# Microfluidic sorting of lung cancer cells from leukapheresis product as an alternative to metastatic tumor biopsy

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $443,269

## Abstract

With the advent of precision oncology, including both small molecule inhibitors targeting specific genetic drivers of
cancer and modulators of the immune response to cancer neoantigens, there is a pressing need for advanced diagnostics to
direct and monitor therapeutic interventions. Currently, such real time monitoring is performed through repeat, or
resistance, biopsies; however, these surgical biopsies are invasive, may have significant complications including
insufficient tissue for the intended analyses, and only sample one specific site of tumor, which may not be representative
of the entire tumor cell population within a patient. 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. The technological hurdle in isolating sufficient numbers of rare CTCs from routine blood specimens has
been the single major limitation preventing the clinical deployment of CTC-based diagnostic opportunities. Enabled by
the technology proposed here, our shift from processing routine 10 mL blood tubes (0.2% of whole blood volume) to
making use of clinical leukapheresis to sample near-whole blood volumes (40-100%) addresses this challenge. The
fundamental basis of the technology is the highly efficient depletion of antibody-tagged blood cells away from
unmanipulated CTCs (“negative depletion” as opposed to “positive selection”), thereby enabling tumor antigen–
independent enrichment of unperturbed, viable CTCs. This strategy is applicable to cells disseminated from virtually any
solid tumor type without making any a priori assumption on the physical or biological properties of tumor cells. Our
hypothesis is that liquid biopsy of large number of CTCs using leukopheresis is equivalent to the invasive biopsies
of metastatic tumor lesions, currently performed at the time of on-treatment disease progression in lung cancer.
To address our hypothesis, we formulated 3 Aims. In Aim 1, we will develop a large-volume CTC isolation technology
based on microfluidic negative selection. In Aim 2, we will integrate microfluidic components designed in Aim 1 into a
monolithic chip for sorting of CTCs from leukopaks. In Aim 3, we will test our hypothesis by a direct comparison of
tumor biopsy and liquid biopsy, performed within a few weeks of each other, assessing both their success rate and
diagnostic accuracy. We believe that the convergence of resources and multidisciplinary expertise available in our team
will lead to a transformative bioengineering technology, paired with a highly clinically-relevant clinical challenge,
providing a new tool for preclinical lung cancer therapeutics. A positive outcome in this pilot study would set the stage for
testing more complex clinical applications, ranging from measuring cancer cell signaling effects of drug therapy
(“noninvasive pharmacokinetics”) and quantitation of cell surface protein targets for...

## Key facts

- **NIH application ID:** 10455704
- **Project number:** 5R01CA260304-02
- **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:** $443,269
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455704

## Citation

> US National Institutes of Health, RePORTER application 10455704, Microfluidic sorting of lung cancer cells from leukapheresis product as an alternative to metastatic tumor biopsy (5R01CA260304-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10455704. Licensed CC0.

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