Singapore-MIT Alliance for Research & Technology

Biosystems and Micromechanics

BioSystems and Micromechanics (BioSyM) Inter-Disciplinary Research Group

BioSyM Research

Thrust 4: In vivo cell systems analysis

Digital Scanned Laser Sheet microscope (DSLM) for live small animal imaging
Temporal focusing for developmental biology & microrheology
DSLM imgae: Neurulation
High Throughput Image Cytometry Technologies

Thrust 4 focuses on developing technologies required for in vivo cellular systems research ranging from embryo development to human patient care. For these in vivo systems, important research directions involve the development of non-invasive assay techniques such as imaging and spectroscopy. Many of these tissue characterization assays are high content and high throughput thus the development; of computational signal and image processing techniques are critical to handle the inherently massive data flow. The development of bioinformatics modeling methodologies are further critical for understanding the underlying molecular and cellular level mechanisms that drive these tissue-level processes. Specific projects include high content imaging of stem cell differentiation and embryo development; new miniaturized optics to study and diagnose diseases including cancer of the liver; and new optical indices for disease progression.

Capabilities developed:

  • Multi-photon technology based fluorescence microscopy systems
  • Multifocal Multi-photon Microscope (MMM) system
    • System has an 8x8 array of excitation foci for high speed multi-photon imaging applications.
    • 2 Systems are developed. One system is now installed in IBN, A*star for Liver Cancer imaging applications. The second system is installed in Centre of Bio imaging Sciences (CBIS), NUS
  •  Wide-field two-photon microscopy system
  • Two-photon light sheet is generated at the imaging plane that provides entire field imaging in single shot. This system is further miniaturized as an endoscope prototype.
  • Structured light illumination is incorporated with the system which provides the improvement in the image quality, for deeper tissue imaging applications, by subtracting the background haze.
  • High throughput 3D wide-field imaging cytometer
    • This system is based on structured light based microscopy and able to acquire 3D image stack at 1000 adherent cells per second, including the capability of spectral imaging.
    • The system is installed in Centre of Bio imaging Sciences (CBIS), NUS.
  • Digital Scanned Laser sheet Microscope with structured illumination
    • Bio-imaging platform for numerous “developmental”, “immunological” problems in different model systems.
    • An approach to understand the mechano-biology of embryogenesis - A whole embryo modeling.
  • Focal Modulation Microscopy: With optimized pupil plane filters for improving the depth resolution in thick tissue imaging.
  • Volume Holography: Fast non-scanning 3D imaging. Multi-depth imaging with high sensitivity to angular and wavelength information. Optical sectioning ability.
  • Digital Holography: Applicable to Imaging cells and particle dynamics in a fluid flow. A novel method for noise removal from inline digital holograms is developed that can be used in various holographic imaging and microscopy applications.
  • Imaging Algorithms
    • Photon Reassignment algorithm for structured light based 3D fluorescence microscopy. (Used for structured light based microscopy systems for reconstruction of depth resolved high SNR imaging).
    • 3D HiLo method for DSLM (Digitally Scanned Light sheet Microscope) system. (Useful for deep tissue imaging application for high quality reconstruction).
    • Photon reassignment method for MMM (Multifocal Multiphoton Microscope) system. (Used to reassign scattered emission photon in MMM image for tissue imaging).
    • Spectral decomposition method based on maximum likelihood estimation and Poisson de-noising. (Used for spectral imaging system for un-mixing of multiple fluorescence spectrum).
    • Image stitching and foci segmentation algorithm. (Algorithms developed in BioSyM and used in collaboration with Prof. Bevin’s group in the SMART ID IRG).

 

People

Research Highlights
During the earliest stages of a developing embryo, a steady stream of cells aggregate into primitive tissues which soon become the first stages in the formation of the backbone and nervous system, muscles, intestine and other organs and structures. Much on the minds of biologists is the choreography of cell and tissue movements where cells from different parts of the embryo congregate to form the tissues and organs. However, the migration of these cells, especially those deep in the embryo, has been difficult to photograph because the images rapidly fade with time and are also obscured by a background haze. SMART Researchers,........More
(DSLM) for live small animal imaging

Osteoclast cell migration on Spine

Live Histone-EGFP tagged Zebrafish embryo development

 

Wide-field optical microscopy is a robust and efficient imaging method but has no depth sectioning capability. The 3D optical transfer function of wide field imaging shows that high spatial frequency structures are always in-focus while low frequency (especially zero frequency) components are always transmitted from every depth (the “missing-cone” problem). In contrast, scanning microscopy methods, e.g., confocal microscopy and two-photon microscopy, has 3D capability but their frame rates are often limited by the pixel residence time required to generate images with sufficient signal-to-noise ratio (SNR). BioSyM researchers have proposed a method, extending structured light 3D imaging methods, such as HiLo microscopy, which can assign photons generated from off-focal plane excitation improving final image SNR. This method seeks to better utilize these “lost” photons by using the ‘prior knowledge’ about the optical transfer function of the structured light illumination.

Project 3 Liver fibrosis is a wound-healing process in response to various toxic injuries and associated with almost all chronic liver diseases.Inflammatory responses and excessive deposition of extracellular matrix (ECM) are often observed with cirrhosis, marking the end stage of fibrosis that is the major causes of morbidity and mortality worldwide. There is increasing evidence that fibrosis is treatable and reversible in its early stages, and even cirrhosis can regress in some clinical studies. Therefore, accurate staging of liver fibrosis is of paramount importance to determine the state of disease progression, responses to therapy, and optimization of treatment to direct disease management.
The goal of this project is to elucidate the molecular mechanism underlying fibrogenesis of the liver. This goal will be accomplished by cross-scale image quantification and informatics analysis. We study the complex pathological tissue transformation associated liver diseases such as fibrosis, cirrhosis, and cancer. High throughput optical imaging capabilities are being developed to quantify molecular and cellular features in disease models in 3D tissue models, mice and rats; and we correlate with data from clinical imaging modalities (MRI, ultrasound etc) to establish the biological basis of the diagnostic imaging of liver diseases (cancer, cirrhosis and fatty liver).
We have shown that Second Harmonic Generation / Two-Photon-Excited Fluorescence (SHG/TPEF) imaging is a good substitute for Conventional Histological Imaging. A strong correlation between liver fibrosis progression on the anterior surface and the liver interior based on quantitative analysis of morphological features in both regions has been discovered. We are now one step closer to applying reflective or laparoscopic imaging of the liver surface to stage liver fibrosis, which can potentially be used clinically to complement or eventually replace the more invasive liver biopsy.

