# High-flow microfluidics of leukapheresis blood products for functional analysis of breast circulating tumor cells

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $631,907

## Abstract

Liquid biopsies are poised to revolutionize cancer therapies, by enabling frequent blood-based monitoring of
tumor-derived materials, as cancers evolve in response to therapeutic interventions. Nowhere is this more
evident than in triple negative metastatic breast cancer, where women may undergo multiple serial courses of
therapy over many years, each associated with an initial response, followed by the acquisition of drug
resistance. Plasma DNA (ctDNA) mutation analyses provide a measure of tumor burden and may identify
targetable mutations for small molecule inhibitors, but they do not allow ex vivo culture of intact circulating
tumor cells (CTCs) for individualized preclinical drug sensitivity (“precision oncology”). Isolation of CTCs has
been achieved using small blood volumes (5-10 mL), but these cells are so rare that it has not been feasible to
establish clinically robust ex vivo CTC cultures. Our hypothesis is that we can massively increase the amount of
blood screened through standard clinical leukapheresis (1-2 L), and in return, achieve 100+-fold increase in the
number of isolated CTCs to establish routine ex vivo culture of CTCs. It is also important to note that ex vivo
CTC cultures obtained by sampling 1-2 L blood will reflect the “real time” molecular subtype, genetic
composition, and evolving drug sensitivity profile of an individual patient's metastatic breast cancer, including
multiple lesions that together contribute to the blood-borne CTC population and the patient's overall tumor
burden. We will develop a high-throughput microfluidic technology that achieves highly efficient depletion of
tagged blood cells away from unmanipulated single and clustered CTCs and provides “tumor independent
enrichment” performance, which is applicable to cells disseminated from any solid tumor type without making
any a priori assumption on the physical and/or biological properties of tumor cells. We will also establish the
microenvironmental conditions conducive to high efficiency ex vivo CTC cultures from women with metastatic
triple negative breast cancer. Success would be transformative both for new drug development and for
individualized patient selection among existing therapies for breast cancer patients, and others.

## Key facts

- **NIH application ID:** 10327299
- **Project number:** 5R01CA255602-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Daniel A. Haber
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $631,907
- **Award type:** 5
- **Project period:** 2021-01-08 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327299

## Citation

> US National Institutes of Health, RePORTER application 10327299, High-flow microfluidics of leukapheresis blood products for functional analysis of breast circulating tumor cells (5R01CA255602-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10327299. Licensed CC0.

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