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Molinero-Fernandez, A., Wang, Q., Xuan, X., Konradsson-Geuken, Å., Crespo, G. A. & Cuartero, M. (2024). Demonstrating the Analytical Potential of a Wearable Microneedle-Based Device for Intradermal CO2 Detection. ACS Sensors, 9(1), 361-370
Open this publication in new window or tab >>Demonstrating the Analytical Potential of a Wearable Microneedle-Based Device for Intradermal CO2 Detection
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2024 (English)In: ACS Sensors, E-ISSN 2379-3694, Vol. 9, no 1, p. 361-370Article in journal (Refereed) Published
Abstract [en]

Monitoring of carbon dioxide (CO2) body levels is crucial under several clinical conditions (e.g., human intensive care and acid–base disorders). To date, painful and risky arterial blood punctures have been performed to obtain discrete CO2 measurements needed in clinical setups. Although noninvasive alternatives have been proposed to assess CO2, these are currently limited to benchtop devices, requiring trained personnel, being tedious, and providing punctual information, among other disadvantages. To the best of our knowledge, the literature and market lack a wearable device for real-time, on-body monitoring of CO2. Accordingly, we have developed a microneedle (MN)-based sensor array, labeled as CO2–MN, comprising a combination of potentiometric pH- and carbonate (CO32–)-selective electrodes together with the reference electrode. The CO2–MN is built on an epidermal patch that allows it to reach the stratum corneum of the skin, measuring pH and CO32– concentrations directly into the interstitial fluid (ISF). The levels for the pH–CO32– tandem are then used to estimate the PCO2 in the ISF. Assessing the response of each individual MN, we found adequate response time (t95 < 5s), sensitivity (50.4 and −24.6 mV dec–1 for pH and CO32–, respectively), and stability (1.6 mV h–1 for pH and 2.1 mV h–1 for CO32–). We validated the intradermal measurements of CO2 at the ex vivo level, using pieces of rat skin, and then, with in vivo assays in anesthetized rats, showing the suitability of the CO2–MN wearable device for on-body measurements. A good correlation between ISF and blood CO2 concentrations was observed, demonstrating the high potential of the developed MN sensing technology as an alternative to blood-based analysis in the near future. Moreover, these results open new horizons in the noninvasive, real-time monitoring of CO2 as well as other clinically relevant gases. 

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2024
Keywords
blood correlation, CO2 sensing, in vivo measurements, interstitial fluid, ion-selective microneedles, wearable sensor
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:kth:diva-367150 (URN)10.1021/acssensors.3c02086 (DOI)001152678300001 ()38175931 (PubMedID)2-s2.0-85182013919 (Scopus ID)
Note

QC 20250715

Available from: 2025-07-15 Created: 2025-07-15 Last updated: 2025-07-15Bibliographically approved
Wang, Q., Molinero Fernandez, A., Wei, Q., Xuan, X., Konradsson-Geuken, Å., Cuartero, M. & Crespo, G. A. (2024). Intradermal Lactate Monitoring Based on a Microneedle Sensor Patch for Enhanced In Vivo Accuracy. ACS Sensors, 9(6), 3115-3125
Open this publication in new window or tab >>Intradermal Lactate Monitoring Based on a Microneedle Sensor Patch for Enhanced In Vivo Accuracy
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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
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:kth:diva-353060 (URN)10.1021/acssensors.4c00337 (DOI)001230325600001 ()38778463 (PubMedID)2-s2.0-85194131014 (Scopus ID)
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
Xuan, X., Chen, C., Pérez Ràfols, C., Swaren, M., Wedholm, L., Cuartero, M. & Crespo, G. A. (2023). A Wearable Biosensor for Sweat Lactate as a Proxy for Sport Performance Monitoring. Analysis & Sensing, 3(4), Article ID e202200047.
Open this publication in new window or tab >>A Wearable Biosensor for Sweat Lactate as a Proxy for Sport Performance Monitoring
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2023 (English)In: Analysis & Sensing, E-ISSN 2629-2742, Vol. 3, no 4, article id e202200047Article in journal (Refereed) Published
Abstract [en]