 

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Journal Publications

  

Conference Presentations / Publications
  1. Jiangwa Xing (A*STAR-IBN), Yue Cao (A*STAR-IBN), Yu Yang (NUS/SMART), Huan Li (A*STAR-IBN), Z.Song (A*STAR-IBN/NUS), Hanry Yu (NUS/A*STAR-IBN), In Vitro Micropatterned Human Pluripotent Stem Cell Test for Morphometric based Teratogen Screening, Scientific Reports, 7: 8491 (2017)
  2. Jiangwei Shang**(NUS) and Zhengyun Zhang**(SMART) and Hui-Khoon NG(NUS), "Superfast maximum-likelihood reconstruction for quantum tomography", Phys. Rev. A 95(6), 062336, June 2017
  3. Jie Yan (A*STAR-IBN), Yu Yang (NUS/SMART), J.W.Kang (MIT), Tam Zhi Yang (SMART), Xu Shuoyu (InvetroCure), Eliza LSF (NUS), S.P.Singh (MIT), Z.Song (A*STAR-IBN/NUS), Lisa Tucker-Kellog (Duke-NUS), Peter So (MIT/SMART), Hanry Yu (NUS/A*STAR-IBN), Development of a classification model for non-alcoholic steatohepatitis (NASH) using confocal Raman micro-spectroscopy, Journal of Biophotonics, Published online June 2017
  4. Dushan (SMART/MIT), Vijay Raj Singh (SMART/MIT), Heejin Choi (MIT), Zahid Yaqoob (MIT), Hans Heemskerk (SMART), Paul Matsudaira (NUS), Peter So (MIT/SMART), "Near-common-path interferometer for imaging Fourier-transform spectroscopy in wide-field microscopy, Optica, 4 (5), May 2017
  5. Po-Hao Wang (NTU/Taiwan), Vijay Raj Singh (SMART/MIT), J.M.Wong (NTU/Taiwan), K.B.Sung (NTU/Taiwan) and Yuan Luo (NTU/Taiwan),  Non-axial-scanning multifocal confocal microscopy with multiplexed volume holographic gratings, Optics Letters, Vol. 42, pp. 346-349 (2017)
  6. Krishna Agarwal (SMART) and Radek Machan (CBIS), "Multiple signal classification algorithm for super-resolution fluorescence microscopy", Nature Communications, 7:13752 (2016)
  7. BP Nguyen** (Duke-NUS), H Heemskerk** (Duke-NUS), PTC So (MIT/SMART) and L Tucker-Kellogg (Duke-NUS) “Superpixel-based segmentation of muscle fibers in multi-channel microscopy.” BMC Systems Biology 10 (Suppl 5): 124 (2016)
  8. CY Lin, WT Lin, HH Chen, JM Wong, VR Singh (SMART), Y Luo, "Talbot multi-focal holographic fluorescence endoscopy for optically sectioned imaging", Optics letters 41 (2), 344-347, 2016
  9. X Zhai, WT Lin, HH Chen, PH Wang, LH Yeh, JC Tsai, VR Singh, Y Luo, "In-line digital holographic imaging in volume holographic microscopy", Optics letters 40 (23), 5542-5545 (2015)
  10. Shuoyu Xu (SMA2/NUS), Chiang Huen Kang, Xiaoli Gou (NUS), Qiwen Peng (SMA2/NUS), Jie Yan (SMA3/NUS) Shuangmu Zhuo (SMART), Chee Leong Cheng (NUS), Yuting He (SMA2/NUS), Yuzhan Kang(SMART), Wuzheng Xia(Guangdong General Hospital, China) Peter T. C. So(MIT), Roy Welsch(MIT), Jagath C. Rajapakse(MIT) and Hanry Yu(NUS/A*STAR-IBN), “Quantification of liver fibrosis via second harmonic imaging of the Glisson's capsule from liver surface”, Journal of Biophotonics, Epub 1 July 2015.
  11. Wai Jin Tan (A*STAR-IBN), Jie Yan (SMA3/NUS), Shuoyu Xu (SMA2/NUS), Aye Aye Thike (NUS), Boon Huat Bay (NUS), Hanry Yu (NUS/A*STAR-IBN), Min-Han Tan (A*STAR-IBN), Puay Hoon Tan (Singapore General Hospital/Duke-NUS), “Second harmonic generation microcopy is a novel technique for differential diagnosis of breast fibroepithelial lesions”, Journal of Clinical Pathology”, (in press), Epub 24 July 2015.
  12. H.-H. Chen (NTU Taiwan), V.R. Singh (SMART), L. Yuan (NTU Taiwan), "Speckle-based volume holographic microscopy for optically sectioned multi-plane fluorescent imaging", Optics Express, Vol. 23(6), 7075-7084, 2015
  13. Qiwen Peng (SMART/NUS), Shuangmu Zhuo (SMART), Peter So (MIT/SMART) and Hanry Yu (NUS/A*STAR IBN), "Improving liver fibrosis diagnosis based on forward and backward second harmonic generation signals", Applied Physics Letters, 106, 083701 (2015)
  14. Zhengyun Zhang (SMART), Zhi Chen (SMART), Shakil Rehman (SMART), and George Barbastathis (MIT/SMART), "Phase imaging using shifted wavefront sensor images", Optics Letters, 39(21), pp. 6177-6180 (2014)
  15. Yunhui Zhu (MIT), Zhengyun Zhang (SMART), and George Barbastathis (MIT/SMART), "Phase imaging for absorptive phase objects using hybrid uniform and structured illumination Transport of Intensity Equation", Optics Express, Vol. 22, Issue 23, pp. 28966-28976 (2014)
  16. Jie Yan (NUS/SMART),  Yuzhan Kang (SMART), Shuoyu Xu (SMART), Lee-Ling S. Ong (SMART), Shuangmu Zhuo (SMART), Ralph M Bunte (Duke-NUS), Nanguang Chen (NUS), H.HarryAsada (MIT/SMART), Peter T. C. So (MIT/SMART), Ian R. Wanless (Dalhousie University, Canada), Hanry Yu (NUS/A*-IBN), "In vivo label-free quantification of liver microcirculation using dual-modality microscopy", J. Biomed. Opt. 19(11), 116006 (Nov 11, 2014). 
  17. L. Yuan (NTU, Taiwan), V.R. Singh (SMART), D. Bhattacharya (SMART), E.Y.S. Yew (SMART), P. Matsudaira (NUS), P.T. So (MIT/SMART), G. Barbastathis (MIT/SMART), “Talbot Holographic Non-scanning (THIN) Fluorescence Microsocpy”, Laser and Photonics Reviews, 8 (5), L71-L75, 2014.
