Research ArticleCancer Diagnostics

Ultrasensitive Clinical Enumeration of Rare Cells ex Vivo Using a Micro-Hall Detector

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Science Translational Medicine  04 Jul 2012:
Vol. 4, Issue 141, pp. 141ra92
DOI: 10.1126/scitranslmed.3003747

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Magnetic Microchip Counts Tumor Cells

The idiom “looking for a needle in a haystack” could not be applied more appropriately in medicine than to describe the detection of circulating tumor cells (CTCs). Often, only 10 of these rare cells are present in 10 ml of blood; that’s about 1 CTC for every 1 billion blood cells. Despite their scarcity, these cells may hold a wealth of information to help guide treatment decisions for cancer patients. Undaunted, Issadore and colleagues developed a miniature device that combines microfluidics and magnets to measure CTCs in patient blood at single-cell resolution.

The authors designed a micro-Hall detector (μHD) that senses the magnetic moment of particles. In this system, cells were first labeled with magnetic beads conjugated to antibodies directed at a target cell surface molecule. The magnetically labeled cells could then be flowed through the microfluidic channel, where tiny Hall detectors would sense their presence. Issadore et al. first tested the μHD with cells derived from human epithelial cancers (such as breast and brain), looking for three different cancer-related markers: human epidermal growth factor receptor 2 (HER2)/neu, epidermal growth factor receptor (EGFR), and EpCAM. Out of a mixture of blood cells—some labeled, some not—the authors only missed a cancer cell 10% of the time, compared with flow cytometry (the gold standard in the clinic), which had a false-negative rate of 81%. The μHD was also able to detect multiple biomarkers on individual cells simultaneously, which could work toward further refining subpopulations of rare cells according to surface expression.

To show use in the clinic, Issadore and coauthors noted elevated numbers of CTCs in the blood of 20 ovarian cancer patients, but not in any of the 15 healthy volunteers. By comparison, CellSearch (the gold standard technology for CTC enumeration) only detected CTCs in 25% of the same patient samples. The μHD appears to be a more sensitive cell counter than existing devices, with the potential to change patient management and disease monitoring in the clinic. The needles are still there, but we now have a rapid way of sorting through the haystack.