====== Current Research Projects ====== 

==== Multiplexed Confocal Fluorescence Lifetime Imaging Microscopy  ====
Comparing with conventional wide-field imaging microscopes, confocal microscopy hold significant advantages in image contrast enhancement, 3D sectioning capabilities, and compatibility with specialized detectors. For applications such as live cell imaging, slow acquisition speed is a key barrier to adaption of confocal microscopy. While wide-field microscopy is typically faster, multiplexed confocal schemes such as using a spinning foci array can significantly increase the image acquisition rate. The moving foci array in the spinning disc, however, prevents the use of specialized discrete photo detectors arrays. 

We have developed a suite of technologies to generate, scan, and measure 1000+ confocal foci simultaneously, while is compatible with stationary discrete detectors. Another key feature of the technique is that it can be retrofitted to a conventional wide-field fluorescence microscope. We are also developing various related technologies for its applications in drug discovery and in vivo imaging.  
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**Publications:** 
  * Elizabeth J. Osterlund, Nehad Hirmiz, James M. Pemberton, Adrien Nougarede, Qian Liu, Brian Leber, Qiyin Fang, and David W. Andrews, "Efficacy and specificity of inhibitors of BCL-2 family protein interactions assessed by affinity measurements in live cells," Science Advances, 8(16): 2022, doi: 10.1126/sciadv.abm7375 ([[https://doi.org/10.1126/sciadv.abm7375|Open Access]])
  * Nehad Hirmiz, Anthony Tsikouras, Elizabeth J. Osterlund, Morgan Richards, David W. Andrews, and Qiyin Fang, "Highly Multiplexed Confocal Fluorescence Lifetime Microscope Designed for Screening Applications," IEEE Selected Topics in Quantum Electronics, 27(5):1-9, 2020, doi.org/10.1109/JSTQE.2020.2997834  ({{:public:publications:mcfocal_flim_2020_jstqe_pre.pdf|Preprint PDF}})
  * Nehad Hirmiz, Anthony Tsikouras, Elizabeth J. Osterlund, Morgan Richards, David W. Andrews, and Qiyin Fang, "Multiplexed confocal microscope with a refraction window scanner and a single-photon avalanche photodiode array detector," Opt. Lett. 45(1), 69-72 (2020), https://doi.org/10.1364/OL.45.000069 ([[https://doi.org/10.1364/OL.45.000069|online]])
  * Nehad Hirmiz, Anthony Tsikouras, Elizabeth J. Osterlund, Morgan Richards, David W. Andrews, and Qiyin Fang, "Cross-talk reduction in a multiplexed synchroscan streak camera with simultaneous calibration," Opt. Express 27, 22602-22614 (2019), doi.org/10.1364/OE.27.022602 ([[https://doi.org/10.1364/OE.27.022602|online]])
  * Anthony Tsikouras, Pietro Peronio, Ivan Rech, Nehad Hirmiz, M. Jamal Deen, and Qiyin Fang, "Characterization of SPAD Array for Multifocal High-Content Screening Applications," Photonics 3(4):56, 2016; doi: 10.3390/photonics3040056, ([[http://www.mdpi.com/2304-6732/3/4/56/html|Open Access]])
  *  Bo Xiong, Qiyin Fang, “Luminescence lifetime imaging using a cellphone camera with an electronic rolling shutter”, Optics Letters, 45(1): 81-84, 2020, doi.org/10.1364/OL.45.000081 (https://www.osapublishing.org/ol/abstract.cfm?uri=ol-45-1-81)
  *   Anthony Tsikouras, Richard Berman, David W. Andrews and Qiyin Fang, "High-speed multifocal array scanning using refractive window tilting," Biomedical Optics Express 6, 3737-3757, 2015. ([[https://www.osapublishing.org/boe/abstract.cfm?uri=boe-6-10-3737|Open Access]])
  * Anthony Tsikouras, Jin Ning, Sandy Ng, Richard Berman, David W. Andrews, and Qiyin Fang, “Streak camera crosstalk reduction using  a multiple decay optical fiber bundle,” Optics Letters 37(2): 250-252, 2012. ({{:public:publications:fangq_tsikourasa_streak-flim_ol_2012.pdf|PDF}})\\

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==== Ultrafast lasers in surgical applications and advanced manufacturing of biomedical devices ====
Microstructure materials are currently used in different fields. One of these areas is sensor devices such as microfluidic devices. The devices are made from transparent materials such as glass and PDMS (Polydimethylsiloxane). There are several techniques that are currently used to remove substance and create microchannels on material surface, laser ablation is one of the important methods that can be used in microfabrication. This importance results from the development of laser. In the past, laser with long pulse duration (>picosecond) had been used to fabricate microstructure materials, but because pulse duration of laser was longer than thermal relaxation time of ablated material, the thermal effect was present and caused micro crackers into materials. However, after ultrafast pulse laser (pulse duration <picosecond) is generated, the micro processing of materials using this laser allows for the possibility of material removal on order of micro scale with low thermal damage. In fact, manufacture of microstructure materials using ultrafast pulse laser is still under study. 