  18. Jae Won Cha  (MIT), Vijay Raj Singh (SMART), Ki Hean Kim (Postec, Korea), Jaychander Subramanian (MIT), Elly Nedivi (MIT), Qiwen Peng (SMART), Hanry Yu (SMART/NUS), Peter So (SMART/MIT), "Reassignment of Scattered Emission Photons in Miltifocal Multiphoton Microscopy", Scientific Reports (Nature Publishing), Vol. 4, Article number: 5153, 2014.
  19. Shuangmu Zhuo (SMART), Jie Yan (SMART/IBN/NUS), Yuzhan Kang (SMART), Shuoyu Xu (SMART/NUS), Qiwen Peng (NUS/MBI/IBN), Peter T. C. So (MIT/SMART) and Hanry Yu (SMART/A*STAR- IBN/MBI/NUS), "In vivo, label-free, three-dimensional quantitative imaging of liver surface using multi-photon microscopy", Applied Physics Letters, 105, 023701 (2014)
  20. Shuoyu Xu (NUS/SMART), Yan Wang, Dean C.S. Tai (A*STAR/IBN), Shi Wang (NUH), Chee Leong Cheng (NUH), Qiwen Peng (NUS/SMART), Jie Yan (NUS/SMART), Yongpeng Chen, Jian Sun, Xieer Liang, Youfu Zhu, Jagath C. Rajapakse (NTU), Roy E. Welsch (MIT), Peter T.C. So (MIT/SMART), Aileen Wee (NUH), Jinlin Hou, Hanry Yu (NUS/A*STAR IBN/SMART), "qFibrosis: A fully-quantitative innovative method incorporating histological features to facilitate accurate fibrosis scoring in animal model and chronic hepatitis B patients", Journal of Hepatology, Published online (2014), http://dx.doi.org/10.1016/j.jhep.2014.02.015
  21. Stefan G. Stanciu, Sh (ETH, Zurich), Shuoyu Xu (SMART/NUS), Qiwen Peng (SMART/NUS), Jie Yan (NUS/SMART), George A. Stanciu E, Roy E. Welsch (MIT), Peter T. C. So (MIT/SMART), Gabor Csucs (ETH, Zurich) & Hanry Yu (NUS/A*STAR IBN/SMART), "Experimenting Liver Fibrosis Diagnostic by Two Photon Excitation Microscopy and Bag-of-Features Image Classification", Scientific Reports (Nature Publishing), 4, 4636 (2014) DOI: 10.1038/srep04636
  22. Kizhmuri P. Divya (CSIR-NIIST,India), Sivaramapanicker Sreejith(NTU), Pichandi Ashokkumar (Univ.of Madras), Kang Yuzhan (SMART), Qiwen Peng (SMART/NUS), Swarup Kumar Maji (NTU), Yan Tong (NUS), Hanry Yu(NUS/SMART), Yanli Zhao (NTU), Perumal Ramamurthy (Univ.of Madras) and Ayyappanpillai Ajayaghosh (CSIR-NIIST,India), “A ratiometric fluorescent molecular probe with enhanced two-photon response upon Zn2+ binding for in vitro and in vivo bioimaging”, Chemical Science, Published online (2014)
  23. Yubo Duan (SMA3/NUS), George Barbastathis (MIT/SMART), Baile Zhang (NTU), Classical imaging theory of a micro-lens with super-resolution, Optics Letters, 38(16), 2988-2990 (2013)
  24. H. Choi (MIT), Elijah Y. S. Yew (SMART), V.R. Singh (SMART), B. Hallacoglu, S. Fantini, J. Rajapakse (NTU), C.J.R. Sheppard (NUS), P.T.C. So (MIT/SMART), “Improvement of axial resolution and contrast in temporally focused widefield two-photon microscopy with structured light illumination”. Biomed Opt Express, 4, 995—1005, 2013
  25. Elijah Y. S. Yew (SMART), Colin J. R. Sheppard (NUS), and Peter T. C. So (MIT/SMART), "Temporally Focused Widefield Two-photon Microscopy: Paraxial to Vectorial," Optics Express, 21, 12951-12963 (2013)
  26. Z. Zhang (SMART), Z. Chen (SMART/NUS), S. Rehman (SMART), and G. Barbastathis (MIT/SMART), "Factored form descent: a practical algorithm for coherence retrieval," Opt. Express  21, 5759-5780 (2013).
  27. Jussi Rahomäki (Univ.of Finland), Heikki J Hyvärinen (Rocsole, Finland), Shakil Rehman [SMART] and Jari Turunen (Univ. of Eastern Finland), “Free-field characterization via directional transmission through a nanoaperture”, Nanoscale Research Letters, 8, 326 (2013).
  28. L. Tian (MIT), Z. Zhang (SMART), J. Petruccelli (MIT), and G. Barbastathis (MIT/SMART), "Wigner function measurement using a lenslet array," Opt. Express  21, 10511-10525 (2013).
  29. Utkur Mirsaidov (NUS/MBI),   V.R.S.S. Mokkapati,   Dipanjan Bhattacharya (SMART),   Henrik Andersen,   Michel Bosman,   Barbaros Ozyilmaz and    Paul Matsudaira (NUS/CBIS)  “Scrolling Graphene into Nanofluidic Channels”, Lab Chip (2013, In Press)
  30. Y. Luo (National Taiwan Univ, Taiwan), B. Zhang (NTU), T. Han (Sounthwest Univ. China), Z. Chen (SMART/NUS), Y. Duan (SMA3/NUS), C.W. Chu (National Taiwan Univ, Taiwan), G. Barbastathis (MIT/SMART), and C. W. Qiu (NUS), "Phase-preserved optical elevator," Opt. Express 21, 6650-6657 (2013)
  31. B. Narmada (NUS), Y. Kang (SMART), L. Venkatraman (NUS/MBI), Q. Peng (SMA/IBN), R. Sakban,(NUS), B.  Nugraha (NUS/IBN), X.  Jiang (JHU), R. Bunte (Duke-NUS), P. So (MIT/SMART), L. Tucker-Kellogg (NUS/MBI), H. Mao(JHU), and H. Yu (NUS/IBN/SMART), “Hepatic stellate cell-targeted delivery of hepatocyte growth factor transgene via bile duct infusion enhances its expression at fibrotic foci to regress dimethylnitrosamine-induced liver fibrosis”,  Human gene therapy, 24, 508-519 (2013).
