Tumor antigen-independent and cell size variation-inclusive enrichment of viable circulating tumor cells

Wujun Zhao; Yang Liu; Brittany D. Jenkins; Rui Cheng; Bryana N. Harris; Weizhong Zhang; Jin Xie; Jonathan R. Murrow; Jamie Hodgson; Mary Egan; Ana Bankey; Petros G. Nikolinakos; Haythem Y. Ali; Kristina Meichner; Lisa A. Newman; Melissa B. Davis; Leidong Mao

doi:10.1039/C9LC00210C

Tumor antigen-independent and cell size variation-inclusive enrichment of viable circulating tumor cells†

Wujun Zhao,

‡^ab Yang Liu,

‡^a Brittany D. Jenkins,^c Rui Cheng,^b Bryana N. Harris,^d Weizhong Zhang,

^a Jin Xie,

^a Jonathan R. Murrow,^e Jamie Hodgson,^f Mary Egan,^f Ana Bankey,^f Petros G. Nikolinakos,^f Haythem Y. Ali,^g Kristina Meichner,^h Lisa A. Newman,^ij Melissa B. Davis*^cjk and Leidong Mao

*^b

Author affiliations

* Corresponding authors

^a Department of Chemistry, The University of Georgia, Athens, GA 30602, USA

^b School of Electrical and Computer Engineering, The University of Georgia, Athens, GA 30602, USA
E-mail: mao@uga.edu

^c Department of Genetics, The University of Georgia, Athens, GA 30602, USA

^d Department of Chemical Engineering, Auburn University, Auburn, AL 36830, USA

^e Department of Medicine, Augusta University–The University of Georgia Medical Partnership, Athens, GA 30602, USA

^f University Cancer & Blood Center, LLC, Athens, GA, USA

^g Department of Hematology and Oncology, Henry Ford Health System, Detroit, MI 48202, USA

^h Department of Pathology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, USA

ⁱ Department of Surgery, Henry Ford Health System, Detroit, MI 48202, USA

^j Department of Surgery, Weill Cornell Medicine, New York, NY 10021, USA
E-mail: mbd4001@med.cornell.edu

^k Department of Public Health Sciences, Henry Ford Health System and Henry Ford Cancer Institute, Detroit, MI 48202, USA

Abstract

Isolation of circulating tumor cells (CTCs) from blood provides a minimally-invasive alternative for basic understanding, diagnosis, and prognosis of metastatic cancer. The roles and clinical values of CTCs are under intensive investigation, yet most studies are limited by technical challenges in the comprehensive enrichment of intact and viable CTCs with minimal white blood cell (WBC) contamination. Here, we report a novel method based on contrast of cell magnetization in biocompatible ferrofluids (a colloidal magnetic nanoparticle suspension), termed as integrated ferrohydrodynamic cell separation (iFCS), that enriches CTCs in a tumor antigen-independent and cell size variation-inclusive manner, achieves a high throughput (12 mL h⁻¹), high recovery rate (99.08% at down to ∼10 cells per mL spike ratio), and low WBC contamination (533 cells for every one milliliter blood processed) and is biocompatible. This method will enable large cohort research to define the clinical and diagnostic value of CTC subtypes.

This article is part of the themed collection: Personalised Medicine: Liquid Biopsy

Lab on a Chip

Tumor antigen-independent and cell size variation-inclusive enrichment of viable circulating tumor cells†

Abstract

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Tumor antigen-independent and cell size variation-inclusive enrichment of viable circulating tumor cells

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