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

SBIR一期项目旨在开发一种无创、超灵敏的结核病分子检测系统。尽管结核病的流行率有所下降，但它仍然是导致传染病死亡的第二大原因。世界卫生组织最新的全球结核病报告汇编了来自205个国家的数据，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）特性将TB生物标志物的检测信号增强100倍以上。这导致检测浓度在飞克/毫升范围内，从而早期发现和治疗。该系统的特异性、更快的结果、低成本和易于使用，使其成为结核病诊断市场上的一项实质性创新。结核病检测市场每年占15亿美元，其中北美因结核病检测价格较高而成为第二大收入市场。所提出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。凭借这项技术所提供的所有优势，它有望在市场上获得可观的份额，并产生收入流。免疫测定的主要限制是它们无法检测与超低浓度生物标志物相关的极小荧光信号。所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，高信噪比和定向激发/发射。因此，与玻璃基板或聚氨酯孔板相比，P-GRAT的荧光增强是100倍或更高。这些改进转化为超灵敏的检测和早期诊断。商业免疫测定法需要数小时到数天才能达到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pg/mL范围的浓度。P-GRAT采用简化设计，排除昂贵的光学元件，如激光源，高倍率物镜和滤光片。使用3d打印部件制造系统，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）的结核病分子检测系统并将其商业化。TB特异性生物标志物脂arabinmanannan （LAM）和干扰素γ (IFN-g)将在尿液和唾液中检测。P-GRAT是一种平台技术，可以很容易地用于其他疾病的超灵敏检测和诊断，如寨卡病毒、埃博拉病毒、艾滋病毒和癌症。该奖项反映了美国国家科学基金会的法定使命，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。

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.