Development of A Lab-on-a-Chip System for Saliva-Based Diagnostics

描述（由申请人提供）：唾液是一种重要的诊断液体，有潜力用于检测口腔和全身疾病的基本生物标志物。不幸的是，目前缺乏可靠的检测方法来测量这种复杂生物基质中的重要分析物，阻碍了唾液诊断的进展。为了帮助消除这一障碍，最近在基于微流体的芯片实验室（LOC）系统中开展了有希望的活动。虽然目前正在开发几个小型平台，但这些系统中很少有发展到可以使用真实唾液样本在生理范围内测量重要蛋白质生物标志物的程度。为了实现这一重要目标，来自UT和英国的研究团队已经开发并仔细记录了一个集成的生物芯片检测系统，该系统适用于测量唾液中重要的炎症标志物（例如CRP， il -1 β, MMP-8, tnf - α, IL-6）。这种新型的超灵敏方法已被用于将基于唾液的诊断扩展到唾液中发现的低水平CRP，因此允许首次比较健康，牙周炎和无牙患者之间的CRP水平。小型化的系统与已建立的宏观“金标准”方法很好地相关。因此，现在重要的是采取下一步措施，将这些功能组件和相关方法结合起来，以创建一个灵活的平台系统，可用于促进和扩大唾液诊断领域。这项U01更新计划的目标是开发可用于完成唾液诊断测试的便携式设备。该项目将在前两年完成重要的生物芯片、分析仪和免疫分析开发里程碑。在第一年，集成的生物芯片和分析仪将开发和测试。这些alpha原型将用于定义更多最终系统的规格。在第二年，完全开发的生物芯片和分析仪适合服务，作为beta原型将成型。这些功能强大的便携式系统将在3-5年内用于完成临床前测试和验证。我们的团队已经定义的唾液生物标记指纹将用于1)区分牙周炎的阶段，2)识别冠状动脉疾病患者未来心脏事件的风险。最终数据采集和FDA批准将在第5年完成。

DESCRIPTION (provided by applicant): Saliva is an important diagnostic fluid that has the potential to be used for detection of essential biomarkers for both oral and systemic diseases. Unfortunately, the current lack of reliable detection methods for measurement of important analytes within this complex biomatrix has hindered progress in salivary diagnostics. To help remove this barrier, recent promising activities have been initiated in microfluidic-based Lab-on-a-Chip (LOC) systems. While several miniaturized platforms are being developed now, few of these systems have evolved to the point where important protein biomarkers can be measured over the physiological range using real saliva samples. Towards this essential goal, the team of investigators from UT and UK have developed and documented carefully an integrated biochip assay system that is suitable for measurement of panels of important inflammatory markers (e.g. CRP, IL-1beta, MMP-8, TNF-alpha, IL-6) in saliva. This newly fashioned ultra-sensitive method has been used to extend saliva-based diagnostics to the low levels of CRP found in saliva, therefore allowing for the first comparison of CRP levels between healthy, periodontitis, and edentulous patients. The miniaturized system correlates nicely with established macroscopic "gold standard" methods. Thus, it now important to take the next steps to combine these functional components and associated methodologies so as to create a flexible platform system that may be used to promote and expand the field of salivary diagnostics. This U01 renewal program targets the development of portable devices that can be used to complete salivary diagnostic tests. The program will evolve with important biochip, analyzer and immunoassay development milestones to be completed in the first two years of the program. In year 1, integrated biochips and analyzers will be developed and tested. These alpha prototypes will be used to define specifications for more final systems. In year 2, fully developed biochips and analyzer suitable to serve, as beta prototypes will be fashioned. These highly functional portable systems will be used in years 3-5 to complete pre-clinical testing and validation. Salivary biomarker fingerprints that our team has already defined will be used to 1) discriminate stages of periodontitis and 2) identify risk for future cardiac events in coronary artery disease patients. Final data acquisition and FDA approval will be completed by year 5.