Core-shell microcapsules for iterative biological processing
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Solution Overview
Problem
Existing methods for processing biological entities and molecules in microcapsules face challenges such as disruptive degradation conditions that can harm encapsulated contents, and the inability to perform multiple iterative reactions without substantial dilution, leading to inefficiencies in downstream analysis.
Innovation Solution
Core-shell microcapsules with a polysaccharide-based shell and core, modified by cross-linking and hydrophilicity/hydrophobicity moieties, allow for mild degradation and efficient processing of biological entities and molecules, enabling multiple iterative reactions without significant dilution through controlled reagent exchange and release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If conventional microcapsule degradation methods are used, then the microcapsule shell can be degraded, but the encapsulated biological contents are harmed or degraded
Solution Approach 1:
The patent divides the microcapsule structure into two distinct components with different degradation properties: a shell polymer that is susceptible to enzymatic degradation and a core polymer that is resistant to the same degradation conditions. This segmentation allows selective degradation of the shell while protecting the core contents from harmful degradation effects.
Solution Approach 2:
The patent applies different chemical and physical properties to different parts of the microcapsule structure. The shell polymer is designed with specific functional groups and molecular weight characteristics that make it vulnerable to enzymatic degradation, while the core polymer has different properties that confer resistance. This local differentiation of material properties enables selective degradation behavior.
2Adaptability or versatility
If iterative reactions are performed in emulsions, then multiple reactions can be conducted, but substantial dilution occurs leading to inefficiency
Solution Approach 1:
The patent creates a universal microcapsule platform that can serve multiple functions across different reaction steps. The same microcapsule structure is used for encapsulation, reaction containment, and product release without requiring dilution or replacement of the core contents. The shell acts as a reusable barrier that can be selectively degraded at different stages of the reaction sequence.
Solution Approach 2:
The microcapsule shell acts as an intermediary barrier between the reaction environment and the encapsulated contents. It allows selective permeability and controlled exchange of reagents and products while maintaining the concentration of core contents. The shell mediates the interaction between external reagents and internal substrates, enabling iterative reactions without dilution.
3Ease of manufacture
If harsh degradation conditions are applied to microcapsule shells, then the shell can be degraded, but the microcapsule integrity and encapsulated contents are compromised
Solution Approach 1:
The patent converts the potential harm of harsh degradation conditions into a benefit by designing the shell polymer to be specifically vulnerable to mild enzymatic degradation. The shell is constructed with enzymatic cleavable bonds and appropriate molecular weight that allow it to be degraded under gentle conditions, transforming what would normally be a harmful process into a controlled and beneficial mechanism for capsule disassembly.
Solution Approach 2:
The patent utilizes parameter changes in polymer molecular weight and chemical composition to achieve differential degradation behavior. The shell polymer is selected with specific molecular weight ranges and functional group compositions that make it susceptible to enzymatic attack, while the core polymer has different parameters that confer resistance. This parameter differentiation enables selective degradation under mild conditions.
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 core-shell microcapsules maintain the integrity of encapsulated contents during degradation and facilitate multiple iterative reactions, enhancing the efficiency of downstream analysis by allowing predictable and efficient reagent replacement, thereby improving the processing and release of biological molecules.
Implementation Method 1
a shell polymer that includes a polysaccharide modified by cross-linking moieties
Implementation Method 2
Degradation is accomplished through contacting to an enzyme such as a glycosylase
Implementation Method 3
An example of such an enzyme described herein is a glycosidase, which degrades microcapsules as described above without chemically impacting the composition of the reaction products that they harbored
Implementation Method 4
a shell polymer that includes a polysaccharide modified by cross-linking moieties and optionally modified by hydrophilicity/hydrophobicity-modifying moieties
Data Source
AI summary
Provided herein are core-shell microcapsules useful for compartmentalizing biological molecules in solution. Also provided are processes for manufacturing core-shell microcapsules and methods for using core-shell microcapsules to compartmentalize and optionally process biological entities and molecules.