INSTRUMENT TO CHARACTERIZE CELL-FREE 0XYGEN CARRIERS

表征无细胞 0XYGEN 载体的仪器

• 批准号: 6017329
• 负责人: KIM VANDEGRIFF
• 金额: $ 10.54万
• 依托单位: SANGART, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6017329
• 关键词: artificial membranes; biomedical equipment development; blood /plasma substitute; capillary; cell free system; computer data analysis; computer program /software; computer system design /evaluation; diffusion; hemoglobin; oxygen transport; polyethylene glycols; vasoconstriction

A new instrument to characterize O2 transport by cell-free hemoglobin and/or mixtures of cell-free hemoglobin and red blood cells has been invented, and a patent has been applied for. This instrument measures diffusional O2 transport using a small sample, and is applicable both to the development of cell-free hemoglobin solutions and to monitoring patients who have received them. The goal of this proposal is to optimize the design of this instrument to measure O2 transport by cell-free hemoglobin solutions in vitro using an artificial capillary system. Under Specific Aim 1, we will build an artificial capillary system to assess O2 transport by cell- free hemoglobin solutions in vitro. We will optimize the breadboard design of our present artificial capillary instrument. Measurements of O2 transport will be made using cell-free hemoglobin solutions, including model solutions of PEG-hemoglobin and cross-linked tetrameric hemoglobin, and RBC suspensions. Under Specific Aim 2, we will automate the capillary apparatus and further develop software for data interpretation. The data- analysis model uses mathematical concepts based on the Krogh cylinder model for O2 transport out a cylindrical tube of defined geometry (i.e., the artificial capillary). This programs requires 1) optimization for run time efficiency and 2) testing against experimental data from hemoglobin solutions and/or red blood cells in the artificial capillary device. The hypothesis underlying this proposal is that a new method to assess O2 transport by cell-free oxygen carriers is required before candidate products can be evaluated accurately. This is due to the phenomenon of facilitated diffusion of O2 in the presence of cell-free carriers, which can lead to autoregulatory vasoconstriction. PROPOSED COMMERCIAL APPLICATIONS: Methods of clinical evaluation of O2 transport (Hb, Het) in the presence of cell-free oxygen carriers are inadequate. We have invented a new instrument to characterize O2 transport by cell-free hemoglobin that includes evaluation of facilitated diffusion. This instrument has great potential for clinical measures in patients who have received hemoglobin- based products, as well as potential in the testing of new candidate solution.

发明了一种表征无细胞血红蛋白和/或无细胞血红蛋白与红细胞混合物的 O2 运输的新仪器，并已申请专利。该仪器使用小样本测量氧气扩散输送，既适用于无细胞血红蛋白溶液的开发，也适用于监测接受该溶液的患者。该提案的目标是优化该仪器的设计，以使用人工毛细管系统在体外测量无细胞血红蛋白溶液的 O2 运输。在具体目标 1 下，我们将建立一个人工毛细血管系统，以评估体外无细胞血红蛋白溶液的氧气输送。我们将优化现有人工毛细血管仪器的面包板设计。氧气输送的测量将使用无细胞血红蛋白溶液进行，包括 PEG 血红蛋白和交联四聚体血红蛋白的模型溶液以及红细胞悬浮液。在具体目标 2 下，我们将实现毛细管装置自动化并进一步开发数据解释软件。 数据分析模型使用基于 Krogh 圆柱模型的数学概念，将 O2 输送出具有定义几何形状的圆柱管（即人造毛细管）。该程序需要 1) 优化运行时间效率，2) 根据人工毛细管装置中血红蛋白溶液和/或红细胞的实验数据进行测试。该提案的假设是，在准确评估候选产品之前，需要一种新的方法来评估无细胞氧载体的氧气运输。这是由于在无细胞载体存在的情况下促进氧气扩散的现象，这可以导致自动调节血管收缩。拟议的商业应用：在无细胞氧载体存在的情况下 O2 运输（Hb、Het）的临床评估方法尚不充分。我们发明了一种新仪器来表征无细胞血红蛋白的 O2 运输，其中包括对易化扩散的评估。该仪器对于接受基于血红蛋白的产品的患者进行临床测量以及测试新的候选解决方案具有巨大的潜力。