Circulating tumor cell detection using a parallel flow micro-aperture chip system

Chun Li Chang, Wanfeng Huang, Shadia I. Jalal, Bin Da Chan, Aamer Mahmoud, Safi Shahda, Bert H. O'Neil, Daniela E. Matei, Cagri A. Savran

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

We report on-chip isolation and detection of circulating tumor cells (CTCs) from blood samples using a system that integrates a microchip with immunomagnetics, high-throughput fluidics and size-based filtration. CTCs in a sample are targeted via their surface antigens using magnetic beads functionalized with antibodies. The mixture is then run through a fluidic chamber that contains a micro-fabricated chip with arrays of 8 μm diameter apertures. The fluid runs parallel to the microchip while a magnetic field is generated underneath to draw the beads and cells bound to them toward the chip surface for detection of CTCs that are larger than the apertures and clear out free beads and other smaller particles bound to them. The parallel flow configuration allows high volumetric flow rates, which reduces nonspecific binding to the chip surface and enables multiple circulations of the sample fluid through the system in a short period of time. In this study we first present models of the magnetic and fluidic forces in the system using a finite element method. We then verify the simulation results experimentally to determine an optimal flow rate. Next, we characterize the system by detecting cancer cell lines spiked into healthy human blood and show that on average 89% of the spiked MCF-7 breast cancer cells were detected. We finally demonstrate detection of CTCs in 49 out of 50 blood samples obtained from non-small cell lung cancer (NSCLC) patients and pancreatic cancer (PANC) patients. The number of CTCs detected ranges from 2 to 122 per 8 mL s of blood. We also demonstrate a statistically significant difference between the CTC counts of NSCLC patients who have received therapy and those who have not.

Original languageEnglish
Pages (from-to)1677-1688
Number of pages12
JournalLab on a Chip - Miniaturisation for Chemistry and Biology
Volume15
Issue number7
DOIs
Publication statusPublished - 7 Apr 2015
Externally publishedYes

Fingerprint

Circulating Neoplastic Cells
Parallel flow
Tumors
Cells
Fluidics
Blood
Non-Small Cell Lung Carcinoma
Flow rate
Fluids
Magnetic Fields
Surface Antigens
Antigens
Pancreatic Neoplasms
Antibodies
Cell Count
Throughput
Magnetic fields
Breast Neoplasms
Finite element method
Cell Line

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)
  • Bioengineering
  • Biomedical Engineering

Cite this

Circulating tumor cell detection using a parallel flow micro-aperture chip system. / Chang, Chun Li; Huang, Wanfeng; Jalal, Shadia I.; Chan, Bin Da; Mahmoud, Aamer; Shahda, Safi; O'Neil, Bert H.; Matei, Daniela E.; Savran, Cagri A.

In: Lab on a Chip - Miniaturisation for Chemistry and Biology, Vol. 15, No. 7, 07.04.2015, p. 1677-1688.

Research output: Contribution to journalArticle

Chang, CL, Huang, W, Jalal, SI, Chan, BD, Mahmoud, A, Shahda, S, O'Neil, BH, Matei, DE & Savran, CA 2015, 'Circulating tumor cell detection using a parallel flow micro-aperture chip system', Lab on a Chip - Miniaturisation for Chemistry and Biology, vol. 15, no. 7, pp. 1677-1688. https://doi.org/10.1039/c5lc00100e
Chang, Chun Li ; Huang, Wanfeng ; Jalal, Shadia I. ; Chan, Bin Da ; Mahmoud, Aamer ; Shahda, Safi ; O'Neil, Bert H. ; Matei, Daniela E. ; Savran, Cagri A. / Circulating tumor cell detection using a parallel flow micro-aperture chip system. In: Lab on a Chip - Miniaturisation for Chemistry and Biology. 2015 ; Vol. 15, No. 7. pp. 1677-1688.
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