**Publications:** 
  * Mostafa Yakout, Ian Phillips, M.A. Elbestawi, Qiyin Fang, "In-situ monitoring and detection of spatter agglomeration and delamination during laser-based powder bed fusion of Invar 36," Optics & Laser Technology, 106741, ISSN 0030-3992, doi:10.1016/j.optlastec.2020.106741. ([[https://doi.org/10.1016/j.optlastec.2020.106741|Online]])
  *   Fahad Aljekhedab, Wenbin Zhang, Harold K. Haugen, Gregory R. Wohl, Munir M. El-Desouki, Qiyin Fang, "Influence of environmental conditions in bovine bone ablation by ultrafast laser," Journal of Biophotonics, 12(6): e201800293, 2019; doi.org/10.1002/jbio.201800293([[https://doi.org/10.1002/jbio.201800293|online]])
  *  Ran An; Ghadeer W. Khadar; Emilia I. Wilk; Brent Emigh; Harold K. Haugen; Gregory R. Wohl; Brett Dunlop; Mehran Anvari; Joseph E. Hayward; Qiyin Fang, "Ultrafast laser ablation and machining large-size structures on porcine bone," Journal of Biomedical Optics 18 (7):070504, 2013, doi: 10.1117/1.JBO.18.7.070504, ([[http://biomedicaloptics.spiedigitallibrary.org/article.aspx?articleid=1720637|Open Access]]) 

  * Brent Emigh, Ran An, Eugene M. Hsu, Travis H. R. Crawford, Harold K. Haugen, Gregory R. Wohl, Joseph E. Hayward, and Qiyin Fang, "Porcine cortical bone ablation by ultrafast pulsed laser irradiation," Journal of Biomedical Optics, 17(2):028001, 2012 ({{:public:publications:brent_bone_jbo_2012.pdf|PDF}})
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==== Imaging in the Gastrointestinal Tract ("Google Streetview" of the Colon) ====
In colonoscopy, it is important to monitor the progression or recurrence of suspected cancerous lesions (e.g., polyps). Because the colon is contractile and mobile, however, it is very difficult to relocate a lesion (e.g., a polyp) even during the same procedure. We are developing a novel 360 degree panoramic imaging method to build a map of colon lining, during colonoscopy, and use it to locate and track cancerous and pre-cancerous lesions. This research will make colon cancer screening and treatments more effective. 

A motion tracking device was previously developed to provide the accurate position, rotation, and velocity of the endoscope to be used in both upper and lower gastrointestinal procedures. It will help gastroenterologists during examination, diagnosis, treatments, and follow-ups to record precise location information during a procedure whether it is for determining the exact area for follow-ups, training doctors, or comparing the size of a tumour. In the current phase, this prototype design is being optimized using modern camera and imaging features as well as hardware and software design to produce a more efficient product that can be used in a clinical setting. The benefits of this design as compared to other solutions are the cost-effective, small-sized, real-time, and software based approach that can simplify the design and minimize the weight of the device. It is also placed externally on the endoscope and does not go inside the patient which allows for it to be removed or disposed.  

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**Publications:** 
  * Ian H. D. Phillips, David Armstrong and Qiyin Fang, "A Real-Time Endoscope Motion Tracker," IEEE Journal of Translational Engineering in Health and Medicine, 10:1-9, 2022, ([[http://doi.org/10.1109/JTEHM.2022.3214148|Open Access]]). 
  *   Samir Sahli, Roy, C. C. Wang, Aparna Murthy, David Armstrong, M. Jamal Deen, and Qiyin Fang, "a 360 degree side view endoscope for lower GI tract mapping," Physics in Canada, 71(1): 18-20, 2015 ([[https://pic-pac.cap.ca/index.php/Issues/showpdf/article/v71n1.0-a2394.pdf|online]])
  * Roy Chih Chung Wang, M. Jamal Deen, David Armstrong, and Qiyin Fang, "development of a catadioptric endoscope objective with forward and side views," Journal of Biomedical Optics, 16(6):066015, 2011. ({{:public:publications:fangq_wangrcc_dual-view_jbo_2011.pdf|PDF}})
  * M. Kfouri, O. Marinov, P. Quevedo, N. Faramarzpour, S. Shirani, L. W-C. Liu, Q. Fang, M. J. Deen, “Towards a Miniaturized Wireless Fluorescence-Based Diagnostic Imaging System,” IEEE Journal of Selected Topics in Quantum Electronics, 14(1): 226-234, 2008. ({{:public:publications:kfourim_ieee_2008.pdf|PDF}})  

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==== Micro and Nano-Biosensing/Imaging Devices ====
Conventional optical spectroscopy and imaging systems are large, complex and costly optoelectronic instruments comprised of lasers, spectrophotometers, and detectors. Often, their size is the limiting factor for their use in certain applications such as in-situ monitoring of physiological processes and distributed environmental sensing. In practice, there are strong demands for miniaturized, integrated devices for biomedical applications.

Recent advances in micro-photonics and electronic devices have led to small but efficient components/modules. These technologies are mostly built upon well-established microelectronic technologies for integrated circuitry.  When conventional devices are replaced with micro-components, new applications and capabilities can be facilitated.  Moreover, it usually leads to significant cost reductions and increases in yield associated with mass production. 

The overall objectives of this project area include (i) develop novel micro-optical sensing and imaging device technology with spectrally- and temporally-resolved optical signal acquisition; (ii) investigate the integration and packaging of complete sensing/imaging devices; and (iii) study the applications of such devices in biomedical and environmental applications. The proposed program will be based on the Micro/Nano Systems Lab and focus on integrated device technology development. Its success will allow translation of such technology to applications in biomedical diagnosis, drug discovery, and environmental monitoring.

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**Publications:** 
  *   Bo Xiong, Tian-Qi Hong, Herb Schellhorn, Qiyin Fang, "Dual-Modality Imaging Microfluidic Cytometer for Onsite Detection of Phytoplankton," Photonics 8, 435, 2021. doi:10.3390/photonics8100435 ([[https://doi.org/10.3390/photonics8100435|Open Access]])
  *   Bo Xiong, Eric Mahoney, Joe F. Lo, Qiyin Fang, "A Frequency-domain optofluidic dissolved oxygen sensor with total internal reflection design for in situ monitoring", IEEE Selected Topics in Quantum Electronics, 27(4):1-7 2021, doi.org/10.1109/JSTQE.2020.2997810 ({{:public:publications:do_time_2020_jstqe_pre.pdf|Preprint PDF}}) 
  * Eric James Mahoney, Bo Xiong, and Qiyin Fang, "Optical model of light propagation in total internal reflection fluorescence sensors," Applied Optics 59(34):10651-10660, 2020, doi:10.1364/AO.404112 ([[https://doi.org/10.1364/AO.404112|online]])
  *   Bo Xiong, Qiyin Fang, "Luminescence lifetime imaging using a cellphone camera with an electronic rolling shutter", Optics Letters, 45(1): 81-84, 2020, doi.org/10.1364/OL.45.000081 ([[https://www.osapublishing.org/ol/abstract.cfm?uri=ol-45-1-81|Online]]) 
  *   Eric Mahoney, Jessica Kun, Marek Smieja, Qiyin Fang, "Review—Point-of-Care Urinalysis with Emerging Sensing and Imaging Technologies," Journal of Electrochemical Society, 167(3): 037518, 2020, doi.org/10.1149/2.0182003JES ([[http://jes.ecsdl.org/content/167/3/037518.abstract|Open Access]])
  *   Jessica Kun, Marek Smieja, Bo Xiong, Leyla Soleymani, Qiyin Fang, "The Use of Motion Analysis as Particle Biomarkers in Lensless Optofluidic Projection Imaging for Point of Care Urine Analysis," Scientific Reports 9, 17255, 2019, doi.org/10.1038/s41598-019-53477-8 ([[https://www.nature.com/articles/s41598-019-53477-8|Open Access]])
  * Eric Mahoney, Huan-Huan Hsu, Fei Du, Bo Xiong, P. Ravi Selvaganapathy, and Qiyin Fang, "Optofluidic Dissolved Oxygen Sensing With Sensitivity Enhancement Through Multiple Reflections," IEEE Sensors 19(22): 10452-10460, 2019, doi.org/10.1109/JSEN.2019.2932414 ([[https://doi.org/10.1109/JSEN.2019.2932414|online]])
  *   Christina M. Gabardo, Robert C. Adams-McGavin, Barnabas C. Fung, Eric J. Mahoney, Qiyin Fang, Leyla Soleymani, “Rapid prototyping of all-solution-processed multi-lengthscale electrodes using polymer-induced thin film wrinkling,” Scientific Reports 7, 42543, 2017. ([[http://www.nature.com/articles/srep42543|Open Access]])
  *   S. C. Goh, Y. Luan, XG Wang, H. Du, C. Chau, H. E. Schellhorn, J. L. Brash, H. Chen, and Q. Fang, “Polydopamine-polyethylene glycol-albumin antifouling coatings on multiple substrates,” Journal of Materials Chemistry B, 6: 940-949, 2018 ([[http://pubs.rsc.org/en/Content/ArticleLanding/2018/TB/C7TB02636F#!divAbstract|Online]])
  *   Yushan Zhang, Benjamin R. Watts, Tianyi Guo, Zhiyi Zhang, Changqing Xu, and Qiyin Fang, "Optofluidic Device Based Microflow Cytometers for Particle/Cell Detection: A Review," Micromachines 7(4): 70, 2016; doi: 10.3390/mi7040070.  ([[http://www.mdpi.com/2072-666X/7/4/70/html|Open Access]])
