Single particle collision is emerging as a powerful and sensitive technique for analyzing small molecules, however, its application in biomacromolecules detection, for example, protein, in complex ...biological environments is still challenging. Here, we present the first demonstration on the single particle collision that can be developed for the detection of platelet-derived growth factor (PDGF), an important protein involved in the central nervous system in living rat brain. The system features Pt nanoparticles (PtNPs) conjugated with the PDGF recognition aptamer, suppressing the electrocatalytic collision of PtNPs toward the oxidation of hydrazine. In the presence of PDGF, the stronger binding between targeted protein and the aptamer disrupts the aptamer/PtNPs conjugates, recovering the electrocatalytic performance of PtNPs, and allowing quantitative, selective, and highly sensitive detection of PDGF in cerebrospinal fluid of rat brain.
DJ‐1 protein deficiency caused by PARK7 gene mutation has been suggested to closely relate to Parkinson's disease (PD), mainly through the attenuation D2 dopamine receptor activity in mice; however, ...whether or how it affects the vesicular storage and exocytosis of neurochemicals remains unclear. By using electrochemical methods at a single vesicle/cell level with nano/micro‐tip electrodes, we for the first time find that DJ‐1 protein deficiency caused by PARK7 gene knockout (KO) in mice has little effect on vesicular catecholamine content but significantly prolongs the exocytotic events, especially the closing time of exocytotic fusion pores. Further studies suggest the inhibition of α‐synuclein aggregation by DJ‐1 protein might be one way that DJ‐1 protein acts on neurotransmission. This finding offers the first direct link between DJ‐1 protein deficiency and vesicular chemical storage and release of chemicals, providing a new chemical insight into the pathology of PD caused by PARK7 gene mutation.
Catch and release: The vesicular storage and release of catecholamine in adrenal chromaffin cells from wild type andDJ‐1 protein‐deficient mice were quantified by electrochemical methods at the single vesicle/cell level. It was found that DJ‐1 deficiency prolongs the duration of exocytotic events, providing new chemical insights into the pathology of Parkinson's disease.
Alpha‐synuclein (α‐Syn) localizes at presynaptic terminal and modulates synaptic functions. Increasing evidence demonstrate that α‐Syn oligomers, forming at the early of aggregation, are cytotoxic ...and is thus related to brain neurodegenerative diseases. Herein, we find that vitamin D (VD) can reduce neurocytotoxicity. The reduced neurocytotoxicity might be attributed to the less amount of large‐sized α‐Syn oligomers inhibited by VD, measured by electrochemical collision at single particle level, which are not observable with traditionally ensembled method. Single‐cell amperometry (SCA) results show that VD can recover the amount of neurotransmitter release during exocytosis induced by α‐Syn oligomers, further verifying the neuroprotection of VD. Our study reveals the neuroprotective role of VD through inhibiting α‐Syn aggregation, which is envisioned to be of great importance in treatment and prevention of the neurodegenerative diseases.
Electrochemical measurement of the early aggregation of α‐Syn and exocytosis event of PC12 revealed a new neuroprotective role of VD that can inhibit the α‐Syn monomers aggregation into α‐Syn oligomers and modulate exocytosis. This research provides an efficient strategy for early treatment and prevention of the neurodegenerative diseases associated with α‐Syn oligomers.
Over the past two decades, there has been increasing focus on ascorbic acid (AA) due to its anti-oxidant and neuroprotective properties as well as its neuromodulating capability. Conventional ...analytical methods for selective in vivo monitoring of AA mainly involve complex procedures, which lower the temporal resolution and throughput of data gathering. Moreover, analytical methods for selective real-time monitoring of AA exocytosis at a single-cell level is still lacking. The lack of effective methods for AA detection in the central nervous system (CNS) has rendered difficulties in better understanding the roles of AA in brain function. AA is, in itself, electrochemically active, and thereby rationally tailoring the structure of an electrode/solution interface would offer an effective approach to selective electrochemical measurements in the CNS. Guided by this, electrochemical methods have been recently established for AA detection by combining selective electrochemical oxidation of AA at functionalized electrodes with microelectrode techniques and with in vivo microdialysis. This review mainly focuses on recent updates on in vivo detection of AA by modulating the electron transfer of AA to achieve the selectivity for its detection in the CNS, an environment with high chemical complexity. Additionally, the practical implications of the methods in selective and sensitive monitoring the dynamics of AA in different brain functions are also reviewed.
•Main electrochemical approaches for selective and real-time in vivo quantification of AA in living brains are discussed.•This review offers insight into modulating the electron transfer kinetics of AA for selective in vivo quantification of AA.•Applications of in vivo analytical methods in studying the molecular mechanism in brain functions are also highlighted.
Resisting biomolecule adsorption onto the surface of brain‐implanted microelectrodes is a key issue for in vivo monitoring of neurochemicals. Herein, we demonstrate that an ultrathin ...cell‐membrane‐mimic film of ethylenedioxythiophene tailored with zwitterionic phosphorylcholine (EDOT‐PC) electropolymerized onto the surface of a carbon fiber microelectrode (CFE) not only resists protein adsorption but also maintains the sensitivity and time response for in vivo monitoring of dopamine (DA). As a consequence, the as‐prepared PEDOT‐PC/CFEs could be used as a new reliable platform for tracking DA in vivo and would help understand the physiological and pathological functions of DA.
