Optofluidic real-time cell sorter for longitudinal CTC studies in mouse models of cancer
Name
2232.full.pdf
Description
Published version
Size
1.05 MB
Format
Adobe PDF
Checksum (MD5)
f76b2c63a86c1e6f76e1e610fb362291
Author(s)
Hamza, Bashar M.
Ng, Sheng Rong
Prakadan, Sanjay
Delgado, Francisco Feijo
Chin, Christopher R.
King, Emily M.
Yang, Lucy F.
Davidson, Shawn Michael
DeGouveia, Kelsey L.
Cermak, Nathan
Date Issued
January 2019
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Citation
Hamza, Bashar et al. "Optofluidic real-time cell sorter for longitudinal CTC studies in mouse models of cancer." Proceedings of the National Academy of Sciences 116, 6 (January 2019): 2232-2236 © 2019 The Author(s)
Version
Final published version
Abstract
Circulating tumor cells (CTCs) play a fundamental role in cancer progression. However, in mice, limited blood volume and the rarity of CTCs in the bloodstream preclude longitudinal, in-depth studies of these cells using existing liquid biopsy techniques. Here, we present an optofluidic system that continuously collects fluorescently labeled CTCs from a genetically engineered mouse model (GEMM) for several hours per day over multiple days or weeks. The system is based on a microfluidic cell sorting chip connected serially to an unanesthetized mouse via an implanted arteriovenous shunt. Pneumatically controlled microfluidic valves capture CTCs as they flow through the device, and CTC-depleted blood is returned back to the mouse via the shunt. To demonstrate the utility of our system, we profile CTCs isolated longitudinally from animals over 4 days of treatment with the BET inhibitor JQ1 using single-cell RNA sequencing (scRNA-Seq) and show that our approach eliminates potential biases driven by intermouse heterogeneity that can occur when CTCs are collected across different mice. The CTC isolation and sorting technology presented here provides a research tool to help reveal details of how CTCs evolve over time, allowing studies to credential changes in CTCs as biomarkers of drug response and facilitating future studies to understand the role of CTCs in metastasis.
MIT Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1814102116
