Optofluidic real-time cell sorter for longitudinal CTC studies in mouse models of cancer
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 c...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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Other Authors: | , , , , , , |
Format: | Article |
Language: | English |
Published: |
National Academy of Sciences,
2020-07-22T21:51:00Z.
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Subjects: | |
Online Access: | Get fulltext |
Summary: | 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. National Institutes of Health (Grant 1R01-CA184956, Grant 5U24AI118672, Grant 1U54CA217377, Grant 1R33CA202820, Grant 2U19AI089992, Grant 1R01HL134539, Grant 2RM1HG006193 and Grant 2P01AI039671) National Institutes of Health (Award 1DP2GM119419) National Cancer Institute (Grant P30-CA14051) |
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