Temperature-Responsive Gelatin Layers for Selective Particle Capture and Release
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Solution Overview
Problem
Current methods for isolating specific target particle populations, such as living cells or microvesicles, from complex mixtures like whole blood are limited in their ability to achieve selective capture and release, often resulting in attached cells that are difficult to phenotype and genotype due to adhesion to substrates.
Innovation Solution
The development of particle capture systems involving a substrate with multiple layers of gelatin functionalized with binding pairs and nanostructures, allowing for selective capture and release of target particles through temperature or shear stress manipulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional substrate-based capture methods are used, then target particles can be captured, but the captured cells remain attached to the substrate making phenotyping and genotyping difficult
Solution Approach 1:
The patent uses temperature-responsive gelatin layers that change their binding properties based on temperature. At lower temperatures, the gelatin layers bind strongly to capture target particles. When heated to higher temperatures (above the gelatin melting point), the layers detach, enabling easy release of captured cells without mechanical scraping or harsh chemical treatments.
Solution Approach 2:
The invention employs a composite structure consisting of multiple gelatin layers with different functional properties. The first gelatin layer provides temperature-responsive binding, while subsequent layers enhance capture capacity. This composite material system enables both high capture efficiency and easy thermal release of target particles.
2Quantity of substance
If multiple layers of gelatin with binding pairs are used, then capture capacity increases, but system complexity increases
Solution Approach 1:
The capture system is divided into multiple functional layers: a first gelatin layer providing temperature-responsive binding, and additional gelatin layers that can be added to increase capture capacity. Each layer serves a specific function, allowing the system to be scaled by simply adding more layers rather than redesigning the entire structure.
Solution Approach 2:
The gelatin layers are functionalized with universal binding pairs (such as biotin-streptavidin) that can bind to various target particles depending on the specific antibodies or ligands used. This universal binding mechanism allows the same multi-layer structure to capture different types of target particles (circulating tumor cells, microvesicles, exosomes) without requiring fundamental structural changes.
3Reliability
If gelatin layers are used for capture, then selective binding is achieved, but release requires temperature increase or shear stress
Solution Approach 1:
The gelatin layers undergo a phase transition from a bound state at lower temperatures to a detached state when heated above their melting point. This phase change enables the release of captured target particles without requiring mechanical force or chemical treatments, simply by controlling the temperature of the system.
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
Enables high-yield, accurate capture and release of rare cells like CTCs, microvesicles, and exosomes, maintaining cell integrity for downstream assays, with high release efficiency and purity, suitable for various analytical methods.
Implementation Method 1
a first layer of gelatin bound to the substrate by physical adsorption
Implementation Method 2
functionalized with a plurality of first members of a binding pair; a second layer of gelatin wherein the gelatin is functionalized with a plurality of the first members of the binding pair and the second layer is bound to the first layer via a plurality of second members of the binding pair
Implementation Method 3
The captured particles can then be bulk released from the systems by melting the gelatin layers at an increased temperature, e.g., a temperature over 30° C., e.g., 37° C.
Implementation Method 4
The captured particles can also be selectively released from the systems by increasing a localized shear stress on the gelatin layers, e.g., by applying a frequency-controlled force with a microtip
Data Source
AI summary
Systems, methods, and devices for selective capture and release of target particles, e.g., living cells, from liquid samples, e.g., blood, are provided. The particle capture systems include a substrate; a first layer of gelatin bound to the substrate by physical adsorption, wherein the gelatin is functionalized with a plurality of first members of a binding pair; a second layer of gelatin wherein the gelatin is functionalized with a plurality of the first members of the binding pair and the second layer is bound to the first layer via a plurality of second members of the binding pair that are associated with the first members of the binding pair on both the first and the second layers; and a plurality of nanostructures bound to the second members of the binding pair and to one or more particle-binding moieties that selectively bind to the target particles.