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. 2021 Jun 4;21(12):2306–2329. doi: 10.1039/d0lc01305f

Summary of microfluidic publications concerning cell interaction/migration studies in I/O. Legend: Ab: antibody, BCG: Bacillus Calmette–Guérin, CAR-T: chimeric antigen receptor T cells, DC: dendritic cell, FPR1: frizzled-related protein, EMT: epithelial–mesenchymal transition, ICB: immune checkpoint blockade, IT: immunotherapy, NK: natural killer cells, NP: nanoparticle, PBMC: peripheral blood mononuclear cells, PDMS: polydimethylsiloxane, TCR: T cell receptor.

Author Topic IT type Model Chip material 2D/3D Static/perfusion Chip layout
Hsu et al., 2012 (ref. 33) Interactions between human lung cancer cells, macrophages and myofibroblasts General cell interactions/migration Cell lines PDMS 2D Pneumatic conduits and microvalves allowed control over conditioned medium available to each cell type Three cell culture chambers connected by y-shaped channel designed so all angles were at 120° to allow for symmetrical distribution of conditioned mediaInline graphic
Businaro et al., 2013 (ref. 34) Role of IRF-8 in communications between cancer and immune cells General cell interactions/migration Mixed PDMS 3D Static – manual pipetting Three cell culture chambers connected by an array of microchannels to permit chemical and physical contact amongst the two cell typesInline graphic
Agliari et al., 2014 (ref. 35) Benefit of integrating microfluidics with mathematical models to fully quantify experimental image data of real-time interactions between cells General cell interactions/migration Mixed PDMS 3D Static – manual pipetting Three cell culture chambers connected by an array of microchannels to permit chemical and physical contact amongst the two cell typesInline graphic
Mattei et al., 2014 (ref. 36) Role of IRF-8 in communications between cancer and immune cells General cell interactions/migration Mixed PDMS 3D Static – manual pipetting Three cell culture chambers connected by an array of microchannels to permit chemical and physical contact amongst the two cell typesInline graphic
Bai et al., 2015 (ref. 37) Effect of different macrophage subtypes on tumour aggregate dispersion (mimicking EMT) General cell interactions/migration Mixed PDMS 3D Static – manual pipetting Four cell culture chambers connected by an array of microchannels to permit chemical and physical contact amongst multiple cell types and allowing hydrogel formationInline graphic
Zhao et al., 2015 (ref. 38) Role of lactate on macrophage recruitment by and cytotoxicity against cancer cells (relevant to BCG vaccine immunotherapy) General cell interactions/migration Cell lines PDMS 3D Static – manual pipetting Four culture chambers with one media channel, each of which could house a different cell type. One matrigel channel and seven migration channels lay between each adjacent culture chamber with each chamber having its own media channelInline graphic
Liu et al., 2015 (ref. 39) Sensitivity of cancer cells to six different chemotherapy regimes General cell interactions/migration Cell lines PDMS 3D Microscale vacuum suction apparatus Culture channels interconnected by microchannels to allow exchange of soluble biological factors and metabolites between cell types. Four cell culture areas connected to a central pool through microchannels which functioned to provide a pressure balance during matrigel perfusionInline graphic
Vacchelli et al., 2015 (ref. 40) Effect of FPR1 expression on DC response to cancer cells after chemotherapy treatment General cell interactions/migration Mixed PDMS 3D Static – manual pipetting Three cell culture chambers connected by an array of microchannels to permit chemical and physical contact amongst the two cell typesInline graphic
Biselli et al., 2017 (ref. 41) Interactions between human breast and colon cancer cells and human PBMC General cell interactions/migration Mixed PDMS 3D Static – manual pipetting Three cell culture chambers connected by an array of microchannels to permit chemical and physical contact amongst the two cell typesInline graphic
Lucarini et al., 2017 (ref. 42) Effect of the drug decitabine (DAC) in enhancing anti-tumour effects of IFN through immune cell recruitment to the tumour site General cell interactions/migration Mixed PDMS 3D Static – manual pipetting Three cell culture chambers connected by an array of microchannels to permit chemical and physical contact amongst the two cell typesInline graphic
Chen et al., 2018 (ref. 43) Role of inflamed neutrophils in promoting cancer cell metastasis under perfusion conditions General cell interactions/migration Mixed PDMS 3D Perfusion of vascular network – manual pipetting Formation of 8 independent vascular beds with a single gel injection port connected by a branching network. Each sub-unit consisted of 4 parallel channelsInline graphic
Boussommier-Calleja et al., 2019 (ref. 44) Migration and development of various subsets of monocytes and monocyte-derived macrophages as targets for anti-metastatic immunotherapies and their effect on cancer cell extravasation General cell interactions/migration Cell lines PDMS 3D Perfusion of vascular network – manual pipetting Three parallel channels where monocytes can be observed over a 5 day period migrating through an endothelial barrier to interact with fibroblasts in a central hydrogel channelInline graphic
Lei et al., 2020 (ref. 45) Interactions between cancer and immune cells involved in tumour escape from immune surveillance General cell interactions/migration Mixed Paper layer on top of PMMA layer 3D Static – manual pipetting Paper layer containing 5 microreactors on top of a PMMA layer with hydrogel diffusion channelsInline graphic