Fabrication of 3D microdevices from planar electroplating for the isolation of cancer associated cells in blood

Abstract

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.

Liquid Biopsy Based on Circulating Cancer‐Associated Cells: Bridging the Gap from an Emerging Concept to a Mainstream Tool in Precision Medicine

“…More recently, the work by Kim et al has demonstrated the advantage of placing CTC enrichment systems in aphaeretic conditions for longer periods of time (2 h) to substantially increase the number of isolated cells . Alternatively and along the same line, some techniques for in vivo detection/isolation of CTCs and early recruitment of metastatic cells, have also been reported . Despite that sophisticated methods have been proposed in the field of microfluidics to increase sensitivity (efficiency 80–100%) and selectivity (purity <70%), their intrinsic nature as point‐of‐care platforms limits the processing of large blood volumes (throughput ≤10 mL h −1 ).…”

Preparation and electrochemical application of an AgNW/graphene/SU‐8 composite conductive photoresist

“…[5][6][7][8][9] Nevertheless, this singlecomponent photoresist is an electrical insulator and additional secondary treatment, such as electroplating, is required to obtain electrical conductivity. 10,11 This increases the process steps and equipment requirements for applications of this photoresist in devices. With the rise of composite materials, researchers have found that the introduction of fillers into the polymer matrix can produce functional materials with both the fundamental properties of the initial material and characteristics of the fillers.…”

“…It has unique and superior properties for applications in devices like sensors, photonic devices, and new nano‐electronics 5–9 . Nevertheless, this single‐component photoresist is an electrical insulator and additional secondary treatment, such as electroplating, is required to obtain electrical conductivity 10,11 . This increases the process steps and equipment requirements for applications of this photoresist in devices.…”