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

产品说明：许多协同疾病的多重床旁诊断提出了一个根本性的挑战：最先进的诊断测定将需要在单个平台中进行蛋白质和核酸检测。除此要求外，至关重要的是，诊断平台在恶劣的现场条件和低资源环境下是快速的、廉价的和高度稳健的。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每年共造成约500万人死亡。这些疾病具有协同相互作用，其中每种疾病加重另一种疾病的进展，并且通常导致诊断延迟。广泛使用的侧向流测定通常不能实现可靠的多重诊断，这是由于感兴趣的分子与膜材料的差异结合。微流体技术提供了解决这个问题的潜力，并允许高度多路复用的分析，同时满足成本、速度和鲁棒性要求。然而，在便携式、低成本和鲁棒的微流体装置中为流动提供动力代表了这种平台成功的主要挑战。DiAssess专有的自供电集成微流控血液分析系统（SIMBAS）是一种集成的样品到答案（全血到视觉读数）一次性诊断设备。SIMBAS将样品制备、多重检测、扩增和读出集成到一个快速、廉价和强大的系统中，用于同时检测结核病和艾滋病病毒。SIMBAS系统区别于其他微流体平台的一个关键组成部分是其自供电脱气驱动流。该流动系统允许该装置在一系列稳定的条件下操作，而无需任何外部管道、电源或复杂的装置材料。在第一阶段，DiAssess将展示核酸和蛋白质生物标志物的概念整合检测，使用与低成本/大批量生产兼容的技术和材料。这包括微流体设备制造，试剂图案化，以及演示一个单步，独立的血液分析系统，结合RNA和蛋白质诊断检测HIV和潜伏性TB。这些目标将共同证明SIMBAS平台的可行性。在第二阶段，DiAssess将表征和优化SIMBAS对临床样本的选择性和灵敏度，在恶劣环境条件下的稳健性，并开发制造工艺，从而生产出可销售的器械。虽然直接在加州大学伯克利分校的校园工作，DiAssess是由微制造和生物工程的顶尖人才包围。所需的所有设备都可以在校园内以低成本直接获得。此外，我们与Luke Lee实验室和加州定量生物科学研究所（QB 3）的紧密联系确保了充满活力的学术氛围和获得扩展的资源网络。 公共卫生相关性：DiAssess项目将开发和提供一种自供电集成微流控血液分析系统（SIMBAS），该系统将实现核酸和蛋白质生物标志物的多路护理点检测。将演示结核病和人类免疫缺陷病毒（艾滋病毒）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.