scholarly journals Design and Evaluation of a Lactate Microbiosensor: Toward Multianalyte Monitoring of Neurometabolic Markers In Vivo in the Brain

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 514
Author(s):  
Eliana Fernandes ◽  
Ana Ledo ◽  
Rui M. Barbosa

Direct in vivo measurements of neurometabolic markers in the brain with high spatio-temporal resolution, sensitivity, and selectivity is highly important to understand neurometabolism. Electrochemical biosensors based on microelectrodes are very attractive analytical tools for continuous monitoring of neurometabolic markers, such as lactate and glucose in the brain extracellular space at resting and following neuronal activation. Here, we assess the merits of a platinized carbon fiber microelectrode (CFM/Pt) as a sensing platform for developing enzyme oxidase-based microbiosensors to measure extracellular lactate in the brain. Lactate oxidase was immobilized on the CFM/Pt surface by crosslinking with glutaraldehyde. The CFM/Pt-based lactate microbiosensor exhibited high sensitivity and selectivity, good operational stability, and low dependence on oxygen, temperature, and pH. An array consisting of a glucose and lactate microbiosensors, including a null sensor, was used for concurrent measurement of both neurometabolic substrates in vivo in the anesthetized rat brain. Rapid changes of lactate and glucose were observed in the cortex and hippocampus in response to local glucose and lactate application and upon insulin-induced fluctuations of systemic glucose. Overall, these results indicate that microbiosensors are a valuable tool to investigate neurometabolism and to better understand the role of major neurometabolic markers, such as lactate and glucose.

2021 ◽  
Author(s):  
Luis David Rosales-Vazquez ◽  
Alejandro Dorazco-González ◽  
Victor Sanchez-Mendieta

Optical sensors with high sensitivity and selectivity, as important analytical tools for chemical and environmental research, can be accomplished by straightforward synthesis of luminescent one-, two- and three-dimensional Zn(II) and...


Materials ◽  
2020 ◽  
Vol 13 (11) ◽  
pp. 2577 ◽  
Author(s):  
Yuanying Liang ◽  
Ting Guo ◽  
Lei Zhou ◽  
Andreas Offenhäusser ◽  
Dirk Mayer

The detection of chemical messenger molecules, such as neurotransmitters in nervous systems, demands high sensitivity to measure small variations, selectivity to eliminate interferences from analogues, and compliant devices to be minimally invasive to soft tissue. Here, an organic electrochemical transistor (OECT) embedded in a flexible polyimide substrate is utilized as transducer to realize a highly sensitive dopamine aptasensor. A split aptamer is tethered to a gold gate electrode and the analyte binding can be detected optionally either via an amperometric or a potentiometric transducer principle. The amperometric sensor can detect dopamine with a limit of detection of 1 μM, while the novel flexible OECT-based biosensor exhibits an ultralow detection limit down to the concentration of 0.5 fM, which is lower than all previously reported electrochemical sensors for dopamine detection. The low detection limit can be attributed to the intrinsic amplification properties of OECTs. Furthermore, a significant response to dopamine inputs among interfering analogues hallmarks the selective detection capabilities of this sensor. The high sensitivity and selectivity, as well as the flexible properties of the OECT-based aptasensor, are promising features for their integration in neuronal probes for the in vitro or in vivo detection of neurochemical signals.


2019 ◽  
Vol 10 ◽  
pp. 204062231988220 ◽  
Author(s):  
Timothy E. Yap ◽  
Shiama I. Balendra ◽  
Melanie T. Almonte ◽  
M. Francesca Cordeiro

