4.8 Article

Wearable microneedle-based electrochemical aptamer biosensing for precision dosing of drugs with narrow therapeutic windows

Journal

SCIENCE ADVANCES
Volume 8, Issue 38, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abq4539

Keywords

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Funding

  1. National Science Foundation [1847729]
  2. Brain and Behavior Foundation (National Alliance for Research on Schizophrenia and Depression Young Investigator Grant)
  3. Precise Advanced Technologies and Health Systems for Underserved Populations (PATHS-UP, NSF Engineering Research Center) [648451]
  4. UCLA Innovation Fund
  5. NIH/NCI [CA221296-01A1]
  6. Melanoma Research Alliance [564714]
  7. UCLA Dissertation Year Fellowship
  8. UCLA Graduate Dean's Scholar Award

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The study introduces a microneedle-based electrochemical aptamer biosensing patch for minimally invasive monitoring of interstitial fluid and real-time measurement of drug pharmacokinetics. By transforming a clinical-grade needle into a high-quality gold nanoparticle-based substrate through a cost-effective fabrication scheme, reliable in vivo detection of ISF analytes, including those without natural recognition elements, is achieved.
Therapeutic drug monitoring is essential for dosing pharmaceuticals with narrow therapeutic windows. Nevertheless, standard methods are imprecise and involve invasive/resource-intensive procedures with long turnaround times. Overcoming these limitations, we present a microneedle-based electrochemical aptamer biosensing patch (mu NEAB-patch) that minimally invasively probes the interstitial fluid (ISF) and renders correlated, continuous, and real-time measurements of the circulating drugs' pharmacokinetics. The mu NEAB-patch is created following an introduced low-cost fabrication scheme, which transforms a shortened clinical-grade needle into a high-quality gold nanoparticle-based substrate for robust aptamer immobilization and efficient electrochemical signal retrieval. This enables the reliable in vivo detection of a wide library of ISF analytes-especially those with nonexistent natural recognition elements. Accordingly, we developed mu NEABs targeting various drugs, including antibiotics with narrow therapeutic windows (tobramycin and vancomycin). Through in vivo animal studies, we demonstrated the strong correlation between the ISF/circulating drug levels and the device's potential clinical use for timely prediction of total drug exposure.

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