  32. Dipanjan Bhattacharya (SMART/CBIS/MBI), Vijay Raj Singh (SMART), Chen Zhi (SMART), Peter T. C. So (SMART/MIT), Paul Matsudaira (NUS/MBI) and George Barbastathis (SMART/MIT), "Three dimensional HiLo-based structured illumination for a digital scanned laser sheet microscopy (DSLM) in thick tissue imaging", Optics Express, 20(25), 27337 (2012)
  33. VR Singh (SMART), H. Choi(MIT), EYS. Yew (SMART), D. Bhattacharya(SMART), L. Yuan(National Taiwan Univ.), CJ R. Sheppard(NUS), JC. Rajapakse(NTU), G. Barbastathis(MIT/SMART), PTC So(MIT/SMART), "Improving signal-to-noise ratio of structured light microscopy based on photon reassignment", Biomed Opt Express, 3(1), 206-214 (2012)
  34. U. Mirsaidov (NUS/MBI), H. Zheng (Berkeley), D. Bhattacharya, (SMART), Y. Casana (NUS), P. Matsudaira (NUS), "Direct observation of the stick-slip movement of nm-size water droplets" Proc. Natl. Acad. Sci. (PNAS), 109(19), 7187 (2012)
  35. TT. To (NUS), PE Witten(Ghent Univ, Belgium), J Renn (NUS), D Bhattacharya(SMART), A. Huysseune(Ghent Univ, Belgium) and C. Winkler(NUS), "Rankl-induced osteoclastogenesis leads to loss of mineralization in a medaka osteoporosis model",Development, 139 (1), 141-150 (2012)
  36. L.Waller, M.Tsang, S.Ponda, S.Y.Yang, and G.Barbastathis,  “Phase and amplitude imaging from noisy images by Kalman filtering,” Opt. Express 19: 2805- (2011).
  37. Y. Luo, E. de Leon, J.Lee, J. M.Castro, J.K.Barton, R.K.Kostuk, & G. Barbastathis, “Phase contrast volume holographic imaging system,” Optics Letters, 36: 1290 (2011).
  38. Baile Zhang, Yuan Luo, Xiaogang Liu and George Barbastathis, "Macroscopic Invisibility Cloak for Visible Light", Physical Review Letters 106, 033901 (2011)
  39. H.Gao, S.Takahashi, L.Tian and G.Barbastathis, "Aperiodic Subwavelength Luneburg Lens with Nonlinear Kerr Effect Compensation," Optics Express 19, 2257 (2011).
  40. Hanhong Gao, Lei Tian, B. Zhang and George Barbastathis, “Iterative nonlinear beam propagation using Hamiltonian ray tracing and Wigner distribution function,” Optics Letters, 35(24), 4148 (2010).
  41. L. Waller, Y. Luo, and G. Barbastathis “Transport of intensity phase imaging in a volume holographic microscope,” Optics Letters 35: 2961-2963, Aug.,2010.
  42. Y. Luo, J. M. Castro, J. K. Barton, R. K. Kostuk, & G. Barbastathis, “Simulations and experiment of aperiodic and multiplexed gratings in volume holographic imaging systems,” Optics Express, 18:19273-19285, Aug. 2010
  43. He, Y., Kang, C.H., Xu, S., Tuo, X., Trasti, S. L., Tai, D. C., Raja, A. M., Peng, Q., Peter So, Rajapakse, J.C. , Welsch, R., Yu, Hanry, "Towards Surface Quantification of Liver Fibrosis Progression", J. Biomed. Optics, Vol. 15, 056007, 2010.
  44. Raja, A.M., Xu, S., Sun, W., Zhou, J., Tai, D.C.S., Chen, C.S., J.C.Rajapakse, Peter So, and Yu, H., "Pulse Modulated Second Harmonic Imaging Microscope (PM-SHIM) imaging quantitatively demonstrates marked increase of collagen in tumor stroma after chemotherapy", J. Biomed. Optics, Vol. 15, 056016, 2010.
  45. Mondal, P. P., Gilbert, R. J., and So, P.T.C., “Photobleaching Reduced Fluorescence Correlation Spectroscopy,” Appl. Phys. Lett., 97, 103704—103706, (2010).
  46. Kim, D. and So, P.T.C., “High-Throughput Three-Dimensional Lithographic Microfabrication,” Optics Lett., 35, 1602 (2010)
  47. Tang, W. T., Chung, E., Kim, Y-H, So, P. T. C., and Sheppard, C.J.R., “Surface plasmon-coupled emission microscopy with a spiral phase plate,” Optics Express, 35, 517 (2010)
  48. Cha, J.W., Ballesta, J., and So, P. T. C., “A Shack-Hartmann Wavefront Sensor Based Adaptive Optics System for Multiphoton Microscopy,” J. Biomed Optics, 15, 046022, (2010).
  49. B. Zhang and G. Barbastathis, “Dielectric metamaterial magnifier creating a virtual color image with far-field subwavelength information,” Optics Express, 18, 11216, (2010).
  50. Y. Luo, S. B. Oh and G. Barbastathis, "Wavelength-coded multi-focal microscopy", Optics Letters 35, 781-783, March 2010
  51. Wai Teng Tang, Elijah Y. S. Yew and Colin J. R. Sheppard, "Polarization conversion in confocal microscopy with radially polarized illumination", Optics Letters, 34, 2147 (2009)
  52. Colin J.R. Sheppard, Shakil Rehman, Naveen K. Balla, Elijah Y.S. Yew, Tang Wai Teng "Bessel beams: Effects of polarization", Optics Communications 282, 4647 (2009)
  53. Tai, D., Tan, N., Xu, S., Kang, C. H., Chia S. M., Cheng, C. L., Wee A., Chiang, L. W., Raja, A., Xiao G., Rajapakse, J., So P., Tang H., Yu, H., "Fibro-C-Index - A comprehensive, morphology-based quantification of liver fibrosis using second harmonic generation and two-photon microscopy," J. Biomed. Opt. 14, 044013 (2009)
  54. S. B. Oh and G. Barbastathis, “The Wigner distribution function of volume holograms,” Optics Letters, 34, 2584 (2009)
  55. Chung, E., Kim, Y. H., Tang, W. T., Sheppard, C. J. R., So, P. T. C., “Wide-field extended-resolution fluorescence microscopy with standing surface-plasmon-resonance waves,” Opt. Lett., 34, 2366-2368 (2009)
  
