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Electronic Tongue for Direct Assessment of SARS-CoV-2-Free and Infected Human Saliva-A Feasibility Study
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
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2023 (English)In: Biosensors, ISSN 2079-6374, Vol. 13, no 7, article id 717Article in journal (Refereed) Published
Abstract [en]

An electronic tongue is a powerful analytical instrument based on an array of non-selective chemical sensors with a partial specificity for data gathering and advanced pattern recognition methods for data analysis. Connecting electronic tongues with electrochemical techniques for data collection has led to various applications, mostly within sensing for food quality and environmental monitoring, but also in biomedical research for the analyses of different bioanalytes in human physiological fluids. In this paper, an electronic tongue consisting of six electrodes (viz., gold, platinum, palladium, titanium, iridium, and glassy carbon) was designed and tested in authentic (undiluted, unpretreated) human saliva samples from eight volunteers, collected before and during the COVID-19 pandemic. Investigations of 11 samples using differential pulse voltammetry and a principal component analysis allowed us to distinguish between SARS-CoV-2-free and infected authentic human saliva. This work, as a proof-of-principle demonstration, provides a new perspective for the use of electronic tongues in the field of enzyme-free electrochemical biosensing, highlighting their potential for future applications in non-invasive biomedical analyses.

Place, publisher, year, edition, pages
MDPI, 2023. Vol. 13, no 7, article id 717
Keywords [en]
electronic tongue, differential pulse voltammetry, principial component analysis, authentic human saliva, SARS-CoV-2
National Category
Analytical Chemistry
Identifiers
URN: urn:nbn:se:mau:diva-61908DOI: 10.3390/bios13070717ISI: 001038044400001PubMedID: 37504115Scopus ID: 2-s2.0-85165896609OAI: oai:DiVA.org:mau-61908DiVA, id: diva2:1788456
Available from: 2023-08-16 Created: 2023-08-16 Last updated: 2024-02-26Bibliographically approved
In thesis
1. Electrochemical (bio-)sensors operating in human physiological fluids
Open this publication in new window or tab >>Electrochemical (bio-)sensors operating in human physiological fluids
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis is focused on developing electrochemical (bio-)sensors specifically designed to detect biomolecules and bacteria in human physiological fluids. A more comprehensive understanding of their performance can be obtained by exposing the sensors to real human physiological fluids. Thus, four biosensors were designed and tested in saliva, plasma, blood, and urine. Specifically, a voltammetric electronic tongue, integrating six different electrode materials, was developed to qualitatively assess SARS-CoV-2 in saliva samples using principal component analysis. A tubular enzyme-based sensor utilizing incorporated cellobiose dehydrogenase in an Os(bpy)PVI redox polymer was employed for continuous glucose sensing in human plasma and undiluted whole blood under homeostatic conditions. Two different sensing concepts were developed for the label-free detection of bacteria (Escherichia coli, Enterococcus faecalis, and Klebsiella pneumoniae) in artificial urine and human urine based on metabolic activity due to bacterial growth. The first sensor enabled continuous bacterial detection by reducing Prussian Blue deposited on screen-printed electrodes with wireless data transfer. The second bacterial-sensitive sensor utilized electrochemical characterization to identify three bacteria types based on artificial urine metabolic changes. For a qualitative investigation of the metabolic changes, nuclear magnetic resonance was utilized, and flow cytometry was used to quantify and correlate bacterial growth with electrochemistry. Multivariate statistical data analysis was applied to distinguish bacteria-free and bacteria-infected artificial urine. Finally, an overview of the recent advances in the field of non-invasive electrochemical biosensors operating in secreted human physiological fluids, viz., tears, sweat, saliva, and urine, was given.

