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，但同时迫切需要能够为加拿大人带来诊断和个性化医疗进步的新技术。因此，这些新技术必须具有成本效益并易于部署。复合核燃料的制造可以使这种技术成为可能。我们建议开发和制造结合磁性和超亮荧光的多功能复合纳米颗粒。这些粒子将结合几种成分材料，产生新的复合纳米颗粒，其能力超过单独的成分材料。组成材料包括我们实验室的荧光半导体量子点(QDts)、半导体聚合物点(Pdots)和两亲性化学功能化聚合物，以及我们的行业合作伙伴温哥华干细胞技术公司的磁性氧化铁纳米粒子。聚合物和QD或PDot组件将在中心磁性纳米粒子周围以分层分层结构自组装，然后进一步与我们将开发的四聚体抗体复合体或核酸适配体等生物活性分子的外层自组装。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可控性和重复性，这也是我们建议开发的一种过程。复合纳米颗粒的亮度、磁性和生物活性的组合将使目标细胞能够简单、低成本地从复杂样本(如血液)中分离出来，并在智能手机上进行目标细胞的检测和计数。将为智能手机开发一种外围设备来实现这一功能。这项拟议的技术具有潜在的变革性，因为它可以使基于细胞的诊断分析符合医疗保健点诊断和个性化医学(例如，检测循环中的肿瘤细胞)，超过了目前成本高昂、需要特殊培训且只能在专门实验室获得的技术。

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.