SBIR Phase I: Ultra-sensitive Detection of Lipoarabinomannan (LAM) and Interferon-Gamma (IFN-g) as Biomarkers for Detection of Tuberculosis (TB)

这个SBIR第一阶段项目旨在开发一种非侵入性、超灵敏的分子检测系统，用于结核病(TB)检测。尽管结核病的流行率有所下降，但它仍然是传染病死亡的第二大原因。世界卫生组织的最新全球结核病报告收集了来自205个国家的数据，数据显示，每年有150万人死亡，960万人感染。该技术利用纳米等离子体光栅(P-GRAT)的特性将结核生物标志物的检测信号增强100倍以上。这将导致检测浓度在毫微克/毫升范围内，从而导致早期发现和治疗。该系统的特异性、快速结果、低成本/检测和易用性使该系统成为结核病诊断市场的一项实质性创新。结核病检测市场每年占15亿美元，其中北美是创收第二大市场，这是因为结核病检测的价格较高。建议的技术将有利于患者的早期诊断，并为卫生保健专业人员提供早期治疗选择。凭借这项技术所具有的所有优势，预计它将在市场上获得相当大的份额并产生收入流。免疫分析的主要局限性是无法检测与超低浓度生物标记物相关的极小荧光信号。提出的纳米等离子体光栅(P-GRAT)技术可以克服这一限制，因为它具有非常有效的光耦合、减少散射、高信噪比和方向性激发/发射。因此，P-GRAT的荧光增强比玻璃基板或聚氨酯孔板高100倍或更高。这种增强转化为超灵敏的检测和早期诊断。商业免疫分析需要数小时到数天的时间才能达到pg/ml的灵敏度。相比之下，P-GRAT可以在不到3小时的时间内检测到Pg/mL范围的浓度。P-GRAT采用简化的设计，排除了昂贵的光学元件，如激光光源、高倍率物镜和滤光镜。使用3D打印部件来制造系统，并使用智能手机作为探测器，进一步降低了成本。我们打算开发一种无创、超灵敏(Fg/ml)的结核病(TB)分子检测系统并将其商业化。将在尿液和唾液中检测到结核特异性生物标志物脂阿拉伯甘露聚糖(LAM)和干扰素-γ(IFN-g)。P-GRAT是一种平台技术，可以很容易地适用于其他疾病的超敏感检测和诊断，如寨卡病毒、埃博拉病毒、艾滋病毒和癌症。该奖项反映了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。

This SBIR Phase I project is intended to develop a noninvasive, ultra-sensitive moleculardetection system for Tuberculosis (TB). Although the prevalence of TB has diminished, it stillremains the second leading cause of death from an infectious disease. The latest global TB reportfrom the World Health Organization with data compiled from 205 countries put the figures at 1.5million fatalities and 9.6 million infections annually. The proposed technology uses the nano-Plasmonic Grating (P-GRAT) properties to enhance the detection signal of the TB biomarker bymore than 100X. This results in detecting concentrations in femto-gram/milliliter range resultingin early detection and treatment. The specificity, faster results, low cost/test and ease of use,makes this system a substantive innovation in the TB diagnostic market. The TB testing marketaccounts for $1.5 billion annually of which North America is the second largest in terms ofgenerated revenue due to the higher pricing for TB detection. The proposed technology willbenefit the patients with early diagnosis and provide the health care professionals with earlytreatment options. With all the advantages this technology has to offer, it is expected to gain asignificant share in the market place and generate a revenue stream.The main limitation of the immunoassays is their inability to detect extremely small fluorescencesignals that are associated with ultra-low concentrations of biomarkers. The proposed nano-Plasmonic Grating (P-GRAT) technology can overcome this limitation due to its exceptionallyefficient light coupling, reduced scattering, high signal-to-noise ratio and directionalexcitation/emission. As a result, a fluorescence enhancement of P-GRAT is 100X or highercompared to a glass substrates or polyurethane well plates. Such enhancements translate to ultrasensitivedetection and early diagnosis. Commercial immunoassays require hours to days toachieve pg/ml sensitivity. In comparison, P-GRAT can detect pg/mL range concentrations in lessthan three hours. P-GRAT utilizes a simplified design to exclude expensive optics like lasersources, high-magnification objective lenses and filter cubes. The use of 3-D printed parts tofabricate the system and use a smartphone as the detector further reduces the cost. We intend todevelop and commercialize a noninvasive, ultra-sensitive (fg/ml) molecular detection system forTuberculosis (TB). TB specific biomarkers Lipoarabinomannan (LAM) and Interferon gamma(IFN-g) will be detected in urine and saliva. P-GRAT is a platform technology and can easily beadapted for the ultra-sensitive detection and diagnosis of other diseases, such as Zika, Ebola,HIV and Cancer.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.