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

Shuyu Lin; Xuanbing Cheng; Jialun Zhu; Bo Wang; David Jelinek; Yichao Zhao; Tsung-Yu Wu; Abraham Horrillo; Jiawei Tan; Justin Yeung; Wenzhong Yan; Sarah Forman; Hilary A Coller; Carlos Milla; Sam Emaminejad

doi:10.1126/sciadv.abq4539

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

Sci Adv. 2022 Sep 23;8(38):eabq4539. doi: 10.1126/sciadv.abq4539. Epub 2022 Sep 23.

Authors

Shuyu Lin^{1

2}, Xuanbing Cheng^{3

2

4}, Jialun Zhu^{3

2

4}, Bo Wang^{3

2}, David Jelinek^{5

6}, Yichao Zhao^{3

2

4}, Tsung-Yu Wu^{3

2

4}, Abraham Horrillo⁵, Jiawei Tan^{3

2

4}, Justin Yeung^{3

4}, Wenzhong Yan⁷, Sarah Forman^{3

5}, Hilary A Coller^{5

8

9}, Carlos Milla¹⁰, Sam Emaminejad^{3

2

11}

Affiliations

¹ Interconnected and Integrated Bioelectronics Lab (I2BL), University of California, Los Angeles, Los Angeles, CA, USA.
² Department of Electrical and Computer Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
³ Interconnected and Integrated Bioelectronics Lab (IBL), University of California, Los Angeles, Los Angeles, CA, USA.
⁴ Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
⁵ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Weintraub Center for Reconstructive Biotechnology, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
⁷ Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
⁸ Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁹ Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA.
¹⁰ The Stanford Cystic Fibrosis Center, Center for Excellence in Pulmonary Biology, Stanford School of Medicine, Stanford, CA, USA.
¹¹ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.

Abstract

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 (μNEAB-patch) that minimally invasively probes the interstitial fluid (ISF) and renders correlated, continuous, and real-time measurements of the circulating drugs' pharmacokinetics. The μNEAB-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 μNEABs 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.