Microscale Cell-Laden Matrices via Aqueous Two-Phase System
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Solution Overview
Problem
Current methods for evaluating fibrotic remodeling events require large volumes and fail to consider key factors such as environmental conditions and epigenetics, limiting high-throughput screening and disease diagnosis for fibrosis and wound healing disorders.
Innovation Solution
The development of a method using an aqueous two-phase system (ATPS) to form microscale cell-laden matrices by mixing enzymes and proteins with cells, allowing for controlled crosslinking and imaging of remodeling events, enabling high-throughput analysis and diagnostic capabilities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If current approaches are used to evaluate fibrotic remodeling events, then the evaluation can be performed, but large volumes are required which hinders high-throughput adaption
Solution Approach 1:
The invention divides the evaluation system into microscale units (microtiter plates with individual wells) that can be processed in parallel. Each well contains a miniaturized version of the fibrotic system, allowing simultaneous evaluation of multiple samples and conditions, thereby achieving high-throughput screening while using minimal volumes of each reagent.
Solution Approach 2:
The invention changes the scale parameter from macroscopic to microscopic dimensions. By reducing the system size to microscale (nanoliter to picoliter volumes), the patent enables thousands of parallel experiments to be conducted simultaneously, transforming a low-throughput macroscopic assay into a high-throughput microscopic platform.
2Loss of information
If current approaches are used to evaluate fibrotic remodeling events, then the evaluation can be performed, but key contributing factors such as specific environmental factors, epigenetics, or senescence are not considered
Solution Approach 1:
The microtiter plate platform serves multiple functions simultaneously: it controls environmental factors through standardized well conditions, accommodates different cell types and genetic modifications, enables parallel testing of multiple conditions, and allows integration of various measurement techniques. This multi-functional design captures comprehensive biological information without proportionally increasing system complexity.
Solution Approach 2:
The invention allows different environmental conditions, genetic modifications, and cell types to be established in individual wells while maintaining a unified platform. Each well can have customized local conditions (different sera, growth factors, cell lines) while the overall system remains manageable through standardized protocols and automated processing.
3Manufacturing precision
If an aqueous two-phase system is used to form microscale matrices, then precise control over crosslinking is achieved, but the system complexity increases
Solution Approach 1:
The aqueous two-phase system acts as an intermediary that separates the crosslinking chemistry from the cellular environment. The phase boundary controls thrombin diffusion and activity, providing precise spatial and temporal control over fibrin crosslinking. This intermediary system simplifies the overall process by decoupling matrix formation from cell culture conditions, despite the apparent complexity of maintaining two phases.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enables precise control over fibrin matrix formation and degradation, facilitating high-throughput screening and diagnosis of fibrosis and wound healing diseases by providing detailed insights into cellular behavior and matrix remodeling.
Implementation Method 1
an aqueous two-phase system ('ATPS') comprising a mixture of a first material and a second material having a phase boundary between the first and second materials
Implementation Method 2
at least one of the enzyme or the cells in the first material can be configured to diffuse into the second material
Data Source
AI summary
An exemplary embodiment of the present disclosure provides A method and system for forming a microscale cell-laden matrix using an aqueous two-phase system (“ATPS”) comprising a mixture of a first material and a second material having a phase boundary between the first and second materials. The method can comprise mixing an enzyme with the first material, mixing a protein with the second material, and mixing a suspension comprising cells with one of the first material or the second material, wherein the enzyme, protein, and suspension comprising cells generate the cell-laden matrix and wherein the first material comprises a first polymer comprising polyethylene glycol and the second material can be a second polymer selected from the group consisting of dextran, polyvinyl pyrrolidone, polyvinyl alcohol, or ficoll.