Infection and immunity on a chip: a compartmentalised microfluidic platform to monitor immune cell behaviour in real time

Abstract

Cells respond to their environments and self-organise into multicellular assemblies with dedicated functions. The migratory and homing response of cells to soluble ligands can be studied by using different techniques, but for real time studies of complex multicellular self-organisation, novel and simpler systems are required. We fabricated a flexible open access microsystem and tested the design by studying cell recruitment from an immune cell reservoir towards an infectious compartment. The two compartments were connected by a network of bifurcated microchannels allowing diffusion of signalling molecules and migration of cells. Bacterial filters were incorporated in the design to prevent bacteria and activated cells from entering the network, permitting migration only from the recruitment reservoir. The fabricated microsystem allows real-time continuous monitoring of cellular decision-making based on biologically produced gradients of cytokines and chemokines. It is a valuable tool for studying cellular migration and self-organisation in relation to infections, autoimmunity, cancer, stem cell homing, and tissue and wound repair.

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

“…In 2015, another lung-on-a-chip technology investigated cell recruitment and migration during infection and immune responses [171]. Instead of introducing a pro-inflammatory mediator, tumor necrosis factor-α (TNF-α) was directly added to system to replicate the live, cellproduced immune responses that closely mimic in vivo conditions [172,173].…”

Biocompatibility assay of cellular behavior inside a leaf-inspired biomimetic microdevice at the single-cell level

“…To display the biocompatibility of this leaf-inspired microdevice, we further cultured human melanoma cells, which are highly life threatening 41 and cause 80% of deaths related to skin cancer. 42 Through professional video processing [43][44][45][46][47] of the cellular biophysics at the single-cell level (e.g., cell deformation, extracellular communication, cell division, cell mobility, and membranal 48-51 local shear stress), we affirmed a good cellular activity in the microdevice, proving that such a device can be applied for downstream biomedical studies.…”

High-throughput screening approaches and combinatorial development of biomaterials using microfluidics

“…Gopalakrishnan et al [64] developed a real-time screening platform for studying infection and immunological response through tracking of cell migration. In this design, a chemokine gradient was created, propagating from a source, and representing therewith infectious foci (Mycobacterium avium), to study migration of adherent macrophages, non-adherent T-cell hybridomas and dendritic cells.…”