Phage-Based Biomarker Detection Using Lanthanide Labels
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Solution Overview
Problem
Current methods for detecting biomarkers, such as prostate cancer, often result in false positives and negatives due to the ambiguity of antibody assays and the non-specific elevation of PSA levels, leading to overtreatment and mental stress, and lack suitability for population-level screening.
Innovation Solution
A phage-based method using europium, terbium, or samarium ions and a quenching dye is employed to detect biomarkers, where a phage specific to the biomarker is contacted with a sample, and luminescence or color changes are measured to determine biomarker presence, allowing for a quick, reliable, and cost-effective screening without the need for antibody development or laborious assay production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If PSA detection is used for prostate cancer screening, then the method is easy to perform and cost-effective, but it produces high false positive results due to non-specific elevation of PSA levels
Solution Approach 1:
The invention segments the detection approach by using multiple different phages, each specific to different biomarkers (PSA, CRP, etc.), rather than relying on a single PSA antibody assay. This allows differentiation between true cancer signals and non-specific elevations by detecting patterns across multiple biomarkers simultaneously.
Solution Approach 2:
The phage-based detection system serves multiple functions: it can detect various biomarkers (PSA, CRP, and others) using the same fundamental technology platform. The lanthanide label system provides universal detection capability across different disease states and biomarker types, improving reliability while maintaining ease of operation.
2Measurement precision
If antibody assays with known biomarkers are used, then disease state can be assessed, but false positives and false negatives occur due to ambiguous results
Solution Approach 1:
The invention introduces phages as intermediary detection agents that bind to biomarkers with high specificity. These phages serve as mediators between the biomarker and the lanthanide label detection system, providing more consistent and reliable binding interactions compared to traditional antibody assays, thereby reducing false positives and negatives.
Solution Approach 2:
The invention changes the detection parameter from traditional antibody-antigen binding to phage-biomarker binding followed by lanthanide luminescence detection. This parameter change enables more precise and reliable measurements through the use of luminescence intensity as a quantifiable readout, improving both measurement precision and result consistency.
3Productivity
If population level screening is implemented, then more cases can be detected, but current methods are not suitable due to high false positive rates
Solution Approach 1:
The invention performs preliminary detection using multiple phage-biomarker specificities before making a definitive diagnosis. By initially screening with multiple different phages targeting different biomarkers, the system can pre-filter samples and reduce false positives before committing to further diagnostic procedures, making population-level screening feasible and reliable.
Solution Approach 2:
The detection system uses a composite approach combining multiple different phages, each specific to different biomarkers, working together in a single assay. This composite phage mixture provides enhanced reliability for population screening by detecting patterns across multiple biomarkers, allowing accurate differentiation between true positive and false positive cases at scale.
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 method provides a simple, fast, and reliable way to detect biomarkers, reducing false positives and negatives, and is suitable for screening various disease states, including prostate cancer, with improved p-values compared to commercial PSA assays, and allows for visual detection of biomarker presence.
Implementation Method 1
measuring luminescence emission intensity or absorption emission intensity
Implementation Method 2
a dye typically capable of quenching the said label
Data Source
AI summary
According to an example aspect of the present invention, there is provided a method for determining the presence of a biomarker for disease in a pretreated biological sample comprising the steps of diluting the sample, contacting the sample with a europium label, a terbium label or a samarium label, and a dye, contacting the sample with a phage, incubating the sample, measuring luminescence emission intensity or absorption emission intensity, and determining the presence of the biomarker based on the measurement of the luminescence emission intensity or the absorption emission intensity.