Protein Characterization Using Non-Specific Antibody Deconvolution
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Solution Overview
Problem
Current protein identification techniques, such as those relying on mass spectrometry or specific antibodies, are inefficient and time-consuming, particularly when identifying a large number of proteins in complex mixtures.
Innovation Solution
A method involving a substrate with spatially resolved protein portions, application of non-specific affinity reagents, and deconvolution algorithms to infer protein identities based on binding patterns, allowing for rapid and accurate identification of multiple proteins without prior separation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If mass spectrometry-based methods are used for protein identification, then measurement precision is improved, but productivity deteriorates due to time-consuming analysis
Solution Approach 1:
The patent segments the protein identification process into two independent stages: (1) spatial encoding of proteins on a substrate where each protein receives a unique spatial address, and (2) parallel affinity reagent binding assays. This segmentation allows simultaneous processing of multiple proteins without sequential mass spectrometry analysis, thereby improving productivity while maintaining identification accuracy through the spatial address system.
Solution Approach 2:
The patent replaces the mechanical mass spectrometry analysis system with an optical detection system using affinity reagents and spatial encoding. Instead of using mass spectrometry to identify proteins sequentially, the system uses optically detectable affinity reagents bound to spatially encoded proteins, enabling parallel processing and significantly faster identification while maintaining precision through the unique spatial address system.
2Measurement precision
If specific antibodies are used for protein detection, then measurement precision is improved, but device complexity worsens due to requirement for highly specific reagents
Solution Approach 1:
The patent applies universality by using non-specific affinity reagents that can bind to multiple different proteins simultaneously. Each protein is uniquely identified not by the specificity of the reagent, but by its unique spatial address on the substrate. This allows a single set of universal affinity reagents to detect multiple proteins, eliminating the need for highly specific antibodies for each protein and reducing device complexity.
Solution Approach 2:
The patent introduces spatial encoding as an intermediary system that decouples the detection process from reagent specificity. The spatial address acts as a mediator that provides unique identification information independent of the affinity reagent's binding specificity. This intermediary system allows non-specific reagents to be used effectively, reducing the complexity of developing and maintaining highly specific antibody panels.
3Reliability
If traditional protein identification methods are used, then reliability is improved through established techniques, but loss of time worsens due to extended analysis duration
Solution Approach 1:
The patent applies preliminary action by pre-encoding proteins with unique spatial addresses before the actual identification process. This preliminary spatial encoding step allows subsequent affinity reagent binding assays to proceed in parallel without requiring time-consuming sequential analysis. The spatial addresses are assigned in advance, enabling rapid simultaneous detection of multiple proteins while maintaining reliability through the established spatial encoding framework.
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 the identification of at least 400 different proteins with 50% accuracy 10% faster than mass spectrometry-based methods and up to 1000 proteins with similar accuracy, using a fraction of the sample amount and time.
Implementation Method 1
applying a fluid containing a first through nth set of one or more affinity reagents to the substrate... determining that each portion of the one or more proteins having an identified unique spatial address contains the one or more epitopes associated with the one or more observed signals
Data Source
AI summary
Systems for identifying a protein within a sample are provided herein. A panel of antibodies are acquired, none of which are specific for a single protein or family of proteins. Additionally, the binding properties of the antibodies in the panel are determined. Further, the protein is iteratively exposed to a panel of antibodies. Additionally, a set of antibodies which bind the protein are determined. The identity of the protein is determined using one or more deconvolution methods based on the known binding properties of the antibodies to match the set of antibodies to a sequence of a protein.