Hydrogel Particles Passive Optical Barcoding Multiplexed Assays
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Solution Overview
Problem
Existing technologies for multiplexed assays are limited by the use of polystyrene beads, which have fixed passive optical properties, restricting the ability to distinguish subpopulations based on these properties alone, and are further limited by the number of fluorescence detectors available, which restricts the dimensions of multiplexing.
Innovation Solution
The development of hydrogel particles with engineered passive optical properties, such as forward scatter (FSC) and side scatter (SSC), allows for the creation of beads with unique optical signatures while maintaining the same diameter, enabling high-dimensional multiplexed assays to be performed in a single reaction using cytometric instrumentation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If polystyrene beads are used for multiplexed assays, then the assay can be performed with standardized materials, but the passive optical properties are fixed and cannot be used to distinguish subpopulations
Solution Approach 1:
The patent applies parameter changes by modifying the passive optical properties of hydrogel particles through controlled variation in particle size, composition, and internal structure. This enables each particle population to have unique forward scatter and side scatter signatures that can be distinguished by flow cytometry, resolving the limitation of fixed optical properties in polystyrene beads while maintaining ease of manufacture through systematic parameter control
2Adaptability or versatility
If the number of fluorescence detectors is increased to expand multiplexing dimensions, then more targets can be detected simultaneously, but the device complexity and cost increase
Solution Approach 1:
The patent applies dimensionality change by transitioning from fluorescence-based detection to passive optical property-based detection (forward scatter and side scatter). This moves the multiplexing capability from the fluorescence intensity dimension to the spatial scattering dimension, allowing multiple particle populations to be distinguished using the existing flow cytometry detection system without adding more fluorescence detectors, thereby expanding multiplexing dimensions while reducing device complexity
3Adaptability or versatility
If hydrogel particles with engineered passive optical properties are used, then high-dimensional multiplexed assays can be performed, but the manufacturing process becomes more complex
Solution Approach 1:
The patent applies preliminary action by pre-engineering the passive optical properties of hydrogel particles during the manufacturing stage. Particle size, composition, and internal structure are controlled during synthesis to create distinct forward scatter and side scatter signatures. This preliminary engineering of optical properties allows the particles to be readily distinguished by flow cytometry without requiring complex post-manufacturing modifications, thereby enabling high-dimensional multiplexing while keeping the manufacturing process manageable
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 enables the segregation and deconvolution of hydrogel particles and their associated biochemical targets based on their passive optical properties, facilitating high-dimensional multiplexed assays with improved assay performance and quantitative measurements.
Implementation Method 1
hydrogel particles having passive optical properties (e.g., FSC and/or SSC) that are deliberately engineered, or 'modulated,' without altering the size (e.g., the diameter) of the particle itself
Data Source
AI summary
Compositions comprising multiple hydrogel particles having substantially the same diameter, but with each subgrouping of particles from the multiple hydrogel particles having different associated values for one or more passive optical properties that can be deconvoluted using cytometric instrumentation. Each hydrogel particle from the multiple hydrogel particles can be functionalized with a different biochemical or chemical target from a set of targets. A method of preparing hydrogel particles includes forming droplets and polymerizing the droplets, with optional functionalization.