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1
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Ruckodanov DA, Maidment NT, Monbouquette HG. Electrochemical Sensing of Dopamine with an Implantable Microelectrode Array Microprobe Including an On-Probe Iridium Oxide Reference Electrode. ACS Chem Neurosci 2025; 16:642-648. [PMID: 39909725 DOI: 10.1021/acschemneuro.4c00658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2025] Open
Abstract
Inclusion of an on-probe iridium oxide (IrOx) reference electrode on an implantable microelectrode array (MEA) microprobe enabled dopamine (DA) sensing with high sensitivity, an ultralow limit of detection, and high selectivity against common electroactive interferents. The monitoring of DA signaling in vivo is important for the study of brain disorders such as Parkinson's disease and substance abuse. A postfabrication method for electrochemical deposition of an IrOx film onto a targeted microelectrode enabled integration of an IrOx reference electrode (RE) onto the same MEA as the DA sensing, working electrode (WE). The on-probe IrOx RE is an attractive alternative to commonly used external Ag/AgCl wire REs, which can be unstable and can cause inflammatory responses in vivo. The on-probe IrOx RE was tested for support of DA sensing performance in two-electrode (i.e., WE and RE) and three-electrode (i.e., WE, RE and counter electrode) configurations. The sensitivities of the integrated and externally referenced DA sensing microprobes were comparable at ∼2500 nA/(μM·cm2), however the integrated three-electrode configuration exhibited a 6-fold lower limit of detection of ∼9 nM due to an 82% reduction in baseline noise. In addition, excellent 1000:1 selectivity against common electroactive interferents makes these DA sensing microprobes attractive for implementation in vivo.
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Affiliation(s)
- Dmitriy A Ruckodanov
- Chemical and Biomolecular Engineering Department, University of California, Los Angeles, Los Angeles, California 90095, United States
| | - Nigel T Maidment
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California 90095, United States
| | - Harold G Monbouquette
- Chemical and Biomolecular Engineering Department, University of California, Los Angeles, Los Angeles, California 90095, United States
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2
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Alizadeh Z, Mazloum-Ardakani M, Asadpour F, Yavari M. Highly Efficient Enzyme-Free Glutamate Sensors Using Porous Network Metal-Organic Framework-Ni-NiO-Ni-Carbon Nanocomposites. ACS APPLIED MATERIALS & INTERFACES 2023; 15:59246-59257. [PMID: 38102092 DOI: 10.1021/acsami.3c15861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2023]
Abstract
This study introduces an innovative electrochemical sensor designed to detect glutamate using a nonenzymatic approach. The sensor utilizes a porous network metal-organic framework (Ni-MOF)-NiO-Ni-Carbon nanocomposite (PNM-NiO-Ni-Carbon) as an electrode modifier, which was synthesized and assessed for its effectiveness. Cyclic voltammetry measurements demonstrated that the PNM-NiO-Ni-Carbon nanocomposite, synthesized at 450 °C, displayed remarkable electrocatalytic activity for glutamate oxidation. The linear range for detection spanned from 5 to 960 μmol/L, and the sensor achieved a low detection limit of 320 nmol/L (S/N = 3), which was comparable to previously reported data. Moreover, the sensor exhibited high accuracy and favorable recovery rates when tested with real samples, thus, demonstrating its potential for rapid glutamate detection. The real samples were analyzed using both electrochemical and high-performance liquid chromatography methods, and the results obtained from the two methods did not differ significantly, validating the sensor's excellent practical performance. Based on our findings, the PNM-NiO-Ni-Carbon system exhibits potential for a wide range of biomedical applications.
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Affiliation(s)
- Zahra Alizadeh
- Department of Chemistry, Faculty of Science, Yazd University, Yazd 89195-741, Islamic Republic of Iran
| | - Mohammad Mazloum-Ardakani
- Department of Chemistry, Faculty of Science, Yazd University, Yazd 89195-741, Islamic Republic of Iran
| | - Farzaneh Asadpour
- Department of Chemistry, Faculty of Science, Yazd University, Yazd 89195-741, Islamic Republic of Iran
- Department of Chemistry, University of Cincinnati, 312 College Drive 404 Crosley Tower, Cincinnati, Ohio 45221-0172, United States
| | - Mozhgan Yavari
- Department of Chemistry, Faculty of Science, Yazd University, Yazd 89195-741, Islamic Republic of Iran
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3
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Kimble L, Twiddy JS, Berger JM, Forderhase AG, McCarty GS, Meitzen J, Sombers LA. Simultaneous, Real-Time Detection of Glutamate and Dopamine in Rat Striatum Using Fast-Scan Cyclic Voltammetry. ACS Sens 2023; 8:4091-4100. [PMID: 37962541 PMCID: PMC10683757 DOI: 10.1021/acssensors.3c01267] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 10/24/2023] [Accepted: 11/01/2023] [Indexed: 11/15/2023]
Abstract
Glutamate and dopamine (DA) represent two key contributors to striatal functioning, a region of the brain that is essential to motor coordination and motivated behavior. While electroanalytical techniques can be utilized for rapid, spatially resolved detection of DA in the interferent-rich brain environment, glutamate, a nonelectroactive analyte, cannot be directly detected using electroanalytical techniques. However, it can be probed using enzyme-based sensors, which generate an electroactive reporter in the presence of glutamate. The vast majority of glutamate biosensors have relied on amperometric sensing, which is an inherently nonselective detection technique. This approach necessitates the use of complex and performance-limiting modifications to ensure the desired single-analyte specificity. Here, we present a novel glutamate microbiosensor fabricated on a carbon-fiber microelectrode substrate and coupled with fast-scan cyclic voltammetry (FSCV) to enable the simultaneous quantification of glutamate and DA at single recording sites in the brain, which is impossible when using typical amperometric approaches. The glutamate microbiosensors were characterized for sensitivity, stability, and selectivity by using a voltammetric waveform optimized for the simultaneous detection of both species. The applicability of these sensors for the investigation of neural circuits was validated in the rat ventral striatum. Electrically evoked glutamate and DA release were recorded at single-micrometer-scale locations before and after pharmacological manipulation of glutamatergic signaling. Our novel glutamate microbiosensor advances the state of the art by providing a powerful tool for probing coordination between these two species in a way that has previously not been possible.