  *   Tianyi Guo, M. Jamal Deen, C-Q, Xu, Qiyin Fang, P. Ravi Selvaganapathy, Haiying Zhang, “Observation of ultraslow stress release in silicon nitride film on CaF2,” J. of Vacuum Science & Technology A, 33, 041515, 2015 ({{:public:publications:deenmj_guot_fangq_sin_2015.pdf|PDF}})
  *   R. Liu, Z. Zhao, L. Zou, Q. Fang, L. Chen, A. Argento, J. F. Lo, "Compact, non-invasive frequency domain lifetime differentiation of collagens and elastin," Sensors and Actuators, B: Chemical, 219(8): 289-293, 2015 ({{:public:publications:lojf_liur_fangq_fd_lifetime_collagen_elastin_2015.pdf|PDF}})
  *   Tianyi Guo, Yin Wei, Changqing Xu, Benjamin R. Watts, Zhiyi Zhang, Qiyin Fang, Haiying Zhang, P. Ravi Selvaganapathy, and M. Jamal Deen, "Counting of E. Coli by a Micro-flow Cytometer Based on a Photonic-Microfluidic Integrated Device," Electrophoresis, 36(2): 298-304, 2015 ({{:public:publications:xucq_guoty_optofluidics_bact_2014.pdf|PDF}}). 
  *   Leo Hsu, P. Ravi Selvaganapathy, J. Brash, Q. Fang, C-Q. Xu, M. Jamal Deen, and Hong Chen, "Development of a low-cost Hemin-based dissolved oxygen sensor with anti-biofouling coating for water monitoring,” IEEE Sensors, 14(10):3400-3407, 2014 ({{:public:publications:hsuhh_do_ieee-sensor_2014.pdf|PDF}})
  * Zhiyun Li, M. Jamal Deen, Qiyin Fang, and P. R. Selvaganapathy, "Design of a flat field concave-grating-based micro-Raman spectrometer for environmental applications," Applied Optics, 51(28):6855-6863, 2012 ({{:public:publications:liz_concave-grating_ao_2012.pdf|PDF}}). 
  * Munir El-Desouki, Ognian Marinov, M. Jamal Deen, Qiyin Fang, "CMOS Active-Pixel Sensor With In-Situ Memory for Ultrahigh-Speed Imaging," IEEE Sensors Journal, 11(6): 1375-1379, 2011. ({{:public:publications:deenmj_el-desoukimm_marinovo_fangq_ieee_sensors_2011.pdf|PDF}}) 
  * Munir El-Desouki, Darek Palubiak, M. Jamal Deen, Qiyin Fang, Ognian Marinov, "A novel, high-dynamic range, high-speed, and high sensitivity CMOS imager using time-domain single-photon counting and avalanche photodiodes," IEEE Sensors Journal, 11(4): 1078-1083, 2011. ({{:public:publications:deenmj_el-desoukimm_marinovo_fangq_ieee_sensors_2011a.pdf|PDF}}) 
  * J. F. Lo, P. Butte, Q. Fang, S. J. Chen, T. Papaioannou, E. S. Kim, M. Gundersen, L. Marcu, "Multilayered MOEMS tunable spectrometer for fluorescence lifetime detection," IEEE Photonics Technology Letters, 20(7):486-488, 2010.  ({{:public:publications:loj_ieee_photonics_2010.pdf|PDF}})
  * Joe Lo, Shi-Jui Chen, Qiyin Fang, Thanassis Papaioannou, Eun-Sok Kim, Martin Gundersen and Laura Marcu, “Performance of Diaphragmed Microlens for a Packaged Microspectrometer,” Sensors, 9: 859-868, 2009 ({{:public:publications:loj_sensors_2009.pdf|PDF}})
  * Munir El-Desouki, M. Jamal Deen, Qiyin Fang, Louis W. C. Liu, Frances Tse and David Armstrong, “CMOS Image Sensors for High Speed Applications,” Sensors, 9: 430-444, 2009. ({{:public:publications:el-desoukim_sensors_2009.pdf|PDF}}) 
  * N. Faramarzpour, M. M. El-Desouki, M. J. Deen, S. Shirani, Q. Fang, “CMOS photodetector systems for low-level light applications,” Journal of Material Sciences: Materials in Electronics, invited, 20(S1): 87-93, 2009. ({{:public:publications:faramarzpourn_mater_2009.pdf|PDF}})
  * N. Faramarzpour, M. J. Deen, S. Shirani and Q. Fang, “Fully Integrated Single Photon Avalanche Diode Detector in Standard CMOS 0.18μm Technology,” IEEE Transactions on Electron Devices, Vol. 55(3): 760-767, 2008. ({{:public:publications:faramarzpourn_ieee_2008.pdf|PDF}})
  * N. Faramarzpour, M. M. El-Desouki, M. J. Deen, Q. Fang, S. Shrani and L. W-C. Liu, “CMOS Imaging for Biomedical Applications,” IEEE Potentials, May/June: 31-36, 2008. ({{:public:publications:faramarzpourn_ieee_potentials_2007.pdf|PDF}}) 
  * N. Faramarzpour, M. J. Deen, S. Shirani, Q. Fang, L. W. C. Liu, F. Campos, and J. W. Swart, “CMOS based active pixel for low-light-level detection: analysis and measurements,” IEEE Transactions on Elec-tron Devices, 54(12): 3229-3237, 2007. ({{:public:publications:faramarzpourn_ieee_2007.pdf|PDF}})
  * J. F. Lo, Q. Fang, L. Marcu and E. S. Kim, “Wafer-level packaging of three-dimensional MOEMS device with lens diaphragm,” IEEE International Conference on Micro-Electrical-Mechanical Systems (MEMS), Jan. 21-25, 2007, Japan.  ({{:public:public:publications:loj_mems_2007.pdf|PDF}})

