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

Summary of microfluidic publications concerning mechanistic and mode of action studies I/O. Legend: Ab: Antibody, BCG: Bacillus Calmette–Guérin, CAF: cancer associated fibroblasts, CAR-T: chimeric antigen receptor T cells, COP: cyclo olefin polymer, CTC: circulating tumour cells, DC: dendritic cell, FPR1: frizzled-related protein, EMT: epithelial–mesenchymal transition, ICB: immune checkpoint blockade, IFNα: interferon alpha, IT: immunotherapy, MDOTS: murine-derived organotypic tumour spheroids, NK: natural killer cells, NP: nanoparticle, PBMC: peripheral blood mononuclear cells, PDMS: polydimethylsiloxane, SCC: squamous cell carcinoma, TCR: T cell receptor, TIL: tumour-infiltrating lymphocytes, TME: tumour microenvironment.

Author and ref no. Topic IT type Model Chip material 2D/3D Static/perfusion Chip layout
Zervantonakis et al., 2012 (ref. 64) Examining the mode of action by which macrophages influence tumour cells via TNF release Ab 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
Lu et al., 2015 (ref. 65) DC/tumour fusions to elicit anti-tumour immunity DC vaccine Cell lines PDMS 3D Perfusion – syringe pump, electrodes 960 pairs of trapping channels. Cell electrofusion device that can pair and fuse homogeneous and heterogeneous cellsInline graphic
Jenkins et al., 2017 (ref. 66) Novel TBK1/IKKε inhibitor mechanisms ICB Primary 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
Kulasinghe et al., 2017 (ref. 67) Non-invasive method to identify candidates for anti-PD-L1 therapy. Involved blood sample from a SCC patient to determine the PD-L1 expression of CTCs ICB Mixed PDMS 3D Perfusion – syringe pump Spiral microfluidic channelInline graphic
Parlato et al., 2017 (ref. 68) Effect of biochemical stimuli on DC migration. IFNα-conditioned dendritic cells for use as a therapeutic vaccine in combinations with romidepsin DC vaccine Cell lines PDMS 3D Static – manual pipetting Five cell culture chambers connected by an array of microchannels to permit chemical and physical contact amongst the two cell typesInline graphic
Aref et al., 2018 (ref. 62) ICB in conjunction with small hydrophobic molecules ICB Primary COP plastic device from AIM BIOTECH 3D – MDOTS viability affected by PD-1 blockade in 3D microfluidic culture but not in 2D culture using 384-well plates 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
Huh et al., 2018 (ref. 69) Mimicking the drug toxicity-induced pulmonary oedema seen in cancer patients after IL-2 treatment Cytokines-IL-2 Cell lines PDMS 2D Perfusion – syringe pump, vacuum pump Two parallel microchannels separated by a thin and porous ECM coated membrane, permitting perfusion and cyclic stretching of the cell layers attached to a flexible membrane, mimicking physiological breathing motionsInline graphic
Moore et al., 2018 (ref. 63) Study of the mechanisms by which anti-PD-1 antibodies augment the cytotoxicity of TILs ICB Primary COC plastic EVIDENT device 3D Perfusion – pressure-pump driven system Tumour fragment trapped in V-designed channelsInline graphic
Nguyen et al., 2018 (ref. 70) Effects of trastuzumab and CAF on cancer cell proliferation, cell death and motility. Effects of co-culture with CAF and immune cells in 3D Ab Mixed PDMS 3D – the drug decreased mitosis, tumour growth and apoptosis. In 2D experiments the drug did not inhibit the growth of cancer cells Perfusion – syringe pump Five cell culture chambers connected by an array of microchannels to permit chemical and physical contact amongst the two cell typesInline graphic
Yin et al., 2018 (ref. 71) Antibodies for the identification of the stage of cancer progression and determination of the optimum course of treatment Ab Mixed PDMS and patterned nickel micropillar substrate 3D Syringe pump and magnets used to immobilize antibodies onto micropillars of device Chaotic mixer with a patterned nickel micropillar substrateInline graphic
Wimalachandra et al., 2019 (ref. 46) Chemokine-loaded folic-acid conjugated NPs for targeting folic-acid receptor expressing cancer cells and attracting immune cells towards the target cells Chemokine-loaded NPs 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