  1. Vijay Raj Singh (SMART), and Peter So (MIT/SMART), "Confocal reflectance quantitative phase microscopy system for 3D refractive index mapping", Photonics West, BIOS, San Francisco, 13-18 February 2016
  2. Dushan N Wadduwage(SMART/NUS), Vijay Raj Singh (SMART), Paul Matsudaira (NUS/SMART) and Peter So (NUS/SMART), "High-throughput light-sheet Raman microscope based on full field Fourier transform spectroscopy", : Photonics West, BIOS, San Francisco, 13-18 February 2016
  3. Wadduwage, Dushan N. (NUS/SMART), Marcus Parrish, Heejin Choi (MIT), Bevin P. Engelward (MIT), Paul Matsudaira (NUS), and Peter TC So (MIT/SMART), "Subnuclear foci quantification using high-throughput 3D image cytometry." In European Conferences on Biomedical Optics, pp. 953607-953607. International Society for Optics and Photonics, June 2015
  4. Zhengyun Zhang (SMART), Wensheng Chen (NUS), and George Barbastathis (MIT), "Phase Imaging Using a Hybrid Approach: Combining Wavefront Sensing With the Transport-of-Intensity Equation", OSA Digital Holography (DH), Shanghai, May 2015
  5. Vijay Raj Singh (SMART), Dushan N. Wadduwage (SMART/NUS), Paul Matsudaira (SMART/NUS) and Peter T. C. So (SMART/NUS), “Development of common path interferometer design based Fourier transform spectrometer for high-throughput spectral imaging” International Conference of Optical and Photonic Engineering, Singapore, April 2015
  6. Shakil Rehman (SMART), Yubo Duan (SMA3/NUS), George Barbastathis (MIT), “Wide-field Structured Illumination Microscopy with Compressive optimization Approach”, Focus on Microscopy, FOM 2015, Göttingen, Germany, March 29 - April 1, 2015
  7. Zhengyun Zhang (SMART) and George Barbastathis (MIT), "Phase Imaging Using a Hybrid Approach: Combining Wavefront Sensing With the Transport-of-Intensity Equation", Focus on Microscopy 2015, Goettingen, Germany, March 2015
  8. Zhi Chen (SMART), and George Barbastathis (MIT), "Optimizing the point spread function of a volume holographic imaging system", Focus on Microscopy, FOM2015, Göttingen, Germany, 29 Mar- 1 April, 2015
  9. Vijay Raj Singh (SMART), Peter T.C. So (MIT/SMART), "Confocal based quantitative reflection phase microscopy system development", SPIE Photonics West conference, BIOS during 7-12 Feb 2015.
  10. Dushan N. Wadduwage (SMART/NUS), Vijay Raj Singh (SMART), Heejin Choi (MIT), Zahid Yaqoob (MIT), Paul T. Matsudaira (NUS/SMART), Peter T.C. So (MIT/SMART), Novel common path interferometer design for high-throughput widefield spectral imaging", SPIE Photonics West conference, BIOS during 7-12 Feb 2015.
  11. Zhengyun Zhang (SMART), Zhi Chen (SMART), Shakil Rehman (SMART), and George Barbastathis (MIT/SMART), "Regularized Phase Retrieval from Wavefront Sensor Images and the Importance of Priors", Signal Recovery and Synthesis, Seattle, Washington United States, July 13-17, 2014
  12. H. Yu (NUS/A*STAR-IBN), S. Xu (SMART)), S. Zhuo (SMART), J. Yan (NUS/SMART), P. So (MIT/SMART), R. Welsch (MIT), "Optical Signatures Correlative of Metastatic Cancers in Distorted Environment", 7th World Congress of Biomechanics, July 6-11, 2014, Boston, MA
  13. Yan Jie (NUS/SMART), Peter So (MIT/SMART) and Hanry Yu (NUS), "Combining Laser Speckle Contrast Imaging with Speckle Illumination HiLo microscope to achieve 3D imaging of flow", Focus on Microscopy, FOM 2014, Sydney, Australia, 13-16 April 2014.
  14. Zhang Zhengyun (SMART) and G. Barbastathis (MIT/SMART), “Amplitude and phase from light field micrograph”, Focus on Microscopy, FOM 2014, Sydney, Australia, 13-16 April 2014.
  15. Shakil Rehman (SMART), K. Matsuda and G. Barbastathis (MIT/SMART), “Digital phase contrast imaging with hard X-rays", Focus on Microscopy, FOM 2014, Sydney, Australia, 13-16 April 2014.
  16. Y.Duan (NUS/SMART), S. Rehman (SMART), G. Barbastathis (MIT/SMART) & N. Chen (NUS), “FMM-guided 3D image reconstruction using compressive sensing”, Focus on Microscopy, FOM 2014, Sydney, Australia, 13-16 April 2014.
  17. Y.Duan (NUS/SMART), C.J.R Sheppard (NUS), S. Rehman (SMART), G. Barbastathis (MIT/SMART) & N. Chen (NUS), “Performance of cylindrically polarized light in focal modulation microscopy”, Focus on Microscopy, FOM 2014, Sydney, Australia, 13-16 April 2014.
  18. H.Gao (MIT) and G.Barbastathis (MIT/SMART), "Transformation of volume holographic pupils for microscopic imaging", Focus on Microscopy, FOM 2014, Sydney, Australia, 13-16 April 2014.
  19. Shakil Rehman (SMART), Y. Duan (NUS/SMART), W.Chen (NUS/SMART) & G. Barbastathis (MIT/SMART), “Compressive sensing approach to reconstruct HiLo images”, Focus on Microscopy, FOM 2014, Sydney, Australia, 13-16 April 2014.
