Center for Bioelectronics, Biosensors and Biochips (C3B), Clemson University Advanced Materials Center, 100 Technology Drive, Anderson, SC 29625, USA.
Anal Bioanal Chem. 2011 Jan;399(1):403-19. doi: 10.1007/s00216-010-4271-x. Epub 2010 Oct 21.
Following hemorrhage-causing injury, lactate levels rise and correlate with the severity of injury and are a surrogate of oxygen debt. Posttraumatic injury also includes hyperglycemia, with continuously elevated glucose levels leading to extensive tissue damage, septicemia, and multiple organ dysfunction syndrome. A temporary, implantable, integrated glucose and lactate biosensor and communications biochip for physiological status monitoring during hemorrhage and for intensive care unit stays has been developed. The dual responsive, amperometric biotransducer uses the microdisc electrode array format upon which were separately immobilized glucose oxidase and lactate oxidase within biorecognition layers, 1.0-5.0 μm thick, of 3 mol% tetraethyleneglycol diacrylate cross-linked p(HEMA-co-PEGMA-co-HMMA-co-SPA)-p(Py-co-PyBA) electroconductive hydrogels. The device was then coated with a bioactive hydrogel layer containing phosphoryl choline and polyethylene glycol pendant moieties [p(HEMA-co-PEGMA-co-HMMA-co-MPC)] for indwelling biocompatibility. In vitro cell proliferation and viability studies confirmed both polymers to be non-cytotoxic; however, PPy-based electroconductive hydrogels showed greater RMS 13 and PC12 proliferation compared to controls. The glucose and lactate biotransducers exhibited linear dynamic ranges of 0.10-13.0 mM glucose and 1.0-7.0 mM and response times (t(95)) of 50 and 35-40 s, respectively. Operational stability gave 80% of the initial biosensor response after 5 days of continuous operation at 37 °C. Preliminary in vivo studies in a Sprague-Dawley hemorrhage model showed tissue lactate levels to rise more rapidly than systematic lactate. The potential for an implantable biochip that supports telemetric reporting of intramuscular lactate and glucose levels allows the refinement of resuscitation approaches for civilian and combat trauma victims.
在导致出血的损伤后，乳酸水平升高，并与损伤的严重程度相关，是氧债的替代物。创伤后还包括高血糖症，持续升高的血糖水平导致广泛的组织损伤、败血病和多器官功能障碍综合征。已经开发出一种用于在出血期间和重症监护病房进行生理状态监测的临时、可植入、集成的葡萄糖和乳酸生物传感器和通信生物芯片。双响应、安培生物传感器使用微盘电极阵列格式，在该格式上，葡萄糖氧化酶和乳酸氧化酶分别固定在生物识别层内，厚度为 1.0-5.0 μm，为 3 mol%四乙二醇二丙烯酸酯交联的 p(HEMA-co-PEGMA-co-HMMA-co-SPA)-p(Py-co-PyBA)导电水凝胶。然后，该装置用含有磷酰胆碱和聚乙二醇支链的生物活性水凝胶层进行涂层[ p(HEMA-co-PEGMA-co-HMMA-co-MPC)]用于留置生物相容性。体外细胞增殖和活力研究证实两种聚合物均无细胞毒性；然而，基于 PPy 的导电水凝胶显示出比对照物更高的 RMS 13 和 PC12 增殖。葡萄糖和乳酸生物传感器的线性动态范围分别为 0.10-13.0 mM 葡萄糖和 1.0-7.0 mM，响应时间（t(95)）分别为 50 和 35-40 s。在 37°C 连续运行 5 天后，操作稳定性为初始生物传感器响应的 80%。在 Sprague-Dawley 出血模型中的初步体内研究表明，组织乳酸水平的升高比系统性乳酸更快。具有可植入生物芯片的潜力，可以支持肌肉内乳酸和葡萄糖水平的遥测报告，从而可以改进平民和战斗创伤受害者的复苏方法。
