Capillary Microsampling with Isopropanol for Accurate Low-Volume Blood Analysis
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Solution Overview
Problem
Current diagnostic methods for drug and metabolite testing face challenges in accurately measuring low blood volumes and are prone to variability and interference, particularly in neonatal testing, where inconsistent blood spotting on filter papers compromises the accuracy of Dried Blood Spot (DBS) measurements.
Innovation Solution
The method employs capillary microsampling (CMS) with a biocompatible solution containing isopropanol, allowing for the accurate detection of analytes in small blood volumes (1-50 µL) using techniques like mass spectrometry, reducing variability and interference, and enabling serial monitoring of drug levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If Dried Blood Spot (DBS) method is used for diagnostic testing, then sample collection is non-invasive and easy to store, but measurement accuracy deteriorates due to inconsistent blood spotting and inability to accurately test low amounts of blood
Solution Approach 1:
The invention changes the physical state parameter of the blood sample from dried (DBS) to liquid form by adding a stabilizing solvent. This allows the sample to be accurately tested in liquid form while still maintaining the ease of collection advantage of DBS, as the capillary tube collects blood via capillary action without requiring invasive phlebotomy.
Solution Approach 2:
The invention introduces a stabilizing solvent as an intermediary substance that enables accurate liquid-phase analysis of blood samples collected via capillary microsampling. The stabilizing solvent mediates between the collected blood and the analytical instrumentation, allowing precise measurement while maintaining sample stability.
2Quantity of substance
If standard DBS method requires 40-50 microliters of blood, then sufficient sample is available for analysis, but the invasiveness and sample volume required increase
Solution Approach 1:
The invention uses only a portion (1-10 microliters) of the blood sample that would traditionally be required, collecting just enough blood via capillary action in a microtube. This partial sampling approach reduces the invasiveness and total blood volume required while still providing sufficient material for accurate analyte measurement.
3Ease of manufacture
If DBS samples are spotted on filter paper, then sample storage and mailing is simplified, but inhomogeneity introduces variability and compromises accuracy
Solution Approach 1:
The invention extracts the blood sample from the filter paper matrix entirely, collecting it in liquid form in a capillary tube instead. This eliminates the filter paper spotting step that causes inhomogeneity, while the collected liquid sample can be easily stored and transported without the precision problems associated with spotted blood.
4Productivity
If acetonitrile is used as stabilizing solvent, then analyte extraction efficiency is improved, but safety concerns arise for clinical environments
Solution Approach 1:
The invention replaces the toxic but effective acetonitrile solvent with a safer alternative (isopropanol or ethanol) that can be used in clinical environments. The slight reduction in extraction efficiency is acceptable given the significant safety improvement, and the sample can be processed quickly without requiring the highly efficient but hazardous acetonitrile.
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 provides more accurate and reliable measurements of drug concentrations compared to traditional DBS methods, with high concordance between CMS and plasma samples, offering improved precision and reduced human error, thus enhancing healthcare quality and patient care.
Implementation Method 1
obtain a small volume blood sample, about 1-10 microliters, from a subject using a capillary tube
Implementation Method 2
the stabilizing solvent comprises isopropanol, methanol, ethanol or a mixture thereof... adding said sample obtained through capillary microsampling (CMS) to a biocompatible solution
Data Source
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AI summary
Methods, kits and systems described herein provide collecting, preparing, processing and/or analyzing a clinical sample, such as a blood. The methods, kits and systems may use a biocompatible solution comprising water and a stabilizing solvent, such as isopropanol, for accurate testing of the presence and/or amount of drug, nutrient, or metabolite.