Bi-layer multi-well cell culture platform
Inventors
Coppeta, Jonathan R. • Charest, Joseph L • Vedula, Else M. • Borenstein, Jeffrey T. • Spencer, Abigail June • Isenberg, Brett C.
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Assignees
Charles Stark Draper Laboratory Inc
Member
DraperDraper is an independent nonprofit engineering innovation company with a legacy spanning over 90 years, dedicated to delivering transformative solutions for national security, prosperity, and global challenges. Renowned for its pioneering work in guidance, navigation, and control (GN&C) systems, Draper partners with government, industry, and academia to engineer advanced technologies in space, defense, biotechnology, and electronic systems. The company leverages multidisciplinary expertise, digital engineering, and a collaborative approach to provide field-ready prototypes, mission-critical systems, and innovative research. Draper’s mission is to ensure the nation's security and prosperity by delivering sustainable, cutting-edge solutions that address the toughest problems of today and tomorrow, while fostering an inclusive and diverse workforce. Draper also invests in the next generation of innovators through robust educational programs, including internships, co-ops, and the Draper Scholars Program, integrating academic research with real-world problem-solving.
Draper is an independent nonprofit engineering innovation company with a legacy spanning over 90 years, dedicated to delivering transformative solutions for national security, prosperity, and global challenges. Renowned for its pioneering work in guidance, navigation, and control (GN&C) systems, Draper partners with government, industry, and academia to engineer advanced technologies in space, defense, biotechnology, and electronic systems. The company leverages multidisciplinary expertise, digital engineering, and a collaborative approach to provide field-ready prototypes, mission-critical systems, and innovative research. Draper’s mission is to ensure the nation's security and prosperity by delivering sustainable, cutting-edge solutions that address the toughest problems of today and tomorrow, while fostering an inclusive and diverse workforce. Draper also invests in the next generation of innovators through robust educational programs, including internships, co-ops, and the Draper Scholars Program, integrating academic research with real-world problem-solving.
Publication Number
US-12247190-B2
Publication Date
2025-03-11
Expiration Date
Abstract
The methods and systems described herein provide a cell culture platform with an array of tissue modeling environments and dynamic control of fluid flow. The cell culture platform includes an array of wells that are fluidically coupled by microchannel structures. The dynamically controlled flow of fluid interacts with cells grown within the microchannels.
Core Innovation
The invention provides a cell culture platform comprising an array of tissue modeling environments and dynamic control of fluid flow. The cell culture platform includes an array of wells that are fluidically coupled by microchannel structures, and a dynamically controlled flow of fluid interacts with cells grown within the microchannels. The platform is described as enabling conditioning of cells, maintaining growth, perfusing tissue, supplying media/fluids, administering mechanical forces and stresses, introducing therapeutic molecules, and collecting samples, and includes integrated real time sensors to enable characterization of tissue conditions and tissue response.
The apparatus is a well plate having a plurality of structural layers and a membrane separating two structural layers, wherein each tissue modeling environment includes a first, second, third and fourth fluid reservoir each configured to hold a column of fluid, a first microchannel fluidically coupling one pair of reservoirs and a second microchannel fluidically coupling the other pair of reservoirs, with at least a portion of the first microchannel overlapping at least a portion of the second microchannel across the membrane. The platform further includes a pump assembly arranged above the well plate with outputs and intakes extending into respective reservoirs for inducing distinct fluid flows through the tissue modeling environments. Methods for modeling tissue are described conceptually, including seeding different cell types and applying feeder flows and perturbations to replicate conditions such as hypoxia [procedural detail omitted for safety].
Claims Coverage
One independent claim is presented (an apparatus). The claim centers on a multi-layer well plate with overlapping microchannels across a membrane and a pump assembly arranged above the well plate providing per-environment outputs and intakes to induce sets of fluid flows.
Bi-layer well plate with overlapping microchannels
A well plate comprising a plurality of structural layers, and a membrane, wherein the membrane separates two structural layers, and the well plate defines an array of tissue modeling environments; wherein at least a portion of the first microchannel overlaps at least a portion of the second microchannel across the membrane.
Tissue modeling environment with four fluid reservoirs
Each tissue modeling environment includes a first fluid reservoir, a second fluid reservoir, a third fluid reservoir and a fourth fluid reservoir, each fluid reservoir configured to hold a column of fluid; a first microchannel fluidically coupling the first fluid reservoir to the second fluid reservoir; and a second microchannel fluidically coupling the third fluid reservoir to the fourth fluid reservoir.
Pump assembly arranged above well plate with per-environment inputs and outputs
A pump assembly arranged above the well plate that, for each tissue modeling environment, comprises a first output extending down into the first fluid reservoir for pumping a first fluid into the first fluid reservoir; a first intake extending down into the second fluid reservoir for pumping the first fluid out of the second fluid reservoir; a second output extending down into the third fluid reservoir for pumping a second fluid into the third fluid reservoir; and a second intake extending down into the fourth fluid reservoir for pumping the second fluid out of the fourth fluid reservoir.
Pump assembly configured to induce distinct sets of fluid flows
A pump assembly configured to induce a first set of fluid flows through a first set of tissue modeling environments in the array of tissue modeling environments and to induce a second set of fluid flows through the first set of tissue modeling environments in the array of tissue modeling environments.
The independent claim defines a multi-layer well plate with overlapping microchannels separated by a membrane, tissue modeling environments each with four reservoirs and paired microchannels, and a pump assembly positioned above the plate providing per-environment outputs and intakes to induce controllable sets of fluid flows through the array.
Stated Advantages
Dynamic control of fluid flow through arrays of tissue modeling environments to interact with cells grown within microchannels.
Compatibility with standard well plate arrangements to enable use with standard industry equipment such as micropipettes and imaging systems.
Integrated real-time sensors enabling direct quantification of culture conditions and tissue response without removing the platform from an incubator.
Ability to subject each tissue modeling environment to unique conditions for tissue culture optimization, drug screening, drug delivery analysis, and disease modeling.
Variable hydraulic resistance and time-varying controls to allow customized and pulsatile shear stress profiles across cultured cell populations.
Sensor-enabled measurement modalities including electrochemical impedance/TEER and optical sensing for monitoring tissue integrity and analytes.
Documented Applications
Tissue culture optimization tool in which each tissue modeling environment may be subjected to unique conditions to optimize cell cultures.
Drug screening array in which tissue in each tissue modeling environment can be screened against different drugs and/or different doses.
Drug delivery analysis in which fluid flow in each tissue unit can be configured to simulate distribution and delivery of a drug in the bloodstream to a tissue.
Disease modeling in which tissue modeling environments or groups of environments can be subjected to unique conditions to model varying disease states.
Modeling specific tissue arrangements by seeding complementary cell types on opposite sides of the membrane, including examples given such as renal proximal epithelial with endothelium, intestinal epithelium with endothelium, airway epithelium with endothelium, tumor with endothelium, liver sinusoid configurations, vascular tissue, oral and skin tissues, blood–brain barrier, and placental barrier.
Simulating hypoxic conditions by altering fluid flow rates or oxygen access to replicate hypoxia and measuring impacts on tissue structure and function.
Integrated sensing applications including TEER measurements and optical/phosphorescence sensors for analytes such as oxygen and glucose.
Arrayed multi-environment experiments including introducing biologically active agents at different amounts or flow conditions to measure effects across environments.
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