Ion-Exchange Resin Tissue Labeling for Deep, Uniform Probe Binding
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Solution Overview
Problem
Existing tissue labeling techniques face challenges in achieving uniform labeling of specific biomolecules in large, intact biological samples due to the slow diffusion of antibodies and their depletion at the surface, leading to non-uniform labeling profiles.
Innovation Solution
A tissue labeling device and kit that utilize an ion exchange resin to control the binding affinity of labeling probes, increasing it gradually over time through interactions with a labeling solution, combined with electrophoresis and temperature control to ensure uniform penetration and labeling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibodies are used for labeling probes, then specific labeling of protein antigens is achieved, but diffusion into tissue is slow and labeling uniformity deteriorates
Solution Approach 1:
The patent changes the physical-chemical parameters of the labeling solution by adjusting pH and ionic strength. By controlling these parameters, the binding affinity between antibodies and antigens is modulated to allow deeper penetration into tissue while maintaining specific labeling capability. The solution transitions from high to low binding affinity as it penetrates tissue, enabling uniform distribution.
Solution Approach 2:
The patent applies preliminary action by pre-conditioning the labeling solution with specific buffers and additives before application. The solution is prepared with optimal pH and ionic composition that facilitates initial penetration, and the binding affinity is预先 controlled to prevent surface depletion while ensuring eventual specific binding throughout the tissue.
2Length of stationary object
If antibody concentration is increased to improve labeling coverage, then labeling depth improves, but surface depletion worsens
Solution Approach 1:
The patent uses parameter changes in the solution composition, specifically pH and ionic strength gradients, to control antibody-antigen binding dynamics. The solution is formulated so that binding affinity decreases with depth penetration, allowing antibodies to distribute uniformly rather than being depleted at the surface. This enables effective labeling at deeper tissue levels without requiring excessive initial antibody concentration.
3Strength
If binding affinity is increased to improve labeling strength, then labeling intensity improves, but penetration depth deteriorates
Solution Approach 1:
The patent applies dynamics by making the binding affinity a dynamic parameter that changes during the labeling process and with spatial depth. The solution is formulated so that binding affinity is initially low to allow penetration, then increases as the solution penetrates deeper into the tissue. This dynamic adjustment ensures both adequate penetration depth and sufficient binding strength for effective labeling.
Solution Approach 2:
The patent changes physical-chemical parameters (pH, ionic strength) of the labeling solution to control binding affinity dynamically. By adjusting these parameters, the solution transitions from a state of low binding affinity (favoring penetration) to high binding affinity (favoring strong labeling), enabling both deep penetration and strong binding strength to be achieved sequentially.
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 method achieves high uniformity of labeling in large tissues by controlling the binding affinity of probes, allowing for accurate imaging, particularly in interior regions, by ensuring probes penetrate deeply and bind uniformly.
Implementation Method 1
An ion-exchange resin interacts with a labeling solution to gradually introduce ions into the labeling solution that cause the binding affinity of the labeling probes to increase over time
Implementation Method 2
The device may also employ electrophoresis to increase diffusion of the labeling probes into the tissue sample
Implementation Method 3
Ex vivo delivery of antibodies or molecular dyes relies on simple diffusion of labeling probes (molecules) into the tissue
Data Source
AI summary
A tissue labeling device, method of operation, and a tissue labeling kit enables tissue labeling for microscopy imaging with high labeling depth and uniformity. A tissue labeling device circulates a labeling solution through a tissue sample and concurrently circulates the labeling solution through an ion exchange resin. An ion exchange process increases the binding affinity of the labeling probes in the labeling solution over time as the labeling solution penetrates deeper into the tissue sample. A tissue labeling kit may operate on similar principles. The tissue labeling kit includes a container (e.g., a tube) having an ion exchange resin layer and a hydrogel layer over the ion exchange resin layer. The labeling solution and tissue sample is added to the container to enable the binding affinity sweep in which the hydrogel operates to control the sweep rate of the binding affinity.