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==== Hyperspectral Imaging of Skin Erythema for Individualized Radiotherapy ====
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**Publications:** 
  * Ramy Abdlaty, Lilian Doerwald-Munoz, Joseph Hayward, Thomas Farrell, Qiyin Fang, "Hyperspectral imaging assessment for radiotherapy induced skin-erythema: Pilot study,", Photodiagnosis and Photodynamic Therapy, 33: 102195, 2021, doi.org/10.1016/j.pdpdt.2021.102195 ([[https://doi.org/10.1016/j.pdpdt.2021.102195|online]])
  * Ramy Abdlaty, Joseph Hayward, Thomas Farrell, Qiyin Fang, "Skin erythema and pigmentation: a review of optical assessment techniques", Photodiagnosis and Photodynamic Therapy, 33: 102127, 2021, ([[https://doi.org/10.1016/j.pdpdt.2020.102127|online]])
  * Ramy Abdlaty, Qiyin Fang, "A novel dual-path high-throughput acousto-optic tunable filter imaging spectropolarimeter," Journal of Spectral Imaging, 9:a20, 2020. doi.org/10.1255/jsi.2020.a20 ([[http://doi.org/10.1255/jsi.2020.a20|open access]])
  *   Ramy Abdlaty, Lilian Doerwald-Munoz, Ali Madooei, Samir Sahli, Shu-Chi Allison Yeh, Josiane Zerubia, Raimond K. W. Wong, Joseph E.Hayward, Thomas J. Farrell, Qiyin Fang, "Hyperspectral Imaging and Classification for Grading Skin Erythema," Frontiers in Physics, 6, 72, 2018, DOI:10.3389/fphy.2018.00072([[https://www.frontiersin.org/article/10.3389/fphy.2018.00072|Open access]])
  *   Zhaojun Nie, Ran An, Joseph E. Hayward, Thomas J. Farrell, Qiyin Fang, "Hyperspectral fluorescence lifetime imaging for optical biopsy," Journal of Biomedical Optics 18 (9):096001,  2013, doi: 10.1117/1.JBO.18.9.096001, ({{:public:publications:fangq_niez_jbo_2013.pdf|PDF}})

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==== Smart Aging ====
We aim to develop wearable and ambient sensing device technologies and personalized AI/ML algorithms for continuous, longitudinal assessment of older adults' health conditions during their daily living activities (ADL).  Such longitudinal health dataset will enable early detection and personalized management of chronic and neurodegenerative diseases. 
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[[:public:research:shape-2021|Smart IPS Study]] \\
[[:public:research:shape|McMaster Smart Home for Aging-in-PlacE]]


**Publications:**\\ 
  * Brenda Vrkljan, Marla K. Beauchamp, Paula Gardner, Qiyin Fang, Ayse Kuspinar, Paul D. McNicholas, K. Bruce Newbold, Julie Richardson, Darren Scott, Manaf Zargoush and Vincenza Gruppuso, "Re-engaging in Aging and Mobility Research in the COVID-19 Era: Early Lessons from Pivoting a Large-Scale, Interdisciplinary Study amidst a Pandemic," Canadian Journal on Aging / La Revue Canadienne Du Vieillissement, 1-7, 2021, doi:10.1017/S0714980821000374 ([[http://doi.org/10.1017/S0714980821000374|Open Access]])
  * Sinead Dufour, Donna Fedorkow, Jessica Kun, Shirley S.X. Deng, & Qiyin Fang, "Exploring the Impact of a Mobile Health Solution for Postpartum Pelvic Floor Muscle Training: Pilot Randomized Controlled Feasibility Study." JMIR MHealth and UHealth, 7(7): e12587, 2019, doi.org/10.2196/12587 ([[https://doi.org/10.2196/12587|Open Access]])
  * Eric Mahoney, Colleen Chau, Qiyin Fang, "Experiential learning of data acquisition and sensor networks with a cloud computing platform," Proc. SPIE 11143, Fifteenth Conference on Education and Training in Optics and Photonics: ETOP 2019, 111433X, 2 July 2019, doi.org/10.1117/12.2535399 ([[https://doi.org/10.1117/12.2535399|Open Access]]);
  *   Henry Y.-H. Siu, B. Delleman, J. Langevin, Dee Mangin, Michelle Howard, Qiyin Fang, David Price, David  Chan, "Demonstrating a Technology-Mediated Intervention to Support Medication Adherence in Community-Dwelling Older Adults in Primary Care: A Feasibility Study." Gerontology and Geriatric Medicine, 5:1-11, 2019, doi.org/10.1177/2333721419845179 ([[https://doi.org/10.1177/2333721419845179|online]])

