Multilayer architecture microfluidic network array for combinatorial drug testing on 3D-cultured cells

Abstract

In vitro testing of drug compounds on cell models during the drug development process represents an indispensable step in the initial screening process. Although drug testing on three-dimensional (3D) cultured cells may provide a more accurate prediction of drug efficacy, it is relatively costly and time-consuming to perform compared with conventional 2D cultures due to the thick z-axis of the 3D models. In this study, we have presented a microfluidic platform with integrated pneumatic valves for producing a thin-gel 3D cell culture-based combinatorial drug screening array (3D-μCDS array). The multilayer architecture and microfluidic layout has a smaller device footprint than a single-layer microfluidic channel arrangement, making it well suited to scaling up for high-throughput combinatorial drug screening on 3D cell model. We performed 8 × 8 combination drug screening experiments with the device using two anti-cancer drugs (doxorubicin and paclitaxel) on MDA-MB-231 and MCF-7 breast cancer cell lines for demonstration. Our results indicate that our 3D-μCDS array device allows the successful screening of multiple drug combinations while reducing the operation time and the number of sample/reagents required, making it an ideal tool for general combinatorial drug screening, as well as for applications using valuable tissues and clinical samples.

The Fabrication and Application Mechanism of Microfluidic Systems for High Throughput Biomedical Screening: A Review

“…They performed a combination drug screening of two anti-cancer drugs (doxorubicin and paclitaxel) on the breast cancer cell lines of MDA-MB-231 and MCF-7 for demonstration (shown in Figure 5B). The device is confirmed by building a combinatorial gradient successfully for multiple drug screening with reducing the operation time and the number of samples [129].…”

“…(B) A combinatorial drug screening system was developed based on 3D-cultured cells. The figure shows the representative fluorescent micrographs of cells after 24 h combinatorial treatment with two anti-cancer drugs (doxorubicin and paclitaxel), reproduced with permission from[129]. (C) A breast-on-a-chip is fabricated using basement membrane extract (BME) as the ECM for therapeutic evaluation of drug delivery with high throughput.…”

Latest Updates on the Advancement of Polymer-Based Biomicroelectromechanical Systems for Animal Cell Studies

“…As previously mentioned, a precise monitoring of culture conditions is of vital importance which, in turn, initiated development of novel strategies for 3D cell culture. These new developments cover a range of advancements from the shape of the culture chambers [75][76][77] to the fabrication materials [76,78]. The temperature, in particular, plays a great role as it should remain homogeneous across the device Breast cancer cells and human adipose stromal cells were cultured in the inner culture channels while fresh media was supplied by the outer channels.…”

Anti-Cancer Drug Screening with Microfluidic Technology

“…Chang et al developed an automated microfluidic platform based on Kim et al platform [58] using pneumatic valves. The combinatorial treatment of doxorubicin and paclitaxel on a thin-gel 3D cell-culture from MDA-MB-231 and MCF-7 breast cancer cell lines is tested [68]. They assembled two air-controlled channel layers, two drug channel layers and two porous membrane layers top and bottom of a cell culture layer.…”