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An Autonomous Microfluidic Device for Generating Volume-Defined Dried Plasma Spots
KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.ORCID iD: 0000-0003-3601-0342
KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
Karolinska Univ Hosp, Clin Pharmacol, S-11486 Stockholm, Sweden..
Karolinska Univ Hosp, Clin Pharmacol, S-11486 Stockholm, Sweden..
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2019 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 91, no 11, p. 7125-7130Article in journal (Refereed) Published
Abstract [en]

Obtaining plasma from a blood sample and preparing it for subsequent analysis is currently a laborious process involving experienced health-care professionals and centrifugation. We circumvent this by utilizing capillary forces and microfluidic engineering to develop an autonomous plasma sampling device that filters and stores an exact amount of plasma as a dried plasma spot (DPS) from a whole blood sample in less than 6 min. We tested 24 prototype devices with whole blood from 10 volunteers, various input volumes (40-80 mu L), and different hematocrit levels (39-45%). The resulting mean plasma volume, assessed gravimetrically, was 11.6 mu L with a relative standard deviation similar to manual pipetting (3.0% vs 1.4%). LC-MS/MS analysis of caffeine concentrations in the generated DPS (12 duplicates) showed a strong correlation (R-2 = 0.99) to, but no equivalence with, concentrations prepared from corresponding plasma obtained by centrifugation. The presented autonomous DPS device may enable patient-centric plasma sampling through minimally invasive finger-pricking and allow generatation of volume-defined DPS for quantitative blood analysis.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2019. Vol. 91, no 11, p. 7125-7130
National Category
Biomedical Laboratory Science/Technology
Identifiers
URN: urn:nbn:se:kth:diva-254080DOI: 10.1021/acs.analchem.9b00204ISI: 000470793800027PubMedID: 31063366Scopus ID: 2-s2.0-85066116426OAI: oai:DiVA.org:kth-254080DiVA, id: diva2:1330278
Note

QC 20190625

Available from: 2019-06-25 Created: 2019-06-25 Last updated: 2022-09-12Bibliographically approved
In thesis
1. Capillary-Driven Microfluidic Devices for Sample Preparation of Bio-Medical Specimens
Open this publication in new window or tab >>Capillary-Driven Microfluidic Devices for Sample Preparation of Bio-Medical Specimens
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Sample preparation is an integral part of bio-medical analysis routines, as it makes specimens of interest compatible with downstream instrumentation. Correct and proper sample preparation is of critical importance for reliable analysis results. However, conventional preparation procedures often entail numerous manual user interactions, which cause variations in sample quality and can lead to biased results. Microfluidics is a promising technology to address these problems since on-chip integration of sample preparation steps, such as volume metering, liquid handling, and sample fixation, can minimize critical user interactions. This thesis explores capillary-driven microfluidic devices for sample preparation of bio-medical specimens in patient-centric blood analysis workflows and laboratory environments. Patient-centric blood analysis, where patients take and send samples to a central laboratory for quality-assured readout, is an emerging field where capillary-driven microfluidic solutions can enable consistent sample preparation in remote locations. Blood plasma, the gold standard in blood analysis routines, is typically extracted by centrifugation, which is not readily available in remote settings. To address this limitation, we realized a microfluidic device for capillary-driven blood plasma separation from undiluted human whole blood. Based on this approach, we developed a device that generates a volume-defined dried plasma spot ready to be shipped to a laboratory for mass spectrometry. Using the same plasma separation approach, we developed a device that performs the critical analyte binding step of a multiplexed immunoassay at the time of sample collection. Sample drying and shipment to a laboratory then allow to make use of the unparalleled performance of highly specialized laboratory equipment. Along the same line of patientcentric workflows, we showed that specially treated dry blood samples enablered and white blood cell quantification with good correlation to gold standard hematology analyzer data. In addition, this thesis describes microfluidic devices that prepare samples in laboratory environments. We present microfluidic alternatives to manual procedures for the preparation of virus particles and proteins for transmission electron microscopy, and for the preparation of liquid biopsy samples for cytology investigations.

Abstract [sv]

Provberedning är en kritisk del i biomedicinska analysrutiner för att göra prover kompatibla med instrument i analysens senare moment. Korrekt provberedning är kritiskt för att få pålitliga analysresultat. Konventionell provberedning innehåller dock ofta flera manuella steg, vilket orsakar variation i provkvalitet och kan leda till felaktiga resultat. Mikrofluidik är en lovande teknologi för att hantera dessa problem. Genom att integrera provberedningssteg som exempelvis volymmätning, vätskehantering och provfixering på ett mikrofluidiskt chip, kan manuell interaktion med provet minimeras. Den här avhandlingen utforskar kapillärdrivna mikrofluidiska chip för provberedning av biomedicinska prover för analys i både patientcentrerade arbetsflöden och labbmiljöer. Patientcentrerad blodanalys, där patienterna själva tar och skickar provet till ett centralt labb för kvalitetssäkrad avläsning, är ett framväxande fält där kapillärdrivna mikrofluidiska lösningar kan möjliggöra pålitlig provberedning även utanför labbet. Blodplasma är guldstandard i blodanalysrutineroch extraheras vanligtvis med centrifugering – en utrustning som sällan finns tillgängligt utanför en labbmiljö. För att adressera denna begränsning så utvecklade vi ett mikrofluidiskt chip för kapillärdriven blodplasma-separation från outspädda helblodsprover från människa. Baserat på denna teknik för blodplasma-separation utvecklade vi två olika chip. Det ena extraherar en specifik volym blodplasma som torkar in, och är därefter redo att transporteras till ett labb för masspektrometri. Det andra utför den kritiska analytbindningen i multiplexa immunanalyser under tiden som provet tas. Intorkning av vätskeprovet och efterföljande transport till ett labb möjliggör användandet av högspecialiserad labbutrustning. Vi visar även att en speciell behandling avtorkade blodprover gör det möjligt att kvantifiera röda och vita blodkroppar med god korrelation till guldstandard inom hematologi. Utöver detta beskriver den här avhandlingen mikrofluidiska chip som förbereder prover i labbmiljöer. Vi presenterar mikrofluidiska alternativ till manuella procedurer för beredning av viruspartiklar och proteiner för transmissionselektronmikroskopi och för beredningen av biopsiprover i vätskeform för cytologiska utvärderingar.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2022. p. xi, 66
Series
TRITA-EECS-AVL ; 2022:38
National Category
Medical Engineering
Identifiers
urn:nbn:se:kth:diva-312124 (URN)978-91-8040-248-4 (ISBN)
Public defence
2022-06-10, Kollegiesalen, Brinellvägen 6, Stockholm, 13:00 (English)
Opponent
Supervisors
Note

QC 20220518

Available from: 2022-05-18 Created: 2022-05-11 Last updated: 2023-02-28Bibliographically approved

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Hauser, JanoschLenk, GabrielStemme, GöranRoxhed, Niclas

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