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Affiliation(s)
- Laney
C. Kimble
- Department
of Chemistry, Department of Biological Sciences, and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Jack S. Twiddy
- Department
of Chemistry, Department of Biological Sciences, and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States
- Joint
Department of Biomedical Engineering, North
Carolina State University and University of North Carolina at Chapel
Hill, Raleigh, North Carolina 27695, United States
| | - Jenna M. Berger
- Department
of Chemistry, Department of Biological Sciences, and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Alexandra G. Forderhase
- Department
of Chemistry, Department of Biological Sciences, and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Gregory S. McCarty
- Department
of Chemistry, Department of Biological Sciences, and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - John Meitzen
- Department
of Chemistry, Department of Biological Sciences, and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Leslie A. Sombers
- Department
of Chemistry, Department of Biological Sciences, and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States
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Chu SS, Nguyen HA, Lin D, Bhatti M, Jones-Tinsley CE, Do AH, Frostig RD, Nenadic Z, Xu X, Lim MM, Cao H. Development of highly sensitive, flexible dual L-glutamate and GABA microsensors for in vivo brain sensing. Biosens Bioelectron 2023; 222:114941. [PMID: 36455372 DOI: 10.1016/j.bios.2022.114941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 11/11/2022] [Accepted: 11/20/2022] [Indexed: 11/25/2022]
Abstract
Real-time tracking of neurotransmitter levels in vivo has been technically challenging due to the low spatiotemporal resolution of current methods. Since the imbalance of cortical excitation/inhibition (E:I) ratios are associated with a variety of neurological disorders, accurate monitoring of excitatory and inhibitory neurotransmitter levels is crucial for investigating the underlying neural mechanisms of these conditions. Specifically, levels of the excitatory neurotransmitter L-glutamate, and the inhibitory neurotransmitter GABA, are assumed to play critical roles in the E:I balance. Therefore, in this work, a flexible electrochemical microsensor is developed for real-time simultaneous detection of L-glutamate and GABA. The flexible polyimide substrate was used for easier handling during implantation and measurement, along with less brain damage. Further, by electrochemically depositing Pt-black nanostructures on the sensor's surface, the active surface area was enhanced for higher sensitivity. This dual neurotransmitter sensor probe was validated under various settings for its performance, including in vitro, ex vivo tests with glutamatergic neuronal cells and in vivo test with anesthetized rats. Additionally, the sensor's performance has been further investigated in terms of longevity and biocompatibility. Overall, our dual L-glutamate:GABA sensor microprobe has its unique features to enable accurate, real-time, and long-term monitoring of the E:I balance in vivo. Thus, this new tool should aid investigations of neural mechanisms of normal brain function and various neurological disorders.
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Affiliation(s)
- Sung Sik Chu
- Department of Biomedical Engineering, University of California Irvine, CA, 92697, USA
| | - Hung Anh Nguyen
- Department of Electrical Engineering and Computer Sciences, University of California Irvine, 92697, CA, USA
| | - Derrick Lin
- Department of Neurology, University of California Irvine, CA, 92697, USA
| | - Mehwish Bhatti
- Department of Neurobiology and Behavior, University of California, CA, 92697, USA
| | - Carolyn E Jones-Tinsley
- VA Portland Health Care System, Department of Neurology, Oregon Health and Science University, OR, 97239, USA
| | - An Hong Do
- Department of Neurology, University of California Irvine, CA, 92697, USA
| | - Ron D Frostig
- Department of Biomedical Engineering, University of California Irvine, CA, 92697, USA; Department of Neurobiology and Behavior, University of California, CA, 92697, USA
| | - Zoran Nenadic
- Department of Biomedical Engineering, University of California Irvine, CA, 92697, USA
| | - Xiangmin Xu
- Department of Biomedical Engineering, University of California Irvine, CA, 92697, USA; Department of Anatomy and Neurobiology, University of California Irvine, CA, 92697, USA; Center for Neural Circuit Mapping, University of California Irvine, CA, 92697, USA
| | - Miranda M Lim
- VA Portland Health Care System, Department of Neurology, Oregon Health and Science University, OR, 97239, USA
| | - Hung Cao
- Department of Biomedical Engineering, University of California Irvine, CA, 92697, USA; Department of Electrical Engineering and Computer Sciences, University of California Irvine, 92697, CA, USA; Center for Neural Circuit Mapping, University of California Irvine, CA, 92697, USA; Department of Computer Science, University of California Irvine, CA, 92697, USA.
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5
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Dias C, Fernandes E, Barbosa RM, Ledo A. A Platinized Carbon Fiber Microelectrode-Based Oxidase Biosensor for Amperometric Monitoring of Lactate in Brain Slices. SENSORS (BASEL, SWITZERLAND) 2022; 22:7011. [PMID: 36146360 PMCID: PMC9501957 DOI: 10.3390/s22187011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/12/2022] [Accepted: 09/14/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND Direct and real-time monitoring of lactate in the extracellular space can help elucidate the metabolic and modulatory role of lactate in the brain. Compared to in vivo studies, brain slices allow the investigation of the neural contribution separately from the effects of cerebrovascular response and permit easy control of recording conditions. METHODS We have used a platinized carbon fiber microelectrode platform to design an oxidase-based microbiosensor for monitoring lactate in brain slices with high spatial and temporal resolution operating at 32 °C. Lactate oxidase (Aerococcus viridans) was immobilized by crosslinking with glutaraldehyde and a layer of polyurethane was added to extend the linear range. Selectivity was improved by electropolymerization of m-phenylenediamine and concurrent use of a null sensor. RESULTS The lactate microbiosensor exhibited high sensitivity, selectivity, and optimal analytical performance at a pH and temperature compatible with recording in hippocampal slices. Evaluation of operational stability under conditions of repeated use supports the suitability of this design for up to three repeated assays. CONCLUSIONS The microbiosensor displayed good analytical performance to monitor rapid changes in lactate concentration in the hippocampal tissue in response to potassium-evoked depolarization.
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Affiliation(s)
- Cândida Dias
- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal
- Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Eliana Fernandes
- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal
- Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Rui M. Barbosa
- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal
- Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Ana Ledo
- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal
- Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
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6
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Lei L, Zhao C, Zhu X, Yuan S, Dong X, Zuo Y, Liu H. Nonenzymatic Electrochemical Sensor for Wearable Interstitial Fluid Glucose Monitoring. ELECTROANAL 2022; 34:415-422. [DOI: 10.1002/elan.202060601] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Accepted: 02/03/2021] [Indexed: 12/21/2022]
Abstract
AbstractWe report on a nonenzymatic electrochemical sensor for wearable glucose monitoring in interstitial fluid. The sensor exhibited acceptable selectivity and reliability for continuous glucose detection for up to 30 days. The sensor tip is coated with polyurethane, and the biocompatibility of the tip is investigated by tissue staining. A fully integrated wearable glucose monitoring system is developed with a wireless connection with a smartphone. The test results are in agreement with reference methods. So, we believe the sensor is promising for the development of a continuous glucose monitoring system and diabetes management.
