Integrated Electrochemical Aptamer Biosensing and Colorimetric pH Monitoring via Hydrogel Microneedle Assays for Assessing Antibiotic Treatment

Author:

Keyvani Fatemeh1,GhavamiNejad Peyman1,Saleh Mahmoud Ayman2,Soltani Mohammad1,Zhao Yusheng3,Sadeghzadeh Sadegh1,Shakeri Arash3,Chelle Pierre3,Zheng Hanjia1,Rahman Fasih A.4,Mahshid Sarah2,Quadrilatero Joe4,Rao Praveen P. N.3,Edginton Andrea3,Poudineh Mahla1ORCID

Affiliation:

1. Department of Electrical and Computer Engineering Faculty of Engineering University of Waterloo Waterloo Ontario N2L 3G1 Canada

2. Department of Bioengineering McGill University 815 Sherbrooke St. W Montreal Quebec H3A 0C3 Canada

3. School of Pharmacy University of Waterloo Waterloo Ontario N2L 3G1 Canada

4. Department of Kinesiology and Health Sciences University of Waterloo Waterloo Ontario N2L 3G1 Canada

Abstract

AbstractCurrent methods for therapeutic drug monitoring (TDM) have a long turnaround time as they involve collecting patients' blood samples followed by transferring the samples to medical laboratories where sample processing and analysis are performed. To enable real‐time and minimally invasive TDM, a microneedle (MN) biosensor to monitor the levels of two important antibiotics, vancomycin (VAN) and gentamicin (GEN) is developed. The MN biosensor is composed of a hydrogel MN (HMN), and an aptamer‐functionalized flexible (Flex) electrode, named HMN‐Flex. The HMN extracts dermal interstitial fluid (ISF) and transfers it to the Flex electrode where sensing of the target antibiotics happens. The HMN‐Flex performance is validated ex vivo using skin models as well as in vivo in live rat animal models. Data is leveraged from the HMN‐Flex system to construct pharmacokinetic profiles for VAN and GEN and compare these profiles with conventional blood‐based measurements. Additionally, to track pH and monitor patient's response during antibiotic treatment, an HMN is developed that employs a colorimetric method to detect changes in the pH, named HMN‐pH assay, whose performance has been validated both in vitro and in vivo. Further, multiplexed antibiotic and pH detection is achieved by simultaneously employing the HMN‐pH and HMN‐Flex on live animals.

Publisher

Wiley

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