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==== Optical Biopsy based on time-resolved fluorescence and diffuse reflectance spectroscopy ====
Time resolved fluorescence (TRF) spectroscopy and diffuse reflectance (DR) spectroscopy have been used as minimally-invasive optical biopsy modalities. They offer real-time alternatives to invasive tissue biopsies. Fluorescence lifetime is independent of intensity variations and adds an additional source of contrast compared to steady state fluorescence. Diffuse reflectance allows for quantitative measurement of optical properties of tissue. Combining both DR and TRF modalities in one optical biopsy instrument allows for the integration of diffuse reflectance, time-resolved, and steady-state spectra for tissue diagnosis as well as real-time correction of the fluorescence lifetime and spectrum based on optical property measurements in-situ. 
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**Publications:** 
  * Zhaojun Nie, Shu-Chi Allison Yeh, Michelle LePalud, Fares Badr, Frances Tse, David Armstrong, Louis W. C. Liu, M. Jamal Deen, and Qiyin Fang, "Optical Biopsy of the Upper GI Tract Using Fluorescence Lifetime and Spectra," Frontiers in Physiology, 11:339, 2020,  doi.org/10.3389/fphys.2020.00339| ([[https://doi.org/10.3389/fphys.2020.00339|open access online]])
  *   Le V. N. Du, Manser Myla, Gurm Sunny, Wagner Ben, Hayward Joseph E., Fang Qiyin, "Calibration of Spectral Imaging Devices With Oxygenation-Controlled Phantoms: Introducing a Simple Gel-Based Hemoglobin Model," Frontiers in Physics, 7: 192, 2019, DOI=10.3389/fphy.2019.00192  ([[https://www.frontiersin.org/article/10.3389/fphy.2019.00192|Open Access]])       
  *  N. Shalaby, A. Al-Ebraheem, D. Le, Q. Fang, T. Farrell, P. Lovrics, M. Farquharson, “Time-Resolved Fluorescence (TRF) and Diffuse Reflectance Spectroscopy (DRS) for Margin Analysis in Breast Cancer,” Lasers in Surgery and Medicine, 50(3):236–245, 2018
  *   Vinh Nguyen Du Le, John Provias, Naresh Murty, Michael S. Patterson, Zhaojun Nie, Joseph E. Hayward, Thomas J. Farrell, William McMillan, Wenbin Zhang, Qiyin Fang, "Dual-modality optical biopsy of glioblastomas multiforme with diffuse reflectance and fluorescence: ex vivo retrieval of optical properties," J. Biomed. Opt. 22(2):027002, 2017; ({{:public:publications:du_brain-ex-vivo_jbo_2017.pdf|PDF}})
  *   Zhaojun Nie, Vinh Nguyen Du Le ; Derek Cappon ; John Provias ; Naresh Murty ; Joseph E. Hayward ; Thomas J. Farrell ; Michael S. Patterson ; William McMillan ; Qiyin Fang, "Integrated Time-Resolved Fluorescence and Diffuse Reflectance Spectroscopy Instrument for Intraoperative Detection of Brain Tumor Margin," IEEE Journal of Selected Topics in Quantum Electronics, 22(3): 6802109, 2016 ({{:public:publications:fangq_niez_brain_ieee_stqe_2016.pdf|PDF}})
  *   Vinh Nguyen Du Le, Michael S. Patterson, Thomas J. Farrell, Joseph E. Hayward, Qiyin Fang, "Experimental recovery of intrinsic fluorescence and fluorophore concentration in the presence of hemoglobin: spectral effect of scattering and absorption on fluorescence," Journal of Biomedical Optics 20(12), 127003, 2015.  doi:10.1117/1.JBO.20.12.127003, ({{:public:publications:led_fluo_retrieval_jbo_2015.pdf|PDF}})
  *   Vinh Nguyen Du Le, Zhaojun Nie, Joseph E. Hayward, Thomas J. Farrell, and Qiyin Fang, "Measurements of extrinsic fluorescence in Intralipid and polystyrene microspheres," Biomedical Optics Express, 5(8): 2726-2735 ([[http://www.opticsinfobase.org/boe/abstract.cfm?uri=boe-5-8-2726|Open Access]])
  * Derek J. Cappon, Thomas J. Farrell, Qiyin Fang, Joseph E. Hayward, “A Novel Fibre Optic Probe Design and Optical Property Recovery Algorithm for Optical Biopsy of Brain Tissue,” Journal of Biomedical Optics 18(10):107004, 2013 ({{:public:publications:HaywardJE_CapponDJ_FangQ_2013.pdf|PDF}})
