Concentration gradients in microfluidic 3D matrix cell culture systems

Abstract

Microfluidic technology enables the creation of well-defined cell culture environments, which integrate the control of multiple biophysical and biochemical cues for designing novel in vitro assays. Growth-factor concentration gradients play a critical role in a wide range of biological processes ranging from development to cancer, guiding cell migration and influencing cell signaling. We present a microfluidic device capable of generating stable concentration gradients in a 3D matrix, while allowing for direct imaging of cellular behavior. The design consists of polydimethylsiloxane microchannels interconnected through 3D matrices. Optical access of the 3D matrix permits direct observation of invasive properties of cells seeded inside the channels or embedded in the matrix. An important characteristic of the microfluidic platform is the capability to generate reproducible, stable and quantifiable concentration gradients that are essential for systematic studies of soluble factor signaling in chemotaxis as...