Discrete microenvironment chamber
Inventors
Assignees
Publication Number
US-12070747-B2
Publication Date
2024-08-27
Expiration Date
2041-12-17
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Abstract
The present invention provides a discrete microenvironment chamber (DIMIC) configured to accurately mimics the microenvironment of poorly perfused tissue. In one embodiment, the DIMIC of the present invention is further designed to allow the extraction of cells and media from different local environments for any type of biochemical analysis.
Core Innovation
The invention discloses a discrete microenvironment chamber (DIMIC) device engineered to accurately mimic the microenvironment of poorly perfused tissue, such as those observed in ischemic conditions in vivo. The DIMIC consists of a chamber with defined structural components—including a bottom layer, sidewalls, two end walls, and a top plate—with specific dimensional relationships and strategically positioned openings and ports. This configuration allows for the culture of cells under controlled gradients of nutrient supply and metabolic waste removal, recreating spatially heterogeneous environments similar to those found in pathological tissues.
A key challenge addressed by this invention is the lack of experimental models capable of recreating essential features of the tissue microenvironment, particularly the gradients of ischemia that occur in vivo, while enabling the sampling of cells and media from defined locations for biochemical analysis. Existing in vivo and conventional in vitro models fail to capture both the physiological gradients and allow for site-specific sampling without disturbing environmental conditions. The DIMIC meets this need by enabling extraction of cells and media from discrete local environments, supporting comprehensive and localized biochemical analysis.
The DIMIC features removable cell trays with perforations that allow easy separation into multiple sectors, each of which can be analyzed separately to preserve spatial information about the cellular microenvironment. The ports connected to the chamber are of varying lengths to facilitate sampling across the ischemic gradient. Furthermore, the DIMIC is designed to be versatile, scalable, and affordable, supporting a wide variety of cell types and experimental formats, and enabling analyses such as flow cytometry, RNA sequencing, proteomics, and metabolomics from discrete regions within a single culture system.
Claims Coverage
The patent contains two independent claims that define the primary inventive features of the DIMIC device and its method of use.
Discrete microenvironment chamber with plurality of ports and removable perforated cell tray
The device comprises: - A chamber constructed with a bottom layer, two sidewalls, a first end wall, a second end wall, and a top plate, with the bottom layer connected at peripheral edges to the other elements. - The first end wall incorporates a plurality of openings positioned between the bottom layer and the top plate. - A plurality of ports, each extending outward from the first end wall and fluidly connected to one of the openings, wherein each port has a different length to allow extraction from multiple local environments. - At least one removable cell tray located in the chamber, the tray further comprising perforations that allow it to be split into different sectors for separate analysis.
Method for analyzing effects of ischemia on a cell population using the DIMIC device
The method includes: 1. Providing a discrete microenvironment chamber device as disclosed, with a chamber, a plurality of ports of different lengths fluidly connected to individual openings, and at least one removable perforated cell tray. 2. Introducing and culturing cells into the chamber, specifically on the bottom layer. 3. Using at least one port to extract cells and culture media from different local environments within the chamber. 4. Removing the cell tray from the chamber and splitting it into different sectors to enable separate analysis of the cells from each sector.
The claims broadly cover a device that mimics microenvironmental gradients using a structured chamber with offset ports for spatial sampling and removable, sector-dividable cell trays, along with a method for culturing and analyzing cells in spatially distinct environments to assess the effects of ischemia.
Stated Advantages
Accurately mimics the microenvironment of poorly perfused tissue, including gradients of ischemia.
Allows extraction and analysis of cells and media from different local environments, preserving spatial information.
Enables study of tissue ischemia and pathological changes with cellular and molecular resolution.
Versatile, scalable, modular, and affordable system for a range of experimental needs.
Facilitates high-throughput screens and multiplexing by adapting dimensions and modular design.
Supports a wide range of analytical methods, including flow cytometry, sequencing, proteomics, and metabolomics.
Permits analysis of cellular behavior in gradients that are physiologically relevant.
Documented Applications
Screening-based identification of novel therapeutic targets.
Discovery and validation of disease biomarkers.
Screening of key genes or molecular players relevant to adaptation and survival under ischemic conditions.
Modeling the tumor microenvironment and studying resistance to chemotherapy.
Cancer immunotherapy research.
Study of the effect of vascular stroke on neurons and brain damage.
Study of the effect of ischemia on tissue damage during viral infections.
Study of the role of inflammation on cell degeneration and tissue damage.
Study of the role of oxidative stress and other metabolic changes in drug resistance.
Study of the role of oxidative stress and DNA damage.
Study of metabolic immunosuppression during viral infection.
Study of the effect of the metabolic microenvironment on stem cell differentiation.
Study of regulation of tissue damage and regeneration.
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