Encoded Hydrogel Particles Probe Loading via Unreacted Ends
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Solution Overview
Problem
Conventional methods for synthesizing encoded hydrogel particles suffer from low probe loading yield and non-uniform distribution, leading to poor detection performance due to unreacted reactive groups and probe aggregation, which results in false-positive signals and reduced sensitivity in biomolecule detection.
Innovation Solution
The method involves synthesizing hydrogel particles first and then conjugating probes through unreacted ends via radical reactions or electron transfer, ensuring improved probe loading efficiency and uniform distribution, thereby preventing non-specific binding and enhancing detection sensitivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If probes are directly mixed with precursor and crosslinked during particle synthesis, then probe loading occurs, but probe loading yield is low (only about 10% of probes are crosslinked)
Solution Approach 1:
The process is divided into two separate stages: first synthesizing the hydrogel particles without probes, then subsequently conjugating probes to the synthesized particles. This segmentation allows each stage to be optimized independently, achieving high probe loading yield (at least 8.2-fold increase) and maintaining high detection performance without the limitations of simultaneous synthesis and loading.
2Stability of the object's composition
If probes are mixed with precursor for long time to improve dispersion, then probe distribution improves, but probe aggregation occurs and detection capability deteriorates
Solution Approach 1:
The hydrogel particles are synthesized first as a stable base structure before probe conjugation. This preliminary action creates a ready-made scaffold with sufficient unreacted ends, allowing probes to be subsequently attached uniformly without requiring prolonged mixing that would cause aggregation. The probe conjugation step follows particle formation, ensuring uniform distribution while preventing aggregation-related detection failures.
3Productivity
If flow lithography is used to synthesize particles quickly (within milliseconds), then particle synthesis efficiency is high, but only about 10% of monomer is polymerized leaving unreacted ends
Solution Approach 1:
The unreacted ends that remain after rapid flow lithography synthesis are not treated as defects but are intentionally utilized as conjugation sites for probe attachment. This converts the harmful factor (unreacted reactive groups causing false positives) into a beneficial feature (available sites for high-yield probe loading). The method leverages these unreacted ends to achieve at least 8.2-fold increase in probe loading while eliminating the harmful effects through proper probe conjugation.
4Adaptability or versatility
If unreacted ends remain in hydrogel particles, then probe conjugation sites are available, but false-positive signals occur due to non-specific binding
Solution Approach 1:
The unreacted ends are strategically utilized as localized conjugation sites specifically for probe attachment. By concentrating the functional reactivity at these specific locations rather than throughout the entire particle, the method achieves high probe loading yield while maintaining detection accuracy. The probes are selectively attached at unreacted end sites, preventing non-specific binding elsewhere and eliminating false-positive signals.
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 approach allows for an at least 8.2-fold increase in probe loading, improved specificity, and increased detection sensitivity, reducing false-positive signals and enabling rapid and accurate multiplexed detection of biomolecules.
Implementation Method 1
patterned UV is irradiated onto a precursor flow through a photomask to induce selective polymerization of the precursor
Implementation Method 2
conjugating probes to the synthesized hydrogel particles through unreacted ends remaining in the hydrogel particles via radical reactions or electron transfer
Implementation Method 3
conjugating probes to the synthesized hydrogel particles through unreacted ends remaining in the hydrogel particles via radical reactions or electron transfer
Data Source
AI summary
The present invention relates to a method for preparing encoded hydrogel particles for high sensitive detection of a target biomolecule with high accuracy, and encoded hydrogel particles prepared thereby and, specifically, to a method for preparing encoded hydrogel particles, comprising a step of synthesizing hydrogel particles, and then binding a probe thereto, and encoded hydrogel particles prepared thereby. According to the present invention, probes can be loaded with remarkably improved high efficiency, loaded probes can be uniformly distributed, and the potential problem of biomolecule detection inhibition caused by an unreacted end can be resolved. In addition, the present invention can be applied to the diagnosis of diseases or screening of drugs through high sensitive multiplex detection of target biomolecules such as nucleic acids and proteins, and therefore, can be widely used in the field of medical diagnosis including molecular diagnosis.