Self-powered Integrated Microfluidic Blood Analysis System (SIMBAS) for Molecular

描述：针对许多协作性疾病的多路复用点诊断是一个根本挑战：最先进的诊断分析将需要在单一平台中同时检测蛋白质和核酸。除了这一要求外，诊断平台在恶劣的现场条件和低资源环境下具有快速、廉价和高度健壮的特性也是至关重要的。需要多重检测的一个例子是结核病(TB)和人类免疫缺陷病毒(HIV)，这两种主要的全球优先疾病加起来每年导致约500万人死亡。这些疾病具有协同作用，其中每种疾病都会加剧另一种疾病的进展，并往往导致延误诊断。由于感兴趣的分子与膜材料的结合不同，广泛使用的侧向流动分析通常不能实现可靠的多重诊断(S)。微流体提供了解决这一问题的潜力，并允许高度多路分析，同时满足成本、速度和稳健性要求。然而，在便携式、低成本和坚固的微流控设备中为流动提供动力是此类平台成功的主要挑战。Diassess拥有专利的自给式集成微流控血液分析系统(SIMBAS)是一种集成的样本到答案(全血到视觉读数)一次性诊断设备。SIMBAS将样品制备、多路分析、放大和读数集成到一个快速、廉价和强大的系统中，用于同时检测结核病和艾滋病毒。Simbas系统的一个关键组件使其有别于其他微流控平台，那就是它的自供能脱气驱动流动。这种流动系统允许设备在不需要任何外部管道、电源或复杂的设备材料的情况下在一系列坚固的条件下运行。在第一阶段，Diassess将使用与低成本/大批量制造兼容的技术和材料，展示核酸和蛋白质生物标记物的概念教授集成检测。这包括制造微流控装置、试剂构图，以及演示一步独立的血液分析系统，该系统结合了RNA和蛋白质对艾滋病毒和潜伏性结核病的诊断检测。这些目标加在一起将证明Simbas平台的可行性。在第二阶段，Diassess将利用临床样本来表征和优化SIMBAS的选择性和灵敏度、在恶劣环境条件下的稳定性，并开发制造工艺，从而实现适销对路的设备。在加州大学伯克利分校直接工作时，Diassess被微型制造和生物工程领域的顶尖人才包围着。所需的所有设备都可以在校园内以较低的价格直接获得。此外，我们与Luke Lee实验室和加州定量生物科学研究所(QB3)的紧密联系确保了充满活力的知识氛围和对广泛资源网络的访问。 公共卫生相关性：项目Narrative Diassess将开发和提供一种自供电的集成微流控血液分析系统(SIMBAS)，该系统将能够对核酸和蛋白质生物标记物进行多路复用的护理点检测。将演示结核病(TB)和人类免疫缺陷病毒(HIV)的概念验证检测。

DESCRIPTION: Multiplexed point-of-care diagnostics for many synergistic diseases presents a fundamental challenge: a state-of-the-art diagnostic assay will require both protein and nucleic acid detection in a single platform. In addition to this requirement, it is critical that the diagnstic platform is rapid, inexpensive, and highly robust with respect to harsh field conditions and low-resource settings. An example of need for a multiplexed test is for tuberculosis (TB) and human immunodeficiency virus (HIV), major global priority diseases that combined kill about 5 million people per year. The diseases have a synergistic interaction, wherein each disease accentuates the progression of the other and often results in delayed diagnosis. Widely used lateral flow assays generally cannot achieve reliable multiplexed diagnostics, due to the differential binding of molecules of interest to the membrane material(s). Microfluidics offers the potential to solve this problem and allow highly- multiplexed analysis while meeting the cost, speed, and robustness requirements. However, powering the flow in portable, low cost and robust microfluidic devices represents a major challenge in the success of such platforms. DiAssess' proprietary Self-powered Integrated Microfluidic Blood Analysis System (SIMBAS) is an integrated sample-to- answer (whole blood to visual readout) disposable diagnostic device. SIMBAS integrates sample preparation, multiplexed assays, amplification, and readout into a rapid, inexpensive, and robust system for the simultaneous detection of TB and HIV. A critical component of the SIMBAS system that distinguishes it from other microfluidic platforms is its self-powered degas-driven flow. This flow system allows the device to operate under a robust range of conditions without any external tubing, power supply, or complex set of device materials. In Phase I, DiAssess wil demonstrate the prof-of-concept integrated detection of both nucleic acid and protein biomarkers, using techniques and materials compatible with low-cost/high-volume mass manufacturing. This includes microfluidic device fabrication, reagent patterning, and demonstration of a single-step, self-contained blood analysis system with combined RNA and protein diagnostic detection for HIV and latent TB. Together, these aims will demonstrate the feasibility of the SIMBAS platform. In Phase II, DiAssess wil characterize and optimize the SIMBAS selectivity and sensitivity with clinical samples, robustness under harsh environmental conditions, and develop manufacturing processes leading to a marketable device. While working directly on the UC Berkeley campus, DiAssess is surrounded by the top minds in both micro fabrication and bioengineering. All equipment required is readily available directly on the campus at low cost. In addition, our strong ties with the Luke Lee lab and the California Institute for Quantitative Biosciences (QB3) ensure a vibrant intellectual atmosphere and access to an extended network of resources. PUBLIC HEALTH RELEVANCE: Project Narrative DiAssess will develop and deliver a Self-powered Integrated Microfluidic Blood Analysis System (SIMBAS) that will enable multiplexed point-of-care detection for both nucleic acid and protein biomarkers. Proof-of-concept detection of tuberculosis (TB) and human immunodeficiency virus (HIV) will be demonstrated.