Digital Precision Micro NMR Biosensor for Cancer

描述（由申请人提供）：临床诊断越来越需要对每个样本的多种分子标志物进行多重筛选。虽然遗传方法已经迅速发展并允许多重分析，但蛋白质生物标志物或整个细胞/细胞组分的测量一直缺乏。该特定应用的目的是开发一种新的分析检测平台，该平台将极具前景的微核磁共振（μNMR）技术提升到能够进行高通量分子分析的复杂、高灵敏度床旁设备的水平。新的核磁共振电子学和数据采集和重建的补充方法将被实施，重点是最大限度地提高生物标志物分析的通量，准确性和灵敏度。然后将严格评估开发的系统快速分析关键途径标记物样本的能力。在强大的初步数据的指导下，将解决两个具体目标：1）设计下一代精密数字NMR（d-μNMR）系统，具有先进的电子设备和优化的RF脉冲序列，用于高通量，鲁棒和灵敏的检测; 2）评估新开发的d-NMR平台和初步应用于人体样本。随着这两个目标的实现，我们将开发出非常适合这一应用的d-NMR系统，因为它可以提供高灵敏度和特异性，以及以最少的处理步骤进行高通量检测。应用并行检测机制，所有16个测量将快速完成（约1分钟）。此外，我们将首次评估其在1 μL样品体积中检测和区分低至10个异常癌细胞的能力。

DESCRIPTION (provided by applicant): Clinical diagnostics increasingly require multiplexed screening of numerous molecular markers per sample. While genetic approaches have rapidly progressed and allow multiplexed analyses, measurement of protein biomarkers or entire cells/ cellular components has been lacking behind. The objective in this particular application is to develop a new analytical detection platform that advances the highly promising micro- nuclear magnetic resonance (μNMR) technology to the level of a sophisticated, high sensitivity point-of-care device capable of high-throughput molecular analyses. New NMR electronics and complementary methods for data acquisition and reconstruction will be implemented with an emphasis on maximizing the throughput, accuracy, and sensitivity of biomarker analysis. The developed system will then be rigorously evaluated for its ability to rapidly analyses samples for key pathway markers. Guided by strong preliminary data, two specific aims will be addressed: 1) Design the next generation precision digitalNMR (d-μNMR) system with advanced electronics and optimized RF pulse sequences for high throughput, robust and sensitive detection and 2) Evaluation of the newly developed d-NMR platform and initial application to human samples. With the implementation of these two aims we will develop the d-NMR system would be ideally suited for this application, as it can offer high sensitivity and specificity as well as high-throughput detection with minimal processing steps. Applying the parallel detection mechanism, all 16 measurements will be complete rapidly (~1 min). Furthermore, we will evaluate its ability to detect and differentiate as little as 10 abnormal cancer cells in 1 μL sample volume, for the first time.