Abstract [sv]

Denna avhandling är inriktad på utveckling av elektrokemiska (bio-)sensorer som är särskilt utformade för detektering av biomolekyler och bakterier i mänskliga fysiologiska vätskor. Genom att undersöka sensorerna i verkliga mänskliga fysiologiska vätskor, kan man få en mer omfattande förståelse för deras prestanda. Fyra olika biosensorer har utformats och testats i saliv, plasma, blod och urin. En voltammetrisk elektronisk tunga, som integrerar sex olika elektrodmaterial, utvecklades för kvalitativ bedömning av SARS-CoV-2 i salivprover med hjälp av principalkomponentanalys. En rörformad enzymbaserad sensor som använder inkorporerat Cellobiose Dehydrogenase i en Os(bpy)PVI redoxpolymer användes för kontinuerlig glukosmätning i humant plasma och outspätt helblod under homeostatiska förhållanden. Dessutom utvecklades två olika sensorkoncept för märkningsfri detektion av bakterier (Escherichia coli, Enterococcus faecalis och Klebsiella pneumoniae) i artificiell urin och humanurin baserat på metabolisk aktivitet till följd av bakterietillväxt. Den första sensorn möjliggjorde kontinuerlig bakteriedetektion genom reduktion av preussiskt blått elektroder med trådlös dataöverföring. Den andra bakteriekänsliga sensorn använde elektrokemisk karakterisering för att identifiera tre typer av bakterier baserat på metaboliska förändringar i artificiell urin. För en kvalitativ undersökning av de metaboliska förändringarna användes dessutom nukleär magnetisk resonans och flödescytometri för att kvantifiera och korrelera bakterietillväxt med elektrokemi. Multivariat statistisk dataanalys användes för att skilja mellan bakteriefri och bakterieinfekterad (artificiell) urin. Slutligen gavs en översikt över de senaste framstegen inom området för icke-invasiva elektrokemiska biosensorer som arbetar i utsöndrade mänskliga fysiologiska vätskor, dvs. tårar, svett, saliv och urin.

Abstract [de]

Diese Arbeit fokussiert sich auf die Entwicklung elektrochemischer (Bio-)Sensoren, die speziell für den Nachweis von Biomolekülen und Bakterien inmenschlichen physiologischen Flüssigkeiten konzipiert sind. Indem die Sensorenhumanen, physiologischen Flüssigkeiten ausgesetzt werden, kann einumfassenderes Verständnis ihrer Funktionalität gewonnen werden. Im Einzelnenwurden vier verschiedene Biosensoren entwickelt und in Speichel, Plasma, Blutund Urin getestet. Für die qualitative Bewertung von SARS-CoV-2 inSpeichelproben unter Verwendung der Hauptkomponentenanalyse wurde einevoltammetrische „elektronische Zunge“, die sechs verschiedeneElektrodenmaterialien integriert, entwickelt. Zur kontinuierlichenGlukosemessung in menschlichem Plasma und unverdünntem Vollblut unterhomöostatischen Bedingungen wurden tubuläre enzymbasierte Sensorenverwendet, die die eingebaute Cellobiose-Dehydrogenase in einem Os (bpy) -PVI-Redoxpolymer verwenden. Darüber hinaus wurden zwei verschiedeneSensorkonzepte für den Nachweis von Bakterien (Escherichia coli, Enterococcusfaecalis und Klebsiella pneumoniae) in synthetischem und menschlichem Urinentwickelt, basierend auf der Stoffwechselaktivität während bakteriellemWachstum. Der erste Sensor ermöglichte einen kontinuierlichen Nachweis vonBakterien durch die Reduktion von „Prussian Blue“-Elektroden mit drahtloserDatenübertragung. Der zweite Sensor nutzte eine voltammetrische „elektronischeZunge“ zur Identifizierung von drei Bakterientypen aufgrund von spezifischen,metabolischen Veränderungen in synthetischem Urin. Zur qualitativenUntersuchung dieser Veränderungen wurde die Kernspinresonanz eingesetzt. DieDurchflusszytometrie diente zur Quantifizierung und Korrelation desBakterienwachstums mit der Elektrochemie, wobei multivariate statistischeDatenanalysen zur Unterscheidung von bakterienfreiem und bakterieninfiziertem(synthetischen) Urin eingesetzt wurden. Abschließend wurde ein Überblick überdie aktuellen Fortschritte auf dem Gebiet der nicht-invasiven elektrochemischenBiosensoren gegeben, die mit den physiologischen Flüssigkeiten des Menschen,d. h. in Tränen, Schweiß, Speichel und Urin, arbeiten. 

