Next-Generation Point-of-Care System: Custom Integration of Confocal Raman Spectrometer and High-Sensitivity NanoPhotonic-MicroFluidic Devices

尽管传感技术取得了巨大的进步，但我们仍然缺乏在第一时间提供传染病生物和生物标志物(各种疾病的先兆)的快速识别和准确量化的能力，否则这将有助于显著改善和加快疾病的早期诊断，并能够密切监测处方治疗的效率。在许多光学-光子传感方法中，表面增强拉曼光谱(SERS)通过成分分子的振动指纹揭示物种的组成和结构，提供了高度的特异性。为了提高SERS的效率，已经开发了多种SERS衬底，其中主要是金属纳米颗粒用于将光限制在纳米级的空隙中。然而，由于纳米颗粒固有的随机性(尺寸和相对间距)，这些平台受到限制，导致单波长或窄频带的光局部化。*最近，我们通过发现一种新的SERS平台取得了突破性的进展-克服了上述限制，并导致了健壮的多波长SERS传感衬底的开发，在宽梯度纳米光栅中实现了深亚波长光定位，符合经济、可重复制造的要求。*这里，Pi Nazir Kherani(电气和计算机工程(Ece)和材料科学与工程(MSE)新的纳米等离子SERS平台的专业知识)，联席Pi Aaron Wheeler(在数字微流体方面的化学专长)，联席Pi Naomi Matsuura(MSE和生物医学和生物工程研究所)。在病原体和生物标志物方面的深入经验)和合作者Pi Stewart Aitchison(欧洲经委会在病原体和生物标志物光谱学方面经验丰富)建议通过定制集成共焦拉曼光谱仪来构建和验证第一个基于SERS的微流体传感系统。这一研究设施将用于演示并为用于直接血液分析的高效护理点系统奠定坚实的技术基础。*3个PDF和5个博士的多学科合作将推动集成传感系统的建设和验证。该团队将系统地调查和展示血液中一长串病原体和生物标记物的高敏感性和快速筛查。这项研究对提高传感系统的分析和可靠性至关重要，该系统将生成与传染病(如败血症)和急性白血病癌症的病原体和生物标记物相对应的全面光学指纹数据库，并使用标准的多变量技术和现代方法(如机器学习)进行分析。*这项提议被认为是紧迫的，因为它具有改善医疗保健服务和降低成本的巨大潜力。如果获得批准，该提案将提供一个独特的机会，使加拿大成为下一代护理点多路血液分析仪领域的领先者。

In spite of enormous advances in sensing technology, we still lack the ability to provide rapid identification and accurate quantification of infectious organisms and biomarkers (harbingers of various ailments) at the first point-of-care' which otherwise would serve to markedly improve and expedite early-stage diagnosis of diseases and enable close monitoring of the efficiency of prescribed treatments.******Of the many optical-photonic sensing methods, surface enhanced Raman spectroscopy (SERS) provides high specificity by revealing compositional and structural makeup of species through vibrational fingerprinting of constituent molecules. A manifold of SERS substrates, wherein predominantly metal nanoparticles are used to confine light within nanoscale interstices, have been developed to increase the SERS efficiency. However, these platforms are limited due to inherent randomness of nanoparticles (size and relative spacing), resulting in uni-wavelength or narrow band of light localization.******Recently, we have made a ground-breaking advance through the discovery of a new SERS platform - overcoming the above limitations and leading to the development of robust multi-wavelength SERS sensing substrates deep subwavelength light localization in width-graded nano-gratings amenable to economic reproducible manufacturing. ******Here, PI Nazir Kherani (Electrical and Computer Eng. (ECE) and Materials Science and Eng. (MSE) expertise in the new nanoplasmonic SERS platform), co-PI Aaron Wheeler (Chemistry proficiency in digital microfluidics), co-PI Naomi Matsuura (MSE and Institute for Biomedical and BioEng. in-depth experience with pathogens and biomarkers) and co-PI Stewart Aitchison (ECE experienced in spectroscopy of pathogens and biomarkers) propose to build and validate the first SERS based microfluidic sensing system via custom integration of a confocal Raman spectrometer. This research facility will serve to demonstrate and firmly establish the technological foundation for a highly efficacious point-of-care system for direct blood analysis.******Multidisciplinary collaboration of 3 PDFs and 5 PhDs will drive the construction and validation of the integrated sensing system. The team will systematically investigate and demonstrate high-sensitivity and rapid screening of a long list of pathogens and biomarkers in blood. This study is critical to advancing the analysis and reliability of the sensing system, wherein comprehensive optical fingerprint database corresponding to pathogens and biomarkers for infectious disease (such as sepsis) and acute leukemia cancer will be generated and analyzed using standard multivariate techniques and modern approaches such as machine learning.******This proposal is deemed urgent given its enormous potential to improve delivery of health care and reduce cost. If granted, the proposal provides a unique opportunity to establish Canada as a leader in next generation point-of-care multiplexing blood analyzers.*****