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

I-Corps项目更广泛的影响/商业潜力是开发医疗保健点诊断传感器，以支持全球卫生机构战胜结核病(TB)。目前的层流诊断试验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，并不是所有的结核病患者都会将这种分子排泄到尿液中，而LAM浓度会受到感染部位的显著影响。这可能解释了此类检测的低灵敏度(~50%)的原因。结核病是世界上第二大单一感染源致死原因。2020年，1000万人感染，180万人死亡。人们认识到，高死亡率是由于缺乏每年影响300万至600万人的结核病检测，以及误诊、延误诊断、合并感染艾滋病毒和疟疾以及不遵守治疗战略。这项拟议的技术可能会克服目前测试的局限性，特别是对于医疗资源有限的发展中国家。这项i-Corps项目是基于开发一种用于检测生物液中细菌的护理点传感器。该传感器建立在银(Ag+)与细菌相互作用的基础上。研究表明，银离子可以通过外膜蛋白进入细菌体内，尤其是具有三聚体β桶结构的39kD跨膜蛋白OmpF-a，并与细胞质成分结合，包括蛋白质和核酸。提出的方法是基于检测添加到含有细菌的样品中的游离[Ag+]的损失，并确定细菌数量。检测下限可能低至每毫升样本80个细菌。此外，开源电位器为此类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。在结核病检测方面，针对结核分枝杆菌的抗体将被集成到传感器中，以选择性地诊断细菌的存在。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.