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Affiliation(s)
- Lanjie Lei
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
| | - Chao Zhao
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
| | - Xiaofei Zhu
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
| | - Shuai Yuan
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
| | - Xing Dong
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
| | - Yinxiu Zuo
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
| | - Hong Liu
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
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7
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Regiart M, Ledo A, Fernandes E, Messina GA, Brett CMA, Bertotti M, Barbosa RM. Highly sensitive and selective nanostructured microbiosensors for glucose and lactate simultaneous measurements in blood serum and in vivo in brain tissue. Biosens Bioelectron 2021; 199:113874. [PMID: 34920228 DOI: 10.1016/j.bios.2021.113874] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 12/06/2021] [Accepted: 12/07/2021] [Indexed: 02/06/2023]
Abstract
Highly sensitive and selective nanostructured lactate and glucose microbiosensors for their in vivo simultaneous determination in rat brain were developed based on carbon fiber microelectrodes (CFM) modified with nanoporous gold (NPG) using the Dynamic Hydrogen Bubble Template (DHBT) method. Electrodeposition of platinum nanoparticles (PtNP) onto the NPG film enhances the sensitivity and the electrocatalytic properties towards H2O2 detection. The nanostructured microelectrode platform was modified by glucose oxidase (GOx) and lactate oxidase (LOx) enzyme immobilization. High selective measurements were achieved by covering with a perm-selective layer of electropolymerized m-phenylenediamine, deposition of a Nafion® film and by using a null sensor. The morphological characteristics and electroanalytical performance of the microbiosensors were assessed, by scanning electron microscopy and electrochemical techniques, respectively. The PtNP/NPG/CFM shows a high sensitivity to H2O2 (5.96 A M-1 cm-2) at 0.36 V vs. Ag/AgCl, with a linear range from 0.2 to 200 μM, and an LOD of 10 nM. The microbiosensors were applied to the simultaneous determination of lactate and glucose in blood serum samples. Moreover, the basal extracellular concentrations of lactate and glucose were measured in vivo in four different rat brain structures. These results support the potential of the microbiosensor to be used as a valuable tool to investigate brain neurochemicals in vivo.
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Affiliation(s)
- Matias Regiart
- University of Coimbra, Faculty of Pharmacy, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes 748, 05508-000, São Paulo, SP, Brazil
| | - Ana Ledo
- University of Coimbra, Faculty of Pharmacy, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal
| | - Eliana Fernandes
- University of Coimbra, Faculty of Pharmacy, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal
| | - German A Messina
- INQUISAL. Departamento de Química, Universidad Nacional de San Luis. CONICET, Chacabuco 917, D5700BWS, San Luis, Argentina
| | - Christopher M A Brett
- University of Coimbra, Department of Chemistry, CEMMPRE, Faculty of Sciences and Technology, 3004-535 Coimbra, Portugal
| | - Mauro Bertotti
- Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes 748, 05508-000, São Paulo, SP, Brazil
| | - Rui M Barbosa
- University of Coimbra, Faculty of Pharmacy, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal.
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Tan C, Robbins EM, Wu B, Cui XT. Recent Advances in In Vivo Neurochemical Monitoring. MICROMACHINES 2021; 12:208. [PMID: 33670703 PMCID: PMC7922317 DOI: 10.3390/mi12020208] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 02/11/2021] [Accepted: 02/14/2021] [Indexed: 12/20/2022]
Abstract
The brain is a complex network that accounts for only 5% of human mass but consumes 20% of our energy. Uncovering the mysteries of the brain's functions in motion, memory, learning, behavior, and mental health remains a hot but challenging topic. Neurochemicals in the brain, such as neurotransmitters, neuromodulators, gliotransmitters, hormones, and metabolism substrates and products, play vital roles in mediating and modulating normal brain function, and their abnormal release or imbalanced concentrations can cause various diseases, such as epilepsy, Alzheimer's disease, and Parkinson's disease. A wide range of techniques have been used to probe the concentrations of neurochemicals under normal, stimulated, diseased, and drug-induced conditions in order to understand the neurochemistry of drug mechanisms and develop diagnostic tools or therapies. Recent advancements in detection methods, device fabrication, and new materials have resulted in the development of neurochemical sensors with improved performance. However, direct in vivo measurements require a robust sensor that is highly sensitive and selective with minimal fouling and reduced inflammatory foreign body responses. Here, we review recent advances in neurochemical sensor development for in vivo studies, with a focus on electrochemical and optical probes. Other alternative methods are also compared. We discuss in detail the in vivo challenges for these methods and provide an outlook for future directions.
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Affiliation(s)
- Chao Tan
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; (C.T.); (E.M.R.); (B.W.)
| | - Elaine M. Robbins
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; (C.T.); (E.M.R.); (B.W.)
- Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Bingchen Wu
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; (C.T.); (E.M.R.); (B.W.)
- Center for Neural Basis of Cognition, Pittsburgh, PA 15213, USA
| | - Xinyan Tracy Cui
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; (C.T.); (E.M.R.); (B.W.)
- Center for Neural Basis of Cognition, Pittsburgh, PA 15213, USA
- McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15219, USA
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Tao J, Zhu Y, Zhao S, Chen P, Zhang S, Sun J, Shen X. A novel approach with glass needle enclosed movable probe for in vivo real-time detection of glucose in cisternal cerebrospinal fluid. J Electroanal Chem (Lausanne) 2020. [DOI: 10.1016/j.jelechem.2020.114440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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10
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Wang B, Wen X, Cao Y, Huang S, Lam HA, Liu TL, Chung PS, Monbouquette HG, Chiou PY, Maidment NT. An implantable multifunctional neural microprobe for simultaneous multi-analyte sensing and chemical delivery. LAB ON A CHIP 2020; 20:1390-1397. [PMID: 32211718 PMCID: PMC7192313 DOI: 10.1039/d0lc00021c] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/02/2023]
Abstract
A multifunctional chemical neural probe fabrication process exploiting PDMS thin-film transfer to incorporate a microfluidic channel onto a silicon-based microelectrode array (MEA) platform, and enzyme microstamping to provide multi-analyte detection is described. The Si/PDMS hybrid chemtrode, modified with a nano-based on-probe IrOx reference electrode, was validated in brain phantoms and in rat brain.
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Affiliation(s)
- Bo Wang
- Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, California 90095, USA.
