Microfluidic System Based High Throughput Drug Screening System for Curcumin/TRAIL Combinational Chemotherapy in Human Prostate Cancer PC3 Cells

Abstract

We have developed a fully automated high throughput drug screening (HTDS) system based on the microfluidic cell culture array to perform combinational chemotherapy. This system has 64 individually addressable cell culture chambers where the sequential combinatorial concentrations of two different drugs can be generated by two microfluidic diffusive mixers. Each diffusive mixer has two integrated micropumps connected to the media and the drug reservoirs respectively for generating the desired combination without the need for any extra equipment to perfuse the solution such as syringe pumps. The cell array is periodically exposed to the drug combination with the programmed LabVIEW system during a couple of days without extra handling after seeding the cells into the microfluidic device and also, this device does not require the continuous generation of solutions compared to the previous systems. Therefore, the total amount of drug being consumed per experiment is less than a few hundred micro liters in each reservoir. The utility of this system is demonstrated through investigating the viability of the prostate cancer PC3 cell line with the combinational treatments of curcumin and tumor necrosis factor-alpha related apoptosis inducing ligand (TRAIL). Our results suggest that the system can be used for screening and optimizing drug combination with a small amount of reagent for combinatorial chemotherapy against cancer cells.

In vitromicrofluidic models of tumor microenvironment to screen transport of drugs and nanoparticles

“…The microfluidic systems are suitable for development of multiplexing assays for high‐throughput drug‐screening operations. This has been a major focus of recent research with numerous studies exploring ways to rapidly test drug efficacy on isolated single cells cell monolayers, and tumor spheroids . For example, a digital single‐cell assay introduced by Wang et al used a microfluidic hydrodynamic trapping system for trapping individual cells without the need for surface modification, external electric force, or robotic equipment.…”

“…Apart from studies featuring single‐cell assays, there have been efforts to develop microfluidic assays involving cells cultured on 2D substrates. An et al developed an automated high‐throughput screening platform for screening and optimization of drug combinations in combinatorial chemotherapy. The device incorporated microfluidic diffusive mixers with programmed micropumps to generate sequential combinatorial concentrations of two different drugs in 64 different cell culture chambers and enabled testing of drug combinations on cell monolayers simultaneously and with small amount of reagents.…”

“…Microfluidic devices are attractive for generation of tumor microenvironmental cues through formation of gradients of reagents, oxygen, and fluid pressure with a high level of spatial and temporal control. Small diffusion distances result in rapid equilibration of gradients and enable time‐varying profiles of drugs and other macromolecules . Gas permeable nature of poly (dimethylsiloxane) (PDMS) allows development of varying levels of oxygen tension by utilization of adjacent channels separated by thin PDMS membranes .…”

A critical insight into the development pipeline of microfluidic immunoassay devices for the sensitive quantitation of protein biomarkers at the point of care

“…Therefore, they usually involve small sample volumes (µl, nl, pl, fl), a small size (submillimetre channels or capillaries), reduced energy consumption and a controlled microenvironment. 15 Current applications cover several scientific and commercial areas, including screening conditions for protein crystallisation, 16 high-throughput screening in drug development, 17 bioanalysis, 18 single cell analysis 19 and chemical synthesis, 20,21 to name a few.…”

Microfluidics as a new tool in radiation biology

“…The concentration of biomolecules can be controlled spatially and temporally, thus allowing for instance the generation of diffusion-based gradients of given molecules [29]. As such, microfluidics is widely used for studying resistance to chemotherapy, screening and optimizing drug combinations, and monitoring cellular responses [30–34]. However, few studies have used microfluidics to evaluate the effects of ionizing radiations on cells.…”