I-Corps: A point-of-care diagnostic sensor for tuberculosis

I-Corps：结核病即时诊断传感器

• 批准号: 2323442
• 负责人: Chengpeng Chen
• 金额: $ 5万
• 依托单位: University of Maryland Baltimore County
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2323442&HistoricalAwards=false
• 关键词: Corps; point; care; diagnostic; sensor

The broader impact/commercial potential of this I-Corps project is the development of point-of-care diagnostic sensor to support health agencies globally in overcoming tuberculosis (TB). Current laminar-flow diagnostic tests do not target the pathogen directly, but instead detect macromolecules produced by the bacteria, mainly lipoarabinomannan (LAM) in urine. However, not all TB patients excrete this molecule into the urine, and LAM concentrations can be affected significantly by the infection sites. This may explain the low sensitivity (~50%) of such assays. TB is the world’s second leading cause of death from a single infectious agent. In 2020, 10 million people were infected, and 1.8 million died. It is recognized that the high mortality is attributed to lack of TB testing affecting 3-6 million people per year, as well as misdiagnoses, late diagnoses, co-infection with HIV and malaria, and lack of adherence to treatment strategy. The proposed technology may overcome the limitations of current tests, especially for developing areas where medical resources are limited.This I-Corps project is based on the development of a point-of-care sensor for bacteria detection in biological fluids. The proposed sensor is built on the interactions of silver (Ag+) and bacteria. It is established that Ag+ can enter various bacterial species through outer membrane proteins, particularly the OmpF—a 39 kD transmembrane protein with a trimeric β-barrel structure, and binds to cytoplasm components, including proteins and nucleic acid. The proposed method is based on detecting the loss of free [Ag+] added to a sample with bacteria, and determining the bacteria number. The detection limit may be as low as 80 bacteria per milliliter sample. Moreover, an open-source potentiometer provides a low-cost and customizable opportunity for such sensor development and translation, especially in under-developed areas with limited budgets. The sensor also allows for wireless data transfer and storage in smartphones, which may allow for large-scale screening and remote healthcare. For TB detection, antibodies that are specific to m. tuberculosis will be integrated in the sensor for selective diagnosis of the presence of the bacteria.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.

该I-Corps项目的更广泛的影响/商业潜力是开发了保健诊断传感器，以在克服结核病（TB）方面为全球卫生机构提供支持。当前的层流诊断测试并非直接靶向病原体，而是检测细菌产生的大分子，主要是尿液中的脂肪团氨基氨基选择者（LAM）。但是，并非所有TB患者都将该分子过度进入尿液，而LAM浓度可能会受到感染部位的显着影响。这可以解释此类评估的低灵敏度（〜50％）。结核病是世界第二个传染病患者死亡的第二大主要原因。 2020年，1000万人被感染，180万人死亡。人们认识到，高死亡率归因于缺乏影响每年3至600万人的结核病测试，以及误诊，晚期诊断，与HIV和疟疾的共同感染以及缺乏对治疗策略的依从性。所提出的技术可能会克服当前测试的局限性，尤其是对于医疗资源受到限制的发展领域的局限性。该I-Corps项目基于生物液中细菌检测的护理点传感器的开发。所提出的传感器建立在银（Ag+）和细菌的相互作用上。已经确定Ag+可以通过外膜蛋白，尤其是OMPF进入多种细菌种类，尤其是具有三聚体β-桶结构的39 kD跨膜蛋白，并与细胞质成分结合，包括蛋白质和核酸。所提出的方法是基于检测带有细菌样品中添加到样品中的游离[Ag+]的损失，并确定细菌数量。检测极限可能低至每毫升样品80种细菌。此外，开源电位计为这种传感器开发和翻译提供了低成本和可定制的机会，尤其是在预算有限的欠发达地区。该传感器还允许在智能手机中进行无线数据传输和存储，这可能允许大规模筛选和远程医疗保健。对于TB检测，特定于M的抗体。结核病将被整合到传感器中，以选择性诊断细菌的存在。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响评估标准，被认为值得通过评估。