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11
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Huang IW, Clay M, Wang S, Guo Y, Nie J, Monbouquette HG. Electroenzymatic glutamate sensing at near the theoretical performance limit. Analyst 2020; 145:2602-2611. [PMID: 31998887 PMCID: PMC7117983 DOI: 10.1039/c9an01969c] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The sensitivity and response time of glutamate sensors based on glutamate oxidase immobilized on planar platinum microelectrodes have been improved to near the theoretical performance limits predicted by a detailed mathematical model. Microprobes with an array of electroenzymatic sensing sites have emerged as useful tools for the monitoring of glutamate and other neurotransmitters in vivo; and implemented as such, they can be used to study many complex neurological diseases and disorders including Parkinson's disease and drug addiction. However, less than optimal sensitivity and response time has limited the spatiotemporal resolution of these promising research tools. A mathematical model has guided systematic improvement of an electroenzymatic glutamate microsensor constructed with a 1-2 μm-thick crosslinked glutamate oxidase layer and underlying permselective coating of polyphenylenediamine and Nafion reduced to less than 200 nm thick. These design modifications led to a nearly 6-fold improvement in sensitivity to 320 ± 20 nA μM-1 cm-2 at 37 °C and a ∼10-fold reduction in response time to 80 ± 10 ms. Importantly, the sensitivity and response times were attained while maintaining a low detection limit and excellent selectivity. Direct measurement of the transport properties of the enzyme and polymer layers used to create the biosensors enabled improvement of the mathematical model as well. Subsequent model simulations indicated that the performance characteristics achieved with the optimized biosensors approach the theoretical limits predicted for devices of this construction. Such high-performance glutamate biosensors will be more effective in vivo at a size closer to cellular dimension and will enable better correlation of glutamate signaling events with electrical recordings.
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Affiliation(s)
- I-Wen Huang
- Chemical and Biomolecular Engineering Department University of California, Los Angeles, Los Angeles, CA 90095, USA.
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12
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Wang B, Wen X, Chiou P, Maidment NT. Pt Nanoparticle‐modified Carbon Fiber Microelectrode for Selective Electrochemical Sensing of Hydrogen Peroxide. ELECTROANAL 2019. [DOI: 10.1002/elan.201900362] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Bo Wang
- Shirley and Stephan Hatos Center for Neuropharmacology, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human BehaviorUniversity of California, Los Angeles Los Angeles, CA USA
| | - Ximiao Wen
- Department of Mechanical EngineeringUniversity of California, Los Angeles Los Angeles, CA USA
| | - Pei‐Yu Chiou
- Department of Mechanical EngineeringUniversity of California, Los Angeles Los Angeles, CA USA
| | - Nigel T. Maidment
- Shirley and Stephan Hatos Center for Neuropharmacology, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human BehaviorUniversity of California, Los Angeles Los Angeles, CA USA
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13
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Ou Y, Buchanan AM, Witt CE, Hashemi P. Frontiers in Electrochemical Sensors for Neurotransmitter Detection: Towards Measuring Neurotransmitters as Chemical Diagnostics for Brain Disorders. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2019; 11:2738-2755. [PMID: 32724337 PMCID: PMC7386554 DOI: 10.1039/c9ay00055k] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
It is extremely challenging to chemically diagnose disorders of the brain. There is hence great interest in designing and optimizing tools for direct detection of chemical biomarkers implicated in neurological disorders to improve diagnosis and treatment. Tools that are capable of monitoring brain chemicals, neurotransmitters in particular, need to be biocompatible, perform with high spatiotemporal resolution, and ensure high selectivity and sensitivity. Recent advances in electrochemical methods are addressing these criteria; the resulting devices demonstrate great promise for in vivo neurotransmitter detection. None of these devices are currently used for diagnostic purposes, however these cutting-edge technologies are promising more sensitive, selective, faster, and less invasive measurements. Via this review we highlight significant technical advances and in vivo studies, performed in the last 5 years, that we believe will facilitate the development of diagnostic tools for brain disorders.
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Affiliation(s)
- Yangguang Ou
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia SC
| | - Anna Marie Buchanan
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia SC
| | - Colby E. Witt
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia SC
| | - Parastoo Hashemi
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia SC
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14
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Wen X, Wang B, Huang S, Liu TL, Lee MS, Chung PS, Chow YT, Huang IW, Monbouquette HG, Maidment NT, Chiou PY. Flexible, multifunctional neural probe with liquid metal enabled, ultra-large tunable stiffness for deep-brain chemical sensing and agent delivery. Biosens Bioelectron 2019; 131:37-45. [PMID: 30818131 PMCID: PMC6602555 DOI: 10.1016/j.bios.2019.01.060] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 01/21/2019] [Accepted: 01/24/2019] [Indexed: 10/27/2022]
Abstract
Flexible neural probes have been pursued previously to minimize the mechanical mismatch between soft neural tissues and implants and thereby improve long-term performance. However, difficulties with insertion of such probes deep into the brain severely restricts their utility. We describe a solution to this problem using gallium (Ga) in probe construction, taking advantage of the solid-to-liquid phase change of the metal at body temperature and probe shape deformation to provide temperature-dependent control of stiffness over 5 orders of magnitude. Probes in the stiff state were successfully inserted 2 cm-deep into agarose gel "brain phantoms" and into rat brains under cooled conditions where, upon Ga melting, they became ultra soft, flexible, and stretchable in all directions. The current 30 μm-thick probes incorporated multilayer, deformable microfluidic channels for chemical agent delivery, electrical interconnects through Ga wires, and high-performance electrochemical glutamate sensing. These PDMS-based microprobes of ultra-large tunable stiffness (ULTS) should serve as an attractive platform for multifunctional chronic neural implants.
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Affiliation(s)
- Ximiao Wen
- Department of Mechanical and Aerospace Engineering, University of California at Los Angeles, Los Angeles, CA, USA
| | - Bo Wang
- Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, CA, USA
| | - Shan Huang
- Department of Biological Chemistry, University of California at Los Angeles, CA, USA
| | - Tingyi Leo Liu
- Department of Mechanical and Industrial Engineering, University of Massachusetts Amherst, MA, USA
| | - Meng-Shiue Lee
- Department of Mechanical Engineering, National Chiao Tung University, Hsinchu, Taiwan
| | - Pei-Shan Chung
- Department of Bioengineering, University of California at Los Angeles, CA, USA
| | - Yu Ting Chow
- Department of Mechanical and Aerospace Engineering, University of California at Los Angeles, Los Angeles, CA, USA
| | - I-Wen Huang
- Department of Chemical and Biomolecular Engineering, University of California at Los Angeles, CA, USA
| | - Harold G Monbouquette
- Department of Chemical and Biomolecular Engineering, University of California at Los Angeles, CA, USA
| | - Nigel T Maidment
- Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, CA, USA.
| | - Pei-Yu Chiou
- Department of Mechanical and Aerospace Engineering, University of California at Los Angeles, Los Angeles, CA, USA; Department of Bioengineering, University of California at Los Angeles, CA, USA.
