-scan technique for nonlinear materials characterization”, CLEO/IQEC, San Francisco, CA, May 2004 - oral presentation 23. Jie Fu, Mihaela Balu, Joel Hales, David J. Hagan, Eric W. Van Stryland, “Measurement of nondegenerate two-photon absorption spectra of single-crystal polydiacetylene”, CLEO/IQEC, San Francisco, CA, May 2004 - poster presentation 24. Ion Cohanoschi, Florencio E. Hernandez, Kevin D. Belfield, Mihaela Balu, Katherine J. Schafer, “Three and four-photon absorption of a multiphoton absorbing flurescent probe”, CLEO/IQEC, San Francisco, CA, May 2004 - poster presentation 25. Kevin D. Belfield, Katherine J. Schafer, Joel M. Hales, Mihaela Balu, Eric W. Van Stryland, David J. Hagan, “Two-photon absorptivities of common photoinitiators via degenerate and nondegenerate nonlinear methods”, Asia Radiation Curing Technologies Conference, Yokohama, Japan, December 2003 - invited 26. Jie Fu, Mihaela Balu, Joel M. Hales, David J. Hagan, Eric W. Van Stryland, Fumiyo Yoshino, “Measurement of nondegenerate two-photon absorption (2PA) spectrum of single-crystal polydiacetylene”, OISE, Orlando, FL, November 2003 - oral presentation 27. Joel M. Hales, Katherine J. Schafer, Mihaela Balu, Kevin D. Belfield, Eric W. Van Stryland, David J. Hagan, “Two-photon absorption properties of commercial photoinitiators”, SPIE Optics & Photonics, San Diego, CA, August 2003 - invited talk