Optically Encoded Nanoparticles for Multiplexed Biomolecule Detection
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Solution Overview
Problem
Current multiplexed detection methods for biomolecules using fluorescent dyes are limited by spectral overlap, allowing for detection of only a few targets simultaneously due to the physical properties of fluorophores, and are time-consuming, expensive, and prone to errors, especially in in situ hybridization applications.
Innovation Solution
The method employs optically encoded nanoparticles with unique combinations of fluorophores that emit distinct signals, allowing for the simultaneous detection of multiple biomolecules in a one-step process by measuring the wavelength and intensity of emitted signals, enabling the detection of up to 50-100 targets with improved precision and reduced complexity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If multiple fluorophores are used simultaneously for multiplexed detection, then the detection capacity increases, but spectral overlap occurs making it difficult to distinguish individual targets (typically limited to less than 5-10 dyes)
Solution Approach 1:
The patent transitions from using multiple fluorophores with overlapping spectra (1D spectral space) to using a single fluorophore with multiple emission wavelengths detected over time (4D space-time dimension). By detecting emission at multiple wavelengths sequentially and analyzing temporal dynamics, the system achieves high-dimensional discrimination that enables detection of many more targets without spectral overlap limitations.
Solution Approach 2:
The invention changes the detection parameter from static spectral separation to dynamic temporal-spectral analysis. By measuring emission intensity at multiple wavelengths over time and analyzing the temporal patterns, the system creates unique signatures for each target that can be distinguished even when spectral profiles overlap, effectively changing how targets are differentiated.
2Adaptability or versatility
If in situ sequencing technologies are used to increase multiplexing capacity, then the number of detectable targets increases, but the process becomes much longer and more complex requiring iterative chemical steps and advanced hardware
Solution Approach 1:
The patent combines multiple detection capabilities into a single experimental step. By using a single fluorophore that emits at multiple wavelengths and detecting all targets simultaneously through temporal-spectral analysis, the method merges what would otherwise require multiple sequential sequencing steps into one unified detection process, eliminating the need for iterative chemical steps and advanced sequencing hardware.
Solution Approach 2:
The invention creates temporal copies of the emission signal at different wavelengths rather than requiring physical separation or iterative chemical processing. By detecting the same fluorophore emission at multiple wavelengths simultaneously and analyzing temporal patterns, the system generates distinguishable signals for each target without needing to physically separate or sequentially process them through multiple steps.
3Adaptability or versatility
If in situ sequencing technologies are used for multiplexed detection, then more targets can be detected, but the process becomes expensive and sensitive to errors requiring trained personnel and robust integrated hardware
Solution Approach 1:
The patent enables the detection system to self-differentiate targets through intrinsic temporal-spectral patterns without requiring external intervention or complex error correction mechanisms. The method uses the natural emission characteristics of a single fluorophore over time to automatically generate distinguishable signatures for each target, eliminating the need for trained personnel to manually resolve ambiguities or for robust integrated hardware to enforce procedural correctness.
4Productivity
If conventional fluorescent methods are used for multiplexed detection, then the process is simpler and faster, but the detection capacity is limited to less than 5-10 targets due to spectral overlap
Solution Approach 1:
The patent adds temporal and spectral dimensions to the detection process. Instead of relying solely on spectral separation in the frequency domain, the method detects emission at multiple wavelengths over time and uses temporal dynamics to create additional discrimination dimensions, enabling high multiplexing capacity while maintaining the simplicity and speed of conventional fluorescent detection.
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 enhances multiplexing capacity, reduces the number of steps and costs, and decreases sensitivity to handling errors, enabling easier data analysis and use in standard laboratories without advanced instrumentation.
Implementation Method 1
each nanoparticle comprises a plurality of fluorophores that generates a signal which is unique for each nanoparticle type
Data Source
AI summary
Described is a method for multiplexed detection of a plurality of target biomolecules having at least one detection target using optical encoding. The method includes steps:a. providing one or more nanoparticle types having a plurality of nanoparticles, each nanoparticle having a coating that provides binding affinity of the nanoparticle to a type-specific detection target, wherein each nanoparticle has a plurality of fluorophores that generates a signal which is unique for each nanoparticle type;b. providing a sample having a plurality of target biomolecules;c. contacting the sample with the plurality of nanoparticle types, thereby allowing the nanoparticles to bind with the detection targets of the target biomolecules;d. optically decoding the fluorophore signals emitted by the nanoparticle of the nanoparticle type bound to the detection target of the target biomolecules by measuring wavelength and intensity of the emitted signals, thereby detecting the presence and identity of the target biomolecules.