SynTumor 3D Cancer Model​ – Recreating The Tumor Microenvironment

Variations in flow pattern and perfusion profiles within tumor-mimetic chips. Shear rate maps of (A) High perfusion chip (HPC) and (B) Low perfusion chip (LPC) obtained by computational fluid dynamics modeling reveal differences in local shear rates in various channels of the microfluidic network, specifically around the primary tumor chamber (grey region). Perfusion heat map of the primary tumor chamber of (C) HPC and (D) LPC revealed spatial differences in concentration of fluorescent TRITC-dextran perfused from the adjoining vascular channels into the tumor chamber (CTP indicates central tumor port). (E,F) Schematic representation of quantified perfusion profiles in HPC and LPC in different regions of the primary tumor chamber. Arrows indicate direction of vascular perfusion and profile measurement. Red and orange arrows represent relatively higher perfusion regions, green arrows represent intermediate perfusion regions and blue and purple arrows represent low perfusion regions. (G,H) Relative fluorescence intensity profiles in various regions of HPC and LPC corresponding to colored arrows in (E) and (F) Revealed prominent differences in perfusion capability in the various regions of the chips. Intensity values above 1.0 indicate relative accumulation or entrapment of fluorescent dye within the primary tumor chamber.

Drug-testing in tumor-mimetic chips. Reduction in viable cell density due to (A) Doxorubicin and (B) Paclitaxel. Viable MDA-MB-231 cell density (co-encapsulated with fibroblasts) following doxorubicin treatment was significantly lower in the HPC design as compared to the LPC design; this trend was not observed for the MCF7 cells (co-encapsulated with fibroblasts). No significant differences in viable cell density in either chip design were observed following paclitaxel treatment. Reduction in viable tumor area (area occupied by viable cells) due to (C) Doxorubicin and (D) Paclitaxel treatment revealed that doxorubicin caused a significant reduction in viable tumor area for both the cell lines in the HPC design as compared to the LPC design. Paclitaxel treatment caused a significant reduction in viable tumor area of MCF7 cells but not MDA-MB-231 cells. (E) Drug cytotoxicity on endothelial cells demonstrates greater cytotoxicity of doxorubicin as compared to paclitaxel in both chip designs. (F) Decrease in viable cell density of both cell lines in static 3D well plate culture.

Schematic of the bMTM (A) with magnified view of the vascular compartment, vascular-tumor compartment interface and the tumor compartment (B). Optical image of the bMTM (C) with HBTAEC cultured in the vascular compartment (D) and MDA-MB-231 cultured in the tumor compartment (E). HBTAEC cultured under flow in the vascular compartment of bMTM form a complete lumen as shown with 3D reconstruction of confocal images of HBTAEC cultured in bMTM stained with f-actin (green) and Draq5 (red) after 4 days in culture maintained under flow of 0.05μl/min (F–I); images are shown with a Y-axis rotation of 0, 60, 180 and 240 degrees in (F,G,H and I) respectively.

Tumor conditioned media (TCM) (48h treatment) from highly metastatic MDA-MB-231 tumor cells increased liposome extravasation into the tumor compartment as indicated by the ratio of fluorescent liposome intensity in the tumor compartment to the vascular compartment (panel A). Liposomes extravasated more after MDA-MB-231 conditioned media or TNF-α treatment, but were not affected by TCM obtained from non-metastatic MCF-7 tumor cells (panels B–E). Data are presented as mean±SEM (n=3). *Significant difference by ANOVA.

2D Tumor Growth

Tumor cell invasion

3D Tumor Growth

Rapid Assessment of Nanoparticle Extravasation in a Microfluidic Tumor Model

Author(s): Mai N. Vu, Pradeep Rajasekhar, Daniel P. Poole, Song Yang Khor, Nghia P. Truong, Cameron J. Nowell, John F. Quinn, Michael Whittaker, Nicholas A. Veldhuis, and Thomas P. Davis.

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Scientific Reports Volume 8, Article number: 3171(2018)

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Scientific Reports 7, Article number: 9359 (2017)

Microfluidic Co-Culture Devices To Assess Penetration Of Nanoparticles Into Cancer Cell Mass

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Cancer Letters 434 (2018) 11e21

Synthetic Tumor Networks for Screening Drug Delivery Systems

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