Center for Integrative Biomedical Computing

综合生物医学计算中心

• 批准号: 7687506
• 负责人: CHRISTOPHER R. JOHNSON
• 金额: $ 90.19万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-29 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7687506
• 关键词: Center; Integrative; Biomedical; Computing

DESCRIPTION (provided by applicant): Addressing a major transfusion safety issue, as of March 2004, AABB statute 5.1.5.1 mandates testing of all platelet units for bacterial contamination. The only commercially available tests for this purpose in the U.S. are culture-based tests which require 48-72 hours to deliver a result. Such tests are useful only for apheresis platelet testing, but not for random donor platelets. Under prior Phase I and Phase II SBIR grants, applicants developed a 50-minute test for bacterial contamination of platelets capable of detecting both gram-positive and gram-negative species at concentrations down to 103 CFU/ml. The test has been converted into kit form. Its simple procedure and pre-measured single dose reagents are aimed at the needs of transfusion services and blood banks which constitute the principal market. Compared with culture tests performed in the blood bank at the time of platelet collection, from which results must be extrapolated at later times, the proposed test is intended for application to platelet units at the point of release. Current point-of-release test methods rely on pH or glucose reagent strips, which have been shown to be inaccurate and insensitive. This new, fast and accurate test will increase the safety of transfused platelets and reduce the risk of transfusion-associated sepsis due to bacterial contamination, the number one cause of morbidity and mortality in transfusions today. It is the first test of its kind which can be applied to both apheresis and random donor platelet units. The BacTxTM test is based on the detection of peptidoglycan as a universal component of bacterial cell walls in both gram-positive and gram-negative species. The principle technological innovations underlying the BacTxTM test include (1) the application of an ultrasensitive enzymatic detection chemistry which is triggered by peptidoglycan, (2) the development of a sensitive colorimetric indicator to facilitate visualization and measurement of assay results, and (3) means for capturing bacteria from platelet concentrates for detection while avoiding interference and inhibition from platelets or other blood components. The main purpose of this project is to carry out a clinical trial of the diagnostic test kit developed under the previous Phase II program, to be submitted for FDA approval. As a device intended for screening blood products used in transfusion, this kit requires clearance by the FDA Center for Biologics Evaluation and Research (CBER) before it can be marketed with clinical claims as an in vitro diagnostic device. The clinical trial design will validate the sensitivity of the test in detecting bacteria spiked at various levels into platelet units, the specificity of the test in control units, and its reproducibility and stability. Its performance will be compared against culture as gold standard.

描述（由申请人提供）：为了解决一个主要的输血安全问题，截至2004年3月，AABB法规5.1.5.1要求对所有血小板单位进行细菌污染检测。在美国，唯一可用于此目的的商业测试是基于培养的测试，需要48-72小时才能提供结果。这些测试仅适用于单采血小板测试，但不适用于随机供体血小板。在先前的第一阶段和第二阶段SBIR赠款下，申请人开发了一种50分钟的血小板细菌污染测试，能够检测浓度低至103 CFU/ml的革兰氏阳性菌和革兰氏阴性菌。该检测试剂盒已转换为试剂盒形式。其简单的程序和预先计量的单剂量试剂针对构成主要市场的输血服务和血库的需求。 与采集血小板时在血库中进行的培养试验（其结果必须在以后进行外推）相比，拟定试验预期用于放行时的血小板单位。目前的释放点测试方法依赖于pH或葡萄糖试剂条，这已被证明是不准确和不敏感的。这种新的，快速和准确的测试将增加输注血小板的安全性，并降低由于细菌污染导致的输血相关败血症的风险，这是当今输血中发病率和死亡率的头号原因。这是第一个可以应用于单采和随机供体血小板单位的同类测试。 BacTxTM检测是基于检测作为革兰氏阳性和革兰氏阴性菌种细菌细胞壁通用组分的肽聚糖。BacTxTM检测的主要技术创新包括：（1）应用由肽聚糖触发的超灵敏酶检测化学反应，（2）开发灵敏的比色指示剂，以促进测定结果的可视化和测量，以及（3）从血小板浓缩物中捕获细菌进行检测的方法，同时避免血小板或其他血液成分的干扰和抑制。 该项目的主要目的是对根据先前II期计划开发的诊断检测试剂盒进行临床试验，以提交FDA批准。作为一种用于筛查输血中使用的血液制品的器械，该试剂盒需要获得FDA生物制品评价和研究中心（CBER）的批准，然后才能作为体外诊断器械上市销售。临床试验设计将验证该试验在检测以不同水平加标至血小板单位中的细菌时的灵敏度、该试验在对照单位中的特异性及其重现性和稳定性。它的表现将与作为金标准的文化进行比较。