Personalized Clinical Diagnostics and Beyond: Integrated Ring Resonator Arrays

个性化临床诊断及其他：集成环形谐振器阵列

• 批准号: 7430026
• 负责人: Ryan C Bailey
• 金额: $ 232.5万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7430026
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PERSONALIZED CLINICAL DIAGNOSTICS AND BEYOND: INTEGRATED RING RESONATOR ARRAYS AS AN ENABLING MULTIPARAMETER ANALYSIS PLATFORM 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.

个性化临床诊断及其他： 集成环形谐振器阵列作为多参数分析平台 抽象的 生物学范式的转变通常是由测量技术的创新催化的。基因组学 蛋白质组学已经彻底改变了生物学，但如果没有以下领域的发展，这是不可能的： 毛细管测序、cDNA 微阵列和质谱分析等 技术。癌症生物学极大地受益于以下提供的分子水平细节： 这些工具可以阐明疾病发作和进展的许多扰动。 不幸的是，许多相同的测量方法不适用于临床环境，并且 因此，医生无法获得与普通人相同的详细生化信息。 院士。因此，尽管我们对癌症分子基础的了解不断增加， 向临床医学的转化明显滞后。该提案描述了一项革命性的 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。极其灵敏的集成微环谐振器的高密度阵列将允许 从单个患者样本中同时定量许多基因和蛋白质特征。 该技术的显着特点包括： 灵敏度允许无需 PCR 的基因和单一蛋白质 检测、无标签实时操作、超高可扩展性（>50,000 个传感器/cm2）、自动化 微流体操作，以及通过 CMOS 兼容处理进行商业验证的可制造性。 为了展示这项技术的力量，我们将生成分子疾病指纹，从而允许 区分三种临床上无法区分但生化上不同的疾病途径 致命的脑癌多形性胶质母细胞瘤的潜在原因。重要的是，每一条途径都是 已知对不同的治疗药物有有效的反应，因此个性化诊断相当于 个性化治疗。我们还将利用这种使能技术来深入了解 围绕转录后基因调控和分泌物内异质性的问题 个体免疫细胞的反应。这项技术有望广泛影响 生物医学科学，既满足当今的临床诊断挑战，又开创了 明天的范式转变发现。