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基于组织酸中毒的微型可植入式缺氧传感器的体内监测

in vivo Monitoring with micro-implantable hypoxia sensor based on tissue acidosis.

作者信息

Dulay Samuel, Rivas Lourdes, Miserere Sandrine, Pla Laura, Berdún Sergio, Parra Johanna, Eixarch Elisenda, Gratacós Eduard, Illa Míriam, Mir Mònica, Samitier Josep

机构信息

Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC) Barcelona Institute of Science and Technology (BIST), 12 Baldiri Reixac 15-21, Barcelona, 08028, Spain.

Fetal Medicine Research Center, BCNatal. Hospital Clínic and Hospital Sant Joan de Déu, Universitat de Barcelona. Building Helios 2, Sabino Arana Street 1, 08028, Barcelona, Spain.

出版信息

Talanta. 2021 May 1;226:122045. doi: 10.1016/j.talanta.2020.122045. Epub 2020 Dec 25.

DOI:10.1016/j.talanta.2020.122045
PMID:33676640
Abstract

Hypoxia is a common medical problem, sometimes difficult to detect and caused by different situations. Control of hypoxia is of great medical importance and early detection is essential to prevent life threatening complications. However, the few current methods are invasive, expensive, and risky. Thus, the development of reliable and accurate sensors for the continuous monitoring of hypoxia is of vital importance for clinical monitoring. Herein, we report an implantable sensor to address these needs. The developed device is a low-cost, miniaturised implantable electrochemical sensor for monitoring hypoxia in tissue by means of pH detection. This technology is based on protonation/deprotonation of polypyrrole conductive polymer. The sensor was optimized in vitro and tested in vivo intramuscularly and ex vivo in blood in adult rabbits with respiration-induced hypoxia and correlated with the standard device ePOC. The sensor demonstrated excellent sensitivity and reproducibility; 46.4 ± 0.4 mV/pH in the pH range of 4-9 and the selectivity coefficient exhibited low interference activity in vitro. The device was linear (R = 0.925) with a low dispersion of the values (n = 11) with a cut-off of 7.1 for hypoxia in vivo and ex vivo. Statistics with one-way ANOVA (α = 0.05), shows statistical differences between hypoxia and normoxia states and the good performance of the pH sensor, which demonstrated good agreement with the standard device. The sensor was stable and functional after 18 months. The excellent results demonstrated the feasibility of the sensors in real-time monitoring of intramuscular tissue and blood for medical applications.

摘要

缺氧是一个常见的医学问题,有时难以检测,且由不同情况引起。控制缺氧具有重大的医学意义,早期检测对于预防危及生命的并发症至关重要。然而,目前现有的几种方法具有侵入性、成本高且有风险。因此,开发可靠且准确的用于持续监测缺氧的传感器对于临床监测至关重要。在此,我们报告一种可植入传感器以满足这些需求。所开发的设备是一种低成本、小型化的可植入电化学传感器,用于通过pH检测来监测组织中的缺氧情况。该技术基于聚吡咯导电聚合物的质子化/去质子化。该传感器在体外进行了优化,并在成年兔因呼吸诱导缺氧而产生的肌肉内进行了体内测试以及在血液中进行了离体测试,并与标准设备ePOC进行了相关性分析。该传感器表现出优异的灵敏度和重现性;在4 - 9的pH范围内为46.4 ± 0.4 mV/pH,并且选择性系数在体外表现出低干扰活性。该设备呈线性(R = 0.925),值的离散度低(n = 11),体内和离体缺氧的截断值为7.1。采用单因素方差分析(α = 0.05)进行统计,结果显示缺氧状态与正常氧合状态之间存在统计学差异,且pH传感器性能良好,与标准设备表现出良好的一致性。该传感器在18个月后仍保持稳定且功能正常。这些优异的结果证明了该传感器在医学应用中实时监测肌肉组织和血液方面的可行性。

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