  20. W.Chen (NUS/SMART), Z. Zhang (SMART), Y. Liu, Z. Chen (SMART), Y. Duan (NUS/SMART), S. Rehman (SMART), H.P. Lee & G. Barbastathis (MIT/SMART), "Compressive reconstruction of objects through turbid media with a volume hologram" Focus on Microscopy, FOM 2014, Sydney, Australia, 13-16 April 2014.
  21. Dipan Bhattacharya (SMART), V.R. Singh (SMART), P. Matsudaira (NUS), P. So (MIT/SMART) & G. Barbastathis (MIT/SMART), “Development of structured illumination based digital scanned light-sheet microscope (DSLM) system for 3D tissue imaging", Focus on Microscopy, FOM 2014, Sydney, Australia, 13-16 April 2014.
  22. G.Barbastathis (MIT/SMART), “Diverse imaging with sparsity priors", Focus on Microscopy, FOM 2014, Sydney, Australia, 13-16 April 2014.
  23. Vijay Raj Singh (SMART), Dipanjan Bhattacharya (SMART/NUS), Paul Matsudaria (NUS), George Barbastathis (MIT/SMART), Peter T. C. So (MIT/SMART), “Image reconstruction methodologies for structured light based laser sheet microscope for thick tissue imaging”, SPIE BiOS| SPIE Photonics West, 1-6 Feb 2014, San Francicso
  24. Elijah Y. S. Yew (SMART), Peter T. C. So (MIT/SMART), "Improving the optical sectioning capability of temporally focused widefield two-photon microscopy" SPIE BiOS| SPIE Photonics West, 1-6 Feb 2014, San Francicso
  25. Yubo Duan (NUS/SMART), Shakil Rehman (SMART), George Barbastathis (MIT/SMART) and Nanguang Chen (NUS), "Aperture design in focal modulation microscopy to improve
    modulation depth", SPIE BiOS| SPIE Photonics West, 1-6 Feb 2014, San Francicso
  26. Yan Jie (NUS/SMART), Peter So (MIT/SMART) and Hanry Yu (NUS), "In vivo, label-free, three-dimensional quantitative imaging of liver surface using multiphoton microscopy”, 18th Biological Sciences Graduate Congress, Kuala Lumpur, Malaysia, Jan 2014
  27. Vijay Raj Singh (SMART), Dipanjan Bhattacharya (SMART/NUS), Paul Matsudaria (NUS), George Barbastathis (MIT/SMART), Peter T. C. So (MIT/SMART), “Image reconstruction methodologies for structured light based laser sheet microscope for thick tissue imaging”, SPIE BiOS| SPIE Photonics West, 1-6 Feb 2014, San Francicso Elijah Y. S. Yew (SMART), Peter T. C. So (MIT/SMART), "Improving the optical sectioning capability of temporally focused widefield two-photon microscopy" SPIE BiOS| SPIE Photonics West, 1-6 Feb 2014, San Francicso
  28. Yubo Duan (NUS/SMART), Shakil Rehman (SMART), George Barbastathis (MIT/SMART) and Nanguang Chen (NUS), "Aperture design in focal modulation microscopy to improve modulation depth", SPIE BiOS| SPIE Photonics West, 1-6 Feb 2014, San Francicso
  29. S. Xu (SMA2/NTU), Y. Wang (SMU), A. Wee (NUH), J. Hou (SMU), H. Yu (SMART/NUS), “Quantitative characterization of changes in collagen patterns for liver fibrosis assessment”, 23rd Conference for the Asian Pacific Association for the Study of the Liver (APASL 2013), 6th – 9th June, 2013, Singapore
  30. S. Xu (SMA2/NTU), H. Yu (SMART/NUS), “Capusle Index: morphology and texture based quantification of liver fibrosis from the Glisson’s capsule”, 23rd Conference for the Asian Pacific Association for the Study of the Liver (APASL 2013), 6th – 9th June, Singapore
  31. S. Xu (SMA2/NTU), A. Wee (NUH), H. Yu (SMART/NUS), “qFibrosis-a New Tool For Quantitative Characterization of Liver Fibrosis or Tissue Regeneration”, The European Chapter Meeting of the Tissue Engineering and Regenerative Medicine International Society (TERMIS-EU 2013), 17th – 20thJune, Istanbul, Turkey
  32. C. J. R Sheppard (NUS), E. Y. S. Yew (SMART), P. T. C. So (MIT/SMART), “Temporal focusing and focus wave modes”. PIERS, Stockholm, 2013
  33. Yubo Duan (NUS/SMART), Shakil Rehman (NUS/SMART), George Barbastathis (MIT/SMART), Nanguang Chen (NUS/SMART), “Aperture Optimization to Improve Modulation Depth in Focal Modulation Microscopy”, Focus on Microscopy 2013, 24-27 March 2013, Maastricht, The Netherlands
  34. Zhengyun Zhang (SMART) and George Barbastathis (MIT/SMART), "Positivity-induced Implicit Compressed Sensing," OSA Digital Holography and Three-Dimensional Imaging (DH), HI, April 2013.
  35. Zhengyun Zhang** (SMART) and George Barbastathis (MIT/SMART), "Compressive Effects of Positivity in Coherence Retrieval," OSA Computational Optical Sensing and Imaging (COSI), CA, June 2013
  36. Z. Zhang (SMART) and G. Barbastathis (MIT/SMART), "Coherence Synthesis and Kolmogorov Complexity," in Digital Holography and Three-Dimensional Imaging, OSA Technical Digest (online) (Optical Society of America, 2013), paper DW2A.4.
