Particle-Based Biomolecule Quantitation with Labeled Reference Control
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Solution Overview
Problem
Current methods for detecting and quantifying biomolecules suffer from misclassification, reduced signal-to-noise ratio, interference from high abundance biomolecules, and lack of real-time quality control, especially in nanoparticle enrichment processes, leading to inaccurate disease detection and classification.
Innovation Solution
Incorporating internal standards and using particles to adsorb biomolecules, followed by combining with labeled reference biomolecules for measurement, and applying classifiers to improve data quality and accuracy, enabling real-time control of mass spectrometry for enhanced detection and classification of biomolecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If particles are used to adsorb biomolecules for enrichment, then detection sensitivity is improved, but measurement accuracy deteriorates due to interference from high abundance biomolecules
Solution Approach 1:
Labeled reference biomolecules are introduced as intermediary substances that compete with endogenous biomolecules for adsorption sites on particles. These reference biomolecules serve as mediators to establish a known relationship between adsorption signal and actual biomolecule concentration, enabling accurate quantification despite the presence of high abundance interfering biomolecules in the complex biological sample matrix
Solution Approach 2:
The method changes the parameter of biomolecule concentration by adding known amounts of labeled reference biomolecules to the sample. This parameter change allows the system to calibrate the adsorption process and establish quantitative relationships, transforming an unquantifiable adsorption process into a measurable and accurate detection system
2Measurement precision
If internal standards are combined with biomolecules for measurement, then measurement accuracy is improved, but device complexity increases
Solution Approach 1:
The labeled reference biomolecules serve multiple functions simultaneously: they act as internal standards for quantification, compete with endogenous biomolecules for adsorption sites to enable calibration, and provide known concentration references for establishing quantitative relationships. This multi-functionality reduces the need for separate calibration procedures and simplifies the overall assay design
Solution Approach 2:
The system uses the labeled reference biomolecules to self-calibrate the measurement process. By incorporating known concentrations of reference biomolecules that undergo the same adsorption process as endogenous biomolecules, the system automatically establishes quantitative relationships without requiring external calibration curves or complex reference measurements, thereby reducing device complexity
3Reliability
If real-time control is implemented based on internal standard measurements, then quality control is improved, but measurement time increases
Solution Approach 1:
Labeled reference biomolecules are added to samples in advance before the adsorption and measurement process begins. This preliminary action ensures that reference biomolecules are present throughout the entire measurement process, enabling real-time quality control and dynamic adjustments without requiring additional time for separate calibration or reference measurements during data collection
Solution Approach 2:
The system implements real-time feedback by continuously monitoring the ratio of endogenous biomolecule signals to labeled reference biomolecule signals during mass spectrometry data collection. This feedback mechanism allows dynamic adjustment of measurement parameters and immediate identification of quality issues, maintaining high reliability without significantly extending total measurement time because both types of biomolecules are measured simultaneously in the same mass spectrometry run
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 the detection and quantification of biomolecules, improves classification accuracy, and allows for real-time quality control, facilitating non-invasive disease detection and classification, particularly in early stages of conditions like cancer.
Implementation Method 1
contacting a biological sample of a subject with particles, thereby adsorbing endogenous biomolecules of the biological sample to the particles
Data Source
AI summary
Described herein are methods for screening for a disease state. The method may include obtaining multiple data sets and identifying the disease state based on a combination of the data sets. The data sets may include biomolecule measurements obtained by multiple methods, such as through the use of particles and reference biomolecules.