Personalized Clinical Diagnostics and Beyond: Integrated Ring Resonator Arrays

摘要 生物学的范式转变往往受到测量技术创新的催化。Genomics 和蛋白质组学已经彻底改变了生物学，但如果没有以下方面的发展， 毛细管测序、cDNA微阵列和质谱分析，以及其他使 技术.癌症生物学已经大大受益于分子水平的细节， 这些工具，允许阐明疾病发作和进展背后的许多扰动。 不幸的是，许多相同的测量方法不适用于临床环境， 因此，医生不能获得与医生所享有的相同的详细的生物化学信息。 院士。因此，尽管我们对癌症的分子基础有了更多的了解， 临床医学的翻译明显滞后。该提案描述了一种革命性的 生物分析技术有可能深刻改变临床医学的面貌 以及更远的地方高密度阵列的非常敏感的集成微谐振器将允许 许多基因和蛋白质特征可从单个患者样品中同时定量。 该技术的显著特点包括：灵敏度允许PCR少基因和单一蛋白 检测、无标签和真实的时间操作、超高可扩展性（> 50，000个传感器/cm 2）、自动化 微流体操作，以及通过CMOS兼容处理的商业验证的可制造性。 为了证明这项技术的力量，我们将生成一个分子疾病指纹， 三种临床上难以区分但生化上不同的疾病途径之间的差异 导致致命的脑癌多形性胶质母细胞瘤重要的是，这些途径中的每一个都是 已知对不同的治疗剂有有效反应，因此个性化诊断等同于 个性化治疗。我们还将利用这种使能技术， 围绕转录后基因调控和分泌的细胞内异质性的问题， 单个免疫细胞的反应。这项技术有望广泛影响世界的景观， 生物医学科学，既满足了当今的临床诊断挑战， 改变未来范式的发现

ABSTRACT Paradigm shifts in biology are often catalyzed by innovations in measurement technologies. Genomics and proteomics have revolutionized biology but would not have been possible without developments in capillary sequencing, cDNA microarrays, and mass spectrometry, amongst other enabling technologies. Cancer biology has significantly benefited from the molecular-level detail provided by these tools, allowing elucidation of many perturbations underlying disease onset and progression. Unfortunately, many of the same measurement approaches are not applicable in the clinical setting and thus physicians do not have access to the same detailed biochemical information enjoyed by the academician. As a result, despite our increased knowledge of the molecular bases of cancer, the translation to clinical medicine has lagged significantly behind. This proposal describes a revolutionary biological analysis technology which has the potential to profoundly change the face of clinical medicine and beyond. High density arrays of extraordinarily sensitive integrated microring resonators will allow many gene and protein signatures to be simultaneously quantitated from a single patient sample. Distinguishing features of this technology include: sensitivity allowing PCR-less gene and single protein detection, label-free and real time operation, ultra-high scalability (>50,000 sensors/cm2), automated microfluidic operation, and commercially validated manufacturability via CMOS-compatible processing. To demonstrate the power of this technology, we will generate a molecular disease fingerprint allowing differentiation between three clinically indistinguishable yet biochemically distinct disease pathways underlying the deadly brain cancer glioblastoma multiforme. Importantly, each of these pathways is known to respond effectively to different therapeutic agents, thus personalized diagnosis equates to personalized treatment. We will also utilize this enabling technology to provide insight into profound questions surrounding post-transcriptional gene regulation and heterogeneity within the secreted responses of individual immune cells. This technology promises to broadly impact the landscape of the biomedical sciences, both meeting the clinical diagnostic challenges of today and pioneering the paradigm-shifting discoveries of tomorrow.