Editors' ChoiceCancer

One Device to Find Them All

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Science Translational Medicine  30 Oct 2013:
Vol. 5, Issue 209, pp. 209ec177
DOI: 10.1126/scitranslmed.3007772

Circulating tumor cells (CTCs) provide the potential for rapid detection and diagnosis of cancer from blood samples. This would be particularly useful in the case of cancers such as liver and pancreatic cancer, for which early detection is key to survival outcome, but the cancer is often detected too late. In order to make CTC detection and analysis a point-of-care procedure, sensitivity must be improved over existing technology, and all steps—isolation, detection, and analysis—need to be bundled together in a single device. Yoon and colleagues have therefore developed a graphene oxide (GO) chip that integrates isolation, measurement, and analysis of CTCs in one device with high sensitivity.

Single-layer GO sheets with a thickness of 1 to 3 nm were adsorbed onto flower-shaped gold patterns on a planar silicon substrate. The surfaces were then functionalized with antibodies that recognize epithelial cell adhesion molecule (EpCAM), which is the typical marker for CTCs. This device was able to successfully capture CTCs from blood samples obtained from patients with breast, lung, and pancreatic cancer. Yoon et al. isolated up to 22 CTCs per 7.5 ml of blood, with all patients having ≥2 CTCs per milliliter, whereas the Veridex CellSearch platform (the gold standard for CTC enumeration) was only able to detect <5 CTCs per 7.5 ml in 70% of metastatic breast cancer patients and 0 CTCs in 30 to 35% of all cancer patients. Because of the planar nature of the device, CTCs were able to be cultured and characterized by means of immunofluorescence within the device. In a new step toward genetic analysis of CTCs, RNA was directly recovered from the device. Interestingly, analysis of CTCs from metastatic breast cancer patients revealed an increase of HER2+ CTCs from patients with both HER2+ and HER2 primary tumors, identifying patients that may benefit from HER2-directed therapy even though they are diagnosed with HER2 primary tumors.

EpCAM-based capture of CTCs has been demonstrated on three-dimensional (3D) microstructures before, but those microfluidic devices are complicated to fabricate and may require elution steps to analyze the cells. Functionalization of 2D GO with EpCAM allowed Yoon et al. high-affinity isolation and characterization on an easy-to-make, planar surface. Larger clinical studies are needed to further confirm the potential for this device to provide integrated isolation and analysis of CTCs in the clinic. In order to be a true point-of-care testing device, the platform will have to diagnose cancer in a quick and confident manner. This work, however, does represent an important step to making early cancer detection a part of regular medical checkups.

H. J. Yoon et al., Sensitive capture of circulating tumour cells by functionalized graphene oxide nanosheets. Nat. Nanotechnol. 8, 735–741 (2013).[Abstract]

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