One of the major and ongoing challenges in clinical medicine is the accurate detection of disease at sensitivities far higher than that currently achievable. However, in order to improve detection threshold and precision, new sensing strategies are necessary. Fluorochromes already play an essential role in many biological assays, microscopy and imaging and cytometry. A key enabler has been to create fluorescent molecules that change brightness or color when interacting with their target. Unfortunately, one problem for in vivo use has been the relatively modest increase in fluorescence. In a bid to address this, we recently discovered fluorescent turn-on probes that use 'through- bond energy transfer'(TBET) to achieve >1,500-fold amplification of signal;this is more than 100 times higher than that described previously using bioorthogonal reactions (Angew Chem Int Ed, 2013.;PMID 23712730). The goal of this application is to thus now advance this cutting-edge broadly applicable detection platform to single cell imaging, sensing and analysis. To do this, we will initially synthesize and validate a small library of new agents and compare them to the most promising compounds already synthesized. Specifically, we intend to use the detection platform to perform i) perform single cell resolution intravital and intraoperative imaging for cancer detection and ii) a clinical trial to investigate the efficacy of the system for detecting cancer clls in diagnostic specimens. Beyond cancer detection, we anticipate the technology will also be broadly applicable to other pressing healthcare challenges such as testing the distribution and binding of novel drugs, detecting drug resistance, and/or performing experimental imaging using intravital microscopy.
The goal of this application is to further develop new types of fluorescent molecules which, upon recognizing a given target, increase their brightness over one thousand-fold. The efficacy of these new compounds to detect cancers will be investigated intraoperatively and a clinical trial will be performed to detect rare cancer cells in blood. This new technology is anticipated to have multiple applications in biomedical research and to serve as a valuable tool for addressing pressing healthcare problems in diagnostics.
| Carlson, Jonathan C T; Mikula, Hannes; Weissleder, Ralph (2018) Unraveling Tetrazine-Triggered Bioorthogonal Elimination Enables Chemical Tools for Ultrafast Release and Universal Cleavage. J Am Chem Soc 140:3603-3612 |
| Park, Jongmin; Im, Hyungsoon; Hong, Seonki et al. (2018) Analyses of Intravesicular Exosomal Proteins Using a Nano-Plasmonic System. ACS Photonics 5:487-494 |
| Min, Jouha; Nothing, Maria; Coble, Ben et al. (2018) Integrated Biosensor for Rapid and Point-of-Care Sepsis Diagnosis. ACS Nano 12:3378-3384 |
| Vinegoni, Claudio; Feruglio, Paolo Fumene; Gryczynski, Ignacy et al. (2018) Fluorescence anisotropy imaging in drug discovery. Adv Drug Deliv Rev : |
| Kim, Sung-Jin; Wang, Chuangqi; Zhao, Bing et al. (2018) Deep transfer learning-based hologram classification for molecular diagnostics. Sci Rep 8:17003 |
| Shao, Huilin; Im, Hyungsoon; Castro, Cesar M et al. (2018) New Technologies for Analysis of Extracellular Vesicles. Chem Rev 118:1917-1950 |
| Cuccarese, Michael F; Dubach, J Matthew; Pfirschke, Christina et al. (2017) Heterogeneity of macrophage infiltration and therapeutic response in lung carcinoma revealed by 3D organ imaging. Nat Commun 8:14293 |
| Mikula, Hannes; Stapleton, Shawn; Kohler, Rainer H et al. (2017) Design and Development of Fluorescent Vemurafenib Analogs for In Vivo Imaging. Theranostics 7:1257-1265 |
| Miller, Miles A; Chandra, Ravi; Cuccarese, Michael F et al. (2017) Radiation therapy primes tumors for nanotherapeutic delivery via macrophage-mediated vascular bursts. Sci Transl Med 9: |
| Min, Changwook; Park, Jongmin; Mun, Jae Kyoung et al. (2017) Integrated microHall magnetometer to measure the magnetic properties of nanoparticles. Lab Chip 17:4000-4007 |
Showing the most recent 10 out of 95 publications
