NEW OXYGEN SENSOR FOR STUDYING BIOLOGICAL SYSTEMS

用于研究生物系统的新型氧气传感器

基本信息

批准号：
2178340
负责人：
Jane Marie Vanderkooi
金额：
$ 15.4万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-04-01 至 1995-05-31
项目状态：
已结题

项目摘要

Cellular energy ultimately derives form oxidation, with molecular oxygen being the predominate electron acceptor. This research project is directed toward the development of near infrared phosphorescence for determining oxygen concentrations in tissues. The specific goals are: 1. Phosphorescent probe molecules with optimal properties for oxygen measurements in biological systems will be designed. Probes that absorb light and phosphoresce in spectral regions where there is minimal absorption by biological pigments will be evaluated. Probes that remain in the circulatory system and are non-toxic to animals upon injection and/or are rapidly excreted to minimize the possibility of long term toxicity will be selected. Other probes will be designed to be taken up by cells and trapped internally, allowing direct measure of intracellular oxygen concentration. 2. The possible role of oxygen diffusion gradients in mitochondrial respiration will be examined. By comparing the oxygen dependencies of quenching of probes bound to respiring and non-respiring mitochondria, the effective oxygen depletion at the mitochondria can be determined. 3. Trans-plasma membrane oxygen differences will be examined in hepatocytes. To measure intra- and extra-cellular oxygen concentration two oxygen probe molecules will be used, one in the extracellular medium and the other trapped in the cellular cytoplasm. From differences in the oxygen dependence of the two, it will be possible to determine the barrier for oxygen diffusion imposed by the cell membrane and its associated unstirred layer. 4. Instrumentation will be developed for imaging the oxygen distribution in tissue. This will involve real time video imaging of phosphorescence intensity. Data processing will be used to obtain three dimensional images of the oxygen distribution in tissues. Eye lens, a transparent tissue where light scattering is not a problem, will be first examined. Later, rat kidney, a small but highly scattering tissue will be used.

细胞能最终衍生出形成氧化，并用分子氧氧化是主要的电子受体。该研究项目是指导的迈向近红外磷光以确定组织中的氧气浓度。具体目标是： 1。具有氧气最佳特性的磷光探针分子将设计生物系统中的测量。吸收的探针光谱区域的光和磷光区最少将评估生物色素吸收。保留在循环系统在注射和/或注射时对动物无毒迅速排出以最大程度地减少长期毒性的可能性被选中。其他探针将设计为被细胞和内部被困，允许直接测量细胞内氧气专注。 2。氧扩散梯度在线粒体中的可能作用将检查呼吸。通过比较与呼吸和非呼吸线粒体结合的探针的淬灭，可以确定线粒体处的有效氧气耗竭。 3。将在肝细胞。测量细胞内和细胞外氧浓度两个将使用氧探针分子，一个在细胞外培养基中，另一个被困在细胞细胞质中。从差异两者的氧依赖性，可以确定屏障用于细胞膜及其相关的氧扩散未安排的层。 4。将开发用于成像氧分布的仪器在组织中。这将涉及磷光的实时视频成像强度。数据处理将用于获得三维图像组织中的氧分布。眼镜，透明组织如果光散射不是问题，将首先检查。之后，大鼠肾脏将使用小但高度散射的组织。