Cell culture device with an array of microfluidic networks
Inventors
Pant, Kapil • Prabhakarpandian, Balabhaskar
Assignees
Publication Number
US-10012640-B2
Publication Date
2018-07-03
Expiration Date
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Abstract
A cell culture assay device can include: a substrate having a plurality of discrete microfluidic networks and a plurality of wells over the discrete microfluidic networks, each discrete microfluidic network having one or more wells fluidly coupled thereto, the wells extending upward from the discrete microfluidic networks; and a manifold body coupled with the substrate and having at least one fluid conduit pair for each microfluidic network and/or each well, each fluid conduit pair including a fluid inlet conduit and a fluid outlet conduit fluidly coupled to a corresponding microfluidic network and/or well. The substrate can be formed from a substrate base having the microfluidic networks coupled to a well plate having the wells associated with the microfluidic networks.
Core Innovation
A cell culture assay device comprises a substrate having a plurality of discrete microfluidic networks and a plurality of wells over the discrete microfluidic networks, each discrete microfluidic network having one or more wells fluidly coupled thereto, the wells extending upward from the discrete microfluidic networks; and a manifold body coupled with the substrate and having at least one fluid conduit pair for each microfluidic network and/or each well, each fluid conduit pair including a fluid inlet conduit and a fluid outlet conduit fluidly coupled to a corresponding microfluidic network and/or well. The substrate can be formed from a substrate base having the microfluidic networks coupled to a well plate having the wells associated with the microfluidic networks.
There is a well-recognized need to develop high-throughput cell-based assays with increased physiological fidelity in order to be able to improve studies on the effects of therapeutic agents or therapeutic delivery systems on cell cultures.
The invention provides arrays of two or more synthetic microvascular networks (SMNs) and/or idealized microvascular networks (IMNs) in microfluidic chip arrays together with manifold systems, reservoirs, pumps, and detection means to perform a wide variety of assays, including high-throughput cell-based assays for drug delivery, drug screening, drug toxicity, tumor metastasis, inflammation, thrombosis, and microvascular dysfunction, and to enable comparison of particle adhesion in healthy versus diseased microvascular networks.
Claims Coverage
One independent claim was identified (claim 1). The main inventive features extracted below reflect the structural elements recited in claim 1.
Bottom body portion forming a substrate with discrete microfluidic networks
A bottom body portion forming a substrate having a plurality of discrete microfluidic networks.
Middle body portion forming wells over the discrete microfluidic networks
A middle body portion over the bottom body portion forming a plurality of wells over the discrete microfluidic networks such that portions of each of the discrete microfluidic networks in the substrate form bottoms of the wells, each discrete microfluidic network having one or more wells there over and fluidly coupled thereto, the wells extending upward from the substrate and from the portions of discrete microfluidic networks.
Top body portion forming a manifold with inlet and outlet conduit networks
A top body portion over the middle body portion forming a manifold having at least one manifold inlet conduit network and at least one manifold outlet conduit network.
Fluid inlet conduits extending into wells and fluidly coupled to manifold inlet network
The at least one manifold inlet conduit network being fluidly coupled with at least one fluid inlet conduit, each fluid inlet conduit being located within and extending into at least one of the plurality of wells.
Fluid outlet conduits extending into wells and fluidly coupled to manifold outlet network
The at least one manifold outlet conduit network being fluidly coupled with at least one fluid outlet conduit, each fluid outlet conduit being located within and extending into the at least one of the plurality of wells.
At least one fluid conduit pair in a common well for each microfluidic network
There is at least one fluid conduit pair in a common well for each microfluidic network and/or each well, each fluid conduit pair including one fluid inlet conduit and one fluid outlet conduit fluidly coupled to a corresponding microfluidic network and/or well.
Claim 1 defines a multi-layer well plate device with a substrate of discrete microfluidic networks, wells that overlie network portions, and a manifold/top body providing inlet and outlet conduits that extend into wells so that at least one inlet/outlet conduit pair is provided per network/well.
Stated Advantages
Enables high-throughput cell-based assays with increased physiological fidelity.
Allows comparison of particle adhesion in healthy versus diseased microvascular network geometries.
Reduces reagent quantities by orders of magnitude compared with currently used techniques.
Permits development of plastic, disposable chips to eliminate concerns of cross-contamination.
Provides control of multiple fluids through multiple fluid pathways and compatibility with automated assay systems and detection means.
Documented Applications
Drug delivery assays and optimization of drug delivery in the microvasculature.
Drug screening and drug toxicity assays.
Tumor drug delivery and tumor metastasis studies, including assays to assess ability of delivery vehicles to reach and permeate cultured tumor cells.
Leukocyte adhesion cascade (LAC) assays to assess rolling, adhesion, spreading, and extravasation of leukocytes.
Assays for inflammation, thrombosis, and microvascular dysfunction.
Particle adhesion, uptake, and transmigration studies including particle adhesion mapping in SMNs and IMNs.
Organ simulation and multi-organ linked assays including simulations of liver, kidney, heart, lung, brain, stomach, intestine, and blood brain barrier.
High-throughput microfluidic chip array assays integrating manifolds, reservoirs, pumps, detection means, and data processing for automated screening.
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