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. We demonstrate that cell-membrane-mimicking phosphatidylcholine (PC)-terminated monolayers improve the performance of E-AB sensors, reducing the baseline drift from around 70% to just a few 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, achieving micromolar precision over many hours without the use of physical barriers or active drift-correction algorithms.

Impact of Self-Assembled Monolayer Design and Electrochemical Factors on Impedance-Based Biosensing

“…Most notably SAMs with varying backbone composition include either modifying the hydrocarbon chain length [23][24][25] or incorporation of polymeric, hydrophilic backbones [26,27]. Additionally, SAMs have been incorporated with diverse functional groups, including those terminated with carboxylates [25], amines [27], zwitterionic phosphocholine head-groups [28] or bivalent hexanedithiol [29]. However, a more systematic understanding of how these factors influence (1) passivation and voltage drop, (2) anti-fouling properties and (3) sensor performance using impedance spectroscopy is lacking.…”

Plasmonic Sensing with 3D Printed Optics

“…23 Utilization of supported membranes is beneficial as they allow the incorporation of specific recognition elements, including lipid receptors, while minimizing nonspecific binding from nontarget species due to the zwitterionic nature of phosphocholine headgroups. 24 Preformed phosphocholine (POPC) vesicles incorporating 5% (n/n) GM 1 were flowed over the SAM-coated gold prisms to form a supported membrane (I in Figure 3A,B), and thereafter, cholera toxin (0−20 μ g mL −1 ) was introduced (II in Figure 3A−C). Each injection and incubation was followed by a 10 min rinse with phosphate buffer to remove any unbound molecules.…”

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

“…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.…”