Place, publisher, year, edition, pages
Malmö: Malmö university Press, 2023. p. 74
Series
Malmö University Health and Society Dissertations, ISSN 1653-5383, E-ISSN 2004-9277 ; 2023:3
Keywords
biosensor, bacteria, enzyme, sensor, physiological fluid
National Category
Analytical Chemistry Microbiology in the medical area
Identifiers
urn:nbn:se:mau:diva-63045 (URN)10.24834/isbn.9789178773992 (DOI)978-91-7877-398-5 (ISBN)978-91-7877-399-2 (ISBN)
Public defence
2023-09-22, Aulan, Jan Waldenströms gata 25, 14:00 (English)
Opponent
Supervisors
Note

Paper V in dissertation as Manuscript with title "Electrochemical characterization of bacteria-infected artificial urine using an electronic tongue approach"

Available from: 2023-10-10 Created: 2023-10-09 Last updated: 2024-05-24Bibliographically approved
2. Non-invasive biomedical analysis: recent advances, challenges, and future perspectives
Open this publication in new window or tab >>Non-invasive biomedical analysis: recent advances, challenges, and future perspectives
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Non-invasive healthcare technologies are increasingly pivotal in research anddevelopment due to their affordability and the convenience they offer to bothhealthcare recipients and providers. Alongside traditional non-invasive methodssuch as ultrasound imaging, a variety of innovative non-invasive devices havebeen developed. These include cardiovascular diagnostic systems, bioimpedancebasedscales, and various types of analyzers. These analyzers, which can be fluidlessor fluid-based, are capable of measuring not just physical parameters of thebody but also key biomarkers like glucose and lactate. This comprehensive andtransdisciplinary thesis encompasses three distinct yet interconnected segments:1) Advanced ultrasound imaging (Papers I and II): The first explored vortexformation time in female athletes and the second detailed investigations of thesuperficial venous systems of apparently healthy volunteers.2) Validation and application of commercially available fluid-less bloodanalyzers (Papers IV-VI). These papers focus on non-invasive blood glucosemonitoring (Paper IV) and the general use of non-invasive healthcaretechnologies among female participants from socioeconomicallydisadvantaged areas (Papers V and VI).3) Design and testing of novel, fluid-based sensors, and biosensors (Papers II andIII): Paper II delves into biosensing of viruses, and paper III deals withcontinuous ex vivo glucose sensing in human blood using an enzymatic sensorin a vein replica.Each of these segments contribute to the broader understanding and advancementof non-invasive healthcare technologies, highlighting the significant role suchtechnologies play in modern healthcare research. The thesis's transdisciplinaryapproach, spanning from advanced imaging techniques to the development ofnovel biosensors, exemplifies the dynamic and evolving nature of medicaltechnology research.

Place, publisher, year, edition, pages
Malmö: Malmö University Press, 2024. p. 64
Series
Malmö University Health and Society Dissertations, ISSN 1653-5383, E-ISSN 2004-9277 ; 2024:3
National Category
Biomedical Laboratory Science/Technology
Research subject
Health and society
Identifiers
urn:nbn:se:mau:diva-66097 (URN)10.24834/isbn.9789178774562 (DOI)978-91-7877-455-5 (ISBN)978-91-7877-456-2 (ISBN)
Public defence
2024-03-01, Aula, Health, and Society, Jan Waldenströms gata 25, 205 06, Malmö, 13:00 (English)
Opponent
Supervisors
Note

Paper IV in dissertation as manuscript

Available from: 2024-02-27 Created: 2024-02-26 Last updated: 2024-05-24Bibliographically approved

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Falk, MagnusPsotta, CarolinCirovic, StefanOhlsson, LarsShleev, Sergey

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