Nuclear Magnetic Resonance Spectroscopy on a Chip

这项提议的重点是将新型微米和纳米级的核磁共振设备和材料集成到光刻制造的微流体系统中。这种核磁共振系统的小型化和在微流控平台上的实施将导致对较小数量的生物化学重要溶液进行高度并行的化学分析，具有比以前可能的更高的灵敏度。缩小芯片上的磁共振成像(MRI)设备的尺寸也将导致以前所未有的空间分辨率对生物细胞进行无损成像。基于智能优点的微流控芯片核磁共振系统将被设计和制造，实现(A)应用大梯度磁场的组件，(B)提供高局部磁场的永磁基设备，以及(C)将显著提高核磁共振和核磁共振的灵敏度和分辨率的微纳米级电磁线圈。这项研究将为单个细胞的研究提供新的工具，能够对微流体控制的环境变化引发的细胞代谢变化进行光谱和成像观察。此外，微流控核磁共振芯片将提供操作皮升溶液和执行高度并行的核磁共振生化分析的能力。还将探讨弹性微流控芯片中核磁共振微技术小型化和集成的基本限制。广泛的影响该计划将促进博士授予机构(加州理工大学)和大型城市少数族裔非博士授予大学(CSULB)之间的合作。这两所大学的博士和硕士研究生将接触到来自工程、物理和生物化学的多学科技术，同时接受微制造、流体学、传感器设计、磁共振成像和光谱分析技术方面的培训。学生们进行的这项研究有望发现许多其他应用，在这些应用中，必须在廉价的便携式芯片平台上分析小样本并进行成像，特别强调疾病诊断。

This proposal focuses on the integration of novel micrometer and nanometer scale Nuclear Magnetic Resonance (NMR) devices and materials into the lithographically fabricated micro-fluidic systems. Such miniaturization and implementation of NMR systems on a micro-fluidic platform will lead to the highly parallel chemical analysis of smaller volumes of bio-chemically important solutions with significantly greater sensitivity than previously possible. Reducing the size of Magnetic Resonance Imaging (MRI) devices on a chip will also lead to the non-destructive imaging of biological cells with an unprecedented spatial resolution.Intellectual Merit Micro-fluidic chip-based NMR systems will be designed and fabricated implementing (a) components for application of large gradient magnetic fields, (b) permanent magnet-based devices that provide high local fields, and (c) micro/nanometer scale electro-magnetic coils that will significantly improve the sensitivity and resolution of NMR and MRI. This research will offer new tools for the study of individual cells, enabling both spectroscopic and imaging observation of changes in cell metabolism triggered by the micro-fluidic controlled environmental changes. Furthermore, the micro-fluidic NMR chips will provide the ability to manipulate pico-liters of solution and perform highly parallel NMR biochemical analysis. Fundamental limits of miniaturization and integration of NMR micro-technologies within the elastomeric micro-fluidic chips will also be explored.Broader Impact This program will foster collaboration between a Ph.D. granting institution (Caltech) and a large, urban, minority serving non-Ph.D. granting university (CSULB). The Ph.D. and Masters students from both institutions will be exposed to the multi-disciplinary techniques from engineering, physics, and biochemistry, while being trained in micro-fabrication, fluidics, sensor design, and magnetic resonance imaging and spectroscopy techniques. The research that students perform is expected to find many other applications where small samples have to be analyzed and imaged within an inexpensive portable chip-based platform with particular emphasis towards disease diagnostics.