Fluid biopsies potentially offer a minimally invasive alternative to traditional tissue biopsies for the continual monitoring of metastatic cancer. Current established technologies for isolating circulating tumor cells (CTCs) suffer from poor purity and yield and require fixatives that preclude the collection of viable cells for longitudinal analyses of biological function. Antigen specific lysis (ASL) is a rapid, high-purity method of cell isolation based on targeted protective coatings on antigen-presenting cells and lysis depletion of unprotected antigen-negative cells. In ASL, photoinitiators are specifically labeled on cell surfaces that enable subsequent surface-initiated polymerization. Critically, the significant determinants of process yield have yet to be investigated for this emerging technology. In this work, we show that the labeling density of photoinitiators is strongly correlated with the yield of intact cells during ASL by flow cytometry analysis. Results suggest ASL is capable of delivering ∼25% of targeted cells after isolation using traditional antibody labeling approaches. Monomer formulations of two molecular weights of PEG-diacrylate (Mn ∼ 575 and 3500) are examined. The gelation response during ASL polymerization is also investigated via protein microarray analogues on planar glass. Finally, a density threshold of photoinitiator labeling required for protection during lysis is determined for both monomer formulations. These results indicate ASL is a promising technology for high yield CTC isolation for rare-cell function assays and fluid biopsies.
|Number of pages
|Published - Jun 7 2016
Bibliographical noteFunding Information:
This work was supported partially by R01 HL127682-01 and the National Science Foundation under Award CBET-1351531. The authors acknowledge the financial support from the National Cancer Institute (NCI) Grant R25CA153954 and a National Cancer Institute Cancer Nanotechnology Training Center (NCI-CNTC) Traineeship awarded to J.L.L. The views expressed in this manuscript do not represent the views of the NCI, NIH, NSF, or any other government agency or official.
© 2016 American Chemical Society.
ASJC Scopus subject areas
- Materials Science (all)
- Condensed Matter Physics
- Surfaces and Interfaces