Fully-Integrated, Non-Instrumented Device for Molecular Diagnostics

描述(由申请人提供)：这个辅导式职业发展奖(K25)提供的培训和研究经验将使我能够成功地从化学(学士和硕士)、电子工程(博士)背景过渡。机械工程(博士后)成为一名独立的生物医学研究员。为了实现这一目标，我将与我的导师密切合作，他们是HaimH.Bau博士(微流体和纳米流体方面的专家)、Robert Gross博士(传染病方面的国际权威，重点是艾滋病毒)、Frederic Bushman博士(分子病毒学家)和Paul H.Edelstein博士(临床微生物学专家)。培训内容包括：1)遗传学、流行病学、生物统计学、分子生物学和纳米医学方面的课程；2)传染病检测、分子生物学和临床治疗方面的实验技能培训；3)通过研讨会和网络机会开展专业发展活动。这次培训的目的是让我获得必要的知识和技能，以申请独立的NIH资金(例如，R01奖项)。为了补充培训，我提出了一项研究计划，旨在研究和开发一种完全集成的、低成本的、非仪器的POC设备，用于使用血液样本测量HIV病毒载量。这种装置将几乎和“试纸”一样简单，其性能与台式聚合酶链式反应相当。艾滋病毒是一个重大的全球健康问题。最近的估计表明，约有3300万艾滋病毒携带者，其中96%居住在发展中国家。虽然抗逆转录病毒治疗是有效的，而且越来越多地可用，但有必要对患者进行定量监测，以使药物治疗个体化，并控制艾滋病毒耐药株的出现和传播。血浆中循环病毒的水平，或“病毒载量”，是用于监测疾病进展和做出治疗决定的关键指标。通常，评估病毒载量需要基于聚合酶链式反应的定量检测，这种检测需要昂贵的设备、熟练的技术人员和实验室设施，而且在资源有限的情况下不能广泛用于护理点检测。本K25中提出的创新PoC测试设备将满足这一需求。我的职业目标是成为一名独立的、多学科的、久负盛名的生物医学研究员，拥有为全球医疗保健和个性化医学开发低成本诊断技术的专业知识。

DESCRIPTION (provided by applicant): The training and research experience provided by this Mentored Career Development Award (K25) will enable me to successfully transition from a background in chemistry (B.S. and M.S.), electronic engineering (Ph.D.) and mechanical engineering (Postdoc) to become an independent biomedical researcher. To achieve this, I will work closely with my mentors, Dr. Haim H. Bau (an expert in microfluidics and nanofluidics), Dr. Robert Gross (an international authority in infectious disease, with a focus on HIV), Dr. Frederic Bushman (a Molecular Virologist) and Dr. Paul H. Edelstein (a Clinical Microbiology expert). The training includes 1) coursework in genetics, epidemiology, biostatistics, molecular biology and nanomedicine, 2) experimental-skill training in infectious disease assays, molecular biology, and clinical treatment 3) professional development activities through workshops and networking opportunities. The goal of this training is to allow me to gain the knowledge and skills necessary to apply for independent NIH funding (e.g., R01 awards). To complement the training, I propose a research plan aimed at researching and developing a fully-integrated, low-cost, non-instrumented, POC device for HIV viral load measurement using blood samples. This device will be nearly as simple as a 'dipstick' immunoassay with performance that is comparable to that of benchtop PCR. HIV is a significant global health problem. Recent estimates suggest ~33 million people are living with HIV, with 96% residing in the developing world. While antiretroviral therapy is effective and increasingly available, quantitative monitoring of patients is necessary t individualize drug treatment, and to control the emergence and spread of drug-resistant strains of HIV. The level of circulating virus in the blood plasma, or "viral load," is a critical measure used to monitor disease progression and make treatment decisions. Typically, quantitative PCR-based assays, which require expensive equipment, skilled technicians, and laboratory facilities and that are not widely available for point-of-care testing in resource-limited settings are needed to assess viral load. The innovative POC test devices proposed in this K25 will address this need. My career goal is to become an independent, multidisciplinary and well established biomedical researcher with expertise in developing low-cost diagnostic technology for global health care and for individualized medicine.