The concept of liquid biopsy and the isolation and analysis of circulating biomarkers from blood samples is proposed as a surrogate to solid biopsies and can have the potential to revolutionize the management of patients with cancer. The relevance of circulating tumor cells (CTCs) and the importance of the information they carry is acknowledged by the medical community. But what are the barriers to clinical adoption? This review draws a panorama of the biological implications of CTCs, their physical and biochemical properties, and the current technological bottlenecks for their analysis in relation with the medical needs. Keys and considerations to bridge the technological and clinical gaps that still need to be overcome to be able to introduce CTCs in clinical routine are finally synthesized.

Malignant cells detaching from a primary tumor to reach the bloodstream are known as circulating tumor cells (CTCs). Enumeration and molecular characterizations of these cells have been used as prognostic cancer biomarkers. Various in vitro techniques are available to extract these biomarkers from blood samples, although their performances are limited by the amount of blood available for analysis, usually 7.5 mL, and the rareness of these cells as a few per mL. To address this sampling bias we propose a three-dimensional (3D) microdevice adapted to the in vivo isolation of CTCs in the venous blood flow. Our device acts as an in vivo microfilter in which CTCs are specifically retained due to their specific morphological and mechanical properties as compared to normal blood cells. We present the fabrication process of these devices using planar silicon technology and their adaptation to generate a 3D microfilter integrated into a compatible medical consumable for venous access. We demonstrate that these devices are capable to capture human prostate cancer cells (PC3) spiked into whole blood using a fluidic platform mimicking an artificial vein. Moreover, the captured cells can be easily characterized by conventional microscopy and readily available for functional and downstream analysis. This minimally invasive technology could offer high-quality information to physicians and serve as a tool for personalized therapeutic follow-up in clinical routine.