The UK Biobank sample handling and storage protocol for the collection, processing and archiving of human blood and urine

The UK Biobank sample handling and storage protocol for the collection, processing and archiving of human blood and urine
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DOI:
10.1093/ije/dym276
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发表时间:
2008-04-01
影响因子:
7.7
通讯作者:
Peakman, Tim C.
Peakman, Tim C.
中科院分区:
医学1区
文献类型:
--
作者:
Elliott, Paul;Peakman, Tim C.

文献摘要

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英国生物库是英国一项大型前瞻性研究,旨在调查遗传因素、环境暴露和生活方式在中晚期主要疾病病因中的作用。正在从50万名年龄在40至69岁之间的参与者中收集大量数据和生物样本。收集的生物样本以及它们如何处理和储存将对UK Biobank resource.Aims未来的科学有用性产生重大影响英国生物库样本处理和储存协议的目的是指定参与者样本的收集和储存方法,在可用预算范围内提供最大的科学回报。加工或存储方法,尽可能可以预测,将排除当前或未来的assays已经避免。方法该协议是通过对文献的回顾,在学术界和同行评议的样品处理和加工,广泛咨询。方案制定涉及应收集哪些样本、应如何和何时处理样本以及应如何储存处理后的样本以确保其长期完整性。在一系列验证研究中对推荐方案进行了广泛测试。UK Biobank使用vacutainer系统从每个参与者收集约45 ml血液和9 ml尿液,并进行最少的局部处理。根据样本的预期最终用途,使用各种防腐剂、抗凝剂和促凝剂。还考虑采集其他材料(毛发、指甲、唾液和粪便),但拒绝用于整个队列。通过商业快递将受试者的血液和尿液样本连夜运送至中心实验室进行处理,并将尿液、血浆、血清、白色细胞和红细胞的等分试样储存在超低温档案中。还储存全血的等分试样,用于将来可能生产永生化细胞系。对所有参与者的全血进行标准的血液学检测,因为此类检测需要对新鲜样本进行(而其他检测可以对储存样本进行)。在招募阶段结束时,1500万份样本等分试样将储存在两个地理位置不同的档案室中:950万份储存在80 C自动化档案室中,550万份储存在180 C手动液氮档案室中。由于研究的规模和从参与者获得的样本数量,该方案规定了一种高度自动化的样本处理和储存方法。流程、技术、系统和设施的实施遵循了制造业的最佳实践,以降低项目风险并提高质量和稳健性。从样品收集,处理和储存产生的数据是非常复杂的,并通过一个商业上可用的LIMS系统完全集成与整个process.Conclusion英国生物银行通过的样品处理和储存协议管理提供了质量保证和验证的方法,是可行的可用资金范围内,并反映了该项目的规模和目标。招募和处理首批40,000名参与者的经验表明,所采用的方法和技术适用于目的并且可靠。
Background UK Biobank is a large prospective study in the UK to investigate the role of genetic factors, environmental exposures and lifestyle in the causes of major diseases of late and middle age. Extensive data and biological samples are being collected from 500 000 participants aged between 40 and 69 years. The biological samples that are collected and how they are processed and stored will have a major impact on the future scientific usefulness of the UK Biobank resource.Aims The aim of the UK Biobank sample handling and storage protocol is to specify methods for the collection and storage of participant samples that give maximum scientific return within the available budget. Processing or storage methods that, as far as can be predicted, will preclude current or future assays have been avoided.Methods The protocol was developed through a review of the literature on sample handling and processing, wide consultation within the academic community and peer review. Protocol development addressed which samples should be collected, how and when they should be processed and how the processed samples should be stored to ensure their long-term integrity. The recommended protocol was extensively tested in a series of validation studies. UK Biobank collects about 45 ml blood and 9 ml of urine with minimal local processing from each participant using the vacutainer system. A variety of preservatives, anti-coagulants and clot accelerators is used appropriate to the expected end use of the samples. Collection of other material (hair, nails, saliva and faeces) was also considered but rejected for the full cohort. Blood and urine samples from participants are transported overnight by commercial courier to a central laboratory where they are processed and aliquots of urine, plasma, serum, white cells and red cells stored in ultra-low temperature archives. Aliquots of whole blood are also stored for potential future production of immortalized cell lines. A standard panel of haematology assays is completed on whole blood from all participants, since such assays need to be conducted on fresh samples (whereas other assays can be done on stored samples). By the end of the recruitment phase, 15 million sample aliquots will be stored in two geographically separate archives: 9.5 million in a 80C automated archive and 5.5 million in a manual liquid nitrogen archive at 180C. Because of the size of the study and the numbers of samples obtained from participants, the protocol stipulates a highly automated approach for the processing and storage of samples. Implementation of the processes, technology, systems and facilities has followed best practices used in manufacturing industry to reduce project risk and to build in quality and robustness. The data produced from sample collection, processing and storage are highly complex and are managed by a commercially available LIMS system fully integrated with the entire process.Conclusion The sample handling and storage protocol adopted by UK Biobank provides quality assured and validated methods that are feasible within the available funding and reflect the size and aims of the project. Experience from recruiting and processing the first 40 000 participants to the study demonstrates that the adopted methods and technologies are fit-for-purpose and robust.