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Study of measurement of the alcohol biomarker phosphatidylethanol (PEth) in dried blood spot (DBS) samples and application of a volumetric DBS device
KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
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2018 (English)In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 479, p. 38-42Article in journal (Refereed) Published
Abstract [en]

Phosphatidylethanol (PEth) is a group of phospholipids formed in cell membranes following alcohol consumption. PEth measurement in whole blood samples is established as a specific alcohol biomarker with clinical and medico-legal applications. This study further evaluated the usefulness of dried blood spot (DBS) samples collected on filter paper for PEth measurement. Specimens used were surplus volumes of venous whole blood sent for routine LC–MS/MS quantification of PEth 16:0/18:1, the major PEth homolog. DBS samples were prepared by pipetting blood on Whatman 903 Protein Saver Cards and onto a volumetric DBS device (Capitainer). The imprecision (CV) of the DBS sample amount based on area and weight measurements of spot punches were 23–28%. Investigation of the relationship between blood hematocrit and PEth concentration yielded a linear, positive correlation, and at around 1.0–1.5 μmol/L PEth 16:0/18:1, the PEth concentration increased by ~ 0.1 μmol/L for every 5% increase in hematocrit. There was a close agreement between the PEth concentrations obtained with whole blood samples and the corresponding results using Whatman 903 (PEthDBS = 1.026 PEthWB + 0.013) and volumetric device (PEthDBS = 1.045 PEthWB + 0.016) DBS samples. The CV of PEth quantification in DBS samples at concentrations ≥ 0.05 μmol/L were ≤ 15%. The present results further confirmed the usefulness of DBS samples for PEth measurement.

Place, publisher, year, edition, pages
Elsevier, 2018. Vol. 479, p. 38-42
Keywords [en]
Alcohol biomarker, DBS, Dried blood spot, PEth, Phosphatidylethanol
National Category
Analytical Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-221144DOI: 10.1016/j.cca.2018.01.008ISI: 000428493600006Scopus ID: 2-s2.0-85040187806OAI: oai:DiVA.org:kth-221144DiVA, id: diva2:1174143
Note

QC 20180115

Available from: 2018-01-15 Created: 2018-01-15 Last updated: 2018-09-11Bibliographically approved
In thesis
1. Capillary driven devices for patient-centric diagnostics
Open this publication in new window or tab >>Capillary driven devices for patient-centric diagnostics
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lateral flow assays is an example of a successful microfluidic platform relying on passive fluid transport, making them suitable for patient-centric and point-of-care applications. Flow control and valving in capillary driven devices typically rely on design-imprinted functions and operations which can be a limiting factor. This thesis explores dissolvable polymer valves in capillary driven microfluidic systems, a novel type of valves with a timing function. The dissolvable valve technology was used to develop autonomous operations in lamination-based polymer microfluidic systems such as sequential reagent delivery, reagent release and volume-metering, and further utilizes this technology in the Dried Blood Spot (DBS) and Dried Plasma Spot applications described below. Lamination technology is suitable for the integration of the water-dissolvable polymer layers and allows upscaling at a relatively low cost. Advances in the development of LC-MS/MS systems enable the quantification of analytes in microliter-sized blood samples such as DBS. This makes DBS sampling a minimally invasive alternative to venous blood sampling with logistical and ethical advantages for users and health care providers. Unknown sample volume, spot inhomogeneity and hematocrit-related issues have been an obstacle for a wider acceptance of DBS sampling technology. To address these issues, a novel blood-sampling device, the microfluidic DBS card, has been developed within this thesis. The device function is based on capillary driven volume-metering and allows accurate and user independent collection of microliter-sized DBS, directly from a finger-prick. The microfluidic DBS card could help to eliminate some of the issues related to DBS sampling and contribute to a wider acceptance of the technology. Usability and reliability have been considered during the development to enable testing of the microfludic DBS card in a pre-clinical setting. For many analytes and biomarkers, conventional blood sample analysis is performed on plasma or serum samples. This thesis further discusses the use of capillary driven plasma separation based on commercially available asymmetric filtration membranes and capillary driven flow in microchannels. A novel concept for hematocrit and input-volume-independent collection of a 11.6~µl plasma sample from a single drop of blood is demonstrated. The plasma sample is automatically transferred to a sample collection pad forming a Dried Plasma Spot. This could be the next generation of dried sample matrix, enabling an accurate quantification of analytes in Dried Plasma Spots.

Place, publisher, year, edition, pages
Stockholm: Kungliga Tekniska högskolan, 2018. p. 81
Series
TRITA-EECS-AVL ; 2018:58
Keywords
Capillary driven, Microfluidic, Dissolvable valves, PVA, Volume metering, Dried Blood Spots, DBS, Dried Plasma Spots, DPS
National Category
Medical Engineering
Research subject
Medical Technology
Identifiers
urn:nbn:se:kth:diva-234679 (URN)978-91-7729-919-6 (ISBN)
Public defence
2018-09-28, F3, Lindstedtsvägen 26, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

QC 20180910

Available from: 2018-09-10 Created: 2018-09-07 Last updated: 2018-09-10Bibliographically approved

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