BIOCOMPATIBLE CHEMICAL SENSORS VIA NITRIC OXIDE RELEASE

描述：（申请人摘要）迄今为止， 能够连续监测血液的血管内化学传感器 气体（pH，PO 2，PCO 2）和电解质（例如，K（+）、Ca（+2）等）为 危重病人的长期治疗受到一些问题的限制， 与探头表面血栓形成相关， 局部动脉收缩，减少植入物处的血流 绝佳的价钱 拟议研究计划的目标将是探索 制造可植入的电化学和光学器件所需的化学物质 具有外部聚合物膜的血气和电解质传感器 在植入部位局部释放低水平的一氧化氮（NO）。 等 NO的原位释放应防止血小板粘附/活化在 传感器的表面，并同时提供持续释放的NO 或NO前体，其将用于立即扩张动脉 包围传感器，从而保持血液流动。 初步研究 重点论证功能性血液制备的可行性 具有含新型NO供体的外聚合物膜的气体/电解质传感器 化合物（diazeniumdiolates;稳定的NO-NO与胺的加合物） 涉及选择性化学传感所需的试剂。 这些调查 将涉及开发聚合物配方/配置， 降低血小板所需的适当NO释放速率 粘附/活化，但不干扰传感器的分析 性能（例如，选择性、漂移等）。此外，新的，更多 亲脂性和聚合物键合的二醇二氮烯鎓盐将在一种 尽量减少残留供体对样品相的污染 二胺 体外和体内（兔模型）血小板粘附研究 将用于评估不同聚合物/传感器的生物相容性 含有各种NO-NO加合物的膜和结果将相互关联 通过测量聚合物膜表面的NO气体水平， 一种电化学NO微传感器。 体内分析性能 用NO释放聚合物制备的血管内血气传感器将 最终评估（在犬中），无需全身抗凝 动物，以确定局部NO释放对血栓形成的影响， 植入部位的血流。

DESCRIPTION: (applicant's abstract) To date, the analytical performance of intravascular chemical sensors capable of continuously monitoring blood gases (pH, P02, PCO2) and electrolytes (e.g., K(+), Ca(+2), etc.) for extended periods in critically ill patients has been limited by problems associated with initiation of thrombus on the sensor surfaces as well as localized arterial constriction that diminishes blood flow at the implant site. The goal of the proposed research program will be to explore the chemistries required to fabricate implantable electrochemical and optical blood gas and electrolyte sensors with outer polymeric films that slowly release low levels of nitric oxide (NO) locally, at the implant site. Such in-situ release of NO should prevent platelet adhesion/activation on the surface of the sensors and, concomitantly, provide a sustained release of NO or NO precursors that will serve to dilate the artery immediately surrounding the sensor, thereby maintaining blood flow. Initial studies will focus on demonstrating the feasibility of preparing functional blood gas/electrolyte sensors with outer polymer films containing novel NO donor compounds (diazeniumdiolates; stable NO-NO adducts with amines)in addition to reagents required for selective chemical sensing. These investigations will involve developing polymer formulations/configurations that provide the appropriate rates of NO release required to decrease platelet adhesion/activation yet do not interfere with the sensor's analytical performance (e.g., selectivity, drift, etc.). In addition, new, more lipophilic and polymer bonded diazeniumdiolates will be synthesized in an effort to minimize contamination of the sample phase with residual donor diamines. In-vitro and in-vivo (rabbit model) platelet adhesion studies will be used to assess the biocompatibility of the different polymer/sensing films containing the various NO-NO adducts and results will be correlated with measurements of NO gas levels at the surface of the polymer films via an electrochemical NO microsensor. In-vivo analytical performance of intravascular blood gas sensors prepared with the NO release polymers will ultimately be assessed (in dogs) without systemic anticoagulation of the animals to determine the effect of local NO release on thrombogenicity and blood flow at the implant site.