Fabrication of 3D microdevices from planar electroplating for the isolation of cancer associated cells in blood
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 b...
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Veröffentlicht in: | Microelectronic engineering 2019-05, Vol.213, p.69-76 |
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Sprache: | eng |
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Zusammenfassung: | 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.
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•Innovative intravascular device for CTC capture based solely on their physical properties.•Novel strategies to form 3D microdevices from planar fabrication technology•Parallel and low-cost fabrication of devices using a silicon technology•CTC capture from whole blood using a fluidic bench mimicking an artificial vein |
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ISSN: | 0167-9317 1873-5568 |
DOI: | 10.1016/j.mee.2019.04.010 |