  37. Dipanjan Bhattacharya (SMART), George Barbastathis (MIT/SMART) and Paul Matsudaira (NUS), “Three dimensional HiLo-based structured illumination for a digital scanned laser sheet microscopy (DSLM) in thick tissue imaging, Optical Society of America (OSA) meeting on Bio-Optics, 2013, Hawaii, USA.
  38. S. Rehman (SMART), G. Barbastathis (MIT/SMART), and R.W. Beuerman (SERI, Singapore), “Nonlinear optical microscopy of ocular tissue: Imaging Lamina Cribrosa”, presented in Focus on Microscopy (FOM2013) held in Maastricht, The Netherlands, 24-27 March 2013.
  39. Vijay Raj Singh (SMART), Jae Won Cha (MIT), Elly Nedivi (MIT), Peter T. C. So (MIT/SMART), Photon reassignment of scattered emission photons in multifocal multiphoton microscopy (MMM), 2013 Photonics West Conference -BIOS, 2-7 February 2013, San Francisco, USA
  40. Elijah Y. Yew (SMART), Peter T. C. So (MIT/SMART), Temporally focused wide-field two-photon microscopy: From the paraxial to the vectorial, 2013 Photonics West Conference -BIOS, 2-7 February 2013, San Francisco, USA (Invited)
  41. Naveen K. Balla (NUS/SMART), Elijah Y. Yew (SMART), Hayden K. Taylor (NTU), Peter T. C. So (MIT/SMART), 3D microrheology using wide-fi eld two photon microscopy, 2013 Photonics West Conference -BIOS, 2-7 February 2013, San Francisco, USA
  42. S. Rehman (SMART), G. Barbastathis (MIT/SMART) & R.W. Beuerman, “Nonlinear optical microscopy of ocular tissue: Imaging Lamina Cribrosa”, presented in Focus on Microscopy (FOM2013) held in Maastricht, The Netherlands, 24-27 March 2013.
  43. Z.Chen (SMART/NUS), Y. Chevallier, W. Chen (SMART/NUS), G.Barbastathis (MIT/SMART), and Y. Luo (National Taiwan Univ, Taiwan),  “Interactive three-dimensional holographic optical trapping and imaging”, presented in Focus on Microscopy (FOM2013) held in Maastricht, The Netherlands, 24-27 March 2013.
  44. Dipanjan Bhattacharya (SMART/CBIS/MBI), "Development of HiLo Based DSLM to understand tissue migration in different developmental context in fish model system", LSFM meeting, Sept-2012, Frankfurt, Germany - Invited Talk
  45. Dipanjan Bhattacharya (SMART/CBIS/MBI), "Development of HiLo Based DSLM to understand tissue mechanics of embryogenesis", Genetics, Genomics and Imaging in Medaka & Zebrafish, Jointly organized by the National University of Singapore (NUS), Temasek Life Sciences Laboratory Singapore (TLL) and the National Institute of Basic Biology, Okazaki, Japan (NIBB), July-2012, Singapore - Invited Talk
  46. Dipanjan Bhattacharya (SMART/CBIS/MBI), " Development of HiLo Based DSLM to understand tissue mechanics of embryogenesis”, GEM-4 Meeting, MIT, USA, July 2012 - Invited Talk
  47. Zhengyun Zhang (SMART), Zhi Chen(SMART), George Barbastathis (MIT/SMART), "Quartic Optimization for Coherence Retrieval", COSI (COMPUTATIONAL OPTICAL SENSING AND IMAGING), June-2012, USA
  48. Vijay Raj Singh (SMART), Jagath C Rajapakse (NTU), and Peter T.C. So (MIT/SMART), "High Sensitivity Temporal Focusing Widefield Multiphoton Endoscope capable of deep imaging”, Focus on Microscopy Conference, Singapore (1-4 April 2012)
  49. Rehman, S. (SMART), Soh Y. Q., Beuerman, R. W., Barbastathis, G. (MIT/SMART) and Sheppard, C. J. R. (NUS), “Second-Harmonic Generation Microscopy of Lamina Cribrosa”, in Focus on Microscopy, 1-4 April, 2012, Suntec City, Singapore
  50. Rehman, S. (SMART), Matsuda, K., Yamauchi, M., Muramatsu, M., Barbastathis, G.(MIT/SMART) and Sheppard, C. J. R. (NUS), "A Simple Lensless Digital Holographic Microscope”, in Digital Holography and 3-D Imaging (DH), 28 April - 2 May 2012, Miami, Florida, USA.
  51. Vijay Raj Singh (SMART), Jagath C Rajapakse (NTU), and Peter T.C. So (MIT/SMART), "Photon Reassignment for structured illumination microscopy for 3D imaging, SPIE BIOS, Photonics West Conference, San Francisco, USA (24-26 January 2012)
  52. B. Zhang (SMART) and G. Barbastathis (MIT/SMART), "Making Macroscopic Objects Invisible," PIERS’11, Suzhou, China, September 2011
  53. H. Gao (MIT), B. Zhang (SMART) and G. Barbastathis (MIT/SMART), "A Ground-plane Cloak Made of Sub-wavelength Elliptical Rod Arrays," PIERS’11, Suzhou, China, September 2011
  54. H. Xu (NTU), B. Zhang (SMART), G. Barbastathis (MIT/SMART) and H. Sun (NTU), "Homogeneous Beam Squeezer with Low Reflectance," PIERS’11, Suzhou, China, September 2011
  55. Baile Zhang (SMART) and George Barbastathis (MIT/SMART) "Kinetic Trapping of a Single Particle, Multiple Particles and Particle Aggregations in an Optical Vortex," PIERS '11, Marrakesh, Morocco, March 2011
  56. Yew, E. Y. S., Choi, H., Kim, D., So, P. T. C. , “Wide-field Two-photon Microscopy with Spatio-temporal Focusing and HiLo Background Rejection,”Proc of SPIE, to be presented in SPIE photonics west conference at San Francisco, January 2011.
