Planar implantable sensor for in vivo measurement of cellular oxygen metabolism in brain tissue

Tsytsarev, Vassiliy; Akkentli, Fatih; Pumbo, Elena; Tang, Qinggong; Chen, Yu; Erzurumlu, Reha S.; Papkovsky, Dmitri B.

doi:10.1016/j.jneumeth.2017.02.005

Cited by 11 publications

(5 citation statements)

References 40 publications

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“…The development of a medical device able to detect the fetal hypoxia-acidosis status in a precise and continuous manner would be a big step forward in the clinical managing of this population. To this end, previous evidence has demonstrated the feasibility of sensor devices being inserted in different tissues, including in the vascular system [10][11][12][13], the brain [14][15][16][17], the gastric system [18], subcutaneously and intramuscularly [19][20][21][22] to monitor and detect acid-base status. However, most of these sensors are not designed to be used during the intrauterine period.…”

Section: Introductionmentioning

confidence: 99%

Non-invasive monitoring of pH and oxygen using miniaturized electrochemical sensors in an animal model of acute hypoxia

et al. 2021

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Background One 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 the continuous monitoring of oxygen and pH changes in a model of acute hypoxia-acidosis. Methods pH and oxygen electrochemical sensors were evaluated in a ventilatory hypoxia rabbit model. The ventilator hypoxia protocol included 3 differential phases: basal (100% FiO2), the hypoxia-acidosis period (10% FiO2) and recovery (100% FiO2). Sensors were tested in blood tissue (ex vivo sensing) and in muscular tissue (in vivo sensing). pH electrochemical and oxygen sensors were evaluated on the 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 throughout the ventilatory hypoxia protocol (basal, hypoxia-acidosis, and recovery) and were compared with blood gas metabolites results from carotid artery catheterization (obtained with the EPOC blood analyzer). Finally, histological assessment was performed on the sensor insertion site. One-way ANOVA was used for the analysis of the evolution of acid-based metabolites and electrochemical sensor signaling results; a t-test was used for pre- and post-calibration analyses; and chi-square analyses for categorical variables. Results At the short-term evaluation, both the pH and oxygen electrochemical sensors distinguished the basal and hypoxia-acidosis periods in both the in vivo and ex vivo sensing. However, only the ex vivo sensing detected the recovery period. In the long-term evaluation, the pH electrochemical sensor signal seemed to lose sensibility. Finally, histological assessment revealed no signs of alteration on the day of evaluation (short-term), whereas in the long-term evaluation a sub-acute inflammatory reaction adjacent to the implantation site was detected. Conclusions Miniaturized electrochemical sensors represent a new generation of tools for the continuous monitoring of hypoxia-acidosis, which is especially indicated in high-risk pregnancies. Further studies including more tissue-compatible material would be required in order to improve long-term electrochemical sensing.

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Section: Introductionmentioning

confidence: 99%

Non-invasive monitoring of pH and oxygen using miniaturized electrochemical sensors in an animal model of acute hypoxia

et al. 2021

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“…They are typically characterized by a phosphorescent thin-film polymeric-coating applied on an oxygenimpermeable substrate (e.g., polyester films) which is applied onto the target, e.g. brain tissue (Figure 7) [123]; after their application on the target skin, imaging is performed with a CCD camera [124,125].…”

Section: Translation Of Classical Methods To Clinical Settings: Lumin...mentioning

confidence: 99%

“…The skull cortex of the mouse is illuminated with light at 630 nm, and the emitted photons with a wavelength above 690 nm are acquired with a CCD camera. Adapted with permission from [123].…”

Section: Figurementioning

confidence: 99%

The Challenges of O2 Detection in Biological Fluids: Classical Methods and Translation to Clinical Applications

