Detecting cell-secreted growth factors in microfluidic devices using bead-based biosensors

Kyung Jin Son,Pantea Gheibi,Ali Rahimian,Alexander Revzin,Gulnaz Stybayeva

doi:10.1038/micronano.2017.25

Kyung Jin Son, Pantea Gheibi + Show 3 more

Open Access

https://doi.org/10.1038/micronano.2017.25

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Abstract

Microfluidic systems provide an interesting alternative to standard macroscale cell cultures due to the decrease in the number of cells and reagents as well as the improved physiology of cells confined to small volumes. However, the tools available for cell-secreted molecules inside microfluidic devices remain limited. In this paper, we describe an integrated microsystem composed of a microfluidic device and a fluorescent microbead-based assay for the detection of the hepatocyte growth factor (HGF) and the transforming growth factor (TGF)-β1 secreted by primary hepatocytes. This microfluidic system is designed to separate a cell culture chamber from sensing chambers using a permeable hydrogel barrier. Cell-secreted HGF and TGF-β1 diffuse through the hydrogel barrier into adjacent sensing channels and are detected using fluorescent microbead-based sensors. The specificity of sensing microbeads is defined by the choice of antibodies; therefore, our microfluidic culture system and sensing microbeads may be applied to a variety of cells and cell-secreted factors.

Highlights

Microfluidic devices for cell cultivation have garnered considerable interest because they are more economical in terms of cells and reagents, allow precise control over the composition and rates of flow streams, and may be automated through the use of valves/actuators[1]
Work in our laboratory demonstrated that embryonic stem cells, cancer cells, and primary hepatocytes exhibited markedly different phenotypes inside microfluidic devices operated under diffusion-dominated conditions compared with those inside standard multiwell plates[6,7,8]
This paper describes the development of a microfluidic device and sensing microbeads for the cultivation of cells and the on-chip detection of secreted growth factors (GFs)

Summary

Introduction

Microfluidic devices for cell cultivation have garnered considerable interest because they are more economical in terms of cells and reagents, allow precise control over the composition and rates of flow streams, and may be automated through the use of valves/actuators[1]. Work in our laboratory demonstrated that embryonic stem cells, cancer cells, and primary hepatocytes exhibited markedly different phenotypes inside microfluidic devices operated under diffusion-dominated conditions compared with those inside standard multiwell plates[6,7,8]. This phenotype enhancement was due, at least partly, to the rapid accumulation of endogenous signals inside microfluidic channels, underscoring the need for biosensors that locally monitor the levels of these signals. Another strategy has been developed to work with the “microengraving”

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