Development of a Microfluidic Array to Study Drug Response in Breast Cancer

Abstract

Luminal geometries are common structures in biology, which are challenging to mimic using conventional in vitro techniques based on the use of Petri dishes. In this context, microfluidic systems can mimic the lumen geometry, enabling a large variety of studies. However, most microfluidic models still rely on polydimethylsiloxane (PDMS), a material that is not amenable for high-throughput fabrication and presents some limitations compared with other materials such as polystyrene. Thus, we have developed a microfluidic device array to generate multiple bio-relevant luminal structures utilizing polystyrene and micro-milling. This platform offers a scalable alternative to conventional microfluidic devices designed in PDMS. Additionally, the use of polystyrene has well described advantages, such as lower permeability to hydrophobic molecules compared with PDMS, while maintaining excellent viability and optical properties. Breast cancer cells cultured in the devices exhibited high cell viability similar to PDMS-based microdevices. Further, co-culture experiments with different breast cell types showed the potential of the model to study breast cancer invasion. Finally, we demonstrated the potential of the microfluidic array for drug screening, testing chemotherapy drugs and photodynamic therapy agents for breast cancer.

Toward improved in vitro models of human cancer

“… 86 Specifically, a few high throughput platforms have been developed and even commercialized to generate spheroids or luminal structures dedicated to drug testing purposes. 87–89 These platforms present potential advantages of scale and capacity of testing multiple drug conditions and combinations, much needed for anticancer drug screening. 90,91 Further, high throughput platforms are often conceived to be coupled with automatized pipetting systems or automatic drug gradient generation, thereby diminishing user-associated bias and error.…”

Engineering Breast Cancer On-chip—Moving Toward Subtype Specific Models

“…Image in (C) is from Tian et al (2020b) . Image in (D) is adapted from Virumbrales-Munoz et al (2019) .…”

“…Several companies like Mimetas, Synvivo, 4Design Biosciences and AIM Biotech have each commercialized 3D culture plates, largely based on microfluidic technologies, and use alternative materials to PDMS that support several organ-on-chip devices in a single platform. Most companies offer custom designs of their platform for specific applications, and several have been implemented for BC studies ( Lanz et al, 2017 ; Virumbrales-Munoz et al, 2019 ). These multi-chip platforms need further development for use with BC specific subtypes and patient samples, in order to be used as promising tools for BC research and diagnoses ( Figure 5D ).…”

3D tumor model biofabrication

“…h Optical images of microfluidic arrays with multiple chambers in one line and multiple lines in one chip, reproduced with permission from Ref. [59]. level and determined the kinetics by high-resolution imaging (Fig.…”

“…6f and 6g). Efforts have also been made to improve throughput and cell recovery of the microfluid chips [59,60]. Using PDMS-based soft lithography, a microfluidic array capable of testing multiple doses in quadruplet of target compounds has been fabricated, as illustrated in Fig.…”