In the last decade, sport performance assessment has significantly transformed due to the appearance of disruptive technologies. Subjective pen and paper notations have evolved into advanced wearable sensing systems that acquire performance-related data. The selection of adequate performance metric variables always causes a debate in sport physiology, and this becomes more relevant once new biochemical indicators are proposed, such as sweat lactate. Here, we analyze the correlation of real-time sweat lactate, obtained with a validated wearable biosensor, with the typical physiological parameters often recorded in sports laboratories (e.g., blood lactate, Borg scale for the rating of perceived exertion, heart rate, power output, blood glucose, and respiratory quotient). We found that the heart rate, power output, Borg scale, and blood lactate relate to sweat lactate in independent individuals during cycling activity. Hence, we demonstrate the potential to associate non-invasive, quantitative, and personalized analysis with sport practice.

Place, publisher, year, edition, pages
Wiley, 2023
Keywords
Blood Lactate Correlation, Exertion Correlation, Sweat Lactate Analysis, Sports Performance, Wearable Biosensor
National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:kth:diva-338716 (URN)10.1002/anse.202200047 (DOI)001063212900001 ()2-s2.0-85163507917 (Scopus ID)
Note

QC 20231123

Available from: 2023-10-24 Created: 2023-10-24 Last updated: 2025-02-11Bibliographically approved
Xuan, X., Chen, C., Perez-Rafols, C., Swaren, M., Wedholm, L., Cuartero, M. & Crespo, G. A. (2023). A Wearable Biosensor for Sweat Lactate as a Proxy for Sport Performance Monitoring. Analysis & Sensing, 3(4), Article ID e202300027.
Open this publication in new window or tab >>A Wearable Biosensor for Sweat Lactate as a Proxy for Sport Performance Monitoring
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2023 (English)In: Analysis & Sensing, E-ISSN 2629-2742, Vol. 3, no 4, article id e202300027Article in journal, Editorial material (Other academic) Published
Abstract [en]

Invited for this month ' s cover are the collaborating groups of Prof. Cuartero and Prof. Crespo at KTH and UCAM universities with the participation of Dalarna University. The cover picture shows a wearable biosensor for the digitalization of lactate in sweat during sport activity. The biosensor is integrated into a microfluidic system for continue lactate monitoring, producing reliable real-time profiles. It was found out that real-time sweat lactate assessment is a potential proxy of personalized training strategies in sports such as cycling." More information can be found in the Research Article by Maria Cuartero, GastonA. Crespo, and co-workers.

Place, publisher, year, edition, pages
Wiley, 2023
National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:kth:diva-338745 (URN)10.1002/anse.202300027 (DOI)001063212900010 ()2-s2.0-85166353687 (Scopus ID)
Note

QC 20231030

Available from: 2023-10-30 Created: 2023-10-30 Last updated: 2025-02-11Bibliographically approved
Xuan, X., Chen, C., Molinero Fernandez, A., Ekelund, E., Cardinale, D., Swarén, M., . . . Crespo, G. A. (2023). Fully Integrated Wearable Device for Continuous Sweat Lactate Monitoring in Sports. ACS Sensors, 8(6), 2401-2409
Open this publication in new window or tab >>Fully Integrated Wearable Device for Continuous Sweat Lactate Monitoring in Sports
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2023 (English)In: ACS Sensors, E-ISSN 2379-3694, Vol. 8, no 6, p. 2401-2409Article in journal (Refereed) Published
Abstract [en]

