Rapid, Label-free, Multiplex Detection of MicroRNAs

描述（由申请人提供）：全球迫切需要用于检测和监测恶性肿瘤的微创检测，以降低癌症引起的发病率和死亡率。虽然很有前途，但基于血液的蛋白质组学测定尚未在许多常见的人类癌症中得到临床验证。因此，正在研究可能补充或改进现行战略的新办法。特别是，微小RNA（miRNA）作为许多疾病的潜在预测生物标志物已经获得了相当大的关注。该I期研究项目将评估使用称为表面等离子体增强共路径干涉术（SPE-CPI）的新型超灵敏检测技术快速，无标记鉴定和定量血液样本中miRNA的可行性。SPE-CPI与标准表面等离子体共振（SPR）检测方法（例如Biacore）的不同之处在于，它将SPR的高灵敏度与CPI单光束路径的较高稳定性和较低噪声相结合。SPE-CPI还允许同时监测单个样品中的多种miRNA。在第一阶段，将确定和鉴定用于在血清存在下测量癌症相关miRNA的基于SPE-CPI的方案。专属性和检测限将是本可行性证明研究的关键参数。此外，使用优化的SPE-CPI方法，我们将评估SPE-CPI作为诊断工具的潜力，用于检测来自肺癌患者与健康个体的血清样本中的miRNA。如果成功，这项研究将是癌症和其他可能受miRNA调控的疾病的新诊断策略的重要一步。无标记感测技术的进步还将为低丰度蛋白质的测量、蛋白质-蛋白质相互作用研究、传染病检测、生物战病原体检测、蛋白质-药物相互作用、食品安全、化学污染物检测等打开更广泛的应用。将在这些研究中进行评估的SPE-CPI仪器体积小，价格便宜，并且需要最少的样品操作进行分析。负担得起的，易于使用的检测器，用于在护理设施点，即医生办公室进行快速筛查，将是医疗保健行业的重大突破。 公共卫生相关性：该小型企业创新研究（SBIR）第一阶段项目将评估一种超灵敏检测技术，用于血清样本中肺癌生物标志物的非侵入性多重定量。如果成功，这项研究将是癌症和其他疾病的护理点诊断新策略的重要一步。生物传感器技术的进步还将为低丰度蛋白质的测量、蛋白质-蛋白质相互作用研究、传染病检测、生物战病原体检测、蛋白质-药物相互作用、疫苗开发、食品安全、化学污染物检测等打开更广泛的应用。

DESCRIPTION (provided by applicant): Minimally invasive tests for the detection and monitoring of malignancies are urgently needed worldwide to reduce the morbidity and mortality caused by cancer. While promising, blood-based proteonomic assays have yet to be clinically validated for many common human cancers. Accordingly, new approaches are being investigated that will likely complement or improve on current strategies. In particular, microRNAs (miRNAs) have gained considerable attention as potentially predictive biomarkers for a number of disorders. This Phase I research project will evaluate the feasibility of rapid, label-free identification and quantification of miRNAs from blood samples using a novel ultra-sensitive detection technology known as Surface Plasmon Enhanced Common Path Interferometry (SPE-CPI). SPE-CPI differs from standard Surface Plasmon Resonance (SPR) detection methods, such as Biacore, in that it combines the high sensitivity of SPR with the higher stability and lower noise of a CPI single-beam path. SPE- CPI also allows for the simultaneous monitoring of multiple species of miRNA in a single sample. During Phase I, SPE-CPI based protocols for measuring cancer-related miRNAs in the presence of serum will be identified and qualified. Specificity and limit of detection will be critical parameters for this proof-of-feasibility study. Further, using the optimized SPE-CPI methods, we will evaluate the potential of SPE-CPI as a diagnostic tool for the detection of miRNAs using serum samples from patients with lung cancer versus healthy individuals. If successful, this research will be a major step forward in new diagnostic strategies for cancer and possibly other diseases that may be modulated by miRNA. Advancements in label-free sensing technologies will also open broader applications for the measurement of low abundance proteins, protein- protein interaction studies, infectious disease detection, biowarfare pathogen detection, protein- drug interactions, food safety, detection of chemical pollutants, and the like. The SPE-CPI instrument that will be evaluated in these studies is small, inexpensive, and requires minimal sample manipulation for analysis. Affordable, easy-to use detectors for rapid screening at point of care facilities, i.e. doctors' offices, would be a significant breakthrough in the health care industry. PUBLIC HEALTH RELEVANCE: This Small Business Innovation Research (SBIR) Phase I project will evaluate an ultra-sensitive detection technology for the non-invasive multiplex quantification of lung cancer biomarkers in serum samples. If successful, this research will be a major step forward in a new strategy for point of care diagnosis of cancer and other diseases. Advancements in biosensor technologies will also open broader applications for the measurement of low abundance proteins, protein-protein interaction studies, infectious disease detection, biowarfare pathogen detection, protein-drug interactions, vaccine development, food safety, detection of chemical pollutants, and the like.