MOEMS device for fluorescence spectroscopy of tissues and cells

描述（由申请人提供）：总体项目目标是(i)开发一种微型光电机械系统（MOEMS）设备，用于分辨和检测生物组织和细胞的荧光发射；（ii）提供有关如何将光谱微设备集成到现有诊断仪器中的知识和策略；（三）为生化分析和微创医疗诊断和手术提供先进的、完全集成的平台。该设备将具有广泛的适用性，包括癌症和其他疾病的诊断、定位和分期、治疗效果监测、光谱/图像引导活检和手术。由于荧光光谱对生物系统中分子和分子复合物的功能和结构性质的变化非常敏感，因此荧光光谱在生物和医学的广泛应用领域发挥着关键作用。这里提出的进展，使用微制造技术，允许构建集成光谱微设备，能够实时测量组织和细胞的荧光。这将使微型多功能仪器和诊断技术协同发展成为可能。例如，将这种设备集成到内窥镜、活检探针和手术/监测设备中，将同时提供有关被调查侧生化和功能变化的信息，因此这些仪器的诊断能力将得到增强，而不会改变其功能和基本形式。我们建议开发一种由微制造色散系统和光电倍增管组成的MOEMS设备，该设备将取代荧光光谱设备中的传统单色仪和检测器，并允许稳态和时间分辨（寿命）测量。具体目标包括：(1)设计、微制造、集成和测试微型单色仪（MMC）。这将是一个多芯片系统，包括一系列关键元件（带有衍射光栅的压电驱动悬臂，镜子和透镜）。(2)设计、微制造和演示多通道板光电倍增管（MM-MCP-PMT）的功能。此次R21申请的结果将成为足够的知识基础，以便在未来的R01申请中继续将拟议的MMC和MM-MCP-PMT集成到紧凑型MOEMS设备中。这项工作将提供有关MMC的光谱性能（光谱分辨率，灵敏度）和局限性的信息；为最佳的MM-MCP-PMT开发设计解决方案。所获得的知识将用于改进MOEMS设计，并研究与光谱设备相关的电子器件进一步小型化的途径。该设备将为开发完全集成的微型荧光光谱设备和荧光引导手术/诊断微系统提供初始核心。该器件将广泛应用于各种需要波长区分和选择的生物医学仪器。

DESCRIPTION (provided by applicant): The overall project objectives are to (i) develop an Micro-Opto-Electro-Mechanical System (MOEMS) device for resolving and detecting fluorescence emission from biological tissues and cells; (ii) provide knowledge and strategies about how spectroscopic micro-devices can be integrated in existing diagnostic instruments; and (iii) enable advanced, fully integrated platforms for biochemical assays and minimally-invasive medical diagnosis and surgery. The device will have broad applicability including diagnosis, localization and staging of cancer and other diseases, monitoring of therapeutic effects, spectroscopy/image guided biopsy and surgery. Because fluorescence spectroscopy is very sensitive to changes in functional and structural properties of molecules and molecular complexes in biological systems, fluorescence spectroscopy plays a key role on a broad area of biological and medical applications. Advances proposed here, using micro-fabrication techniques, allow construction of integrated spectroscopy micro-devices capable of real-time fluorescence measurements from tissues and cells. This will enable advances in miniature multifunctional instrumentation and synergy of diagnostic technologies. For example, integrating such device in endoscopes, biopsy probes, and surgical/monitoring devices will provide simultaneously information about biochemical and functional changes at the investigated side, thus the diagnostic capability of these instruments will be enhanced without altering their function and basic form. We propose to develop a MOEMS device consisting of a micro-fabricated dispersive system and photomultiplier that will replace the conventional monochromator and detector in a fluorescence spectroscopy apparatus and allow both steady-state and time-resolved (lifetime) measurements. Specific aims include: (1) To design, micro-fabricate, integrate and test a micro-monochromator (MMC). This is to be a multi-chip system including a series of key elements (piezoelectrically actuated cantilever with diffraction grating, mirrors and lenses). (2) To design, microfabricate, and demonstrate functionability of a multichannel plate photomultiplier (MM-MCP-PMT). The results of this R21 application will be a basis of knowledge sufficient to permit continued integration of the proposed MMC and MM-MCP-PMT into a compact MOEMS device in a future R01 application. This work will provide information about the spectroscopic performance (spectral resolution, sensitivity) and limitations of the MMC; and develop design solutions for an optimal MM-MCP-PMT. The knowledge gained will be used to improve the MOEMS design and to investigate pathways for further miniaturization of the electronics associated with the spectroscopic device. The device will provide the initial kernel for development of fully integrated miniature fluorescence spectroscopy devices and fluorescence-guided surgical/diagnostic micro-systems. The device will widely be applied to various biomedical instruments that require wavelength differentiation and selection.