Considering the retina as an extension of the brain provides a platform from which to study diseases of the nervous system. Taking advantage of the clear optical media of the eye and ever-increasing resolution of modern imaging techniques, retinal morphology can now be visualized at a cellular level in vivo. This has provided a multitude of possible biomarkers and investigative surrogates that may be used to identify, monitor and study diseases until now limited to the brain. In many neurodegenerative conditions, early diagnosis is often very challenging due to the lack of tests with high sensitivity and specificity, but, once made, opens the door to patients accessing the correct treatment that can potentially improve functional outcomes. Using retinal biomarkers in vivo as an additional diagnostic tool may help overcome the need for invasive tests and histological specimens, and offers the opportunity to longitudinally monitor individuals over time. This review aims to summarise retinal biomarkers associated with a range of neurological conditions including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and prion diseases from a clinical perspective. By comparing their similarities and differences according to primary pathological processes, we hope to show how retinal correlates can aid clinical decisions, and accelerate the study of this rapidly developing area of research.


Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 470 ◽  
Author(s):  
Surendra Punganuru ◽  
Hanumantha Madala ◽  
Viswanath Arutla ◽  
Kalkunte Srivenugopal

Human NAD(P)H quinone oxidoreductase-1 (hNQO1) is an important cancer-related biomarker, which shows significant overexpression in malignant cells. Developing an effective method for detecting NQO1 activity with high sensitivity and selectivity in tumors holds a great potential for cancer diagnosis, treatment, and management. In the present study, we report a new dicyanoisophorone (DCP) based fluorescent probe (NQ-DCP) capable of monitoring hNQO1 activity in vitro and in vivo in both ratiometric and turn-on model. NQ-DCP was prepared by conjugating dicyanoisophorone fluoroprobe with hNQO1 activatable quinone propionic acid (QPA), which remain non-fluorescent until activation by tumor-specific hNQO1. NQ-DCP featured a large Stokes shift (145 nm), excellent biocompatibility, cell permeability, and selectivity towards hNQO1 allowed to differentiate cancer cells from healthy cells. We have successfully employed NQ-DCP to monitor non-invasive endogenous hNQO1 activity in brain tumor cells in vitro and in xenografted tumors developed in nude mice.


2017 ◽  
Author(s):  
Jiaming Cao ◽  
Pulkit Grover

AbstractUsing a systematic computational and modeling framework, we provide a novel Spatio-Temporal Interference-based stiMULation focUsing Strategy (STIMULUS) for high spatial precision noninvasive neurostimulation deep inside the brain. To do so, we first replicate the results of the recently proposed temporal interference (TI) stimulation (which was only tested in-vivo) in a computational model based on a Hodgkin-Huxley model for neurons and a model of current dispersion in the head. Using this computational model, we obtain a nontrivial extension of the 2-electrode-pair TI proposed originally to multielectrode TI (> 2 electrode pairs) that yields significantly higher spatial precision. To further improve precision, we develop STIMULUS techniques for generating spatial interference patterns in conjunction with temporal interference, and demonstrate strict and significant improvements over multielectrode TI. Finally, we utilize the adaptivity that is inherent in STIMULUS to create multisite neurostimulation patterns that can be dynamically steered over time.


2018 ◽  
Vol 8 (9) ◽  
pp. 1504 ◽  
Author(s):  
Sharmila Durairaj ◽  
Boopathi Sidhureddy ◽  
Joseph Cirone ◽  
Aicheng Chen

Neurotransmitters are molecules that transfer chemical signals between neurons to convey messages for any action conducted by the nervous system. All neurotransmitters are medically important; the detection and analysis of these molecules play vital roles in the diagnosis and treatment of diseases. Among analytical strategies, electrochemical techniques have been identified as simple, inexpensive, and less time-consuming processes. Electrochemical analysis is based on the redox behaviors of neurotransmitters, as well as their metabolites. A variety of electrochemical techniques are available for the detection of biomolecules. However, the development of a sensing platform with high sensitivity and selectivity is challenging, and it has been found to be a bottleneck step in the analysis of neurotransmitters. Nanomaterials-based sensor platforms are fascinating for researchers because of their ability to perform the electrochemical analysis of neurotransmitters due to their improved detection efficacy, and they have been widely reported on for their sensitive detection of epinephrine, dopamine, serotonin, glutamate, acetylcholine, nitric oxide, and purines. The advancement of electroanalytical technologies and the innovation of functional nanomaterials have been assisting greatly in in vivo and in vitro analyses of neurotransmitters, especially for point-of-care clinical applications. In this review, firstly, we focus on the most commonly employed electrochemical analysis techniques, in conjunction with their working principles and abilities for the detection of neurotransmitters. Subsequently, we concentrate on the fabrication and development of nanomaterials-based electrochemical sensors and their advantages over other detection techniques. Finally, we address the challenges and the future outlook in the development of electrochemical sensors for the efficient detection of neurotransmitters.


eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Sebastian A Giusti ◽  
Annette M Vogl ◽  
Marisa M Brockmann ◽  
Claudia A Vercelli ◽  
Martin L Rein ◽  
...  

MicroRNAs (miRNAs) are conserved noncoding RNAs that function as posttranscriptional regulators of gene expression. miR-9 is one of the most abundant miRNAs in the brain. Although the function of miR-9 has been well characterized in neural progenitors, its role in dendritic and synaptic development remains largely unknown. In order to target miR-9 in vivo, we developed a transgenic miRNA sponge mouse line allowing conditional inactivation of the miR-9 family in a spatio-temporal-controlled manner. Using this novel approach, we found that miR-9 controls dendritic growth and synaptic transmission in vivo. Furthermore, we demonstrate that miR-9-mediated downregulation of the transcriptional repressor REST is essential for proper dendritic growth.


2013 ◽  
Vol 66 (1) ◽  
pp. 113 ◽  
Author(s):  
Faze Wang ◽  
Yuangen Wu ◽  
Shenshan Zhan ◽  
Lan He ◽  
Wenting Zhi ◽  
...  

This paper describes a simple and sensitive colorimetric sensor employing single-stranded DNA (ssDNA) ligand, cationic polymer, and gold nanoparticles (AuNPs) to detect silver ions. The positively charged polymer can electrostatically interact with ssDNA and destroy the charge balance leading to induction of AuNP aggregation. Silver ions (Ag+) can bind to cytosine (C)-rich nucleic acids to form the C-Ag+-C hair-pin structure, which can prevent its interaction with polymers. The resulting cationic polymer could aggregate AuNPs causing a remarkable change in colour. The concentration of Ag+ can be determined visually. This sensing platform exhibits high sensitivity and selectivity towards Ag+ versus other metal ions, with a detection limit of 48.6 nM. The assay did not require any labelling or modifying steps. This method is simple, effective, and convenient and can in principle be used to detect other metal ions or small molecules.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pei Li ◽  
Sang Mo Lee ◽  
Hyo Yong Kim ◽  
Soohyun Kim ◽  
Steve Park ◽  
...  

AbstractWe herein described a rapid, sensitive, and selective colorimetric sensing platform for biothiols in human serum, which relies on the dual functions of biothiols as anti-etching and aggregating agent for silver nanoprisms (AgNPRs). In principle, the target biothiols that bind to the surface of AgNPRs through Ag–S covalent interactions protect the AgNPRs from being etched by chloride ion (Cl−) in human serum, thus exhibiting the blue/purple color that is indicative of AgNPRs. On the other hand, the color of AgNPRs turned to yellow in the absence of biothiols or the presence of non-sulfur-containing amino acids, indicating the formation of small silver nanoparticles (AgNPs). Importantly, we found that individual biothiols (Hcy, Cys, and GSH) exert not only the anti-etching effect, but also the aggregating effect on AgNPRs, which can be modulated by simply tuning the pH conditions, and this consequently allows for the discriminative detection of each biothiol. Based on this simple and cost-effective strategy, we successfully determined the Hcy, Cys, and GSH in human serum with high sensitivity and selectivity within 10 min, demonstrating the diagnostic capability and potential in practical applications.


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