Micro-needle implantable electrochemical oxygen sensor: ex-vivo and in-vivo studies

Rivas, Lourdes; Dulay, Samuel; Miserere, Sandrine; Pla, Laura; Berdún, Sergio; Parra, Johanna; Eixarch, E.; Gratacós, E.; Illa, M.; Mir, Mònica; Samitier, J.

doi:10.1016/j.bios.2020.112028

Cited by 46 publications

(39 citation statements)

References 20 publications

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“…Understanding the cellular and molecular mechanisms underlying hypoxia-associated diseases requires O 2 imaging technology capable of detecting the tissue oxygen status in real time and with high resolution. In vivo O 2 detection methods that have been developed so far include oxygen electrodes 4,5 , blood oxygenation level dependent magnetic resonance imaging (Bold MRI) 6,7 , positron emission tomography (PET) with a hypoxia tracer 8 , electron paramagnetic resonance (EPR) oximetry 9,10 , hypoxia markers [11][12][13] , and optical imaging [14][15][16] . These methods can work in vivo, but they have advantages and limitations in terms of applicable targets, spatial resolution, tissue permeability, convenience, reversibility, etc.…”

mentioning

confidence: 99%

In vivo O2 imaging in hepatic tissues by phosphorescence lifetime imaging microscopy using Ir(III) complexes as intracellular probes

Katano

Shiozaki

Yoshihara

et al. 2020

Sci Rep

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Phosphorescence lifetime imaging microscopy (PLIM) combined with an oxygen (O2)-sensitive luminescent probe allows for high-resolution O2 imaging of living tissues. Herein, we present phosphorescent Ir(III) complexes, (btp)2Ir(acac-DM) (Ir-1) and (btp-OH)3Ir (Ir-2), as useful O2 probes for PLIM measurement. These small-molecule probes were efficiently taken up into cultured cells and accumulated in specific organelles. Their excellent cell-permeable properties allowed for efficient staining of three-dimensional cell spheroids, and thereby phosphorescence lifetime measurements enabled the evaluation of the O2 level and distribution in spheroids, including the detection of alterations in O2 levels by metabolic stimulation with an effector. We took PLIM images of hepatic tissues of living mice by intravenously administrating these probes. The PLIM images clearly visualized the O2 gradient in hepatic lobules with cellular-level resolution, and the O2 levels were derived based on calibration using cultured cells; the phosphorescence lifetime of Ir-1 gave reasonable O2 levels, whereas Ir-2 exhibited much lower O2 levels. Intravenous administration of NH4Cl to mice caused the hepatic tissues to experience hypoxia, presumably due to O2 consumption to produce ATP required for ammonia detoxification, suggesting that the metabolism of the probe molecule might affect liver O2 levels.

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mentioning

confidence: 99%

In vivo O2 imaging in hepatic tissues by phosphorescence lifetime imaging microscopy using Ir(III) complexes as intracellular probes

Katano

Shiozaki

Yoshihara

et al. 2020

Sci Rep

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“…As summarized in another review by [101], most of these works are limited to in vitro testing, showing enhancements in sensitivity, selectivity, and stability by utilizing novel modifications, but they lack in vivo validation. Some metals also have catalytic properties that can shift redox potentials into a more desirable range; the classic example of this is platinum's catalytic effect on the reduction of oxygen in a Clark electrode, a technique that is still in use in clinical brain measurements today [102,103]. While oxygen's standard reduction potential is quite high and highly dependent on pH, a Clark electrode [104] reduces oxygen at a platinum electrode at -0.6V, far away from potentials that may cause undesirable reactions [105].…”

Section: Metal Electrodesmentioning

confidence: 99%

Recent Advances in In Vivo Neurochemical Monitoring

Tan

Robbins

et al. 2021

Micromachines

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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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“…The different behavior could be explained by differences in oxygen and protons diffusivity depending on the tissue surrounding the electrochemical sensor. It is known that blood and muscle present different electrolyte composition [31] and depending on that, different electroactive species could also bind to the electrochemical sensor membrane interfering the final signal [23].…”

Section: Electrochemical Sensors At Short-term Evaluationmentioning

confidence: 99%

“…In this study, as a first step we tested the hypothesis that previously developed miniaturized electrochemical sensors [23] could detect and monitor oxygen and pH changes continuously in a model of acute hypoxia-acidosis. If favorable results are obtained, next step will be to evaluate the performance of these electrochemical sensors on fetal tissue.…”

Section: Introductionmentioning

confidence: 99%

Non-Invasive Monitoring of pH and Oxygen Using Miniaturized Electrochemical Sensors in an Animal Model of Acute Hypoxia

Pla

Berdún

Mir

et al. 2020

Preprint

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BackgroundOne of the most prevalent causes of fetal hypoxia leading to stillbirth is placental insufficiency. Hemodynamic changes evaluated with Doppler ultrasound have been used as a surrogate marker of fetal hypoxia. However, Doppler evaluation cannot be performed continuously. As a first step, the present work aimed to evaluate the performance of miniaturized electrochemical sensors in continuous monitoring of oxygen and pH changes in a model of acute hypoxia-acidosis. MethodspH and oxygen electrochemical sensors were evaluated in a ventilatory hypoxia rabbit model. The ventilator hypoxia protocol included three differential phases: basal (100% FiO2), hypoxia-acidosis period (10% FiO2) and recovery (100% FiO2). Sensors were tested in blood tissue (ex vivo sensing) and in the muscular tissue (in vivo sensing). pH electrochemical and oxygen sensors were evaluated at the same day of insertion (short-term evaluation) and pH electrochemical sensors were also tested after 5 days of insertion (long-term evaluation). pH and oxygen sensing were registered during all the ventilatory hypoxia protocol (basal, hypoxia-acidosis and recovery) and were compared with blood gas metabolites results from carotid artery catheterization (EPOC® blood analyzer). Finally, histological assessment was performed on the site of the sensor’s insertion. One-way ANOVA was used for the analysis of the evolution of acid-based metabolites and electrochemical sensor signaling results; T-test was used for pre and post calibration analyses; and chi-square analyses for categorical variables. ResultsAt the short-term evaluation, both pH and oxygen electrochemical sensors distinguished the basal and hypoxia-acidosis periods in the in vivo and ex vivo sensing. However, only the ex vivo sensing detected recovery period. At the long-term evaluation, pH electromechanical sensor signal seemed to lose sensibility. Finally, histological assessment revealed no signs of alteration at the same day of evaluation (short-term), whereas at the long-term evaluation sub-acute inflammatory reaction adjacent to the site of the implantation was detected. ConclusionsThe use of miniaturized electrochemical sensors open a new generation of tools for continuous monitoring of hypoxia-acidosis, especially indicated in high risk pregnancies. Further studies including more tissue-compatible material would be required in order to improve the long-term electromechanical sensing.

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Micro-needle implantable electrochemical oxygen sensor: ex-vivo and in-vivo studies

Cited by 46 publications

References 20 publications

In vivo O2 imaging in hepatic tissues by phosphorescence lifetime imaging microscopy using Ir(III) complexes as intracellular probes

In vivo O2 imaging in hepatic tissues by phosphorescence lifetime imaging microscopy using Ir(III) complexes as intracellular probes

Recent Advances in In Vivo Neurochemical Monitoring

Non-Invasive Monitoring of pH and Oxygen Using Miniaturized Electrochemical Sensors in an Animal Model of Acute Hypoxia

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