Development and manufacture of self-assembled, multifunctional composite nanoparticles with magnetic and fluorescent properties for cell-based assays

加拿大的医疗保健系统因成本和需求而不堪重负，但同时迫切需要新技术，为加拿大人提供先进的诊断和个性化医疗。因此，这些新技术必须具有成本效益并易于部署。复合NP的制造可以实现这样的技术。我们建议开发和制造多功能复合纳米粒子，结合联合收割机的磁性与超亮荧光。这些颗粒将联合收割机的几个组成材料，导致新的复合纳米粒子的能力，超过那些单独的组成材料。组件材料包括荧光半导体量子点（QD）、半导体聚合物点（Pdot）和我们实验室的两亲性化学功能化聚合物，以及我们的行业合作伙伴、位于弗吉尼亚州的STEMCELL Technologies Inc.聚合物和QD或PDot组分将在中心磁性纳米颗粒周围自组装成分层的分级结构，然后进一步与生物活性分子的外层自组装，例如四聚体抗体复合物（也来自STEMCELL）或我们将开发的核酸适体。自组装过程将为复合纳米颗粒的自动化制造、放大和在线表征提供必要的控制和再现性，这也是我们建议开发的过程。复合纳米颗粒的组合亮度、磁性和生物活性将使得能够从复杂样品（例如，血液），并在智能手机上检测和计数靶细胞。将为智能手机开发一种外围设备，以实现这一功能。所提出的技术具有潜在的变革性，因为它可以使基于细胞的诊断测定适合于护理点诊断和个性化医学（例如，检测循环肿瘤细胞），超越了目前昂贵的技术，需要专门的培训，只能在专门的实验室。

Canada's health care system is overburdened with both cost and demand, but at the same time critically needs new technologies that can deliver advances in diagnostics and personalized medicine to Canadians. These new technologies must therefore be cost-effective and easily deployed. The manufacture of composite NPs can enable such technologies. We propose to develop and manufacture multifunctional composite nanoparticles that combine magnetic properties with ultra-bright fluorescence. These particles will combine several component materials, resulting in new composite nanoparticles with capabilities that exceed those of the component materials individually. The component materials include fluorescent semiconductor quantum dots (QDs), semiconducting polymer dots (Pdots), and amphiphilic chemically-functionalized polymers from our laboratories, as well as magnetic iron oxide nanoparticles from our industry partner, Vancouver-based STEMCELL Technologies Inc. The polymer and QD or PDot components will be self-assembled in a layered, hierarchical structure around the central magnetic nanoparticle, then further self-assembled with an outer layer of bioactive molecules such as tetrameric antibody complexes (also from STEMCELL) or nucleic acid aptamers that we will develop. The self-assembly processes will provide the control and reproducibility necessary for the automated manufacture, scale-up, and online characterization of the composite nanoparticles, which is a process that we also propose to develop. The combined brightness, magnetism, and bioactivity of the composite nanoparticle will enable the simple, low-cost separation of target cells from complex samples (e.g., blood) with detection and counting of the target cells on a smartphone. A peripheral device will be developed for the smartphone to enable this capability. The proposed technology is potentially transformative in that it can make cell-based diagnostic assays amenable to point-of-care diagnostics and personalized medicine (e.g., detection of circulating tumour cells), surpassing current technologies that are costly, require special training, and are only available in specialized labs.