CAREER: Novel Nanotechnology for Multiplexed Analysis of Genes and Proteins with PCR-like Sensitivity

尽管在生物分析科学和生物工程方面进行了密集的研究工作，但目前的技术还不具备足够的灵敏度或多重能力来在单拷贝水平上检测疾病生物标志物，这对癌症等致命疾病的早期诊断和有效治疗至关重要。当目标分子是蛋白质时，这尤其有问题，因为它们不能通过聚合酶链式反应(PCR)进行扩增。在这个职业项目中，首席研究员提出了新一代基于纳米颗粒的编码技术，用于基因和蛋白质(甚至病毒和细菌)的多重检测，具有类似于PCR样的灵敏度，这是现有的技术，如聚合酶链式反应，酶联免疫吸附试验，微流控和质谱仪所不可能实现的。新的条形码技术的重要创新来自概念和技术两个层面。与现有技术相比，目标分子是通过使用多功能纳米颗粒掺杂微球的夹心分析来检测的，而不是传统的荧光团。这一多功能和强大的技术平台允许同时分析DNA、RNA和蛋白质癌症标志物，具有前所未有的灵敏度和更低的成本。如果成功，拟议中的项目不仅将在分子肿瘤学方面开辟新的机会，还将对生物战和法医学产生重大影响。这项提议的教育部分包括开发两门新课程以补充传统的生物工程课程，与华盛顿大学纳米技术中心合作，以及计划为正规大学教育编写一本教科书。

0645080GaoDespite the intense research efforts in bioanalytical sciences and bioengineering, current technologies do not have sufficient sensitivity or multiplexing capability to detect disease biomarkers on single copy level, which is critical for early diagnosis and effective treatment of deadly diseases such as cancer. This is particularly problematic when the targeted molecules are proteins, since they cannot be amplified by polymerase chain reaction (PCR). In this CAREER project, the principal investigator proposes a new generation of nanoparticle-based encoding technology for multiplexed detection of genes and proteins (or even viruses and bacteria) with PCR-like sensitivity, which is not possible for the existing techniques such as PCR, ELISA, microfluidics and mass spectrometry. The important innovation of the new barcoding technology arises from both conceptual and technical levels. Compared to prior arts, the target molecules are detected by sandwich assays involving multifunctional nanoparticle doped microbeads rather than conventional fluorophores. This versatile and powerful technology platform allows simultaneous analysis of DNA, RNA and protein cancer markers with unprecedented sensitivity and reduced cost. If successful, the proposed project will not only open new opportunities in molecular oncology but also make a strong impact on bio-warfare and forensic sciences. The educational component of this proposal includes the development of two new courses to augment the traditional bioengineering curricula, partnership with the Center of Nanotechnology at University of Washington, and a plan to produce a textbook for formal college education.