  * Zhaojun Nie, Ran An, Joseph E. Hayward, Thomas J. Farrell, Qiyin Fang, "Hyperspectral fluorescence lifetime imaging for optical biopsy," Journal of Biomedical Optics 18 (9):096001,  2013, doi: 10.1117/1.JBO.18.9.096001, ({{:public:publications:fangq_niez_jbo_2013.pdf|PDF}})
  * P. V. Butte, Q. Fang, J. A. Jo, W. H. Yong, B. K. Pikul, K. L. Black, and L. Marcu, Intraoperative delineation of primary brain tumors using time-resolved fluorescence spectroscopy,” Journal of Biomedical Optics, 15: 027008, 2010 ({{:public:publications:MarcuL_ButteP_Brain_2011.pdf|PDF}})
  * Y. Yuan, J-Y. Hwang, M. Krishnamoorthy, J. Ning, Y. Zhang, K. Ye, R. C. Wang, M. J. Deen, Q. Fang, "High throughput AOTF-based time-resolved fluorescence spectrometer for optical biopsy", Optics Letters, 34(7): 1132-1134, 2009. ({{.:publications:yuany_optics_letters_2009.pdf|PDF}}) 
  * L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J-H. Qiao, J. D. Baker, J. A. Freischlag, M. C. Fishbein, "Detection of Rupture-Prone Atherosclerotic Plaques by Time-Resolved Laser Induced Fluorescence Spectroscopy", Atherosclerosis, Vol. 204(1): 156-164, 2009. ({{.:publications:marcul_elsevier_2009.pdf|PDF}}) 
  * Y. Yuan, T. Papaioannou, Q. Fang, "Single shot acquisition of time-resolved fluorescence spectra using a multiple delay optical fiber bundle", Optics Letters, 33(8): 791-793, 2008. ({{.:publications:yuany_optics_letters_2008.pdf|PDF}})  
  * J. A. Jo, L. Marcu, Q. Fang, T. Papaioannou, J. H. Qiao, M. C. Fishbein, B. Beseth, A. H. Dorafshar, T. Reil, D. Baker, J. Freischlag, "New Methods for Time-resolved Fluorescence Spectroscopy Data Analysis Based on the Laguerre Expansion Technique Applications in Tissue Diagnosis", Methods of Information in Medicine, Vol. 46(2): 206-211, 2007 ({{.:publications:joj_nih_2007.pdf|PDF}})
  * J. A. Jo, Q. Fang, T. Papaioannou, J. D. Baker, A. H. Dorafshar, T. Reil, J. H. Qiao, M. C. Fishbein, J. A. Freischlag, L. Marcu; “Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions,” Journal of Biomedical Optics, Vol. 11 (2): 021004, 2006 ({{:public:public:publications:joj_jbo_2006.pdf|PDF}})
  * W. H. Yong, P. V. Butte, B. K. Pikul, J. A. Jo, Q. Fang, T. Papaioannou, K. L. Black, and L. Marcu, “Distinction of brain tissue, low grade and high grade glioma with time-resolved fluorescence spectroscopy,” Frontiers in Biosciences, Vol. 11: 1255-1263, 2006. ({{:public:publications:yongw_frontiers-in-bioscience_2006.pdf|PDF}})
  * J. A. Jo, Q. Fang, L. Marcu, “Ultrafast method for the analysis of fluorescence lifetime imaging microscopy data based on the Laguerre expansion technique,” IEEE Journal of Selected Topics in Quantum Electronics, Vol. 11(4): 835-845, 2005.  ({{:public:publications:joj_ieee_2005.pdf|PDF}})
  * L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J.H. Qiao, D. Baker, J. A. Freischlag M. C. Fishbein,. In-Vivo Detection of Macrophages in a Rabbit Atherosclerotic Model by Time-Resolved Laser-Induced Fluorescence Spectroscopy. Atherosclerosis, Vol. 181(2): 295-303, 2005. ({{:public:publications:marcul_atherosclerosis_2005.pdf|PDF}})
  * Q. Fang, T. Papaioannou, J. Jo, R. Vaitha, K. Shastry, and L. Marcu, “Time-domain laser-induced fluorescence spectroscopy apparatus for clinical diagnostics,” Review of Scientific Instrument, Vol. 75(1): 151-162, 2004.  ({{:public:publications:fangq_review-of-scientific-instruments_2004.pdf|PDF}})
  * J. A. Jo, Q. Fang, T. Papaioannou, and L. Marcu, “Fast model-free deconvolution of fluorescence decay for analysis of biological systems,” Journal of Biomedical Optics, Vol. 9(4):743-752, 2004. ({{:public:publications:joj_jbo_2004.pdf|PDF}})
  * T. Papaioannou, N. Preyer, Q. Fang, M. Carnohan, R. Ross, A. Brightwell, G. Cottone, L. Jones, and L. Marcu, “Effects of fiber-optic probe design and probe-to-target distance on diffuse reflectance measurements of turbid media: an experimental and computational study at 337 nm,” Applied Optics, Vol. 43(14): 2846-2860, 2004.  ({{:public:publications:papaioannout_applied-optics_2004.pdf|PDF}})

