4.8 Article

Intradermal Glycine Detection with a Wearable Microneedle Biosensor: The First In Vivo Assay

Journal

ANALYTICAL CHEMISTRY
Volume 94, Issue 34, Pages 11856-11864

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.2c02317

Keywords

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Funding

  1. Swedish Research Council [VR-2019-04142]
  2. Stiftelsen Olle Engkvist Byggmas ? [204- 0214]
  3. Novo Nordisk Fonden (Exploratory Pre-Seed Grant) [19OC0056171]
  4. Carl Tryggers Stiftelse [CTS 20:88]
  5. China Scholarship Council
  6. Karolinska Experimental Research and Imaging Centre (KERIC)
  7. Uppsala University Behavior Facility
  8. Swedish Research Council [2019-04142] Funding Source: Swedish Research Council

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This study developed a microneedle-based biosensor for intradermal detection of glycine. The biosensor demonstrated fast response time, acceptable reversibility and stability, a wide linear range of response, and the ability to produce accurate physiological data.
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 mu M) 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.

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