Abstract
Magnetic cell sorting is an enabling tool for the isolation of specific cellular subpopulations for downstream applications and requires the cells to be labeled by a sufficient number of magnetic nanoparticles to leverage magnetophoresis for efficient separation. This requirement makes it challenging to target weakly expressed biomarkers. Here, we developed a new approach that selectively and efficiently amplifies the magnetic labeling on cells through sequentially connected antibodies and nanoparticles delivered to the surface or interior of the cell. Using this approach, we achieved amplification up to 100-fold for surface and intracellular markers. We also demonstrated the utility of this assay for enabling high-performance magnetic cell sorting when it is applied to the analysis of rare tumor cells for cancer diagnosis and the purification of transfected CAR T cells for immunotherapy. The data presented demonstrate a useful tool for the stratification of rare cell subpopulations.
Original language | English (US) |
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Pages (from-to) | 4774-4783 |
Number of pages | 10 |
Journal | Nano letters |
Volume | 22 |
Issue number | 12 |
DOIs | |
State | Published - Jun 22 2022 |
Funding
We thank Dr. Azza Al-Mahrouki at the Centre for Pharmaceutical Oncology, Faculty of Pharmacy, University of Toronto, for access to the DLS, and Dr. Ali Darbandi at the SickKids Nanoscale Biomedical Imaging Facility, Hospital for Sick Children, for his help in TEM. This research was supported in part by the Canadian Institutes of Health Research (grant no. FDN-148415) and the Natural Sciences and Engineering Research Council of Canada (grant no. RGPIN-2016-06090). This research is part of the University of Toronto's Medicine by Design initiative, which receives funding from the Canada First Research Excellence Fund. Z.W. was supported by an Alexander Graham Bell Canada Graduate Scholarship and a Centre for Pharmaceutical Oncology Graduate Student Scholarship.
Keywords
- cancer diagnosis
- cell sorting
- cell therapy
- magnetic nanoparticles
- microfluidics
ASJC Scopus subject areas
- Condensed Matter Physics
- Mechanical Engineering
- Bioengineering
- General Chemistry
- General Materials Science