Nanostructure Sensor Arrays for Bias-Free Proteome Interrogation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for proteomic interrogation are limited by their inability to effectively analyze a wide dynamic range of proteins, particularly low abundance proteins, and are often biased towards disease-focused targets, restricting the number and breadth of biomarkers that can be identified for medical diagnostics and drug discovery.
Innovation Solution
A method involving the construction of a protein panel by splicing protein-coding genes from a whole genome to identify proteins associated with evenly spaced marker locations, using sensors with nanostructure arrays functionalized with binding moieties to detect and quantify proteins across the proteome, exome, or exome-CDS in a bias-free manner.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If current protein panel selection methods are used, then the assay can be performed with existing technologies, but the number of proteins that can be interrogated is limited and the dynamic range is restricted
Solution Approach 1:
The invention segments the proteome into multiple non-overlapping panels, where each panel targets a specific portion of the proteome. This segmentation allows for comprehensive coverage of thousands of proteins across multiple panels while maintaining optimized detection performance within each panel, thereby resolving the contradiction between quantity of proteins interrogated and measurement precision across the full dynamic range.
Solution Approach 2:
The invention transitions from single-panel to multi-panel proteome interrogation, adding the dimension of panel multiplicity. This dimensional expansion enables the system to interrogate a much larger number of proteins (thousands across panels versus hundreds in a single panel) while maintaining the dynamic range performance characteristics of individual optimized panels.
2Ease of manufacture
If disease-focused target selection is used, then the assay design is simplified, but the approach becomes biased and limits proteome-wide interrogation
Solution Approach 1:
The proteome is segmented into multiple panels with non-overlapping protein sets, where each panel can be designed and validated independently. This segmentation maintains the simplicity of targeted assay design for each panel while collectively achieving comprehensive proteome-wide coverage, thus resolving the contradiction between ease of manufacture and adaptability.
Solution Approach 2:
The multi-panel system serves multiple functions: each individual panel can be used for targeted interrogation of its specific protein set, while the collection of panels collectively enables comprehensive proteome-wide analysis. This multi-functionality allows the system to maintain design simplicity for individual panels while achieving versatile proteome-wide coverage.
3Device complexity
If a limited number of sensors are used, then the device complexity is reduced, but the breadth of biomarkers that can be detected is insufficient
Solution Approach 1:
The sensing capability is segmented across multiple panels, where each panel contains sensors for a specific subset of proteins. This segmentation allows the system to manage device complexity by organizing sensors into manageable panels while collectively achieving comprehensive biomarker detection across thousands of proteins through the combination of multiple panels.
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 detection and quantification of a large number of high and low abundance proteins, providing a bias-free proteome-wide interrogation capable of identifying new biomarkers for phenotypes, thereby enhancing medical diagnostics and drug discovery applications.
Implementation Method 1
each nanostructure array is functionalized with one or more binding moieties for binding one or more proteins of a set of test proteins
Data Source
AI summary
The invention relates generally to articles (e.g., sensors) and methods that facilitate proteome, exome, or exome-codon sequence region wide interrogation for the discovery, screening and/or quantification of one or more proteins that contribute to a phenotype.