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

I-Corps项目的更广泛影响/商业潜力是开发即时诊断传感器，以支持全球卫生机构战胜结核病。目前的层流诊断测试并不直接针对病原体，而是检测细菌产生的大分子，主要是尿液中的脂阿拉伯甘露聚糖（LAM）。然而，并非所有结核病患者都将这种分子排泄到尿液中，并且LAM浓度可能受到感染部位的显著影响。这可以解释这种测定的低灵敏度（~50%）。结核病是世界上第二大单一传染性病原体致死原因。2020年，有1000万人感染，180万人死亡。人们认识到，死亡率高的原因是缺乏结核病检测，每年影响300万至600万人，以及误诊、迟诊、艾滋病毒和疟疾合并感染，以及不坚持治疗战略。拟议的技术可能会克服目前的测试的局限性，特别是对于发展中地区的医疗资源是有限的。这个I-Corps项目是基于一个点的护理传感器的生物流体中的细菌检测的发展。该传感器是建立在银（Ag+）和细菌的相互作用。已经确定Ag+可以通过外膜蛋白，特别是具有三聚体β-桶结构的OmpF-a 39 kD跨膜蛋白进入各种细菌物种，并结合到细胞质组分，包括蛋白质和核酸。 所提出的方法是基于检测添加到具有细菌的样品中的游离[Ag+]的损失，并确定细菌数量。检测极限可低至每毫升样品80个细菌。此外，开源电位计为这种传感器的开发和转换提供了低成本和可定制的机会，特别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查和远程医疗。对于TB检测，特异性针对M.该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.