Synthetic microfluidic systems for tumor metastasis
Inventors
Prabhakarpandian, Balabhaskar • Pant, Kapil
Assignees
Publication Number
US-10641761-B2
Publication Date
2020-05-05
Expiration Date
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Abstract
A method of assaying metastasis can include: providing a device of one of the embodiments; introducing the at least one cancer cell into the at least one internal chamber or at least one fluid channel; and studying metastasis of the at least one cancer cell. Optionally: introducing cancer cells into a first internal chamber; detecting escape of the cancer cell from the first internal chamber into the fluid channel; detecting migration of the cancer cell through the fluid channel; detecting adhesion of the cancer cell to a coating on the fluid channel; detecting invasion of the cancer cell into a second internal chamber from the fluid channel; or visualizing metastasis of the cancer cell with a visualization device.
Core Innovation
The present invention includes a device and methodology to study and characterize tumor cell metastasis in physiologically realistic microenvironments (e.g., MIcrofluidic MEtastatic Assay or MIME). The device is configured with an internal chamber and surrounding capillary channels to simulate the cancer metastasis multi-step process, and allows study and visualization in real time of cancer cells escaping from a tissue chamber into a microfluidic circulatory pathway, adhesion of cancer cells to a vascular wall, migration/invasion into other tissue chambers, and subsequent proliferation in tissue chambers. The device and methodologies provide an environment to facilitate studying the interplay between these cellular activities and can provide a platform for developing therapeutics for cancer and inflammatory/autoimmune diseases.
The device can include an optically transparent or transmissive plastic body containing a microcirculatory network with complex fluid channel morphology including branching and loops and a simulated vascular wall with an endothelial layer growing thereon. The device embodiments include porous walls formed by posts/pillars and gaps that fluidly couple internal chambers (tissue spaces) and fluid channels, and any area surrounded by the flow channels can be the tissue space. The device can be fabricated with PDMS and modeled after vascular networks and can be used with automated protocols for real-time visualization and quantitation of metastasis. [procedural detail omitted for safety]
Claims Coverage
This independent claim (claim 1) includes 5 main inventive features extracted from the claim language.
Cell culture device with at least one first internal chamber
At least one first internal chamber configured for an internal cell culture.
First fluidic flow channel network surrounding the first internal chamber
A first fluidic flow channel network fluidly coupled with the at least one first internal chamber, comprising at least one first fluid flow channel bordering and surrounding the at least one first internal chamber, each first fluid flow channel having a single first fluid flow inlet and single first fluid flow outlet and being continuous between the single first fluid flow inlet and single first fluid flow outlet; and at least one first wall separating the at least one first internal chamber and the at least one first fluid flow channel, the at least one first wall having first gaps that fluidly couple the at least one first internal chamber with the at least one first fluid flow channel, wherein each first wall is continuous from the single first fluid flow inlet and single first fluid flow outlet.
Second fluid flow channel surrounding the first fluid flow channel
At least one second fluid flow channel bordering and surrounding the at least one first fluid flow channel such that the at least one first fluid flow channel is between the at least one second fluid flow channel and at least one first internal chamber, each second fluid flow channel having a single second fluid flow inlet and single second fluid flow outlet and being continuous between the single second fluid flow inlet and single second fluid flow outlet; and at least one second wall separating the at least one first fluid flow channel and at least one second fluid flow channel, the at least one second wall having second gaps that fluidly couple the at least one first flow fluid channel and at least one second fluid flow channel, wherein each second wall is continuous from the single second fluid flow inlet and single second fluid flow outlet.
Introducing at least one cancer cell into the device
Introducing at least one cancer cell into the at least one first internal chamber or first fluidic flow channel network.
Monitoring metastasis of the cancer cell
Monitoring metastasis of the at least one cancer cell.
Claim 1 covers a microfluidic cell culture device having nested fluidic channel layers with porous, gap-containing walls that fluidly couple internal tissue chambers and surrounding flow channels, together with the steps of introducing at least one cancer cell into the device and monitoring metastasis.
Stated Advantages
Reproduce physiological features of an appropriate microenvironment for simulated fluid shear and size/topology.
Allow analysis and visualization of the entire metastatic process from breaking away to invasion that can be quantitative.
Provide real-time visualization of cell migration, attachment, and invasion.
Enable simple studies with high throughput and reduced reagent/cell use using disposable chips.
Provide a platform to screen new anti-tumor therapeutics and to study targeted drug delivery to tumor cells or the vascular endothelial layer.
Documented Applications
Studying and characterizing tumor cell metastasis in physiologically realistic microenvironments.
Studying targeted therapy to tumor cells and inhibiting metastasis, including screening agents for anti-metastasis properties.
Drug screening using nanopolymeric vehicles for delivery of drugs or inhibitory siRNA to tumor cells and assessing nanoparticle-based tumor drug delivery.
Assay protocols for analysis of circulation, adhesion, migration, invasion, and metastasis with physiological flow derived from in vivo structures.
Applications in bioMEMS development, hemodynamic and cellular analysis, microcirculation, tumor biology, targeted therapy, oncology, angiogenesis, inflammation, wound healing, and radiation damage research.
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