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Intradermal Lactate Monitoring Based on a Microneedle Sensor Patch for Enhanced In Vivo Accuracy
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. UCAM-SENS, Universidad Católica San Antonio de Murcia, UCAM HiTech, Avda. Andres Hernandez Ros 1, 30107 Murcia, Spain.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Applied Physical Chemistry.ORCID iD: 0000-0003-0811-4259
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Applied Physical Chemistry. UCAM-SENS, Universidad Católica San Antonio de Murcia, UCAM HiTech, Avda. Andres Hernandez Ros 1, 30107 Murcia, Spain.ORCID iD: 0000-0002-4648-1861
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2024 (English)In: ACS Sensors, E-ISSN 2379-3694, Vol. 9, no 6, p. 3115-3125Article in journal (Refereed) Published
Abstract [en]

Lactate is an important diagnostic and prognostic biomarker of several human pathological conditions, such as sepsis, malaria, and dengue fever. Unfortunately, due to the lack of reliable analytical decentralized platforms, the determination of lactate yet relies on discrete blood-based assays, which are invasive and inefficient and may cause tension and pain in the patient. Herein, we demonstrate the potential of a fully integrated microneedle (MN) sensing system for the minimally invasive transdermal detection of lactate in an interstitial fluid (ISF). The originality of this analytical technology relies on: (i) a strategy to provide a uniform coating of a doped polymer-based membrane as a diffusion-limiting layer on the MN structure, optimized to perform full-range lactate detection in the ISF (linear range of response: 0.25–35 mM, 30 s assay time, 8 h operation), (ii) double validation of ex vivo and in vivo results based on ISF and blood measurements in rats, (iii) monitoring of lactate level fluctuations under the administration of anesthesia to mimic bedside clinical scenarios, and (iv) in-house design and fabrication of a fully integrated and portable sensing device in the form of a wearable patch including a custom application and user-friendly interface in a smartphone for the rapid, routine, continuous, and real-time lactate monitoring. The main analytical merits of the lactate MN sensor include appropriate selectivity, reversibility, stability, and durability by using a two-electrode amperometric readout. The ex-vivo testing of the MN patch of preconditioned rat skin pieces and euthanized rats successfully demonstrated the accuracy in measuring lactate levels. The in vivo measurements suggested the existence of a positive correlation between ISF and blood lactate when a lag time of 10 min is considered (Pearson’s coefficient = 0.85, mean difference = 0.08 mM). The developed MN-based platform offers distinct advantages over noncontinuous blood sampling in a wide range of contexts, especially where access to laboratory services is limited or blood sampling is not suitable. Implementation of the wearable patch in healthcare could envision personalized medicine in a variety of clinical settings.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2024. Vol. 9, no 6, p. 3115-3125
National Category
Analytical Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-353060DOI: 10.1021/acssensors.4c00337ISI: 001230325600001PubMedID: 38778463Scopus ID: 2-s2.0-85194131014OAI: oai:DiVA.org:kth-353060DiVA, id: diva2:1896924
Funder
Swedish Research Council, VR-2019-04142Carl Tryggers foundation , CTS 20:88Olle Engkvists stiftelse, 204-0214
Note

QC 20240917

Available from: 2024-09-11 Created: 2024-09-11 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: 2024-09-24Bibliographically approved

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Wang, QianyuMolinero Fernandez, AguedaWei, QikunXuan, XingCuartero, MariaCrespo, Gaston A.

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