\\

==== Applications of Fluorescence Lifetime Imaging ====
Barrett’s esophagus (BE) is a precancerous disease with the potential to become esophageal adenocarcinoma, a malignant cancer with a five year survival rate of 12%. Early detection and treatment of BE is crucial to the survival of the patient; however, current detection techniques can be erroneous and slow. A more favourable method of treatment is a real time seek-and-treat strategy at the cellular level through the use of photodynamic therapy. 5-Aminolevulenic acid (5-ALA) has previously been tested as a contrast agent to highlight features at a single cell level. In addition to this, machine learning can be used to extract these highlighted morphological and textural features of the cells to more accurately target specific cells. This procedure has the potential to alleviate cost and discomfort to the patient in comparison to the current biopsy and histology treatment as there is no need to remove samples from the patient. We are working to enhance the detection of BE and implement confocal microendoscopy as a medium for treatment. In order to do this, we use fluorescence imaging of an in vitro model of BE as well as image processing and tools for classification to properly detect and classify the cells. We iteratively test the classification software to ensure sensitive and specific identification for treatment. Our results determined that the algorithm is quick and both highly sensitive and specific at classifying multiple datasets. This is a promising outcome as it is a step toward the implementation of microendoscopy. The speed and accuracy of the algorithm indicates a feasible system. Photodynamic therapy with the help of machine learning is a promising route for cancer prevention.  

**Publications:** 
  * Shu-Chi Allison Yeh, Celine S.N. Ling, David W. Andrews, Michael S. Patterson, Kevin R. Diamond, Joseph E. Hayward, David Armstrong, and Qiyin Fang, "5-aminolevulinic acid for quantitative seek-and-treat of high-grade dysplasia in Barrett’s Esophagus cellular models," Journal of Biomedical Optics, 20(2):028002, 2015 ({{:public:publications:allison_be_ablation_2015.pdf|PDF}}).
  * Shu-Chi Allison Yeh, Samir Sahli, David W. Andrews, Michael S. Patterson, David Armstrong, John Provias, and Qiyin Fang, "5-aminolevulinic acid induced protoporphyrin IX as a fluorescence marker for quantitative image analysis of high-grade dysplasia in Barrett's esophagus cellular models," Journal of Biomedical Optics, 20(2):028002, 2015 ({{:public:publications:allison_be_imaging_2015.pdf|PDF}}).
  *   Shu-Chi Allison Yeh, Michael S. Patterson, Joseph E. Hayward, and Qiyin Fang, "Time-resolved fluorescence in photodynamic therapy," Photonics, 1(4): 530-564 ([[http://www.mdpi.com/2304-6732/1/4/530/htm|Open Access]])
  * Allison Yeh, Kevin Diamond, Michael Patterson, Zhaojun Nie, Joseph Hayward, Qiyin Fang, "Monitoring Photosensitizer Uptake Using Two Photon Fluorescence Lifetime Imaging Microscopy," Theranostics; 2(9):817-826, 2012 ([[http://www.thno.org/v02p0817.htm|Open Access]]).
  * Regina Won Kay Leung, Shu-Chi Allison Yeh, and Qiyin Fang, "Effects of incomplete decay in fluorescence lifetime estimation," Biomedical Optics Express 2(9):2517–2531, 2011. ({{:public:publications:fangq_yehsc_leungr_boe_2011.pdf|PDF}})
  * J. A. Russell, K. R. Diamond, T. Collins, H. F. Tiedje, J. E. Hayward, T. J. Farrell, M. S. Patterson, Q. Fang, “Characterization of Fluorescence Lifetime of Photofrin and Delta-Aminolevulinic Acid Induced Protoporphyrin IX in Living Cells using Single and Two-photon Excitation,” IEEE Journal of Selected Topics in Quantum Electronics, 14(1): 158-166, 2008. ({{:public:publications:russellj_ieee_2008.pdf|PDF}})


==== Photoacoustic Tomography for Breast Cancer Detection ====
The goal of the project is to develop a breast imager that can generate functional tomograms of neoplasms like MRI, but with the speed and convenience of mammography and without the painful breast compression , risky X-ray radiations or radioactive infusions. This can be achieved by using photoacoustics.