Marassi

Giordani

Kurevija³

et al. 2022

IJMS

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Dissolved oxygen (DO) is deeply involved in preserving the life of cellular tissues and human beings due to its key role in cellular metabolism: its alterations may reflect important pathophysiological conditions. DO levels are measured to identify pathological conditions, explain pathophysiological mechanisms, and monitor the efficacy of therapeutic approaches. This is particularly relevant when the measurements are performed in vivo but also in contexts where a variety of biological and synthetic media are used, such as ex vivo organ perfusion. A reliable measurement of medium oxygenation ensures a high-quality process. It is crucial to provide a high-accuracy, real-time method for DO quantification, which could be robust towards different medium compositions and temperatures. In fact, biological fluids and synthetic clinical fluids represent a challenging environment where DO interacts with various compounds and can change continuously and dynamically, and further precaution is needed to obtain reliable results. This study aims to present and discuss the main oxygen detection and quantification methods, focusing on the technical needs for their translation to clinical practice. Firstly, we resumed all the main methodologies and advancements concerning dissolved oxygen determination. After identifying the main groups of all the available techniques for DO sensing based on their mechanisms and applicability, we focused on transferring the most promising approaches to a clinical in vivo/ex vivo setting.

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“…Among the most effective phosphorescent oxygen sensors which are also commercially available, it is worth mentioning those obtained in the research groups of Sergei Vinogradov (University of Pennsylvania) [11][12][13][14][15][16][17][18][19][20] and Dmitri Papkovsky (University College Cork) [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. These sensors are based on Pt and Pd porphyrin chromophores, which are highly sensitive to oxygen and also protected from the external effects of the biological environment by either being encapsulated within dendrimer layers and subsequently modified by attaching large, linear poly(ethylene glycol) (PEG) chains [11][12][13][14][15][16][17][18][19][20] or by embedding the chromophore into hydrophilic nanoparticles [21][22][23][24][25][26][27][28][29][30]…”

Section: Introductionmentioning

confidence: 99%

Biocompatible Phosphorescent O2 Sensors Based on Ir(III) Complexes for In Vivo Hypoxia Imaging

et al. 2023

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In this work, we obtained three new phosphorescent iridium complexes (Ir1–Ir3) of general stoichiometry [Ir(N^C)2(N^N)]Cl decorated with oligo(ethylene glycol) fragments to make them water-soluble and biocompatible, as well as to protect them from aggregation with biomolecules such as albumin. The major photophysical characteristics of these phosphorescent complexes are determined by the nature of two cyclometallating ligands (N^C) based on 2-pyridine-benzothiophene, since quantum chemical calculations revealed that the electronic transitions responsible for the excitation and emission are localized mainly at these fragments. However, the use of various diimine ligands (N^N) proved to affect the quantum yield of phosphorescence and allowed for changing the complexes’ sensitivity to oxygen, due to the variations in the steric accessibility of the chromophore center for O2 molecules. It was also found that the N^N ligands made it possible to tune the biocompatibility of the resulting compounds. The wavelengths of the Ir1–Ir3 emission maxima fell in the range of 630–650 nm, the quantum yields reached 17% (Ir1) in a deaerated solution, and sensitivity to molecular oxygen, estimated as the ratio of emission lifetime in deaerated and aerated water solutions, displayed the highest value, 8.2, for Ir1. The obtained complexes featured low toxicity, good water solubility and the absence of a significant effect of biological environment components on the parameters of their emission. Of the studied compounds, Ir1 and Ir2 were chosen for in vitro and in vivo biological experiments to estimate oxygen concentration in cell lines and tumors. These sensors have demonstrated their effectiveness for mapping the distribution of oxygen and for monitoring hypoxia in the biological objects studied.

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Planar implantable sensor for in vivo measurement of cellular oxygen metabolism in brain tissue

Cited by 11 publications

References 40 publications

Non-invasive monitoring of pH and oxygen using miniaturized electrochemical sensors in an animal model of acute hypoxia

Non-invasive monitoring of pH and oxygen using miniaturized electrochemical sensors in an animal model of acute hypoxia

The Challenges of O2 Detection in Biological Fluids: Classical Methods and Translation to Clinical Applications

Biocompatible Phosphorescent O2 Sensors Based on Ir(III) Complexes for In Vivo Hypoxia Imaging

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