Circulating tumour cells (CTCs) correlate by their number to the lethal potential of the tumour and can be characterized in terms of molecular properties. The repeated isolation of living CTCs has now appeared as an unavoidable step towards their use as biomarkers in clinical routine. We introduce a 3D stealthy microdevice adapted to the in vivo capture of CTCs in the venous blood flow, on the basis of their physical characteristics, size and rigidity. Embedded in a fluidic bench mimicking an artificial arm vein, it readily captured human prostate cancer cells spiked into donor blood down to a concentration of 1,000 cells/ml. The isolation of cancer cells in venous circulation was validated in an animal model in vivo. These results open new avenues to the characterization of CTCs in prognosis, personalization of treatments and follow‐up, not only as a research tool, but also for repeated monitoring in clinical practice.
e579 Background: Circulating tumor cells (CTCs) are cancer cells that have detached from a tumor and have entered into the blood circulation at a very low concentration (D. Shook, Mech. Dev., Nov 2003). CTCs have a strong prognostic value, as their number has been correlated to overall survival in different metastatic cancers (J. S. de Bono, Clin. Cancer Res., Oct 2008). Considering the rareness of CTCs in blood, capturing them in vitro is very challenging. CTCs being mainly larger and less deformable than most of blood cells, ISET was the first system exploiting their physical traits using a filtration membrane to enrich 10mL blood samples (G. Vona, Am. J. Pathol., Jan 2000). However, placing the trapping system directly within the bloodstream would increase the amount of blood screened and ensure no sampling bias. To our knowledge, the only system developed for in vivo capture of CTCs relies on an immunologic detection targeting CTCs with specific epithelial-cell adhesion molecules (N. Saucedo-Zeni, Int. J. Oncol., Oct 2012). The major drawback of this technique is the selection bias induced, given the strong heterogeneity of antigen expression profiles in CTC population as confirmed by several studies. Methods: Our device combines the advantages of in vivo capture and physical trapping of CTCs. A polymeric 3D net-like microdevice is fabricated using a Direct Laser Writing technique (Nanoscribe) and integrated onto a Nitinol guidewire to be introduced into the basilic vein through a routine 20G catheter. To optimize the design, we conducted simulation studies and in vitro assays using a fluidic platform reproducing in vivo conditions. Results: We succeeded in capturing PC3 human prostate cancer cells from 20 mL healthy donor blood spiked with 1,000 PC3 cells in 2 minutes, demonstrating the capability to capture CTCs in conditions close to those found in vivo, in terms of pressure and flow rate and without any additional treatment or dilution of the blood. Conclusions: This device could facilitate treatment personalization and follow-up. Its versatility should render it transposable to the capture of single or clustered CTCs, derived from all types of cancer and, by extension, to other circulating cellular and molecular biomarkers.
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