Hydrogel-Coated Microspheres for Spatial Transcriptomics
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Solution Overview
Problem
Current spatial transcriptomics platforms face limitations due to the low oligonucleotide capture probe loading capacity and optical interference issues with solid microspheres, which hinder sensitivity and image quality in spatially resolved analysis of biological samples.
Innovation Solution
Development of hydrogel-coated features with a crosslinked polymer and moieties, such as oligonucleotides or organic functional groups, encapsulating solid particles like microspheres, enhancing capture probe density and optical properties to improve sensitivity and image quality.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If solid microspheres are used as features for capture probe immobilization, then the features provide uniform size distribution and are commercially available, but the oligonucleotide loading capacity is limited and the capture probe concentration is too low to support cellular assays at desired sensitivity
Solution Approach 1:
The patent applies porous hydrogel materials to coat the solid microsphere surface, creating a porous structure that dramatically increases the surface area available for oligonucleotide probe immobilization. The hydrogel matrix provides numerous binding sites while maintaining porosity for reagent diffusion, thereby increasing loading capacity without compromising assay sensitivity
Solution Approach 2:
The patent creates a composite structure by coating solid microspheres with hydrogel material. This composite approach combines the mechanical stability and uniform size distribution of solid microspheres with the high surface area and functional versatility of hydrogel, achieving both ease of handling and high oligonucleotide loading capacity
2Ease of manufacture
If solid microspheres are used as features, then they are commercially available in various sizes and materials, but their optical properties interfere with staining and imaging, obstructing or obscuring histological features and spatial biomolecule data
Solution Approach 1:
The porous hydrogel coating allows light to pass through more effectively than solid microsphere material, reducing optical interference. The porous structure scatters and transmits light differently, improving image quality and allowing histological features to be clearly visualized while maintaining the microsphere's mechanical properties
Solution Approach 2:
The hydrogel-coated microsphere composite combines the manufacturing advantages of solid microspheres with the optical transparency of hydrogel material. The hydrogel layer acts as an optical window that allows light to pass through the microsphere without significant interference, enabling clear imaging and staining while retaining the ease of manufacture of the core microsphere structure
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 hydrogel-coated features significantly increase capture probe loading capacity and provide improved optical properties, enhancing the sensitivity and image quality of spatial transcriptomic assays without obstructing tissue features.
Implementation Method 1
the hydrogel comprises a crosslinked polymer
Implementation Method 2
each moiety of the plurality of moieties comprises an oligonucleotide, wherein the oligonucleotide is configured to hybridize to a capture probe
Data Source
AI summary
The present disclosure relates generally to compositions and methods for generating hydrogel coatings on features. In some embodiments, hydrogel-coated features are prepared by horseradish peroxidase-mediated gelation of microspheres. Some embodiments relate to methods for generating hydrogel coatings using particle templated emulsification. The disclosure also relates to the use of hydrogel-coated features in arrays for spatial analysis of biological analytes in biological samples.