SynTumor is a 3D tissue model for real-time visualization and quantitative assessment of cell-cell and cell-drug interactions in a physiologically and morphologically realistic tumor microenvironment. The system enables (a) circulation in the microvasculature, (b) transport across the vessel walls, and (c) delivery to the tumors. Starting with scans of vascular networks incorporated with interstitial and tissue/tumor spaces, the SynTumor 3D tissue model creates an in-vitro tumor microenvironment akin to a viable histological slice.

The SynTumor 3D Cancer model has the following benefits:

  • Side by side architecture enables quantitative real-time visualization
  • Physiological leaky vasculature with engineered porous structures
  • Morphologically realistic in vivo based architecture
  • Physiologically realistic convective and diffusive transport
  • Microfluidic platform with ultra-low consumable volumes
tumor-microenvironment-500
Create a realistic 3D co-culture with real-time monitoring of cell-cell interactions between tumor, stromal, vascular, and immune cells.

Examples of Models Functionalized in SynTumor Devices

3Dtumor-hela
Endothelial cells cultured in the vascular channels. 3D HeLa cells cultured on microfabricated scaffolds
Syntumor cancer model
Tumor-Endothelial Interactions in microvascular networks
BTM2
Idealized co-culture chips- Endothelial cells in vascular channel-tumor cells in tissue chamber
syntumor 3 chamber-metastasis
Multi-chambered model for assessing metastatic potential of tumors

PRODUCT PURCHASING OPTIONS

Chips: Depending on your specific research applications you can select from the idealized IMN2 (radial or linear) or microvascular (SMN2) network chip configurations in single or multi-chamber formats. Chips can be selected based on whether 2D (IMN2, SMN2 chips) or 3D (IMN3, SMN3 chips) tumor growth is needed. Additionally, chips with multi-chambers are also available.

Kits: All the basic components required to run SynTumor assays can be purchased in a kit. Two Kit formats are available.

Starter Kit: Select this for your first-time purchase

  • 10 SynTumor chips (Choice of IMN2 radial, IMN2 linear or SMN2 microvascular network chips)
  • Accessories including tubing, clamps, needles, and syringes
  • Pneumatic priming device (required for priming tubing to remove air)

Assay Kit: Select this kit format if you have previously purchased the pneumatic priming device

  • 10 SynTumor chips (Choice of IMN2 radial, IMN2 linear or SMN2 microvascular network chips)
  • Accessories including tubing, clamps, needles, and syringes

Schematics of the devices used to develop tumor on a chip models. Apical chamber (outer channels-blue) are for culture of vascular (endothelial cells) while basolateral chamber (central chamber-red) are for culture of tissue, stromal or immune components. Porous architecture enables communication between the vascular and tissue cells.

Idealized Co-Culture Network Chips (IMN2 radial)

imn2 radial tumor
IMN2 radial Chips: 2um slits (Cat#: 102004) or 8um pillars (Cat#: 102012). 200μm Outer channel, 1.8mm tissue chamber, 50μm slit spacing, 50μ travel (space between channels), 100μm depth (height). . 8um pillar design- 200um Outer Channel Pillars, 8um Gap, 50um Travel—–8/100 um height of pillars.

Starter Kit

Based on IMN2 radial 2um slit chip:

$1,700Add to cart

Based on IMN2 radial 8um pillar chip:

$1,700Add to cart

Assay Kit

Based on IMN2 radial 2um slit chip:

$1,500Add to cart

Based on IMN2 radial 8um pillar chip:

$1,500Add to cart

SMN2 microvascular network Co-Culture Chips

smn2 micro
SMN2 Co-culture microvascular network: 2 or 8um pillars. 2 um Height Barrier: 20um Dia-3um Separation, 100 um Depth. Cat#: 105007. 8 um Height Barrier: 10um Dia-50um Separation, 100 um Height. Cat#: 105015

Starter Kit

Based on SMN2 2um pillar chip:

$2,100Add to cart

Based on SMN2 8um pillar chip:

$2,100Add to cart

Assay Kit

Based on SMN2 2um pillar chip:

$1,800Add to cart

Based on SMN2 8um pillar chip:

$1,800Add to cart

Idealized Co-Culture Network Chips (IMN2 Linear)

linear tumor
Idealized Co-Culture Network (IMN2 Linear) Chips: 3 or 5 um slits 200um-500um-200um Channel Widths; 50um Travel (distance between channels) – 3um or 5um slits 50um Separation, 100um Depth (height) Cat#: 108011 (3um) and 108007 (5um)

Starter Kit

Based on IMN2 Linear 3um slit chip:

$1,700Add to cart

Based on IMN2 Linear 5um slit chip:

$1,700Add to cart

Assay Kit

Based on IMN2 Linear 3um slit chip:

$1,500Add to cart

Based on IMN2 Linear 5um slit chip:

$1,500Add to cart

A recent publication in Scientific Reports from the Lipke and Arnold Labs at Auburn University titled A Microvascularized Tumor-mimetic Platform for Assessing Anti-cancer Drug Efficacy” reports on using the SynVivo microfluidic platform to develop and validate a three dimensional in vitro breast cancer model with a tumor-mimetic microvascular network. The model recapitulates the in vivo heterogeneity in tumor perfusion and resulting differences in cellular morphology, growth, and drug responses.

