Protein Identification via Spatial Substrate and Deconvolution
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Solution Overview
Problem
Current protein identification techniques are inefficient and time-consuming, particularly when dealing with complex mixtures, as they rely on specific antibodies or peptide data from mass spectrometers, which limits their ability to quickly and accurately identify multiple proteins simultaneously.
Innovation Solution
The method involves conjugating proteins to a substrate with unique spatial addresses and applying a panel of non-specific affinity reagents to identify proteins through binding patterns, using deconvolution methods to determine protein identities, even in complex mixtures, allowing for the simultaneous identification of numerous proteins with high accuracy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional protein identification methods using specific antibodies or mass spectrometry are used, then measurement precision is improved, but productivity deteriorates due to time-consuming analysis
Solution Approach 1:
The substrate is divided into multiple spatially separated locations, each capable of binding a different protein. This segmentation allows parallel analysis of multiple proteins simultaneously, improving throughput while maintaining identification accuracy through deconvolution of binding patterns.
Solution Approach 2:
A single substrate can identify multiple different proteins simultaneously by binding them at distinct spatial locations. The universal binding capability of the substrate, combined with deconvolution algorithms, enables one assay to perform multiple protein identification functions at once.
2Productivity
If a panel of non-specific affinity reagents is used with deconvolution methods, then productivity is improved through simultaneous identification of multiple proteins, but device complexity increases
Solution Approach 1:
The substrate acts as an intermediary that translates complex protein binding interactions into spatially separated, detectable signals. By mediating the interaction between affinity reagents and proteins at distinct locations, the substrate simplifies the readout process while enabling simultaneous multi-protein identification.
Solution Approach 2:
The patent replaces complex mechanical separation systems with a simplified spatial addressing system on a single substrate. Instead of physically separating proteins through multiple steps, the system uses spatial locations and deconvolution algorithms to achieve separation and identification, reducing mechanical complexity.
3Measurement precision
If highly specific and sensitive antibodies are used for protein identification, then measurement precision is improved, but adaptability deteriorates due to limitation in identifying proteins in complex mixtures
Solution Approach 1:
Multiple affinity reagents with different specificities are merged into a single panel that can simultaneously bind to multiple proteins in a mixture. The substrate integrates these reagents at different locations, allowing the system to detect and deconvolute binding patterns for multiple proteins concurrently, enhancing versatility while maintaining sensitivity.
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 rapid and accurate identification of up to 1000 different proteins with 50% accuracy, outperforming traditional methods by identifying proteins at least 10% faster, and can identify over 20% of the human proteome without protein destruction.
Implementation Method 1
The identities of proteins, i.e. their sequence, in a mixture are inferred from a series of measurements that may be highly incomplete and/or are not specific to a particular protein
Data Source
AI summary
Methods and 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.