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

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.

Opportunities and challenges in the diagnostic utility of dermal interstitial fluid

“…A similar approach led to a wearable microneedle patch that enzymatically measured glucose, lactate and alcohol in the ISF of a few individuals, thus allowing for metabolic monitoring 88 . Additionally, electrochemical aptamers have been used in place of enzymes within a microneedle patch to perform therapeutic-drug measurements in rat ISF 89,90 .…”

Emerging biotransduction strategies on soft interfaces for biosensing

“…55 Recently, wearable electrochemical aptamer biosensing (EAB) had been used to realize a precision dosage of drugs. 56 In this EAB system, a redox signal reporter (methylene blue) is coupled with an aptamer which is immobilized on Au NPs. The aptamer-target binding event alters the charge transfer rate between the signal reporter and electrode surface, which can be measured via voltammetry-based approaches.…”

“…The aptamer-target binding event alters the charge transfer rate between the signal reporter and electrode surface, which can be measured via voltammetry-based approaches. 56 In addition, aptamers are often used in the field-effect transistor (FET) system with high sensitivity. The FET sensor is composed of a source, drain, and gate electrode, and any slight change caused by the charged species near the gate electrode can translate into a detectable signal of the FET drain.…”

Nucleic Acid Molecular Systems for In Vitro Detection of Biomolecules

“…22 A wearable aptamer-based detection device has been reported for continuous monitoring of therapeutic drug concentrations in vivo. 23 An all-in-one test kit would have enormous practical application potentials in clinical settings or in fields demanding point-of-care testing. In summary, molecular detection systems consisting of nucleic acids have demonstrated unparalleled capability and versatility for the in vitro detection of biomolecules in laboratories, which will soon be translated into bedside and field applications to largely contribute to and benefit human healthcare.…”