Dissolvable Hydrogel for High-Purity Cell Separation
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Solution Overview
Problem
Current cell separation techniques face challenges in achieving high purity and yield while maintaining cell function, particularly in isolating specific cell populations from complex environments, and often result in residual affinity tags that impede cell proliferation and viability.
Innovation Solution
An affinity chromatography cell sorting system utilizing a biocompatible dissolvable hydrogel that binds target cells without leaving residual affinity tags, allowing for high-purity and high-yield cell separation with minimal functional impact, using a substrate that liquefies upon decreased availability of a crosslinking agent.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If magnetic separation is used for cell isolation, then cell separation can be achieved, but residual magnetic beads remain attached to purified cells and impede proliferation and reduce viability
Solution Approach 1:
The patent extracts and removes the harmful residual magnetic beads from the cell isolation process by using a dissolvable hydrogel substrate that can be completely dissolved after cell capture, leaving no residual affinity tags attached to purified cells
Solution Approach 2:
The patent changes the physical state of the substrate from solid (hydrogel) to dissolved state by controlling the availability of crosslinking agents, enabling complete removal of the substrate after cell capture without leaving residual tags
2Manufacturing precision
If affinity chromatography with solid substrates is used, then high cell purity can be achieved, but the substrate cannot be removed and cells cannot be released for downstream applications
Solution Approach 1:
The patent makes the substrate dynamic by enabling it to transition from a solid hydrogel state during cell capture to a dissolved state for cell release, allowing the same substrate to serve both capture and release functions
Solution Approach 2:
The patent changes the physical state of the substrate by controlling crosslinking agent availability, transitioning from solid hydrogel during capture to dissolved state for release, enabling complete substrate removal
3Quantity of substance
If physical separation techniques are used for pre-purification, then concentration can be achieved, but specificity is low and large-scale processing is difficult
Solution Approach 1:
The patent uses a composite system combining hydrogel material with immobilized binding units (antibodies, aptamers, or ligands) to achieve both concentration capability and high separation specificity through selective molecular recognition
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
The system effectively isolates target cells with high purity and viability, retaining their functional capacity, and is scalable for clinical applications, avoiding the limitations of residual affinity tags and inefficient large-scale processing.
Implementation Method 1
a substrate, e.g., a porous substrate, attached to a binding unit configured to bind a surface of a target cell
Implementation Method 2
wherein all or a portion of the substrate liquefies upon decreased availability of a crosslinking agent
Implementation Method 3
a chelator for a cation that crosslinks the substrate, such as EDTA, EGTA, sodium citrate, BAPTA
Data Source
AI summary
The invention features a substrate and compositions, kits, devices, and methods employing the substrate that produces an isolated population of cells from a general population. The isolated population is enriched for one or more target populations. Substrate is can be liquefied and allows recovery of unlabeled, viable, and functional cells.