Presented by Jessica O. Winter, Ph.D, Distinguished Professor of Engineering, Ohio State University

Pathological analysis is a cornerstone of cancer diagnostics, patient triage for personalized medicine, and prognostic patient follow-up. This presentation will discuss the application of fluorescent and chromophoric nanoparticles in diagnostic pathology. First, we will discuss the use, development, and commercialization of quantum-dot based reagents for diagnostics of blood cancers via flow cytometry. Quantum dots (QDs), semiconductor nanoparticles that fluoresce upon light excitation, were introduced for biological imaging in 1998. They were heralded as a revolutionary product that would transform biological imaging. Yet, despite 20 years of research, there are no clinically approved QD products. My group has identified and solved the numerous challenges hindering translation of this promising technology into practice, which I will discuss. To overcome these challenges, we developed a micelle encapsulation strategy and scale-up methodologies that led to a company. I will discuss the adventure of starting a company, and the journey of one idea from conception to realization.

Next, I will discuss the translation of our encapsulation and manufacturing technologies to chromophoric nanoparticles for solid tissue imaging. Solid tissue imaging primarily relies on tissue sections obtained from biopsy slices that are stained with colored dyes to identify biomarkers. Because the dye spectra overlap, it is very difficult to obtain multiplexed images interrogating multiple biomarkers in the same sample. We have overcome this challenge through the development and implementation of erasable labels. These labels are based on polymer micelles encapsulating dye molecules that serve as imaging reports. We then construct a cage of DNA nanotechnology tiles on the micelle surface. This enables us to bar-code each micelle to DNA-labeled antibodies that bind the biomarker targets. Signal is erased by disrupting DNA hybridization between the DNA-caged micelle and the DNA-modified antibody. This approach enables repeated biomarker interrogation in the same sample without signal overlap. Collectively, these technologies improve upon the accuracy and precision of current diagnostic technologies and offer new avenues for personalized medicine and patient therapeutic design.