Microfluidic 3d cell-culture platforms for drug response monitoring: potential applications for individualized cancer treatment

Shabnam Shahrivari,1 Neda saraygord-afshari,2,* Zeinab bagheri,3

1. Student Research Committee, Iran University of Medical Sciences
2. Department of Medical Biotechnology, Faculty of Allied Medical Sciences, Iran University of Medical Sciences
3. Assistant professor; Protein research center, Shahid Beheshti University, Tehran, Iran

Abstract

Introduction

Individualized monitoring of drug response is supposed as a main constituent of personalized treatment. current methods of drug monitoring (mtt, atp-bioluminescence, disc and …) are generally set to be performed in two-dimensional non-dynamic monolayer cultures in which many bio-effective determinants such as diffusion-based distribution, cell-cell and cell-matrix interactions are hindered and result in misleading judgments. the emergence of microfluidics, a technology capable of controlling small quantities of liquids in a variety of shapes and designs, provided us more real platforms mimicking the natural microenvironment (scales, shear stress, diffusion transport and …) and have fixed the limitations of traditional methods.

Methods

Three-dimensional cell cultures in glass/silicon, polymer or paper-based micro-platforms are created in gel (e.g., collagen gel) or gel-free supports (polycarbonate mesh micro-well, spheroid culture, direct-printed tissues and …). polymerization of gel supports could be controlled by ph and pre-incubation temperatures.

Results

In new micro-platforms dynamic medium perfusion has diminished the effect of medium-starved necrotic regions. gel-free micro-supports have overcome the limitations of transport across the thick and dense hydrogels. moreover, the existence of a linear correlation between the in-vivo ld50 and in-vitro ic50 of many studied drugs, indicates the power of microfluidic systems for predicting in-vivo ld50 values.

Conclusion

Microfabrication, instrumentation and investigation of drugs’ side effects on others organs are still challenging for biologists; but hopefully, microfluidic drug response devices, have the great potential to become a useful tool for clinics and can help efficiently to select an appropriate treatment.

Keywords

Microfluidic; cancer; three-dimensional cell culture; drug response assay;