Jonathan T.C. Liu
Our laboratory develops biomedical optical devices for diagnostics and therapy. Examples include miniature microscopes for real-time optical biopsy of living tissues, as well as spectral imaging devices for in vivo molecular screening of disease biomarkers. Our projects are multi-disciplinary and collaborative, involving the development of advanced optical instrumentation, the use of molecularly-targeted contrast agents, the validation of technologies with preclinical animal models and tissue culture, as well as the translation of devices into the clinic. Specific projects are listed below:
- Diagnostics – Endoscopic and surgical devices are being designed to reach inside the body for the interrogation of disease states. In particular, miniature optical-sectioning microscopes are being developed for molecular imaging with cellular resolution. This is leading to a shift in the diagnostic paradigm from biopsy and conventional histopathology to one of point-of-care in vivo microscopic pathology, which could improve the cost and accuracy of clinical diagnostics, and have major implications for the emerging fields of telepathology and personalized medicine.
- Therapy – Optical imaging may be used to guide traditional surgical interventions or used in conjunction with optically-based therapies. For example, a surgical microscope is being developed for image-guided brain tumor resection. In addition, endoscopic imaging devices are being developed for the molecular detection and treatment of gastrointestinal lesions with the aid of multiplexed targeted nanoparticles.
- Etcetera – Our lab is constantly working on new ideas in biomedical optics, especially those with the potential to impact human lives. Contact us for more details!
a) Vertical image section (ex vivo) of normal esophagus, up to 500- µm deep, acquired with a tabletop dual-axis confocal (DAC) microscope. b) Barrett’s esophagus (ex vivo), a premalignant intestinal metaplasia of the esophagus. c) Colon tissue (ex vivo), exhibiting mild adenoma. d) Ratiometric quantification of the specific vs. nonspecific binding affinity of a HER2-targeted antibody on cultured breast cancer cells, imaged with a multispectral tabletop DAC. e) Reflective bar target imaged with the miniature microscope shown in panel h, scale bar = 50 µm. f) GFP-expressing brain tumor imaged in vivo in an anesthetized mouse, image depth = 30 µm, scale bar = 50 µm. g) Volume rendering of tumor vasculature imaged in a living mouse following intravenous injection of indocyanine green, imaged with a tabletop DAC. h) Miniature DAC microscope with a 1.8-mm diameter gradient-index (GRIN) relay lens for image-guided brain tumor resection. i) Photograph of a packaged surgical microscope. j) Scanning electron micrograph of a 3 by 3-mm biaxial MEMS mirror chip used for beam scanning in the surgical microscope.
- Postdoctoral Fellow (2005 - 2009), Stanford University Department of Electrical Engineering and the School of Medicine, Stanford, CA
- Ph.D. (2005), M.S. (2000), Stanford University Department of Mechanical Engineering, Stanford, CA
- B.S.E. (1999), Princeton University Department of Mechanical and Aerospace Engineering, Certificate in Engineering Physics, Princeton, NJ
- Instructor (2009 - 2010), Stanford University School of Medicine, Stanford, CA
- Assistant Professor (2010 - ), Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, NY
- 2009 - 2013, NIH K99/R00 “Pathway to Independence” Award (NIBIB)
- 2009, Top Oral Presentation Award: Center for Biomedical Imaging at Stanford (CBIS) Symposium
- 2005 - 2008, Canary Foundation / American Cancer Society Postdoctoral Fellowship Award
- 2003, AIAA Foundation Wright Brothers Graduate Award
- 1999 - 2002, NSF Graduate Fellowship Award
- 1999, Sau-Hai Lam *58 Prize as the Top Graduate in Mechanical and Aerospace Engineering
- 1999, Tau Beta Pi, Phi Beta Kappa, Sigma Xi Book Award
Professional Society Membership
- Optical Society of America (OSA)
- Society of Photo-Optical Instrumentation Engineers (SPIE)
- Society for Molecular Imaging (SMI)
- Journal of Biomedical Optics
- Optics Letters
- Optics Express
- NSF review panel on imaging (SBIR)
Refereed Journal Publications
Book Chapters / Perspectives
- J.T.C. Liu, N.O. Loewke, M.J. Mandella, R.L. Levenson, J.M. Crawford, and C.H. Contag, “Point-of-care pathology with miniature microscopes,” Anal. Cell. Pathol. (in press).
- J.T.C. Liu, M.J. Mandella, N.O. Loewke, H. Ra, W. Piyawattanametha, H. Haeberle, O. Solgaard, G.S. Kino, and C.H. Contag, “Micromirror-scanned dual-axis confocal microscope utilizing a gradient-index relay lens for image-guidance during brain surgery,” J. Biomed. Opt. 15, 026029 (2010).
- J.T.C. Liu, M.W. Helms, M.J. Mandella, J.M. Crawford, G.S. Kino, and C.H. Contag, “Quantifying cell-surface biomarker expression in thick tissues with ratiometric three-dimensional microscopy,” Biophys. J. 96, 2405-2414 (2009).
- J.T.C. Liu, M.J. Mandella, J.M. Crawford, C.H. Contag, T.D. Wang, and G.S. Kino “Efficient rejection of scattered light enables deep optical sectioning in turbid media with low-NA optics in a dual-axis confocal architecture,” J. Biomed. Opt. 13, 034020 (2008).
- T.D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P.L. Hsiung, J.T.C. Liu, J.M. Crawford, C.H. Contag, “Functional Imaging of Colonic Mucosa With a Fibered Confocal Microscope for Real-Time In Vivo Pathology,” Clin. Gastroenterol. and Hepatol. 5, 1300-1305 (2007).