The chemical digitalization of sweat using wearable sensing interfaces is an attractive alternative to traditional blood-based protocols in sports. Although sweat lactate has been claimed to be a relevant biomarker in sports, an analytically validated wearable system to prove that has not yet been developed. We present a fully integrated sweat lactate sensing system applicable to in situ perspiration analysis. The device can be conveniently worn in the skin to monitor real-time sweat lactate during sports, such as cycling and kayaking. The novelty of the system is threefold: advanced microfluidics design for sweat collection and analysis, an analytically validated lactate biosensor based on a rational design of an outer diffusion-limiting membrane, and an integrated circuit for signal processing with a custom smartphone application. The sensor covering the range expected for lactate in sweat (1-20 mM), with appropriate sensitivity (−12.5 ± 0.53 nA mM-1), shows an acceptable response time (<90 s), and the influence of changes in pH, temperature, and flow rate are neglectable. Also, the sensor is analytically suitable with regard to reversibility, resilience, and reproducibility. The sensing device is validated through a relatively high number of on-body tests performed with elite athletes cycling and kayaking in controlled environments. Correlation outcomes between sweat lactate and other physiological indicators typically accessible in sports laboratories (blood lactate, perceived exhaustion, heart rate, blood glucose, respiratory quotient) are also presented and discussed in relation to the sport performance monitoring capability of continuous sweat lactate.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2023
Keywords
chemical digitization, outer diffusion-limiting membrane, sensing device, sweat lactate, wearable sensing interfaces
National Category
Sport and Fitness Sciences Analytical Chemistry
Identifiers
urn:nbn:se:kth:diva-334853 (URN)10.1021/acssensors.3c00708 (DOI)001003383700001 ()37289663 (PubMedID)2-s2.0-85163553597 (Scopus ID)
Note

QC 20231123

Available from: 2023-08-28 Created: 2023-08-28 Last updated: 2025-09-29Bibliographically approved
Liu, X., Xuan, X., Park, J. Y. & Yin, J. (2023). Preparation of RGO and CNT Composite Thin Film Electrode for Flexible Energy Storage Devices. In: 2022 10th International Symposium on Next Generation Electronics, ISNE 2022: . Paper presented at 10th International Symposium on Next Generation Electronics, ISNE 2022, Wuxi, China, May 5 2023 - May 12 2023. Institute of Electrical and Electronics Engineers (IEEE)
Open this publication in new window or tab >>Preparation of RGO and CNT Composite Thin Film Electrode for Flexible Energy Storage Devices
2023 (English)In: 2022 10th International Symposium on Next Generation Electronics, ISNE 2022, Institute of Electrical and Electronics Engineers (IEEE) , 2023Conference paper, Published paper (Refereed)
Abstract [en]

Recently, miniaturized systems with multiple functionalities, such as such as flexibility, self-powering and sensing capability are urgently desired for the practical applications. In this work, we reported the fabrication of novel reduced graphene oxide and carbon nanotube based composite electrode on the flexible polyimide substrate and explored its physical and electrochemical properties. The proposed composite electrode shows superior properties, such as high flexibility, high surface area, low inner resistance, as well as a high specific capacitance of 208.7 mF/cm2, and energy density of 5.33 mWh/cm2, indicating its great potential in the integrated supercapacitor and sensor applications.

Place, publisher, year, edition, pages
Institute of Electrical and Electronics Engineers (IEEE), 2023
Keywords
CNT, flexible, RGO, sensor, supercapacitor
National Category
Materials Chemistry Condensed Matter Physics
Identifiers
urn:nbn:se:kth:diva-337880 (URN)10.1109/ISNE56211.2023.10221594 (DOI)2-s2.0-85171481602 (Scopus ID)
Conference
10th International Symposium on Next Generation Electronics, ISNE 2022, Wuxi, China, May 5 2023 - May 12 2023
Note

Part of ISBN 9781665455251

QC 20231010

Available from: 2023-10-10 Created: 2023-10-10 Last updated: 2023-10-10Bibliographically approved
Van Hoovels, K., Xuan, X., Cuartero, M., Gijssel, M., Swaren, M. & Crespo, G. A. (2021). Can Wearable Sweat Lactate Sensors Contribute to Sports Physiology?. ACS Sensors, 6(10), 3496-3508
Open this publication in new window or tab >>Can Wearable Sweat Lactate Sensors Contribute to Sports Physiology?
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2021 (English)In: ACS Sensors, E-ISSN 2379-3694, Vol. 6, no 10, p. 3496-3508Article, review/survey (Refereed) Published
Abstract [en]

