Advancing Clinical Diagnostics Through Improved Blood Sample Self-Collection

通过改进血液样本的自我采集来推进临床诊断

• 批准号: 8523527
• 负责人: Ashwin Kumar Balasubramanian
• 金额: $ 41.06万
• 依托单位: LYNNTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2014-10-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8523527
• 关键词: Biochemical; Biological Markers; Blood; Blood Cells; Blood Volume; Blood capillaries; Blood specimen; Buffers; Clinic; Clinical; Collection; Detection; Development; Devices; Diagnostic; Disease; Elements; Engineering; Environmental Exposure; Epidemiology; FDA approved; Filtration; Fingers; Future; Goals; Health; Hemolysis; Human; Individual; Infection; Institutional Review Boards; Instruction; Journals; Lead; Legal patent; Maintenance; Malignant Neoplasms; Measurement; Medical; Methods; Monitor; Needles; New Drug Approvals; Pain; Pain-Free; Patient Education; Pharmaceutical Preparations; Plasma; Plasma Proteins; Platelet aggregation; Play; Population Heterogeneity; Preventive; Preventive Medicine; Proteins; Proteome; Proteomics; Public Health; Publications; Recruitment Activity; Role; Sample Size; Sampling; Serum; Snakes; Source; Specimen; Spottings; State Medicine; Sterility; Techniques; Technology; Time; United States National Institutes of Health; Vacuum; Validation; Venipunctures; Venous; base; capillary; cost; design; healthy volunteer; human subject; hypodermic needle; improved; meetings; minimally invasive; non-compliance; novel; phase 1 study; point of care; point-of-care diagnostics; population based; pressure; public health relevance; reconstitution; research clinical testing; sample collection; success; validation studies

DESCRIPTION: Despite extraordinary advances in proteomic technologies, we are still very far from realizing the full potential of protein biomarkers for clinical diagnostics. The FDA-approved list of clinically useful protein biomarkers numbers in the low 100s, and the rate of FDA approval has dwindled to less than one per year. And although putative new and more powerful "candidate" biomarkers to various diseases are frequently advanced, clinically validating them remains the biggest challenge facing modern clinical proteomics. Several factors play a role in this, not the least of which is pre-analytical sample acquisition. Biomarker validation requires collection and assessments of biofluids from a large and diverse population. Blood plasma is the biofluid of choice because it is most representative of the human proteome. The most common practice of blood sample collection is by venipuncture, performed by a registered phlebotomist using invasive hypodermic needles in clinical settings. Diurnal fluctuation and analytical variability necessitate multiple samples be drawn from the same individual over a period of time, vastly increase clinical validation study costs and complexity. Dried blood spot (DBS) technology is an emerging alternative. Blood collected by painful lancet-based finger stick can be store on DBS cards for analysis. However, despite patient training and instructions, a number of DBS samples do not meet minimum quality standards. Non-uniform blood distribution on the card often leads to erroneous or inconclusive results. A disk from the DBS has to be reconstituted in buffer, requiring optimization and introducing variability. Needle aversion also i a premier source of non-compliance. Very significantly, the measurement of low concentration analytes obtained from DBS cards is particularly error-prone due to the small sample size (low uL) and sample variability and to extant limitations of analytical sensitivity. This proposal discusses the development of a low-cost, single use device for minimally invasive and pain free self-collection of blood that can overcome limitations of DBS sampling and supplant costly, clinic-based blood sample collection. Our technology combines a pioneering, patented, and highly durable micro needle array with a revolutionary, miniature, low-cost, electrochemical micro vacuum that will allow controlled and reproducible, transdermal collection of intermediate volumes (0.1-0.5 mL) of capillary blood sufficient for most biomarker studies. Long term, our device will be designed to include an integrated blood cell filtration assembly for collecting plasma, which can be stored without degradation for prolonged periods, and it will be engineered to enable precisely controlled delivery of analytical plasma samples to in-line diagnostic devices.

描述：尽管蛋白质组学技术取得了非凡的进步，但我们仍远未充分认识到蛋白质生物标记物在临床诊断中的全部潜力。FDA批准的临床有用蛋白质生物标记物的数量在100多个，FDA批准的速度已经减少到每年不到一个。尽管针对各种疾病的新的、更强大的“候选”生物标记物往往是先进的，但临床验证它们仍然是现代临床蛋白质组学面临的最大挑战。有几个因素在其中发挥了作用，其中最重要的是分析前样品的获取。生物标记物验证需要从大量和多样化的人群中收集和评估生物液。血浆是生物流体的选择，因为它最能代表人类蛋白质组。采集血样最常见的做法是通过静脉穿刺法，由注册的抽血师在临床环境中使用侵入性皮下注射针进行。每天的波动和分析的可变性需要在一段时间内从同一个人身上提取多个样本，这极大地增加了临床验证研究的成本和复杂性。干血斑(DBS)技术是一种新兴的替代技术。基于疼痛柳叶刀的手指棒收集的血液可以存储在DBS卡上进行分析。然而，尽管对患者进行了培训和指导，但仍有一些DBS样本达不到最低质量标准。卡片上的血液分布不均匀往往会导致错误或不确定的结果。来自DBS的盘必须在缓冲器中重建，这需要优化并引入可变性。针头厌恶也是不合规的主要原因。非常重要的是，从DBS卡片获得的低浓度分析物的测量特别容易出错，因为样本量小(低UL)和样本变异性以及分析灵敏度的现有限制。这项提案讨论了一种低成本、一次性使用的微创、无痛自采血液设备的开发，该设备可以克服DBS采样的局限性，取代昂贵的临床血液样本采集。我们的技术结合了一种开创性的、获得专利的、高度耐用的微针阵列和一种革命性的微型、低成本的电化学微真空，它将允许可控和可重复的、经皮采集足够进行大多数生物标志物研究的中间容量(0.1-0.5毫升)的毛细血管血液。从长远来看，我们的设备将设计为包括用于收集血浆的集成血细胞过滤组件，这些血浆可以长期储存而不会降解，并且它将能够精确控制地将分析血浆样本输送到在线诊断设备。