In vitro cancer models that help you bridge the gap between 2D cell culture and animal models for better immuno therapies.
Cancer-on-chip technology can reproduce the tumor microenvironment, immune cell infiltration and dynamic drug application.
The rise of human-specific cancer therapies has made it harder to model anti-cancer drug candidates. Human organ-on-chip models can help to reproduce the complex behavior of cancer cells in vivo.
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Cancer-on-chip highlights
Human cancer model
Targets of novel anti-cancer drugs are rarely conserved in animals and require human-specific systems to model the treatment effectiveness and cancer progression.
Tumor microenvironment
The tumor microenvironment often interferes with drug delivery and helps the tumor evade the immune system. Our models include the TME to clearly assess the effectiveness of novel drugs.
Dynamic drug application
Administration of drug via perfusion system to model intra-venous drug application in a human body in vitro.
Immune cell infiltration
Immune cells can be circulated and can infiltrate tumor spheroids via an endothelial layer to mimic immune cell migration and polarization in vitro.
3D tumor structure
Our spheroid-on-chip method allows the integration of tumor spheroids into a multilayer biochip with a vasculature, immune cells, a tumor microenvironment and a channel for sampling or feeding of the tumor.
Model set up & features
The Dynamic42 cancer-on-chip comprises three compartments: a vascular for perfusion, a microcavity channel able to host 25 tumor spheroid or organoids and a third channel which can be used for spheroid feeding and sampling of tumor conditioned supernatant without disturbing the tumor spheroids themselves. The vasculature is formed by an endothelial lining and can include tissue-resident macrophages.
The Dynamic42 cancer-on-chip can be operated with various cell sources. Additionally, one biochip can cultivate two cancer models in parallel. Please get in contact for further details.
Endothelial Cell
Tumor spheroid
/ Up to 2 x 25 tumor spheroids on one biochip.
/ Immobilization of tumor spheroids, enabling repetitive analysis of the same tumor over time
/ Endothelial channel to recreate the in vivo vascular barrier for nutrition, oxygen supply, immune cell interaction and drug administration
/ Perfusion through vasculature to avoid shear stress on tumor spheroids
/ Spheroid feeding and sampling of tumor conditioned supernatant without disturbance of tumor spheroids
/ Live imaging of tumor, e.g. monitoring mitochondria membrane potential during treatment
/ All tumor spheroids are easily recovered through cutting of the biochip after the experiment for end point analysis
/ Usage of magnetic bead allows for sampling of tumor spheroids during an experiment.
/ Independent perfusion of top and bottom channel allows complex model setups
Workflow
Case study PDAC
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies, with a five-year survival rate of less than 10%. Here, we present a microfluidic system, developed with the HHU (Düsseldorf), that recapitulates the multicellular tumor microenvironment of PDAC for dynamic drug administration and immune cell invasion via an endothelium.
The PDAC tumor spheroids
(A) The vasculature remains stable under flow with an addition of 2.5% Matrigel(TM) in the presence of PANC-1 spheroids. Stained the endothelial markers VE-cadherin (green), von Willebrand factor (vWF) (red) and the nuclear dye DAPI (blue) were stained. Shown as MIP of a Z-stack. Scale bar is 200 μm (B) IF staining of 3D PDAC spheroids after 72 h cultivation on the biochip shown as maximum intensity projection (MIP) of a Z-stack. DAPI-staining of nuclei (blue); staining of the proliferation marker Ki67 (green); staining of fibroblast marker α-SMA (purple); merging of all three channels. Scale bar is 500 μm.
Dynamic drug application of Vorinostat (SAHA)
Dynamic administration of the HDAC inhibitor SAHA in the PDAC biochip model. (A) Investigation of the influence of increasing SAHA concentrations on the vasculature integrity. VE-cadherin (green), von Willebrand factor (red) as marker of the endothelial cells, DAPI for staining the cell nuclei (blue). Shown as MIP of a Z-stack. Scale 200 μm. (B) SAHA was introduced at indicated concentrations into the perfusion of a cell free BC003 Biochip. At 24 h SAHA concentration was determined by LCMS. Grey bars indicate concentrations after perfusion. White bars indicate concentration of the input controls. Experiment was run in triplicate, controls in duplicate. © (C) Permeability assay of HUVEC layer after treatment with SAHA for 72 h. FITC dextran assay was performed to measure the barrier integrity of the HUVEC layer after 72 h treatment with 1.5, 2.5, or 3.5 μm SAHA. FITC dextran solution was added into the top channel. After 1 h the leakage into the mid-channel was determined via fluorescence measurement. (D) Investigation of the viability of the 3D PDAC spheroids in the biochip in the presence of SAHA after 72 h administration. Error bars indicate the standard error of the mean, n=3;**** = p ≤ 0.0001.
Immune cell invasion and polarization
Polarization of monocytes after perfusion in the biochip. (A) IF staining of co-culture spheroids after perfusion with primary monocytes over the endothelial layer. Co-culture spheroids were seeded into the biochip and primary monocytes were perfused over the endothelial layer in the TOP channel. After 72 h of perfusion the co-culture spheroids were stained for the tumor cell marker pan-cytokeratin (purple), the fibroblast marker α-SMA (blue), the immune cell marker CD45 (green), and the M2 marker CD163 (red); merging of all four channels. Shown as MIP of a Z-stack. Scale bar is 500 μm. (B) Marker characterization of polarized macrophages. Polarization after infiltration into PDAC spheroids was analyzed by flow cytometry 72 h after perfusion with monocytes in the biochip. Macrophages identified as CD11b + and CD45 + were analyzed for surface expression of CD163, CD206, CD86, and HLA-DR. Infiltrated cells were compared to unstimulated monocytes as controls. Error bars indicate the standard errors of the mean of three independent experiments, with **= p ≤ 0.01; *** = p ≤ 0.005.
Key results
/ Drug Testing: Vorinostat (SAHA), a histone deacetylase (HDAC) inhibitor, exhibited dose-dependent cytotoxicity against PDAC spheroids while preserving endothelial barrier integrity, confirming its efficacy in a 3D microenvironment.
/ Immune Modulation: Monocytes successfully infiltrated the tumor spheroid fibrotic shell and polarized into M2 macrophages, reflecting the immunosuppressive phenotype characteristic of PDAC’s TME.
Read the paper
Related Products
/ Three-channel biochip
/ Including one channel with microcavities (⌀ 800μm)
/ Cultivation of up to 2×25 tumor spheroids in parallel
/ Two culture chambers per biochip (Multi-organ models or duplicates)
/ Low-adsorption material biochip (for compound testing)
Build human in vitro disease and infection models with the DynamicOrgan System. A system that includes pumps, biochips, consumables and the freedom to keep using standard laboratory equipment. A dynamic system that will help you get greater and more meaningful insights into human biology swiftly and without capital spending.