The rise of wearable sensors to measure lactate content in human sweat during sports activities has attracted the attention of physiologists given the potential of these "analytical tools" to provide real-time information. Beyond the assessment of the sensing technology per se, which, in fact, has not rigorously been validated yet in controlled conditions, there are many open questions about the true usefulness of such wearable sensors in real scenarios. On the one hand, the evidence for the origin of sweat lactate (e.g., via the sweat gland, derivation from blood, or other alternative mechanisms), its high concentration (1-25 mM or even higher) compared to levels in the blood, and the possible correlation between different biofluids (particularly blood) is rather contradictory and generates vivid debate in the field. On the other hand, it is important to point out that accurate detection of sweat lactate is highly dependent on the procedure used to collect and/or reach the fluid, and this can likely explain the large discrepancies reported in the literature. In brief, this paper provides our vision of the current state of the field and a thoughtful evaluation of the possible reasons for present controversies, together with an analysis of the impact of wearable sweat lactate sensors in the physiological context. Finally, although there is not yet overwhelming scientific evidence to provide an unequivocal answer to whether wearable sweat lactate sensors can contribute to sports physiology, we still understand the importance to bring this challenging question up-front to create awareness and guidance in the development, validation, and implementation of wearable sensors.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2021
Keywords
lactate sensor, sweat, sport, physiology, wearable platforms
National Category
Sport and Fitness Sciences Analytical Chemistry Computer Sciences
Identifiers
urn:nbn:se:kth:diva-305099 (URN)10.1021/acssensors.1c01403 (DOI)000711034500002 ()34549938 (PubMedID)2-s2.0-85116709731 (Scopus ID)
Note

QC 20211123

Available from: 2021-11-23 Created: 2021-11-23 Last updated: 2025-02-11Bibliographically approved
Xuan, X., Pérez Ràfols, C., Chen, C., Cuartero, M. & Crespo, G. A. (2021). Lactate Biosensing for Reliable On-Body Sweat Analysis. ACS Sensors, 6(7), 2763-2771
Open this publication in new window or tab >>Lactate Biosensing for Reliable On-Body Sweat Analysis
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2021 (English)In: ACS Sensors, E-ISSN 2379-3694, Vol. 6, no 7, p. 2763-2771Article in journal (Refereed) Published
Abstract [en]

Wearable lactate sensors for sweat analysis are highly appealing for both the sports and healthcare fields. Electrochemical biosensing is the approach most widely used for lactate determination, and this technology generally demonstrates a linear range of response far below the expected lactate levels in sweat together with a high influence of pH and temperature. In this work, we present a novel analytical strategy based on the restriction of the lactate flux that reaches the enzyme lactate oxidase, which is immobilized in the biosensor core. This is accomplished by means of an outer plasticized polymeric layer containing the quaternary salt tetradodecylammonium tetrakis(4-chlorophenyl) borate (traditionally known as ETH500). Also, this layer prevents the enzyme from being in direct contact with the sample, and hence, any influence with the pH and temperature is dramatically reduced. An expanded limit of detection in the millimolar range (from 1 to 50 mM) is demonstrated with this new biosensor, in addition to an acceptable response time; appropriate repeatability, reproducibility, and reversibility (variations lower than 5% for the sensitivity); good resiliency; excellent selectivity; low drift; negligible influence of the flow rate; and extraordinary correlation (Pearson coefficient of 0.97) with a standardized method for lactate detection such as ion chromatography (through analysis of 22 sweat samples collected from 6 different subjects performing cycling or running). The developed lactate biosensor is suitable for on-body sweat lactate monitoring via a microfluidic epidermal patch additionally containing pH and temperature sensors. This applicability was demonstrated in three different body locations (forehead, thigh, and back) in a total of five on-body tests while cycling, achieving appropriate performance and validation. Moreover, the epidermal patch for lactate sensing is convenient for the analysis of sweat stimulated by iontophoresis in the subjects' arm, which is of great potential toward healthcare applications.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2021
Keywords
lactate biosensor, diffusion limiting membranes, real-time monitoring, sweat analysis, wearable sensors
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:kth:diva-299678 (URN)10.1021/acssensors.1c01009 (DOI)000677583700029 ()34228919 (PubMedID)2-s2.0-85111023899 (Scopus ID)
Note

QC 20210823

Available from: 2021-08-23 Created: 2021-08-23 Last updated: 2025-09-29Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-4648-1861

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