A Microvascularized Tumor-mimetic Platform for Assessing Anti-cancer Drug Efficacy
Authors: Shantanu Pradhan, Ashley M. Smith, Charles J. Garson, Iman Hassani, Wen J. Seeto, Kapil Pant, Robert D. Arnold, Balabhaskar Prabhakarpandian & Elizabeth A. Lipke.
Scientific Reports Volume 8, Article number: 3171(2018)

This significant body of work resulted from the collaboration of Dr. Lipke’s tissue engineering background with Dr. Arnold’s cancer biology and drug delivery expertise. According to Dr. Lipke “Replicating the pathophysiological architecture and non-uniform drug distribution of native vascularized breast tumors is critical for a realistic tumor model. SynVivo’s microvascular networks provided just the right environment to monitor the therapeutic circulation in the vasculature, transport across the vessel walls, and delivery to 3D tumors, which renders it ideally suited as a platform for performing cellular assays and drug screening”.

Dr. Arnold adds, “The ability of these engineered cancer tissues for long-term culture, heterogeneous morphology and anti-cancer drug response provides a unique perspective to understand how nanomedicines may interact with various tumors. This will enable development of therapeutics with improved efficacy and minimal toxicity while improving patient outcomes, thereby providing an in vitro model analogous to the heterogeneity observed in vivo”.

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.
Pradhan
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.

Scientific Publication Shows the Utility of the SynVivo Platform for Rapid Screening of Drug Delivery Systems

A Biomimetic Microfluidic Tumor Microenvironment Platform Mimicking the EPR Effect for Rapid Screening of Drug Delivery Systems
Authors: Yuan Tang, Fariborz Soroush, Joel B. Sheffield, Bin Wang, Balabhaskar Prabhakarpandian & Mohammad F. Kiani
Scientific Reports 7, Article number: 9359 (2017) doi:10.1038/s41598-017-09815-9

The SynVivo platform was used to develop a biomimetic microfluidic tumor microenvironment (bMTM) comprising co-culture of tumor and endothelial cells in a 3D environment. The platform consists of a vascular compartment featuring a network of vessels cultured with endothelial cells forming a complete lumen under shear flow in communication with 3D solid tumors cultured in a tumor compartment. Endothelial cell permeability to both small dye molecules and large liposomal drug carriers were quantified using fluorescence microscopy. Endothelial cell intercellular junction formation was characterized by immunostaining. Endothelial cell permeability significantly increased in the presence of either tumor cell-conditioned media (TCM) or tumor cells. The magnitude of this increase in permeability was significantly higher in the presence of metastatic breast tumor cells as compared to non-metastatic ones. Immunostaining revealed impaired endothelial cell-cell junctions in the presence of either metastatic TCM or metastatic tumor cells. Our findings indicate that the bMTM platform mimics the tumor microenvironment including the EPR effect. This platform has significant potential in applications such as cell-cell/cell-drug carrier interaction studies and rapid screening of cancer drug therapeutics/carriers.

bmtm
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.
tcm graph
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.

There are many areas of oncology research that can benefit by using the SynVivo-Tumor model. These include (1) basic research for understanding of the tumor microenvironment comprising of cell viability, proliferation, invasion and tumor-stromal and tumor-endothelium interactions; and (2) drug delivery screening for efficacy and toxicity.

Understanding the Tumor Microenvironment

Cancer metastasis is a multi-step process that starts with the cancer cells leaving the original tumor site and migrating to distant parts of the body via the bloodstream or the lymphatic system.

This process involves complex steps, including breaking of the extracellular matrix by the metastatic tumor cells, escape into the circulatory system, adhesion to the vascular wall at remote locations, followed by migration/invasion into tissue and subsequent proliferation.

SynVivo provides a realistic microenvironment to allow real-time study of these phenomena.