  57. Singh V.R., Rajapakse, J.C., Yu, H., So, P.T.C., “Intensity normalization of two-photon microscopy images for liver fibrosis analysis, Proc of SPIE, to be presented in SPIE photonics west conference at San Francisco, January 2011.
  58. B. Zhang and G. Barbastathis, “Dynamic trapping and release of multiple particles in a polarized optical vortex,” International Conference on Optical MEMS and Nanophotonics, Sapporo, Japan, Aug. 2010.
  59. Satoshi Takahashi, Chih-hao Chang, Se Young Yang, and George Barbastathis, " Design and Fabrication of Dielectric Nanostructured Luneburg Lens in Optical Frequencies," IEEE Optical MEMS and Nanophotonics 2010, Sapporo, Japan, August 2010.
  60. Elijah Yew, Jae Won Cha, Colin Sheppard, Peter So, "Adaptive Optics for a Large Field of view High Throughput, High Resolution Image Cytometer", Gordon Research Conference on Lasers in Medicine and Biology, July 25-30, 2010 at the Holderness School, Holderness, New Hampshire, MA, USA
  61. Baile Zhang and George Barbastathis "Subwavelength imaging with a dielectric magnifier," IERS '10, Cambridge, Massachusetts, July 2010
  62. Y.Luo, S. B. Oh and G.Barbastathis, “Color-coded volume holographic filters for spatial-spectral imaging systems,” paper DTuB6, OSA spring topical meeting on Digital Holography and 3D Imaging, Miami, Florida, April 2010.
  63. S. B. Oh and G.Barbastathis, “Binary depth detection based on cross-spectral density,” paper JMA19, OSA spring topical meeting on Digital Holography and 3D Imaging, Miami, Florida, April 2010
  64. G. Barbastathis, Y. Luo, S. B. Oh and R. K. Kostuk, "Real-time three-dimensional microscopy with volume holographic pupils," (invited) IEEE Winter Topical Meeting on Biomedical Optics, Palma de Mallorca, Spain, February 2010.
  65. Yuan Luo, Paul J. Gelsinger, Erich De Leon, Jennifer Harwell, Jennifer K. Barton, Raymond K. Kostuk, George Barbastathis,"Phase contrast volume-holographic microscope", OSA-Frontiers in Optics, Oct 2009
  66. G. Barbastathis, W. J. Arora, C.-H. Chang, M. Deterre, H. J. In, H. Lee, A. J. Nichol, N. S. Shaar, C. W. Tan, C. W. Tan, Z. Wang, S.-G. Kim, C. Livermore, J. Miao, Y. Shao-Horn, and H. I. Smith, “The Nanostructured Origami™ three-dimensional (3D) fabrication and assembly method” (invited) 2nd International conference: from Nanoparticles & Nanomaterials to Nanodevices & Nanosystems, Rhodes, Greece, p. 19, June 2009
  67. A. J. Nichol, M. Deterre, and G. Barbastathis, “Alignment and stretching of compliant nanomembranes by embedded nanomagnets” EIPBN 2009, Marco Island, Florida, paper 7A.3, June 2009
  68. G. Barbastathis, S. Takahashi, S. B. Oh, Y. Luo, A. J. Nichol, and M. Deterre, “Three dimensional optics in the refractive, diffractive, and subwavelength regimes” (invited) Aegean Nanotechnology Workshop, Rhodes, Greece, p. xxiv, June 2009
  69. G. Barbastathis, S. Takahashi, A. Nichol, and M. Deterre, “3D nanostructured optical element design and assembly” (invited) OSA International Conference on Nanophotonics 2009, Harbin, People’s Republic of China, paper NANO-09-009, May 2009
  70. N. Loomis and G. Barbastathis, “Space-Bandwidth transfer in spherical reference holography using Wigner transforms” OSA Optics and Photonics Congress: Digital Holography and Three Dimensional Imaging (DH), Vancouver, British Columbia, April 2009
  71. Y. Luo, P. Gelsinger, J. Barton, G. Barbastathis, and R. Kostuk, “Spectral-spatial depth sectioning of biological samples using silicon oxide nano-particles doped PMMA” OSA Optics and Photonics Congress: Digital Holography and Three-Dimensional Imaging (DH), Vancouver, British Columbia, paper DTuB5, April 2009
  72. S. B. Oh, R. Raskar, D. Lanman, and G. Barbastathis, “Mask-based vision systems by use of the Wigner distribution function and ambiguity function,” OSA Optics and Photonics Congress: Digital Holography and Three-Dimensional Imaging (DH), Vancouver, British Columbia, paper JTuB5, April 2009
  73. J. A. Domínguez-Caballero, S. Takahashi, S. Lee, G. Barbastathis, “Design and fabrication of computer generated holograms for Fresnel domain lithography” OSA Optics and Photonics Congress: Digital Holography and Three-Dimensional Imaging (DH), Vancouver, British Columbia, paper DWB3, April 2009
  74. S. B. Oh and G. Barbastathis, “The Wigner distribution function of volume holographic optical elements” OSA Optics and Photonics Congress: Digital Holography and Three-Dimensional Imaging (DH), Vancouver, British Columbia, paper DWB4, April 2009