Time to measure your dopamine levels, Pinky: An ultrathin cell‐membrane‐mimic film of ethylenedioxythiophene tailored with a zwitterionic phosphorylcholine (EDOT‐PC) electropolymerized onto the surface of a carbon fiber microelectrode (CFE) was found to not only resist protein adsorption but also maintain sensitivity and temporal resolution for the in vivo monitoring of dopamine (DA).
Reactive oxygen species (ROS)-based therapeutic strategies play an important role in cancer treatment. However, in situ, real-time and quantitative analysis of intracellular ROS in cancer treatment ...for drug screening is still a challenge. Herein we report one selective hydrogen peroxide (H
O
) electrochemical nanosensor, which is prepared by electrodeposition of Prussian blue (PB) and polyethylenedioxythiophene (PEDOT) onto carbon fiber nanoelectrode. With the nanosensor, we find that the level of intracellular H
O
increases with NADH treatment and that increase is dose-dependent to the concentration of NADH. High-dose of NADH (above 10 mM) can induce cell death and intratumoral injection of NADH is validated for inhibiting tumor growth in mice. This study highlights the potential of electrochemical nanosensor for tracking and understanding the role of H
O
in screening new anticancer drug.
One potentiometric nanosensor for monitoring intracellular hydrogen sulfide (H
2
S) with fast potential response, high selectivity and excellent antifouling properties was developed. This study ...constructs a powerful tool to real-time track the changes of intracellular H
2
S
in situ
, promoting the future studies of physiologically relevant processes.
This study demonstrates one potentiometric nanosensor for monitoring intracellular hydrogen sulfide with high selectivity, fast response, and excellent antifouling properties.
In vivo sensing based on implantable microelectrodes has been widely used to monitor neurochemicals due to its high spatial and temporal resolution and engineering interface designability, which has ...become a powerful drive to decode the mysteries of degenerative diseases and regulate neural activity. Over the past few decades, with the development of a variety of advanced materials and technologies, encouraging progress has been made in quantifying various neurochemical transients. However, because of the complex chemical atmosphere including thousands of small and large biomolecules and the inherent low mechanical property of brain tissue, the design of a compatible microelectrode for the in vivo electrochemical tracking of neurochemicals with high selectivity and stability still faces great challenges. This Perspective presents a brief account of recent representative progress in the rational regulation of the microelectrode interface to resolve the questions of selectivity and sensitive decrease resulting from antiprotein adsorption, and how to decrease the mechanical mismatch of an implanted electrode with that of brain tissue. Possible future research directions on further addressing the above key issues and a more biocompatible microelectrode for in vivo long-time electrochemical analysis are also discussed.
In vivo electrochemical analysis is of great significance in understanding the dynamics of various physiological and pathological activities. However, the conventional microelectrodes for ...electrochemical analysis are rigid and permanent, which comes with increased risks for long-term implantation and secondary surgery. Here, we develop one biodegradable microelectrode for monitoring the dynamics of extracellular Ca
in rat brain. The biodegradable microelectrode is prepared by sputtering gold nanoparticles (AuNPs) on a wet-spun flexible poly(l-lactic acid) (PLLA) fiber for conduction and transduction and coating a Ca
ion-selective membrane (ISM) with a PLLA matrix on the PLLA/AuNPs fiber, forming PLLA/AuNPs/Ca
ISME (ISME = ion-selective microelectrode). The prepared microelectrode shows excellent analytical properties including a near-Nernst linear response toward Ca
over the concentration range from 10 μM to 50 mM, good selectivity, and long-term stability for weeks as well as biocompatibility and biodegradability. The PLLA/AuNPs/Ca
ISME can monitor the dynamics of extracellular Ca
following spreading depression induced by high potassium even if in the fourth day. This study provides a new design strategy for the biodegradable ISME and promotes the development of biodegradable microelectrodes for long-term monitoring of chemical signals in brain.
Developing real‐time, dynamic, and in situ analytical methods with high spatial and temporal resolutions is crucial for exploring biochemical processes in the brain. Although in vivo electrochemical ...methods based on carbon fiber (CF) microelectrodes are effective in monitoring neurochemical dynamics during physiological and pathological processes, complex post modification hinders large‐scale productions and widespread neuroscience applications. Herein, we develop a general strategy for the in situ engineering of carbon‐based materials to mass‐produce functional CFs by introducing polydopamine to anchor zeolitic imidazolate frameworks as precursors, followed by one‐step pyrolysis. This strategy demonstrates exceptional universality and design flexibility, overcoming complex post‐modification procedures and avoiding the delamination of the modification layer. This simplifies the fabrication and integration of functional CF‐based microelectrodes. Moreover, we design highly stable and selective H+, O2, and ascorbate microsensors and monitor the influence of CO2 exposure on the O2 content of the cerebral tissue during physiological and ischemia‐reperfusion pathological processes.
