DRAFT: This module has unpublished changes.


 

Raman nanoparticle molecular imaging agents. We have been developing and utiizing surface-enhanced Raman scattering (SERS) nanoparticle imaging agents for small animal imaging and clinical diagnostics. These Raman nanoparticles consist of a 50-nm gold core with a unique Raman active layer adsorbed onto the gold surface and encapsulated within a silica shell totaling 120 nm in diameter. As shown in Fig. 1, there are different “flavors” of Raman nanoparticles each with their own unique Raman spectral fingerprint to allow for multiplexed imaging.

 

Fig. 1 (a) SERS nanoparticles produced by Oxonica, Inc.  Different “flavors” of particles are shown, each with a unique Raman-active coating (b) Fingerprint (barcode) Raman spectra from each of five different flavors of particles. 

 

Biomarker-targeted SERS nanoparticles.  Our lab is developing SERS NPs conjugated with monoclonal antibodies to target a panel of cell-surface biomarkers of cancer.  We are demonstrating that it is possible to topically apply a mixture of these NPs briefly on tissues, rinse away the unbound NPs, and rapidly detect and quantify the specific vs. nonspecific binding levels of these multiplexed NPs with a portable spectral detection device.  These technologies have the potential to enable rapid molecular phenotyping of fresh tissues (ex vivo and in vivo) for surgical guidance, early detection, guiding personalized therapies, and monitoring the molecular response to therapies.

 

Ex vivo surgical guidance.  Approximately 200,000 patients are diagnosed with early-stage breast carcinoma each year in the United States, for which breast-conserving surgery (a.k.a. partial mastectomy or lumpectomy) is a standard intervention. Unfortunately, amongst various institutions, between 20% and 50% of these patients require additional surgery if post-operative pathology reveals that the resection margins are positive for carcinoma. A method for accurate intraoperative tumor detection at the surgical margins could significantly reduce the costs, emotional trauma, and potential complications associated with multiple surgeries, and could also improve patient outcomes by reducing the sampling errors associated with conventional post-operative pathology. We have developed a Raman-encoded molecular imaging (REMI) technique, in which multiplexed surface-enhanced Raman scattering (SERS) nanoparticles (NPs) are topically applied on freshly excised tissues to enable rapid visualization of cell-surface biomarkers at the surfaces (margins) of those tissues. The ability to detect multiple protein biomarkers is critical for accurate tumor detection because the molecular profiles of most cancers, including breast carcinoma, vary greatly between patients as well as spatially and temporally within a single tumor mass.

 

Wide-field spectral endoscopy of SERS nanoparticles.  Due to the weakness of non-enhanced Raman scattering from tissues, previous Raman detection devices have largely been point-measurement devices requiring integration times on the order of seconds to minutes per spectrum.  For rapid endoscopic imaging of the esophagus, our goal is to image tens to hundreds of spectra per sec (pixels per sec) and to comprehensively image the lumenal surface of the esophagus within a few minutes.   We have developed prototype endoscopic spectral imaging devices, with a 2.5-mm diameter, for interrogation of the rat esophagus. 

 

 

Selected publications.

 

S. Kang, X. Xu, E. Navarro; Y. Wang, J.T.C. Liu, and K.M. Tichauer, "Modeling the binding and diffusion of receptor-targeted nanoparticles topically applied on fresh tissue specimens," Physics in Medicine and Biology 64, 045013 (2019) [PDF]

 

S. Kang, Y. Wang, X. Xu, E. Navarro, K.M. Tichauer, and J.T.C. Liu, "Microscopic investigation of topically applied nanoparticles for molecular imaging of fresh tissue surfaces," J. Biophotonics (2018) [PDF | Supplement]

 

Y. Wang*, N.P. Reder*, S. Kang, A.K. Glaser, Q. Yang, M.A. Wall, S.H. Javid, S.M. Dintzis, and J.T.C. Liu, "Raman-encoded molecular imaging (REMI) with topically applied SERS nanoparticles for intraoperative guidance of lumpectomy," Cancer Research 77, 4506 (2017) [PDF | Supplement]   *equal contribution

 

S. Kang, Y. Wang, N.P. Reder, and J.T.C. Liu, "Multiplexed molecular imaging of biomarker-targeted SERS nanoparticles on fresh tissue specimens with channel-compressed spectrometry" PLoS ONE 11, e016473 (2016) [download]

 

Y. Wang, J.D. Doerksen, S. Kang, D. Walsh, Q. Yang, D. Hong, and J.T.C. Liu, "Multiplexed molecular imaging of fresh tissue surfaces enabled by convection-enhanced topical staining with SERS-coded nanoparticles, Small (2016) [download]

 

Y. Wang, S. Kang, A. Khan, P. Bao, and J.T.C. Liu, "In vivo multiplexed molecular imaging of esophageal cancer via spectral endoscopy of topically applied SERS nanoparticles," Biomed. Opt. Exp. 6, 3714 (2015)  [download]

 

Y. Wang, A. Khan, M. Som; D. Wang, Y. Chen, S.Y. Leigh, D. Meza; P.Z. McVeigh, B.C. Wilson, and J.T.C. Liu, “Rapid ratiometric biomarker detection with topically applied SERS nanoparticles,” Technology 2, 1-15 (2014)  [download]

 

DRAFT: This module has unpublished changes.