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Updated: Jan 17, 2026

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Microsampling in Targeted Mass Spectrometry-Based Protein Analysis of Low-Abundance Proteins
Published on: January 13, 2023
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Comparative Evaluation of Smart Sampling for hCG Determination: A New Potential Direction in Protein Biomarker
Ago Mrsa1, Marijana Matijevic1, Yvette Dehnes1,2
1Department of Pharmacy, University of Oslo, Oslo, Norway.
Drug Testing and Analysis
|September 14, 2025
Summary
Smart sampling simplifies protein analysis from dried blood spots, offering a promising alternative to traditional methods. This new technique shows strong agreement with established assays, enhancing bioanalytical efficiency.
Area of Science:
- Biochemistry
- Analytical Chemistry
- Biotechnology
Background:
- Dried blood spots (DBS) are crucial for clinical analysis but require extensive preparation for protein quantification via LC-MS.
- Low-abundance protein analysis is particularly challenging due to time-consuming sample preparation steps.
- Smart sampling integrates sample preparation onto the sampler, streamlining the process.
Purpose of the Study:
- To compare the performance of a novel smart sampling method for protein analysis.
- To evaluate smart sampling against an immunocapture magnetic bead method and a commercial electrochemiluminescence immunoassay (ECLIA).
- To assess the utility of smart sampling for protein biomarker analysis in complex matrices.
Main Methods:
- Three methods were compared: smart sampling, immunocapture on magnetic beads, and ECLIA.
- Human chorionic gonadotropin (hCG) was quantified in 21 single-blind serum samples.
- Performance was evaluated using linear regression and Bland-Altman analysis.
Main Results:
- All methods showed strong correlations (R² > 0.91) with actual sample concentrations.
- Immunocapture on magnetic beads yielded the highest linear correlation (R² = 0.974).
- Smart sampling demonstrated good agreement with both magnetic beads (bias -5.2) and ECLIA (bias 0.4 ± 4 ng/mL).
Conclusions:
- Smart sampling is a viable and promising new approach for bioanalysis.
- The method offers a streamlined alternative for protein biomarker analysis, especially from complex matrices.
- This study provides the first comparison of smart sampling with existing protein analysis techniques.

