Microfluidic Device for Isolating Target Entities via Segmented Capture and Release
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Solution Overview
Problem
Existing methods for isolating rare entities and their clusters from biological fluids are limited by their reliance on specific interactions between target entities and secondary entities, which can restrict the efficiency of capture and release processes.
Innovation Solution
The described techniques exploit interactions between target entities, secondary entities, and engineered surfaces to enable entity-specific isolation of target entities from biological fluids, allowing for non-specific interactions to be used in either capture or release stages while maintaining entity-specific isolation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If specific interactions between target entities and secondary entities are used for isolation, then entity-specific isolation is achieved, but the efficiency of capture and release processes is restricted
Solution Approach 1:
The patent divides the isolation process into two distinct stages: capture and release. During capture, non-specific interactions are used to efficiently collect target entities, while during release, specific interactions are activated to selectively release target entities. This segmentation allows each stage to optimize for its specific function, resolving the contradiction between efficiency and specificity.
Solution Approach 2:
The patent applies preliminary non-specific interactions during the capture stage to efficiently collect target entities before applying specific interactions for release. By performing the efficient capture action first, the system overcomes the limitation of traditional methods that rely solely on specific interactions for both capture and release.
2Productivity
If non-specific interactions are used for capture, then capture efficiency is improved, but entity-specific isolation may be compromised
Solution Approach 1:
The patent segments the isolation process into capture and release stages with different interaction mechanisms. Non-specific interactions are used exclusively for capture to maximize efficiency, while specific interactions are used exclusively for release to ensure entity-specific isolation. This segmentation resolves the contradiction by allowing each stage to use the most appropriate interaction type.
Solution Approach 2:
The patent introduces engineered surfaces as intermediaries that facilitate non-specific interactions during capture. These engineered surfaces act as mediators that enable efficient non-specific binding of target entities while allowing subsequent specific interactions to be applied for selective release, thus resolving the contradiction between efficiency and specificity.
3Device complexity
If limited interactions between target entities and secondary entities are used, then the isolation process is simpler, but the available interactions for capture and release are restricted
Solution Approach 1:
The patent introduces engineered surfaces with binding agents that can provide multiple types of interactions (non-specific and specific) within a single system. This multi-functionality allows the system to access a broader range of interactions without significantly increasing overall complexity, as the engineered surfaces serve multiple purposes in both capture and release stages.
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
These techniques provide a more efficient and flexible approach to isolating rare entities and their clusters by enabling a three-fold increase in available interactions for capture and release, thereby improving the overall isolation process.
Implementation Method 1
The capturing is accomplished using a size-based capture mechanism in a microfluidic device
Implementation Method 2
The capturing is also accomplished using a binding interaction between the secondary entities and a binding agent in a microfluidic device including a channel having an internal surface
Implementation Method 3
the capture and release mechanisms of many known TE isolation processes involve using interactions (e.g., antigen-antibody interactions) between the TEs and SEs
Implementation Method 4
flowing a reagent through the microfluidic device to weaken or break the specific binding interaction between the target entities and the secondary entities or weaken or break binding interactions within or between the secondary entities, thereby releasing the target entities from the target entity-secondary entity complexes
Data Source
AI summary
The present disclosure features systems and methods for isolating target entities (TEs) found in target entity-secondary entity complexes within a biological fluid by exploiting interactions between TE, secondary entities (SEs), and/or engineered surfaces (ESs). TE isolation involves a two-step process in which TE-SE complexes are initially captured using, e.g., size-based approaches or binding interactions between SEs and ESs, and then TEs are specifically released from the captured TE-SE complexes using, e.g., biochemical means, such as disassociating enzymes and/or binding inhibitors, or using physical properties of fluid flow, e.g., flow velocity and/or shear rate.