Multiplex Biomarker Measurement Using Size-Coded Fluorescent Particles
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Solution Overview
Problem
Existing methods like xMAP struggle to distinguish beads with similar fluorescence spectra, limiting the number of biomarkers that can be simultaneously detected, necessitating a technique for simultaneous measurement of multiple types of biomarkers.
Innovation Solution
A method involving particles and labels with different sizes and label properties, allowing biomolecules to bind specifically to these particles, followed by separation based on particle size and detection of label properties to determine biomolecule types.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If xMAP technique uses beads with fluorescent dyes to detect multiple biomarkers, then the number of detectable biomarker types increases, but the ability to distinguish between beads with similar fluorescence spectra deteriorates
Solution Approach 1:
The invention transitions from one-dimensional fluorescence spectrum differentiation to two-dimensional differentiation by combining particle size with fluorescence properties. Particles are classified into different size ranges (e.g., 5-10 μm, 10-15 μm, 15-20 μm) and each size group contains particles with distinct fluorescence spectra, enabling simultaneous detection of many more biomarkers while maintaining clear differentiation capability
Solution Approach 2:
The particle population is segmented into multiple size groups, where each size group serves as a distinct category for biomarker detection. This segmentation allows the system to organize numerous particle types in a structured manner, where particles of different sizes can be independently detected and identified, resolving the confusion that would arise from relying solely on fluorescence spectrum differentiation
2Quantity of substance
If multiple particle subgroups with different fluorescence spectra are used, then the number of simultaneously detectable biomarkers increases, but the complexity of the measurement system increases
Solution Approach 1:
By introducing particle size as an additional dimension for differentiation, the system can manage complexity more effectively. Instead of requiring unique fluorescence spectra for every particle type, the size dimension provides a coarse-grained classification that simplifies the overall system architecture while still enabling detection of numerous biomarkers through the combination of size groups and fluorescence properties within each group
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
Enables simultaneous measurement of multiple biomarkers, enhancing accuracy and sensitivity by differentiating based on particle size and label properties, overcoming the limitations of existing techniques.
Implementation Method 1
The particle of the first particle group and the label of the first label group bind to each other via a biomolecule. The particle of the second particle group and the label of the second label group bind to each other via a biomolecule.
Implementation Method 2
separating among the particles of the first particle group and among the particles of the second particle group based on particle sizes
Implementation Method 3
detecting label properties of the labels bound respectively via the biomolecules to the particles of the first particle group and the particles of the second particle group thus separated based on the particle sizes
Data Source
AI summary
Labels (2a, 2b) of the first label group and labels (2c, 2d) of the second label group are different from each other in label property. In each particle group, a plurality of particle subgroups (a to d) are different from each other in particle size. A measurement method further comprises: mixing a specimen, particles (1a to 1d), and labels (2a to 2d); allowing biomolecules to specifically bind to the labels (2a to 2d) and to the labels (2a to 2d); separating the particles based on particle sizes; detecting label properties of the labels; determining types of the biomolecules bound to the particles based on the particle size and the label property.