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15
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Shadlaghani A, Farzaneh M, Kinser D, Reid RC. Direct Electrochemical Detection of Glutamate, Acetylcholine, Choline, and Adenosine Using Non-Enzymatic Electrodes. SENSORS (BASEL, SWITZERLAND) 2019; 19:E447. [PMID: 30678261 PMCID: PMC6387276 DOI: 10.3390/s19030447] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 01/06/2019] [Accepted: 01/18/2019] [Indexed: 02/06/2023]
Abstract
Non-electroactive neurotransmitters such as glutamate, acetylcholine, choline, and adenosine play a critical role in proper activity of living organisms, particularly in the nervous system. While enzyme-based sensing of this type of neurotransmitter has been a research interest for years, non-enzymatic approaches are gaining more attention because of their stability and low cost. Accordingly, this focused review aims to give a summary of the state of the art of non-enzymatic electrochemical sensors used for detection of neurotransmitter that lack an electrochemically active component. In place of using enzymes, transition metal materials such as those based on nickel show an acceptable level of catalytic activity for neurotransmitter sensing. They benefit from fast electron transport properties and high surface energy and their catalytic activity can be much improved if their surface is modified with nanomaterials such as carbon nanotubes and platinum nanoparticles. However, a general comparison reveals that the performance of non-enzymatic biosensors is still lower than those that use enzyme-based methods. Nevertheless, their excellent stability demonstrates that non-enzymatic neurotransmitter sensors warrant additional research in order to advance them toward becoming an acceptable replacement for the more expensive enzyme-based sensors.
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Affiliation(s)
- Arash Shadlaghani
- Department of Mechanical and Energy Engineering, University of North Texas, Denton, TX 76209, USA.
| | - Mahsa Farzaneh
- Department of Mechanical and Energy Engineering, University of North Texas, Denton, TX 76209, USA.
| | - Dacen Kinser
- Department of Mechanical and Energy Engineering, University of North Texas, Denton, TX 76209, USA.
| | - Russell C Reid
- Department of Mechanical and Energy Engineering, University of North Texas, Denton, TX 76209, USA.
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16
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Nanomaterials-Based Electrochemical Sensors for In Vitro and In Vivo Analyses of Neurotransmitters. APPLIED SCIENCES-BASEL 2018. [DOI: 10.3390/app8091504] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
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.
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17
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Chatard C, Meiller A, Marinesco S. Microelectrode Biosensors forin vivoAnalysis of Brain Interstitial Fluid. ELECTROANAL 2018. [DOI: 10.1002/elan.201700836] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Charles Chatard
- INSERM U1028, CNRS UMR5292; Lyon Neuroscience Research Center, Team TIGER
- Université Claude Bernard Lyon 1; Lyon France
| | - Anne Meiller
- AniRA-Neurochem Technological Platform; Lyon France
- Université Claude Bernard Lyon 1; Lyon France
| | - Stéphane Marinesco
- INSERM U1028, CNRS UMR5292; Lyon Neuroscience Research Center, Team TIGER
- AniRA-Neurochem Technological Platform; Lyon France
- Université Claude Bernard Lyon 1; Lyon France
- Lyon Neuroscience Research Center, Team TIGER; Faculty of Medicine; 8 Avenue Rockefeller 69373 Lyon Cedex 08 France
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18
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Nasr B, Chatterton R, Yong JHM, Jamshidi P, D'Abaco GM, Bjorksten AR, Kavehei O, Chana G, Dottori M, Skafidas E. Self-Organized Nanostructure Modified Microelectrode for Sensitive Electrochemical Glutamate Detection in Stem Cells-Derived Brain Organoids. BIOSENSORS 2018; 8:E14. [PMID: 29401739 PMCID: PMC5872062 DOI: 10.3390/bios8010014] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 01/30/2018] [Accepted: 01/31/2018] [Indexed: 02/05/2023]
Abstract
Neurons release neurotransmitters such as glutamate to communicate with each other and to coordinate brain functioning. As increased glutamate release is indicative of neuronal maturation and activity, a system that can measure glutamate levels over time within the same tissue and/or culture system is highly advantageous for neurodevelopmental investigation. To address such challenges, we develop for the first time a convenient method to realize functionalized borosilicate glass capillaries with nanostructured texture as an electrochemical biosensor to detect glutamate release from cerebral organoids generated from human embryonic stem cells (hESC) that mimic various brain regions. The biosensor shows a clear catalytic activity toward the oxidation of glutamate with a sensitivity of 93 ± 9.5 nA·µM-1·cm-2. It was found that the enzyme-modified microelectrodes can detect glutamate in a wide linear range from 5 µM to 0.5 mM with a limit of detection (LOD) down to 5.6 ± 0.2 µM. Measurements were performed within the organoids at different time points and consistent results were obtained. This data demonstrates the reliability of the biosensor as well as its usefulness in measuring glutamate levels across time within the same culture system.
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Affiliation(s)
- Babak Nasr
- Centre for Neural Engineering, The University of Melbourne, Melbourne, VIC 3053, Australia.
- The Department of Electrical and Electronic Engineering, The University of Melbourne, Melbourne, VIC 3010, Australia.
- ARC Centre of Excellence for Integrative Brain Function, The University of Melbourne, Melbourne, VIC 3010, Australia.
| | - Rachael Chatterton
- Centre for Neural Engineering, The University of Melbourne, Melbourne, VIC 3053, Australia.
| | - Jason Hsien Ming Yong
- Centre for Neural Engineering, The University of Melbourne, Melbourne, VIC 3053, Australia.
- The Department of Electrical and Electronic Engineering, The University of Melbourne, Melbourne, VIC 3010, Australia.
| | - Pegah Jamshidi
- Centre for Neural Engineering, The University of Melbourne, Melbourne, VIC 3053, Australia.
| | - Giovanna Marisa D'Abaco
- The Department of Biomedical Engineering, The University of Melbourne, Melbourne, VIC 3010, Australia.
| | - Andrew Robin Bjorksten
- The Department of Anaesthesia & Pain Management, Royal Melbourne Hospital, Parkville, VIC 3050, Australia.
| | - Omid Kavehei
- Faculty of Engineering and Information Technology, The University of Sydney, Sydney, NSW 2006, Australia.
| | - Gursharan Chana
- Centre for Neural Engineering, The University of Melbourne, Melbourne, VIC 3053, Australia.
- Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC 3050, Australia.
| | - Mirella Dottori
- Centre for Neural Engineering, The University of Melbourne, Melbourne, VIC 3053, Australia.
- The Department of Electrical and Electronic Engineering, The University of Melbourne, Melbourne, VIC 3010, Australia.
- Illawarra Health and Medical Research Institute, Centre for Molecular and Medical Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia.
| | - Efstratios Skafidas
- Centre for Neural Engineering, The University of Melbourne, Melbourne, VIC 3053, Australia.
- The Department of Electrical and Electronic Engineering, The University of Melbourne, Melbourne, VIC 3010, Australia.
- ARC Centre of Excellence for Integrative Brain Function, The University of Melbourne, Melbourne, VIC 3010, Australia.
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19
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Moon JM, Thapliyal N, Hussain KK, Goyal RN, Shim YB. Conducting polymer-based electrochemical biosensors for neurotransmitters: A review. Biosens Bioelectron 2017; 102:540-552. [PMID: 29220802 DOI: 10.1016/j.bios.2017.11.069] [Citation(s) in RCA: 191] [Impact Index Per Article: 23.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 11/25/2017] [Accepted: 11/29/2017] [Indexed: 02/06/2023]
Abstract
Neurotransmitters are important biochemical molecules that control behavioral and physiological functions in central and peripheral nervous system. Therefore, the analysis of neurotransmitters in biological samples has a great clinical and pharmaceutical importance. To date, various methods have been developed for their assay. Of the various methods, the electrochemical sensors demonstrated the potential of being robust, selective, sensitive, and real time measurements. Recently, conducting polymers (CPs) and their composites have been widely employed in the fabrication of various electrochemical sensors for the determination of neurotransmitters. Hence, this review presents a brief introduction to the electrochemical biosensors, with the detailed discussion on recent trends in the development and applications of electrochemical neurotransmitter sensors based on CPs and their composites. The review covers the sensing principle of prime neurotransmitters, including glutamate, aspartate, tyrosine, epinephrine, norepinephrine, dopamine, serotonin, histamine, choline, acetylcholine, nitrogen monoxide, and hydrogen sulfide. In addition, the combination with other analytical techniques was also highlighted. Detection challenges and future prospective of the neurotransmitter sensors were discussed for the development of biomedical and healthcare applications.
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Affiliation(s)
- Jong-Min Moon
- Department of Chemistry and Institute of BioPhysio Sensor Technology (IBST), Pusan National University, Busan 46241, South Korea
| | - Neeta Thapliyal
- Department of Pharmaceutical Chemistry, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa
| | - Khalil Khadim Hussain
- Department of Chemistry and Institute of BioPhysio Sensor Technology (IBST), Pusan National University, Busan 46241, South Korea
| | - Rajendra N Goyal
- Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247667, India.
| | - Yoon-Bo Shim
- Department of Chemistry and Institute of BioPhysio Sensor Technology (IBST), Pusan National University, Busan 46241, South Korea.
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20
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Oomen PE, Mulder JPSH, Verpoorte E, Oleschuk RD. Controlled, synchronized actuation of microdroplets by gravity in a superhydrophobic, 3D-printed device. Anal Chim Acta 2017; 988:50-57. [PMID: 28916103 DOI: 10.1016/j.aca.2017.08.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 07/21/2017] [Accepted: 08/04/2017] [Indexed: 11/18/2022]
Abstract
Droplet manipulation over open surfaces allows one to perform assays with a large degree of control and high throughput, making them appealing for applications in drug screening or (bio)analysis. However, the design, manufacturing and operation of these systems comes with high technical requirements. In this study we employ a commercial, low-friction, superhydrophobic coating, Ultra-Ever Dry®, on a 3D-printed microfluidic device. The device features individual droplet compartments, which allow the manipulation of discrete droplets (10-50 μL) actuated by gravity alone. Simply by angling the device to normal in a 3D-printed holder and rocking in a "to and fro"-fashion, a sequence of droplets can be individually transferred to an electrochemical microelectrode detector and then to waste, while preserving the (chronological) order of samples. Multiple biological fluids (i.e. human saliva, urine and rat blood and serum) were successfully tested for compatibility with the device and actuation mechanism, demonstrating low slip angles and high contact angles. Biological matrix (protein) carryover was probed and effectively mitigated by incorporating aqueous rinse droplets as part of the analysis sequence. As a proof-of-concept, the enzyme-coupled, amperometric detection of glucose was carried out on individual rat serum droplets, enabling total analysis in ≈30 min, including calibration. The device is readily customizable, and the integration of droplet generation techniques and other sensor systems for different analytes of interest or applications can be realized in a plug and play fashion.
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Affiliation(s)
- P E Oomen
- Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1-XB20, 9713 AV Groningen, The Netherlands.
| | - J P S H Mulder
- Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1-XB20, 9713 AV Groningen, The Netherlands.
| | - E Verpoorte
- Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1-XB20, 9713 AV Groningen, The Netherlands.
| | - R D Oleschuk
- Department of Chemistry, Queen's University, 90 Bader Lane, Kingston, Ontario K7L 3N6, Canada.
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21
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Enrico P, Diana M. On the Accuracy of In Vivo Ethanol and Acetaldehyde Monitoring, a Key Tile in the Puzzle of Acetaldehyde as a Neuroactive Agent. Front Behav Neurosci 2017; 11:97. [PMID: 28611604 PMCID: PMC5447755 DOI: 10.3389/fnbeh.2017.00097] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Accepted: 05/09/2017] [Indexed: 11/18/2022] Open
Abstract
Over the last 20 years researchers have explored the postulated role of acetaldehyde (ACD) as a mediator of some of the actions of ethanol (EtOH) in the central nervous system (CNS). However, efforts have been hampered mainly by the difficulty of directly measuring in vivo EtOH and ACD levels in the CNS and thus, our knowledge is based on indirect evidences. Although technically challenging, the development of reliable methods for in vivo measurement of ACD and EtOH is of paramount importance to solve the “puzzle of acetaldehyde as a neuroactive agent.” In this short review we discuss the recent advances on brain EtOH pharmacokinetic and state-of-the-art available techniques that could be used for in vivo detect EtOH and ACD both non-invasively (magnetic resonance spectroscopy), and invasively (microdialysis and biosensors). Among the different in vivo sampling techniques described, particular emphasis is paid to the field of enzyme-based amperometric biosensors. Biosensors have gained much attention in recent years for their ability to online monitor biological signals in vivo, and several micro- and nano-structured devices have been successfully used for in vivo studies. Owing to their high temporal and spatial resolution, biosensors could provide the adequate technology for studying in vivo EtOH pharmacokinetic.
