Application of volumetric absorptive microsampling for robust, high-throughput mass spectrometric quantification of circulating protein biomarkers
Open accessAbstract
Volumetric absorptive micro sampling (VAMS™) allows accurate sampling of 10 µL of blood from a minimally invasive finger prick and could enable remote personalized health monitoring. Moreover, VAMS overcomes effects from hematocrit and sample heterogeneity associated with dried blood spots (DBS). We describe the first application of VAMS with the Mitra® microsampling device for the quantification of protein biomarkers using an automated, high-throughput sample preparation method coupled with mass spectrometric (MS) detection. The analytical performance of the developed workflow was evaluated for 10 peptides from six clinically relevant proteins: apolipoproteins A-I, B, C-I, C-III, E, and human serum albumin (HSA). Extraction recovery from blood with three different levels of hematocrit varied between 100% and 111% for all proteins. Within-day and total assay reproducibility (i.e., 5 replicates on 5 days) ranged between 3.2-10.4% and 3.4-12.6%, respectively. In addition, after 22 weeks of storage of the Mitra microsampling devices at -80 °C, all peptide responses were within ±15% deviation from the initial response. Application to data-independent acquisition (DIA) MS further demonstrated the potential for broad applicability and the general robustness of the automated workflow by reproducible detection of 1661 peptides from 423 proteins (average 15.7%CV (n = 3) in peptide abundance), correlating to peptide abundances in corresponding plasma (R = 0.8383). In conclusion, we have developed an automated workflow for efficient extraction, digestion, and MS analysis of a variety of proteins in a fixed small volume of dried blood (i.e., 10 µL). This robust and high-throughput workflow will create manifold opportunities for the application of remote, personalized disease biomarker monitoring.
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Volumetric absorptive micro-sampling (VAMS) blood collection devices allow patients to mail samples from home to analytical labs to undertake SRM/MRM/PRM assays quantifying cardiovascular disease risk-associated apolipoproteins or other markers.
“Likewise, volumetric absorptive micro-sampling VAMS blood collection devices (e.g., Mitra devices or dried blood spots) allow patients to mail samples from home to analytical labs to undertake SRM/MRM/PRM assays quantifying CVD risk-associated apolipoproteins130 or other markers131.”
From A high-stringency blueprint of the human proteome (2020) · cites this paper as [130]
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Lucas, N., Herbert, B. R., & Molloy, M. P. (2025) · Advances in clinical chemistry · doi:10.1016/bs.acc.2025.04.005
Shipping Conditions May Impact the Reliability of At-Home Microsampling Devices
Raisman, A. V., Naess, J., Kotol, D., & Edfors, F. (2026) · Journal of Proteome Research · doi:10.1021/acs.jproteome.6c00117
Marano, P., Eyk, J. E. V., & Merz, C. N. B. (2026) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-026-10838-9
Emerging biomarkers in breast cancer
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Recent developments in microsampling for oligonucleotides and biologics bioanalysis
Guimaraes, G. J., & Yuan, L. (2026) · Bioanalysis · doi:10.1080/17576180.2026.2739128
Campbell, A., Becker, L., Kreimer, S. D., Gonzales, M., Raedschelders, K., & Eyk, J. E. V. (2026) · Research Square · doi:10.21203/rs.3.rs-11053241/v1
- Authors
- van den Broek, I., Fu, Q., Kushon, S., Kowalski, M. P., Millis, K., Percy, A., Holewinski, R. J., Venkatraman, V., & Van Eyk, J. E.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Cambridge Isotope Laboratories, Inc. (United States) (US)
- Venue
- Clinical Mass Spectrometry
- Publisher
- Stanford University Press
- Published
- 2017-04
- Volume
- 4-5
- Pages
- 25-33
- ISSN
- 2213-8005 (ISSN-L)
- 2376-9998
- PMC
- PMC11322776
- OpenAlex
- W2752931564
- Semantic Scholar
- a67b75ec7354f48e7e10fe9ac3db81732ae174c6
- Cited by
- 62
- References
- 36
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 10 · 2023: 8 · 2022: 6 · 2021: 9 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 1
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Clinical mass spectrometry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1R01HL111362-01A1)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- volumetric absorptive microsampling, dried blood spots, finger prick blood sampling, circulating protein biomarkers, apolipoproteins, human serum albumin, hematocrit effect, automated sample preparation, data-independent acquisition, remote patient monitoring
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