- J.T.C. Liu, M.J. Mandella, H. Ra, L.K. Wong, O. Solgaard, G.S. Kino, W. Piyawattanametha, C.H. Contag, and T.D. Wang, “Miniature near-infrared dual-axes confocal microscope utilizing a two-dimensional microelectromechanical systems scanner,” Opt. Lett. 32, 256-258 (2007).
- G.B. Rieker, H. Li, X. Liu, J.T.C. Liu, J.B. Jeffries, R.K. Hanson, M.G. Allen, S.D. Wehe, P.A. Mulhall, H.S. Kindle, A. Kakuho, K.R. Sholes, T. Matsuura, and S. Takatani, "Rapid Measurements of Temperature and H2O Concentrations in IC Engines with a Spark Plug-Mounted Diode Laser Sensor," 31st Int. Symp. on Combustion, Heidelberg, Aug. 2006; in Proc. Comb. Inst 31, 3041-3049 (2007).
- J.T.C. Liu, M.J. Mandella, J.M. Crawford, C.H. Contag, G.S. Kino, and T.D. Wang, “Performance of a dual-axes reflectance confocal microscope for imaging colonic neoplasia,” J. Biomed. Opt. 11, 054019 (2006).
- J.T.C. Liu, G.B. Rieker, J.B. Jeffries, R.K. Hanson, M.R. Gruber, T. Mathur, and C.D. Carter, "Near-infrared diode laser absorption diagnostic for temperature and water vapor in a scramjet combustor," Appl. Opt. 44, 6701-6711 (2005).
- J.T.C. Liu, J.B. Jeffries and R.K. Hanson, "Large-Modulation-Depth 2f Spectroscopy with Diode Lasers for Rapid Temperature and Species Measurements in Gases with Blended and Broadened Spectra," Appl. Opt. 43, 6500-6509 (2004).
- J.T.C. Liu, J.B. Jeffries and R.K. Hanson, "Wavelength Modulation Absorption Spectroscopy with 2f Detection using Multiplexed Diode Lasers for Rapid Temperature Measurements in Gaseous Flows," App. Phys. B 78, 503-511 (2004).
- J.T.C. Liu, R.K. Hanson, and J.B. Jeffries, "High-sensitivity absorption diagnostic for NO2 using a blue diode laser," J. Quant. Spectrosc. and Radiat. Transfer 72, No. 5, 655-664 (2002).
- D. Wang, S.Y. Leigh, and J.T.C. Liu, "Point-of-care microscopy for guiding brain tumor resection," review/perspective article in BioOptics World, January 2011, pp. 18-22.
- J.T.C. Liu, J. Hardy, and C.H. Contag, “High-resolution confocal endomicroscopy for GI cancer detection,” Advances in Optical Imaging for Clinical Medicine; N.V. Iftimia, W. Brugge, and D.X. Hammer, Eds.; Wiley & Sons (2011) - ISBN: 978-0-470-61909-4.
- J. Hardy, J.T.C. Liu and C.H. Contag, “Molecular probes for optical contrast enhancement in cancer screening,” Advances in Optical Imaging for Clinical Medicine; N.V. Iftimia, W. Brugge, and D.X. Hammer, Eds.; Wiley & Sons (2011) - ISBN: 978-0-470-61909-4.
- J.T.C. Liu, T. Kaltenbach, T.D. Wang, and R.M. Soetikno, “Endoscopy,” Encyclopedia of Biomaterials and Biomedical Engineering; G.L. Bowlin and G. Wnek, Eds.; Taylor and Francis (2006).
Selected Conference Presentations
- D. Wang, F.V. Cochran, H. Haeberle, C.H. Contag, J.T.C. Liu, “Developing targeted fluorescent contrast agents for in vivo micropathology guided resection of medulloblastoma,” SPIE Photonics West, San Francisco, CA, January 2011.
- J.T.C. Liu, et al., “Surgical dual-axis confocal microscope for brain tumor resection,” IEEE/LEOS Winter Topical Meetings, Advanced Imaging in Bio-photonics, Palma de Mallorca, Spain, January 2010.
- J.T.C. Liu, H. Haeberle, M.J. Mandella, G.S. Kino, and C.H. Contag, “Molecular image-guided brain tumor resection with miniature dual-axis confocal microscopy,” Joint Meeting of the Society for Neuro-Oncology and the AANS/CNS Section on Tumors, New Orleans, LA, October 2009.
- J.T.C. Liu, M.J. Mandella, M.W. Helms, J.M. Crawford, C.H. Contag, and G.S. Kino, “Ratiometric 3D scanning cytometer for quantifying cell-surface biomarker expression within intact tissues,” OSA Novel Techniques in Microscopy, Vancouver, BC, Canada, April 2009.
- J.T.C. Liu, M.W. Helms, M.J. Mandella, G.S. Kino, and C.H. Contag, “Quantifying cellular biomarker expression in thick tissues with ratiometric three-dimensional microscopy,” The World Molecular Imaging Congress (WMIC), Nice, France, September 2008 (Recipient of a travel award).
- J.T.C. Liu, M.J. Mandella, J.M. Crawford, C.H. Contag, T.D. Wang, G.S. Kino, “Deep optical sectioning in turbid media with dual-axes confocal microscopy: towards in vivo optical biopsy,” The OSA Biomedical Optics Topical Meeting (BIOMED), St. Petersburg, FL, March 2008.
- J.T.C. Liu, J.B. Jeffries, and R.K. Hanson, "Diode Laser Absorption Diagnostics for Measurements in Practical Combustion Flow Fields," paper AIAA-2003-4581 at 39th AIAA/ASME/SAE/ASEE Joint Propulsion Conference, Huntsville, AL, July 2003. (Recipient of the Outstanding Paper Award and the 2004 AIAA Best Paper by the AIAA Ground Testing Technical Committee).