Pressurizing Device for Antibody Penetration in Thick Tissue
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Solution Overview
Problem
Current methods for 3D tissue imaging face challenges such as poor penetration of antibody molecules in human tissues, variability in procurement and fixation techniques, and internal auto-fluorescence, leading to inconsistent results and limited depth of staining in thick tissue samples.
Innovation Solution
A pressurizing device and method that applies elevated pressure to a staining solution containing biomolecule-specific agents, enhancing the penetration of antibodies and improving staining quality in thick tissue samples by forming an air-tight cavity and using a retainer to secure the sample receptacle, with options for cooling and temperature sensing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If passive diffusion of antibodies is used for staining thick tissue samples, then the staining process is simple, but the penetration depth and consistency of antibody molecules are poor
Solution Approach 1:
The system transitions from static passive diffusion to dynamic active transport by applying alternating electric fields that move antibodies through the tissue sample, dramatically improving penetration depth and uniformity while maintaining operational simplicity through automated field application
Solution Approach 2:
The patent replaces the natural passive diffusion mechanism with an electric field-based transport system, using electrical energy to drive antibody molecules through thick tissue samples, achieving consistent penetration depths of several hundred micrometers to millimeters
2Manufacturing precision
If electric fields are used to enhance antibody penetration, then the penetration depth improves, but the system complexity and reproducibility issues increase
Solution Approach 1:
The system uses a multi-electrode array that can generate various electric field patterns (DC, AC, pulsed) to serve multiple staining functions, reducing the need for multiple specialized devices while maintaining high penetration efficiency across different tissue types and antibody configurations
Solution Approach 2:
The system controls reproducibility by precisely regulating electric field parameters (voltage, frequency, pulse duration) and tissue conditions (clearing state, antibody concentration), creating standardized protocols that eliminate variability while managing system complexity through automated parameter control
3Manufacturing precision
If system-wide binding controlling agents are used, then antibody distribution improves, but the method complexity and potential harm to tissue increase
Solution Approach 1:
The patent replaces chemical binding control agents with physical electric field control, using electrical forces to guide antibody distribution without introducing harsh chemicals that could damage tissue, thereby achieving uniform distribution while preserving tissue integrity
Solution Approach 2:
The electric field acts as an intermediary mechanism that controls antibody-tissue interactions without direct chemical contact, mediating the distribution process through physical forces rather than chemical reagents, thus avoiding tissue damage while maintaining precision
4Length of stationary object
If tissue clearing techniques are applied to enable 3D imaging of thick samples, then the imaging depth increases, but the staining quality and antibody penetration remain limited
Solution Approach 1:
The system applies continuous or repeated electric field stimulation during the staining process, maintaining active transport of antibodies throughout the entire incubation period, ensuring consistent penetration and staining quality throughout the thick cleared tissue sample
Solution Approach 2:
The patent uses dynamic electric field application during and after clearing to actively drive antibodies into the cleared tissue matrix, leveraging the enhanced permeability from clearing while providing the mechanical force needed for deep, uniform penetration that passive diffusion cannot achieve
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 pressurizing device significantly increases the depth and intensity of antibody penetration and staining in thick tissue samples, reducing background noise and improving imaging depth by up to two-fold, while maintaining tissue integrity and reducing artifacts.
Implementation Method 1
applying elevated pressure to a staining solution containing biomolecule-specific agents, enhancing the penetration of antibodies
Implementation Method 2
with options for cooling and temperature sensing
Data Source
AI summary
Provided herein are systems, devices, and methods for improved treatment of tissue, such as brain tissue. The improved treatment described herein can result in improved tissue penetration of various compounds and chemicals, such as stains and immunohistochemistry reagents. For example, provided herein is a pressurizing device that may include a chamber body having an opening in one of a top and a sidewall of the body, and may also include a chamber lid covering the opening and releasably coupled to the chamber body proximate the opening. The chamber lid and chamber body form an air-tight cavity. The pressurizing device may also have an inlet passing through one of the chamber body and the chamber lid and into the air-tight cavity. The device may also include a retainer coupled inside the air-tight cavity and configured to releasably couple to at least one tissue sample receptacles.