Issue 3, 2020

Microfluidic concentration and separation of circulating tumor cell clusters from large blood volumes

Abstract

Circulating tumor cells (CTCs) are extremely rare in the blood, yet they account for metastasis. Notably, it was reported that CTC clusters (CTCCs) can be 50–100 times more metastatic than single CTCs, making them particularly salient as a liquid biopsy target. Yet they can split apart and are even rarer, complicating their recovery. Isolation by filtration risks loss when clusters squeeze through filter pores over time, and release of captured clusters can be difficult. Deterministic lateral displacement is continuous but requires channels not much larger than clusters, leading to clogging. Spiral inertial focusing requires large blood dilution factors (or lysis). Here, we report a microfluidic chip that continuously isolates untouched CTC clusters from large volumes of minimally (or undiluted) whole blood. An array of 100 μm-wide channels first concentrates clusters in the blood, and then a similar array transfers them into a small volume of buffer. The microscope-slide-sized PDMS device isolates individually-spiked CTC clusters from >30 mL per hour of whole blood with 80% efficiency into enumeration (fluorescence imaging), and on-chip yield approaches 100% (high speed video). Median blood cell removal (in base-10 logs) is 4.2 for leukocytes, 5.5 for red blood cells, and 4.9 for platelets, leaving less than 0.01% of leukocytes alongside CTC clusters in the product. We also demonstrate that cluster configurations are preserved. Gentle, high throughput concentration and separation of circulating tumor cell clusters from large blood volumes will enable cluster-specific diagnostics and speed the generation of patient-specific CTC cluster lines.

Graphical abstract: Microfluidic concentration and separation of circulating tumor cell clusters from large blood volumes

Supplementary files

Article information

Article type
Paper
Submitted
12 nov. 2019
Accepted
21 déc. 2019
First published
14 janv. 2020

Lab Chip, 2020,20, 558-567

Microfluidic concentration and separation of circulating tumor cell clusters from large blood volumes

J. F. Edd, A. Mishra, T. D. Dubash, S. Herrera, R. Mohammad, E. K. Williams, X. Hong, B. R. Mutlu, J. R. Walsh, F. Machado de Carvalho, B. Aldikacti, L. T. Nieman, S. L. Stott, R. Kapur, S. Maheswaran, D. A. Haber and M. Toner, Lab Chip, 2020, 20, 558 DOI: 10.1039/C9LC01122F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements