In vitro tissue plate
Inventors
Bobrow, Johanna • Thorsen, Todd • Walsh, David • Zook, Christina • SONG, Min Jae • Ferrer-Alegre, Marc • Michael, Sam • Tung, Yen-Ting • Boutin, Molly Elizabeth
Assignees
Massachusetts Institute of Technology • US Department of Health and Human Services
Publication Number
US-11767498-B2
Publication Date
2023-09-26
Expiration Date
2040-06-26
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Abstract
An in vitro tissue plate may include a well plate, a fluidic plate disposed on a bottom surface of the well plate, and a media manifold disposed on a bottom surface of the fluidic plate. The well plate may have at least two wells, including a tissue well and a waste well. The fluid plate may include a fluid channel extending between and fluidly connecting the tissue well to the waste well. The media manifold may include a one or more media outlets fluidly connected to the fluid channel. A tissue layer may be deposited in the tissue well. The tissue layer may include human cells such as neurovascular cells.
Core Innovation
The invention relates to an in vitro tissue plate comprising a well plate with at least two wells, including a tissue well and a waste well, a fluidic plate disposed on the bottom surface of the well plate, the fluidic plate having a fluid channel fluidly connecting the tissue well to the waste well via a plurality of tissue well pores disposed at different locations along the fluid channel.
The in vitro tissue plate allows a tissue layer, potentially composed of human cells such as neurovascular cells, to be deposited in the tissue well, enabling vascularization through controlled media flow delivered from the media manifold through the fluidic plate. This system supports nutrient delivery, waste removal, and vascularization in a way that models natural tissue environments.
The problem addressed is that conventional therapeutic studies for neurological and other disorders use animal models that have long development cycles and limited applicability to humans, sometimes resulting in late-stage failures. Existing organ-on-chip devices operate on a miniaturized scale that may be unrepresentative and are often incompatible with existing laboratory equipment, increasing deployment cost and limiting rapid testing.
The invention solves these problems by providing an in vitro tissue plate compatible with existing laboratory systems, which operates at scales more representative of human structures and allows rapid testing of therapeutic compounds. The design involves stacking multiple plates with fluid channels and pores aligned to facilitate media flow through tissue wells and waste wells, supporting tissue vascularization, waste extraction, and tissue monitoring, while also allowing easy assembly, use, disassembly, and cleaning.
Claims Coverage
The patent includes two independent claims detailing in vitro tissue plates with key structural and functional features.
Fluid channel connecting tissue and waste wells via tissue well pores
An in vitro tissue plate with a well plate comprising at least two wells (tissue and waste wells) and a fluidic plate having a fluid channel extending between and fluidly connected to both the tissue well and the waste well, wherein the connection to the tissue well is made via a plurality of tissue well pores disposed at different locations along the fluid channel.
Array of wells each with fluid channels connecting tissue and associated waste wells
An in vitro tissue plate with a well plate having an array of wells including multiple tissue wells and associated waste wells, and a fluidic plate having multiple fluid channels each connecting a tissue well to an adjacent waste well, where each tissue well connects to its respective fluid channel via a plurality of tissue well pores disposed at different locations along the fluid channel.
The independent claims collectively cover an in vitro tissue plate architecture where fluidic plates with fluid channels and multiple tissue well pores enable controlled fluid flow between tissue wells and waste wells, supporting tissue vascularization and waste removal across multiple wells arranged in arrays.
Stated Advantages
Allows for rapid testing of therapeutic compounds at scales representative of human body structures.
Provides a more reliable alternative to existing organ-on-chip devices and animal testing.
Compatible with existing laboratory analysis and automation equipment to facilitate deployment.
Simple to manufacture, assemble, use, and disassemble, enhancing scalability and cleaning.
Supports nutrient delivery, waste removal, and vascularization to form a natural tissue environment.
Enables monitoring of tissue via imaging windows and integration of sensors for parameters like electrical resistance and neuronal activity.
Documented Applications
Modeling neurological tissue or other body tissues in vitro for therapeutic testing using human cells such as neurovascular cells.
Testing therapeutic compounds for neurological disorders and other diseases using vascularized tissue layers in tissue wells.
Use in laboratory settings with existing equipment for drug development and therapeutic studies.
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