Microfluidic device to study cell transmigration under physiological shear stress conditions

Abstract

The development of new drug therapies relies on studies of cell transmigration in in vitro systems. Migration has traditionally been studied using two methods, the Boyden chamber and a shear flow chamber assay. Though, commonly applied in cell transmigration studies, they are far from imitating a natural migration process. Here we describe a novel in vitro cell transmigration microfluidic assay, which mimicks physiological shear flow conditions in blood vessels. The device was designed to incorporate the principles of both the Boyden chamber and the shear flow chamber assay, i.e. migration through the membrane under flow conditions. The 3D environment of migrating cells is imitated by injecting cell adhesion proteins to coat the membrane in the device. We tested the developed device with Jurkat cells migration towards medium supplemented with serum, and with chemokine induced lymphocytes migration. The applied continuous flow of cell suspension and chemoattractant ensures that the concentration gradient is maintained in time and space. The cell adhesion proteins used to enhance cell migration in the device were fibronectin and VCAM-1. We successfully observed a multistep transmigration process by means of the developed microfluidic migration assay. The presented device is inexpensive, easy to fabricate and disposable, having a potential to be applied in basic research as well as in the drug development process.

Biosensors in Health Care: The Milestones Achieved in Their Development towards Lab-on-Chip-Analysis

“…Cell based microfluidic technology is most suitable for cell migration assay and invasion assay applicable in drug screening. It can quantify the migrating cells in response to chemotactic gradient across a physical barrier [ 35 ]. Breast cancer cell detection at single-cell resolution was achieved using high density electrochemical impedance biosensor array for tumor cell detection [ 36 ].…”

Engineering approaches for studying immune-tumor cell interactions and immunotherapy

“…Some designs contain multiple cell reservoirs and migratory channels or porous layers to establish a chemotactic gradient, whereas others offer simple controlled environments for observing lymphocytes under flow. One example is that of a microfluidic device coated with adhesion molecules, through which T cells (the Jurkat leukemia line) were introduced by flow, either with or without chemokine gradients ( Kim et al, 2012 , Kwasny et al, 2011 ). Another simple microfluidic device observed PBMC-derived T cell chemotaxis in 2D, in response to gradients of CCL19 or CXCL12 created with a simple Y-shaped geometry ( Lin and Butcher, 2006 ).…”

Cell-Based Biosensors: Electrical Sensing in Microfluidic Devices

“…New gradient generating methods to study chemotactic [ 59 , 60 , 61 ] or haptotactic [ 62 ] cell migration are considered more advantageous than conventional methods such as the transwell assay [ 63 ]. A novel microfluidic migration device imitates the physiological conditions of cell transmigration ( Figure 5 ) [ 64 ]. The principles of a shear flow chamber were combined with the transwell assay in a microfluidic system that closely resembles the natural environment of migrating immune cells.…”

“…The chip was fabricated in PMMA and contained separate channels for cells and chemoattractants. This type of assay has application in drug screening [ 64 ].…”