A Biomimetic Phosphatidylcholine‐Terminated Monolayer Greatly Improves the In Vivo Performance of Electrochemical Aptamer‐Based Sensors

Abstract

The real-time monitoring of specific analytes in situ in the living body would greatly advance our understanding of physiology and the development of personalized medicine. Because they are continuous (wash-free and reagentless) and are able to work in complex media (e.g., undiluted serum), electrochemical aptamer-based (E-AB) sensors are promising candidates to fill this role.E-AB sensors suffer,however,from often-severe baseline drift when deployed in undiluted whole blood either in vitro or in vivo.W ed emonstrate that cellmembrane-mimicking phosphatidylcholine (PC)-terminated monolayers improve the performance of E-AB sensors, reducing the baseline drift from around 70 %t oj ust af ew percent after several hours in flowing whole blood in vitro. With this improvement comes the ability to deploy E-AB sensors directly in situ in the veins of live animals,a chieving micromolar precision over many hours without the use of physical barriers or active drift-correction algorithms.

High-Precision Control of Plasma Drug Levels Using Feedback-Controlled Dosing

“…35−37 Because this signaling mechanism is independent of the chemical reactivity of the target, E-AB sensors can be and have been developed against a wide variety of targets. 31,35,38−48 Their signaling mechanism also renders E-AB sensors reagentless, reversible, and selective enough to support measurements in situ in the living body, 28,32,37,49 attributes critical to the task of performing continuous, in vivo measurements. Building on these advantages, 28,32,37,42,49 here we have adapted indwelling E-AB sensors to the problem of achieving high-precision, feedback-controlled drug delivery (Figure 1).…”

“…31,35,38−48 Their signaling mechanism also renders E-AB sensors reagentless, reversible, and selective enough to support measurements in situ in the living body, 28,32,37,49 attributes critical to the task of performing continuous, in vivo measurements. Building on these advantages, 28,32,37,42,49 here we have adapted indwelling E-AB sensors to the problem of achieving high-precision, feedback-controlled drug delivery (Figure 1). Specifically, from among the large set of E-AB sensors developed to date 31,35,38−48 we selected an aminoglycoside sensor 28,40,42 as the test bed with which to demonstrate such delivery, as the therapeutic windows of these important, last-line-of-defense antibiotics are narrow, greatly complicating their proper dosing.…”

Beyond Sensitive and Selective Electrochemical Biosensors: Towards Continuous, Real-Time, Antibiofouling and Calibration-Free Devices

“…Moreover, triggering of timely countermeasure actions in the food safety and environmental fields would be expected. However, to achieve these goals, sensors must: (i) provide relevant selectivity, precision, and sensitivity; (ii) operate continuously with no sample preparation, batch processing (such as washing steps), or addition of exogenous reagents; and (iii) be insensitive to biofouling such as the detrimental accumulation of proteins and blood cells on the sensor surface [ 12 ].…”

Rationally Design of Near Infrared Light Responsive Micro‐Photoelectrodes for In Vivo Sensing of Neurotransmitter Molecules in Mouse Brain†

“…[1,2] Currently, in vivo electrochemical detection is a powerful and unparalleled approach to achieve this goal with high sensitivity, good selectivity, simplicity, rapidness, and low cost. [3][4][5][6] However, external bias is always inevitable to induce the oxidation/reduction reactions of biomolecules on the electrode surface, which results in undesirable electrophysiological stimulation and thus brings out non-negligibly abnormal secretion of biomolecules from living cells. Therefore, accurately sensing of biomolecules in un-biased conditions is highly desirable.…”

“…The intrinsic basis of abundant life activities is enormous chemical reactions, thus accurately assaying the vital molecules involved in these fundamental reactions in living body is an indispensable means to reveal the physiological mechanisms in molecular level . Currently, in vivo electrochemical detection is a powerful and unparalleled approach to achieve this goal with high sensitivity, good selectivity, simplicity, rapidness, and low cost . However, external bias is always inevitable to induce the oxidation/reduction reactions of biomolecules on the electrode surface, which results in undesirable electrophysiological stimulation and thus brings out non‐negligibly abnormal secretion of biomolecules from living cells.…”