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Affiliation(s)
- Paolo Enrico
- Department of Biomedical Sciences, University of SassariSassari, Italy
| | - Marco Diana
- 'G. Minardi' Cognitive Neuroscience Laboratory, Department of Chemistry and Pharmacy, University of SassariSassari, Italy
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22
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Hasanzadeh M, Shadjou N, Guardia MDL. Current advancement in electrochemical analysis of neurotransmitters in biological fluids. Trends Analyt Chem 2017. [DOI: 10.1016/j.trac.2016.11.001] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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23
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Patrick MM, Grillot JM, Derden ZM, Paul DW. Long-term Drifts in Sensitivity Caused by Biofouling of an Amperometric Oxygen Sensor. ELECTROANAL 2016. [DOI: 10.1002/elan.201600653] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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24
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Characterization of Biosensors Based on Recombinant Glutamate Oxidase: Comparison of Crosslinking Agents in Terms of Enzyme Loading and Efficiency Parameters. SENSORS 2016; 16:s16101565. [PMID: 27669257 PMCID: PMC5087354 DOI: 10.3390/s16101565] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Revised: 09/07/2016] [Accepted: 09/18/2016] [Indexed: 02/05/2023]
Abstract
Amperometric l-glutamate (Glu) biosensors, based on both wild-type and a recombinant form of l-glutamate oxidase (GluOx), were designed and characterized in terms of enzyme-kinetic, sensitivity and stability parameters in attempts to fabricate a real-time Glu monitoring device suitable for future long-term detection of this amino acid in biological and other complex media. A comparison of the enzyme from these two sources showed that they were similar in terms of biosensor performance. Optimization of the loading of the polycationic stabilization agent, polyethyleneimine (PEI), was established before investigating a range of crosslinking agents under different conditions: glutaraldehyde (GA), polyethylene glycol (PEG), and polyethylene glycol diglycidyl ether (PEGDE). Whereas PEI-free biosensor designs lost most of their meager Glu sensitivity after one or two days, configurations with a 2:5 ratio of dip-evaporation applications of PEI(1%):GluOx(400 U/mL) displayed a 20-fold increase in their initial sensitivity, and a decay half-life extended to 10 days. All the crosslinkers studied had no effect on initial Glu sensitivity, but enhanced biosensor stability, provided the crosslinking procedure was carried out under well-defined conditions. The resulting biosensor design based on the recombinant enzyme deposited on a permselective layer of poly-(ortho-phenylenediamine), PoPD/PEI₂/GluOx₅/PEGDE, displayed good sensitivity (LOD < 0.2 μM), response time (t90% < 1 s) and stability over a 90-day period, making it an attractive candidate for future long-term monitoring of Glu concentration dynamics in complex media.
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25
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Weltin A, Kieninger J, Urban GA. Microfabricated, amperometric, enzyme-based biosensors for in vivo applications. Anal Bioanal Chem 2016; 408:4503-21. [PMID: 26935934 PMCID: PMC4909808 DOI: 10.1007/s00216-016-9420-4] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2015] [Revised: 02/08/2016] [Accepted: 02/12/2016] [Indexed: 01/19/2023]
Abstract
Miniaturized electrochemical in vivo biosensors allow the measurement of fast extracellular dynamics of neurotransmitter and energy metabolism directly in the tissue. Enzyme-based amperometric biosensing is characterized by high specificity and precision as well as high spatial and temporal resolution. Aside from glucose monitoring, many systems have been introduced mainly for application in the central nervous system in animal models. We compare the microsensor principle with other methods applied in biomedical research to show advantages and drawbacks. Electrochemical sensor systems are easily miniaturized and fabricated by microtechnology processes. We review different microfabrication approaches for in vivo sensor platforms, ranging from simple modified wires and fibres to fully microfabricated systems on silicon, ceramic or polymer substrates. The various immobilization methods for the enzyme such as chemical cross-linking and entrapment in polymer membranes are discussed. The resulting sensor performance is compared in detail. We also examine different concepts to reject interfering substances by additional membranes, aspects of instrumentation and biocompatibility. Practical considerations are elaborated, and conclusions for future developments are presented. Graphical Abstract ᅟ.
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Affiliation(s)
- Andreas Weltin
- Laboratory for Sensors, Department of Microsystems Engineering – IMTEK, University of Freiburg, Georges-Köhler-Allee 103, 79110 Freiburg, Germany
| | - Jochen Kieninger
- Laboratory for Sensors, Department of Microsystems Engineering – IMTEK, University of Freiburg, Georges-Köhler-Allee 103, 79110 Freiburg, Germany
| | - Gerald A. Urban
- Laboratory for Sensors, Department of Microsystems Engineering – IMTEK, University of Freiburg, Georges-Köhler-Allee 103, 79110 Freiburg, Germany
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26
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Wang Y, Salazar JK. Culture-Independent Rapid Detection Methods for Bacterial Pathogens and Toxins in Food Matrices. Compr Rev Food Sci Food Saf 2015; 15:183-205. [DOI: 10.1111/1541-4337.12175] [Citation(s) in RCA: 161] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Accepted: 09/14/2015] [Indexed: 11/29/2022]
Affiliation(s)
- Yun Wang
- Div. of Food Processing Science and Technology; U.S. Food and Drug Administration; Bedford Park IL U.S.A
| | - Joelle K. Salazar
- Div. of Food Processing Science and Technology; U.S. Food and Drug Administration; Bedford Park IL U.S.A
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27
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Cordeiro C, de Vries M, Ngabi W, Oomen P, Cremers T, Westerink B. In vivo continuous and simultaneous monitoring of brain energy substrates with a multiplex amperometric enzyme-based biosensor device. Biosens Bioelectron 2015; 67:677-86. [DOI: 10.1016/j.bios.2014.09.101] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2014] [Revised: 08/27/2014] [Accepted: 09/22/2014] [Indexed: 01/30/2023]
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28
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Cuartero M, Crespo GA, Ghahraman Afshar M, Bakker E. Exhaustive Thin-Layer Cyclic Voltammetry for Absolute Multianalyte Halide Detection. Anal Chem 2014; 86:11387-95. [DOI: 10.1021/ac503344f] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Affiliation(s)
- Maria Cuartero
- Department
of Inorganic and
Analytical Chemistry, University of Geneva, Quai Ernest-Ansermet 30, CH-1211 Geneva, Switzerland
| | - Gastón A. Crespo
- Department
of Inorganic and
Analytical Chemistry, University of Geneva, Quai Ernest-Ansermet 30, CH-1211 Geneva, Switzerland
