Isotopically Labeled Analyte Calibration for Dried Sample Quantification
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Solution Overview
Problem
Current methods for quantifying analytes in dried biological samples using mass spectrometry face challenges such as complex internal calibration procedures and the need for accurate detection over a range of concentrations, which can be technically demanding and costly.
Innovation Solution
The method involves adding a known amount of an isotopically labeled version of the analyte of interest to a solid substrate, allowing a biological sample to dry on the substrate, and then measuring the amounts of both the analyte and the isotopically labeled version to determine the analyte's concentration in the sample.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional external calibration methods are used for quantifying analytes in dried samples, then measurement accuracy can be achieved, but the calibration process becomes complex and time-consuming
Solution Approach 1:
The isotopically labeled analyte is added to the solid substrate before the biological sample is applied. This preliminary action ensures that the internal standard is already present during sample processing and drying, eliminating the need for separate calibration procedures and simplifying the overall workflow while maintaining measurement accuracy
Solution Approach 2:
The isotopically labeled analyte serves as an internal standard that mediates between the analyte of interest and the measurement process. By spiking the substrate with a known amount of isotopically labeled analyte, the system uses this intermediary substance to correct for variations in extraction efficiency and instrument response, thereby simplifying calibration while preserving accuracy
2Measurement precision
If traditional external calibration methods are used for quantifying analytes in dried samples, then measurement accuracy can be achieved, but the time and cost associated with the process increase
Solution Approach 1:
The isotopically labeled analyte is pre-added to the solid substrate before sample application, eliminating the need for time-consuming external calibration procedures. This preliminary spiking approach integrates the calibration standard into the sample preparation workflow, reducing overall processing time while maintaining measurement accuracy
Solution Approach 2:
The system uses the isotopically labeled analyte as an internal standard that automatically corrects for process variations during the assay. This self-correcting mechanism eliminates the need for separate calibration steps, allowing the system to perform accurate quantification without additional time investment in calibration procedures
3Ease of manufacture
If normalizing analytes distinct from the analyte of interest are used for calibration, then some level of quantification is possible, but technical challenges arise in selecting and measuring appropriate normalizing agents
Solution Approach 1:
The invention changes the fundamental parameter of the calibration approach by using an isotopically labeled version of the analyte itself rather than a different normalizing analyte. This parameter change simplifies the process because the isotopically labeled analyte has identical chemical properties to the analyte of interest, eliminating the technical challenges of selecting and measuring appropriate normalizing agents while maintaining assay simplicity
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 simplifies the calibration process, enhances accuracy and precision in quantifying analytes, and reduces the time and cost associated with external calibration methods, while maintaining clinical relevance.
Implementation Method 1
adding a known amount of a first isotopically labeled version of the analyte of interest to a solid substrate, wherein the isotopically labeled version of the analyte of interest is the analyte of interest labeled with at least one stable isotope
Implementation Method 2
measuring an amount of the analyte of interest and the isotopically labeled version of the analyte of interest present on the solid substrate
Data Source
AI summary
Disclosed are methods and systems to measure the amount of an analyte in a dried sample. The method includes adding a known amount of an isotopically labeled version of the analyte of interest to a solid substrate, wherein the isotopically labeled version of the analyte of interest is the analyte of interest labeled with at least one stable isotope. The method may further include adding the biological sample to the substrate and allowing the biological sample to dry on the substrate. The method may also include measuring an amount of the analyte of interest and the isotopically labeled version of the analyte of interest present on the substrate and determining the amount of the analyte of interest present in the biological sample based on the amounts of the analyte of interest and the isotopically labeled version of the analyte of interest.