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Intradermal Glycine Detection with a Wearable Microneedle Biosensor: The First In Vivo Assay
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Applied Physical Chemistry.ORCID iD: 0000-0002-6128-5340
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Applied Physical Chemistry.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Applied Physical Chemistry.ORCID iD: 0000-0002-6341-1910
Section of Neuropharmacology and Addiction Research, Department of Pharmaceutical Biosciences, Uppsala University, SE-751 05 Uppsala, Sweden.
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2022 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 94, no 34, p. 11856-11864Article in journal (Refereed) Published
Abstract [en]

Glycine (GLY) is gaining importance in medical diagnoses due to its relationship with multiple physiological functions. Today, GLY is exclusively analyzed using instrumentation centralized in clinical labs, and a tangible point-of-care tool that gathers real-time data from the patient for effective and fast evaluations is lacking. Relevant clinical advances are expected as soon as the rapid provision of both punctual and continuous measurements is possible. In that context, this work presents a microneedle (MN)-based biosensor for intradermal GLY detection in interstitial fluid (ISF). The MN tip is externally tailored to detect GLY levels through the hydrogen peroxide formed in its reaction with a quinoprotein-based GLY oxidase enzyme. The analytical performance of the MN biosensor indicates a fast response time (<7 s); acceptable reversibility, reproducibility, and stability; as well as a wide linear range of response (25-600 μM) that covers the physiological levels of GLY in ISF. The MN biosensor conveniently exhibits high selectivity for GLY over other compounds commonly found in ISF, and the response is not influenced by temperature, pH, or skin insertions. Validated intradermal measurements of GLY were obtained at the in vitro (with pieces of rat skin), ex vivo (on-body tests of euthanized rats) and in vivo (on-body tests of anesthetized rats) levels, demonstrating its ability to produce accurate physiological data. The developed GLY MN biosensor is skin-wearable and provides reliable, real-time intradermal GLY measurements in ISF by means of a minimally invasive approach.

Place, publisher, year, edition, pages
American Chemical Society (ACS) , 2022. Vol. 94, no 34, p. 11856-11864
National Category
Analytical Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-329060DOI: 10.1021/acs.analchem.2c02317ISI: 000846740600001PubMedID: 35979995Scopus ID: 2-s2.0-85136467122OAI: oai:DiVA.org:kth-329060DiVA, id: diva2:1768055
Note

QC 20230614

Available from: 2023-06-14 Created: 2023-06-14 Last updated: 2024-09-24Bibliographically approved
In thesis
1. Electrochemical Biosensing Platforms for Human and Plant Monitoring
Open this publication in new window or tab >>Electrochemical Biosensing Platforms for Human and Plant Monitoring
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A growing demand has emerged for new point-of-care (POC) platforms capable of delivering reliable clinical data in real-time through minimally invasive procedures. Currently, the majority of clinical data is derived from analyzing collected biological samples, primarily blood or plant sap. Unfortunately, these methods cost discomfort to patients, and are even destructive to plants. For example, conventional sap collection requires sacrifice the plants. The lack of portable tools for fast, on-site patient/plant monitoring has driven research into alternative strategies using biosensors.

The glucometer (i.e. blood glucose meter) stands out as one of the most successful examples of a POC device. It reflects the key features we strive for in such a biosensing platform: minimal limitations on who and where it can be used, combined with high reliability and affordability. Electrochemical readouts are advantageous in this case due to its fast response, wide detection range, and ease of integration into portable devices. This doctoral thesis introduces advancements of electrochemical biosensing platforms for detecting various analytes both in humans and plants. The key findings are summarized in the Results and Discussion section based on the four published research articles.

Briefly, the first type of electrochemical biosensor was developed for the determination of glycine in various human biofluids (e.g., blood, sweat, and urine). Considering the increasing importance of amino acid detection for clinical applications, we then created a new biosensing platform based on microneedles (MN) that aims to measure in dermal interstitial fluid. This minimally invasive strategy highlights the novelty of our second work. Third, we extended MN-based biosensors to another important analyte, lactate, which is previously widely analyzed in sweat. Finally, we demonstrated the first example of applying the MN sensors for continuous and real-time plant monitoring.

Abstract [sv]

En växande efterfrågan har uppstått på nya point-of-care-plattformar (POC) som kan leverera tillförlitliga kliniska data i realtid genom minimalt invasiva procedurer. För närvarande härrör majoriteten av kliniska data från analys av insamlade biologiska prover, främst blod eller växtsaft. Tyvärr kostar dessa metoder obehag för patienter och är till och med destruktiva för växter, eftersom konventionell savinsamling kräver att växterna offras. Bristen på bärbara verktyg för snabb patient-/anläggningsövervakning på plats har drivit forskning på alternativa strategier som använder biosensorer.

Glukometern (dvs blodsockermätaren) framstår som ett av de mest framgångsrika exemplen på en POC-enhet. Det återspeglar nyckelfunktionerna vi strävar efter i en sådan biosensingplattform: minimala begränsningar för vem och var den kan användas, kombinerat med hög tillförlitlighet och prisvärdhet. Noterbart är den elektrokemiska avläsningen fördelaktig i detta fall på grund av dess snabba svar, breda detekteringsområde och enkla integration i bärbara enheter. I detta avseende introducerar denna doktorsavhandling framsteg inom elektrokemiska bioavkänningsplattformar för att detektera olika analyter både hos människor och växter. De viktigaste resultaten sammanfattas i avsnittet Resultat och diskussion baserat på de fyra publicerade artiklarna.

Först utvecklades den första typen av elektrokemisk biosensor för bestämning av glycin i olika humana biovätskor (t.ex. blod, svett och urin). Med tanke på den ökande betydelsen av aminosyradetektering för kliniska tillämpningar skapade vi sedan en ny biosensingplattform baserad på mikronålar (MN) som syftar till att mäta i interstitiell vätska (ISF). Denna minimalt invasiva strategi framhäver nyheten i vårt andra arbete. För det tredje utökar vi MN-baserade biosensorer till en annan viktig analyt, laktat, som tidigare analyserats flitigt i svett. Slutligen visade vi det första exemplet på att använda MN-sensorer för kontinuerlig och realtidsövervakning av anläggningar.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2024. p. 132
Series
TRITA-CBH-FOU ; 2024:40
Keywords
Biosensor, Microneedle, Interstitial Fluid, Glycine, Lactate, Ions, Plant
National Category
Analytical Chemistry
Research subject
Chemistry
Identifiers
urn:nbn:se:kth:diva-353668 (URN)978-91-8106-062-1 (ISBN)
Public defence
2024-10-16, F3 (Flodis), Lindstedtsvägen 26, Stockholm, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

QC 20240924

Available from: 2024-09-24 Created: 2024-09-20 Last updated: 2025-12-02Bibliographically approved

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Wang, QianyuMolinero Fernandez, AguedaCasanova, AnaCrespo, Gaston A.Cuartero, Maria

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