title: Sequentially pulsed fluid delivery to establish soluble gradients within a scalable microfluidic chamber array.
abstract: This work presents a microfluidic chamber array that generates soluble gradients using sequentially pulsed fluid delivery (SPFD). SPFD produces stable gradients by delivering flow pulses to either side of a chamber. The pulses on each side contain different signal concentrations, and they alternate in sequence, providing the driving force to establish a gradient via diffusion. The device, herein, is significant because it demonstrates the potential to simultaneously meet four important needs that can accelerate and enhance the study of cellular responses to signal gradients. These needs are (i) a scalable chamber array, (ii) low complexity fabrication, (iii) a non-shearing microenvironment, and (iv) gradients with low (near zero) background concentrations. The ability to meet all four needs distinguishes the SPFD device from flow-based and diffusion-based designs, which can only achieve a subset of such needs. Gradients are characterized using fluorescence measurements, which reveal the ability to change the curvature of concentration profiles by simple adjustments to pulsing sequence and flow rate. Preliminary experiments with MDA-MB-231 cancer cells demonstrate cell viability and indicate migrational and morphological responses to a fetal bovine serum gradient. Improved and expanded versions of this technology could form the basis of high-throughput screening tools to study cell migration, development, and cancer.
authors.affiliation: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Park
authors.affiliation: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Difeo
authors.affiliation: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Rand
authors.affiliation: The Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA ; Interdisciplinary Program of Bioengineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Crane
authors.affiliation: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA ; The Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA ; Interdisciplinary Program of Bioengineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Lu