CAREER: Unified sample preparation and micro-scale centrifugal heating for the next generation of portable and inexpensive molecular diagnostic platform

职业：统一样品制备和微尺度离心加热，用于下一代便携式且廉价的分子诊断平台

• 批准号: 2239135
• 负责人: Aashish Priye
• 金额: $ 50.11万
• 依托单位: University of Cincinnati Main Campus
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-15 至 2027-12-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2239135&HistoricalAwards=false
• 关键词: CAREER; Unified; sample; preparation; micro

The recent global pandemic has exposed some of the key limitations in our current health management system, particularly when applied in remote areas. Existing approaches for disease assessment are highly resource-intensive, and this introduces a considerable time lag between sample collection, diagnosis, and implementation of countermeasures. A need, therefore, exists for inexpensive and robust tools that can be broadly deployed to accelerate diagnosis, and provide real-time data to better inform decision making. This CAREER project focuses on developing a new class of simple, inexpensive, portable, and rapid molecular diagnostic platforms with the potential for widespread deployment by adapting a PCR-like test from dedicated laboratories to resource-limited places where they are needed the most. It combines insights from biochemistry, magnetism, fluid physics, and machine learning to engineer an instrument that can reliably and quickly detect infectious diseases in human samples. The project’s educational component integrated with the research includes the development of molecular biology-focused education modules and a series of interactive and explanatory YouTube videos describing scientific concepts in biochemistry, magnetism, and fluid mechanics.One of the most pressing issues facing global public health today is the lack of accessible, affordable, and simple-to-use diagnostic technologies. The goal of this CAREER project is to introduce several innovations towards engineering a novel molecular diagnostics system. First, a new biophysical model will be developed to predict Loop-Mediated Isothermal Amplification (LAMP) - a widely popular but poorly understood nucleic acid amplification reaction. Insights from the model will be used to thermodynamically optimize LAMP primer sets to yield rapid amplification of pathogenic target (10 minutes) and offer fewer false positives. Second, a new mechanism for microfluidic heating will be explored where small fluidic volumes on spinning discs can be heated by converting some of the disc's rotational kinetic energy into thermal energy via magnetically induced eddy currents. Third, machine learning based image classifiers will be developed that will enable smartphone cameras to perform real time temperature sensing (using color sensitive dyes) and quantitative molecular assay readouts with high reproducibility and robustness. Taken together, the resulting molecular diagnostic platform can deliver performance comparable to that of current generation systems while simultaneously providing an order of magnitude reduction in turnaround time, cost, and device complexity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

最近的全球大流行揭示了我们当前的健康管理系统中的一些关键局限性，尤其是在偏远地区应用时。现有的疾病评估方法是高度资源密集型的，这引入了样本收集，诊断和对策的实施之间的考虑时间滞后。因此，需要廉价且健壮的工具，这些工具可以广泛部署以加速诊断，并提供实时数据以更好地告知决策。该职业项目着重于开发一系列新的简单，廉价，便携式和快速的分子诊断平台，这些平台有可能通过适应从专用实验室到最需要的资源有限的地方进行类似PCR的测试来进行宽度部署。它结合了生物化学，磁性，流体物理学和机器学习的见解，以设计一种可以可靠，快速检测到的人类样本中传染病的仪器。该项目与研究的教育组成部分包括开发分子生物学的教育模块以及一系列互动和利用YouTube视频，描述了生物化学，磁性和流体机制中的科学概念。当今面临的全球公共卫生最紧迫的问题之一是缺乏可访问的，可访问的，可访问的，可访问的，可访问的，可访问的，可及可使用的诊​​断技术。这个职业项目的目的是引入一些创新，以设计一种新型分子诊断系统。首先，将开发出一种新的生物物理模型来预测环路介导的等温扩增（LAMP） - 一种广受欢迎但知之甚少的核酸扩增反应。该模型的见解将用于热力学优化灯泡启动组，以产生病原靶标的快速扩增（10分钟），并提供较少的假阳性。其次，将探索一种新的微流体加热机制，即可以通过将圆盘的一些旋转动能转换为通过磁诱导的涡流转换为热能，从而加热旋转盘上的小流体体积。第三，将开发基于机器学习的图像分类器，该分类器将使智能手机摄像机能够执行实时温度敏感性（使用颜色敏感染料）和具有高可重现性和稳健性的定量分子测定读数。综上所述，由此产生的分子诊断平台可以提供与当前一代系统相当的性能，同时在周转时间，成本和设备复杂性的情况下同时减少了数量级。该奖项反映了NSF的法定任务，并被认为是通过使用基金会的智力和更广泛影响的评估来审查Criteria来通过评估来获得支持的珍贵的。