| | - Majid Ghahraman Afshar
- Department
of Inorganic and
Analytical Chemistry, University of Geneva, Quai Ernest-Ansermet 30, CH-1211 Geneva, Switzerland
| | - Eric Bakker
- Department
of Inorganic and
Analytical Chemistry, University of Geneva, Quai Ernest-Ansermet 30, CH-1211 Geneva, Switzerland
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29
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Sirca D, Vardeu A, Pinna M, Diana M, Enrico P. A robust, state-of-the-art amperometric microbiosensor for glutamate detection. Biosens Bioelectron 2014; 61:526-31. [PMID: 24951923 DOI: 10.1016/j.bios.2014.04.054] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2014] [Revised: 04/10/2014] [Accepted: 04/29/2014] [Indexed: 10/25/2022]
Abstract
Scientific knowledge of glutamate (GLU) neurobiology is severely hampered by the inadequacy of the available in vivo brain sampling techniques. Due to the crucial role of GLU in central nervous system function and pathology, the development of a reliable sampling device is mandatory. GLU biosensor holds potential to address many of the known issues of in vivo GLU measurement. We report here on the development and test of a labor- and cost-effective microbiosensor, suitable to be applied for measuring brain GLU. A glycerol-based cryopreservation method was also tested. Needle type Pt biosensors were coated with a permselective Nafion-Poly(o-phenylenediamine) layer and cross-linked to l-glutamate oxidase with poly(ethylene glycol) diglycidyl ether. Tested in vitro, the device shows high sensitivity and specificity for GLU, while being poorly influenced by common interfering substances such as ascorbate, dopamine and dihydroxyphenylacetic acid. Further, the cryopreservation procedure kept sensitivity unaltered for 30 days and possibly longer. We conclude that a highly efficient GLU biosensor of minimal dimensions can be consistently and affordably constructed with relative ease. Together with the possibility of cryopreservation this shall foster diffusion and exploitation of GLU biosensors technology.
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Affiliation(s)
- Donatella Sirca
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Antonella Vardeu
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Milo Pinna
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Marco Diana
- "G. Minardi" Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy
| | - Paolo Enrico
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
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Farina D, Alvau MD, Puggioni G, Calia G, Bazzu G, Migheli R, Sechi O, Rocchitta G, Desole MS, Serra PA. Implantable (Bio)sensors as new tools for wireless monitoring of brain neurochemistry in real time. World J Pharmacol 2014; 3:1-17. [DOI: 10.5497/wjp.v3.i1.1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Revised: 05/01/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Implantable electrochemical microsensors are characterized by high sensitivity, while amperometric biosensors are very selective in virtue of the biological detecting element. Each sensor, specific for every neurochemical species, is a miniaturized high-technology device resulting from the combination of several factors: electrode material, shielding polymers, applied electrochemical technique, and in the case of biosensors, biological sensing material, stabilizers, and entrapping chemical nets. In this paper, we summarize the available technology for the in vivo electrochemical monitoring of neurotransmitters (dopamine, norepinephrine, serotonin, acetylcholine, and glutamate), bioenergetic substrates (glucose, lactate, and oxygen), neuromodulators (ascorbic acid and nitric oxide), and exogenous molecules such as ethanol. We also describe the most represented biotelemetric technologies in order to wirelessly transmit the signals of the above-listed neurochemicals. Implantable (Bio)sensors, integrated into miniaturized telemetry systems, represent a new generation of analytical tools that could be used for studying the brain’s physiology and pathophysiology and the effects of different drugs (or toxic chemicals such as ethanol) on neurochemical systems.
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Moon BU, de Vries MG, Cordeiro CA, Westerink BHC, Verpoorte E. Microdialysis-coupled enzymatic microreactor for in vivo glucose monitoring in rats. Anal Chem 2013; 85:10949-55. [PMID: 24199633 DOI: 10.1021/ac402414m] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Continuous glucose monitoring (CGM) is an important aid for diabetic patients to optimize glycemic control and to prevent long-term complications. However, current CGM devices need further miniaturization and improved functional performance. We have coupled a previously described microfluidic chip with enzymatic microreactor (EMR) to a microdialysis probe and evaluated the performance of this system for monitoring subcutaneous glucose concentration in rats. Nanoliter volumes of microdialysis sample are efficiently reacted with continuously supplied glucose oxidase (GOx) solution in the EMR. The hydrogen peroxide produced is amperometrically detected at a (polypyrrole (PPy)-protected) thin-film Pt electrode. Subcutaneous glucose concentration was continuously monitored in anesthetized rats in response to intravenous injections of 20% glucose (w/v), 5 U/kg insulin, or saline as a control. In vitro evaluation showed a linear range of 2.1-20.6 mM and a sensitivity of 7.8 ± 1.0 nA/mM (n = 6). The physical lag time between microdialysis and the analytical signal was approximately 18 min. The baseline concentration of blood glucose was 10.2 ± 2.3 mM. After administering glucose to the rats, glucose levels increased by about 2 mM to 12.1 ± 2.3 mM in blood and 11.9 ± 1.5 mM in subcutaneous interstitial fluid (ISF). After insulin administration, glucose levels decreased by about 8 mM relative to baseline to 2.1 ± 0.6 mM in blood and 2.1 ± 0.9 mM in ISF. A microfluidic device with integrated chaotic mixer and EMR has been successfully combined with subcutaneous microdialysis to continuously monitor glucose in rats. This proof-of-principle demonstrates the feasibility of improved miniaturization in CGM based on microfluidics.
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Affiliation(s)
- Byeong-Ui Moon
- Biomonitoring and Sensoring, Groningen Research Institute of Pharmacy, University of Groningen , Antonius Deusinglaan 1, P.O. Box 196, 9700 AD Groningen, The Netherlands
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Campbell H, Elzanowska H, Birss V. Towards a reliable and high sensitivity O2-independent glucose sensor based on Ir oxidenanoparticles. Biosens Bioelectron 2013; 42:563-9. [DOI: 10.1016/j.bios.2012.11.023] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2012] [Revised: 10/17/2012] [Accepted: 11/19/2012] [Indexed: 02/05/2023]
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Disposable sensor based on enzyme-free Ni nanowire array electrode to detect glutamate. Biosens Bioelectron 2013; 40:213-8. [DOI: 10.1016/j.bios.2012.07.024] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2012] [Revised: 07/03/2012] [Accepted: 07/15/2012] [Indexed: 11/21/2022]
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