Microfluidic Tissue Screening for Sample Preparation Optimization
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Solution Overview
Problem
Existing biological assays for tissue analysis, such as ISH, FISH, DBIT-seq, scRNA-seq, and snRNA-seq, are time-consuming and resource-intensive due to variations in tissue preparation conditions, reagent performance, and tissue sample quality, which affect analyte amount, quality, and accessibility, necessitating a high throughput screening method to optimize these factors.
Innovation Solution
A microfluidic chip with multiple channels is used to apply varying reagents to different regions of a tissue sample, capturing images before and after reagent interaction, and analyzing the results to determine optimal preparation conditions, thereby marginalizing over biological variations and reducing the need for multiple tissue samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If multiple tissue samples are used to test different reagent concentrations, then statistical account for sample-to-sample variation is achieved, but the number of separate experiments increases significantly
Solution Approach 1:
The patent combines multiple experimental conditions (different reagent concentrations) onto a single tissue section by using a microfluidic device with multiple channels. Each channel applies a different reagent concentration to a specific region of the same tissue section, allowing simultaneous testing of multiple conditions without requiring multiple separate tissue samples or experiments.
2Measurement precision
If many reagent concentrations are tested on separate tissue samples, then optimal concentration is identified, but the quantity of tissue samples required increases
Solution Approach 1:
The patent segments the tissue section into multiple regions, with each region exposed to a different reagent concentration through dedicated microfluidic channels. This segmentation allows parallel testing of multiple conditions on a single tissue section, dramatically reducing the total number of tissue samples needed while maintaining the ability to identify optimal conditions.
3Stability of the object's composition
If traditional single-concentration permeabilization is used, then cellular integrity is maintained, but probe accessibility to analytes is limited
Solution Approach 1:
The patent systematically varies the concentration parameter of permeabilization reagents across different channels of the microfluidic device. By testing a range of concentrations (from low to high) on the same tissue section, the method identifies the optimal concentration that achieves the right balance between maintaining cellular integrity and enabling sufficient probe accessibility for reliable assay performance.
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
This method allows for rapid, cost-effective optimization of tissue preparation conditions, improving assay performance by minimizing sample usage and reducing optimization time, while providing a quality control assay for downstream analyses.
Implementation Method 1
A microfluidic chip with multiple channels is used to apply varying reagents to different regions of a tissue sample
Implementation Method 2
optically marking the tissue sample to identify a quality of the tissue sample and areas in the tissue sample affected by the flow of the plurality of reagents
Data Source
AI summary
The present disclosure relates generally to systems and methods for screening sample preparation conditions and, more specifically, high throughput screening of tissue sample preparation conditions.