Syntumor cancer model
nucleus red

The tumor-endothelium co-culture mimics the tumor microenvironment and in this example captures degradation of the extracellular matrices by the aggressive tumor toward the vasculature channels, a precursor to extravasion and metastasis

Tumor cell Growth and Invasion

2D Tumor Growth

Tumor cell invasion

3D Tumor Growth

Tumor Perfusion via the vascular network in microvascular network chips

Metastatic Potential Characterization

tumor-metastasis
Left: Highly Metastatic Tumor. Right: Non-metastatic Tumor. Monitor in real-time tumor cells phenotypic behavior. A metastatic tumor rapidly spread to adjacent chambers (left) while non-metastatic tumor does not (right). Inset image shows stained images highlighting elongated protrusions for metastatic tumor in contrast to localized for non-metastatic tumor. Use this assay to screen tumor cell populations for their metastatic potential.

Drug Delivery Screening, Efficacy and Toxicity

Drugs or delivery vehicles (nanoparticles, polymers, liposomes, etc.) can be injected via the vascular channel or directly on the tumor under both static and physiological fluid flow conditions and their responses can be observed in real-time mimicking the in vivo conditions.

gene-delivery
Screening of polymers for gene delivery accurately reproduces in vivo responses (candidate A and B both perform well when directly injected into tumor, while under vascular injection candidate A performs well and candidate B performs poorly).

Assay Development and Screening using SynTumor 3D cancer models

Models Available

  • Monoculture using tumor cell lines
  • Co-Culture with endothelial cells
  • Tri-Culture with stromal and endothelial cells
  • Culture tumor cells with stromal, endothelial and immune cells

Assays

  • Efficacy and toxicity screening
  • Tumor-induced vascular leakage
  • Tumor Intravasation and extravasation
  • Tumor Immune interactions
  • Biomarker analysis

Sample Endpoints

Vascular permeability using fluorescent-tagged molecule, Cell viability, biomarker analysis with immunocytochemistry, collect and provide cells or effluents at assay endpoint for downstream genomic, proteomic or metabolomic analysis.

Contact us for a Services quote!

Articles About This Model:

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.

ACS Applied Nano Materials 2 (4), 1844-1856 (2019).

A Microvascularized Tumor-mimetic Platform for Assessing Anti-cancer Drug Efficacy.

Author(s): Shantanu Pradhan, Ashley M. Smith, Charles J. Garson, Iman Hassani, Wen J. Seeto, Kapil Pant, Robert D. Arnold, Balabhaskar Prabhakarpandian & Elizabeth A. Lipke.

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

A Biomimetic Microfluidic Tumor Microenvironment Platform Mimicking the EPR Effect for Rapid Screening of Drug Delivery Systems

Author(s): Yuan Tang, Fariborz Soroush, Joel B. Sheffield, Bin Wang, Balabhaskar Prabhakarpandian & Mohammad F. Kiani

Scientific Reports 7, Article number: 9359 (2017)

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

Author(s): Jarvis M, Arnold M, Ott J, Pant K, Prabhakarpandian B, Mitragotri S.

Bioeng Transl Med. 2017 Sep 26;2(3):268-277

Rational Design And Development Of A Peptide Inhibitor For The PD-1/PD-L1 Interaction

Author(s): Rebecca J. Boohaker, Vijaya Sambandam, Isaac Segura, James Miller, Mark Suto, Bo Xu

Cancer Letters 434 (2018) 11e21

Synthetic Tumor Networks for Screening Drug Delivery Systems

Author(s): B. Prabhakarpandian, MC Shen, J. Nichols, C. Garson, I. Mills, M. Matar, J. Fewell, K. Pant.

J Control Release. 2015, 201, 49-55

Manuals For This Model:

3D Tissue and Organ-on-Chip Models-BROCHURE
SYNTUMOR 3D MODEL (IDEALIZED NETWORK) TECHNICAL MANUAL
SYNTUMOR 3D MODEL (MICROVASCULAR NETWORK) TECHNICAL MANUAL

SynTumor 3D Model – Starter Kits

Includes consumables (10 chips, 100ft tubing, 25 slide clamps, 50 blunt tip needles and 50 1 ml syringes). Starter kits will also include the pneumatic priming device (required for running SynTumor assays).

Note: Does not include other required consumables such as cells, media and matrix. Laboratory equipment required includes incubators, inverted microscopes, and syringe pumps.
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SynTumor 3D Model – Assay Kits

Includes consumables (10 chips, 100ft tubing, 25 slide clamps, 50 blunt tip needles and 50 1 ml syringes).

Note: Does not include other required consumables such as cells, media and matrix. Laboratory equipment required includes incubators, inverted microscopes, and syringe pumps.
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SynTumor 3D Model – Chips

Purchase single chips.

Note: Does not include other required consumables such as tubing, clamps, syringes, needles, cells, media and matrix. Laboratory equipment required includes incubators, inverted microscopes, and syringe pumps.
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