MOEMS device for fluorescence spectroscopy of tissues and cells

描述（由申请人提供）：项目的总体目标是（i）开发一种用于解析和检测生物组织和细胞荧光发射的微光机电系统（MOEMS）设备;（ii）提供有关如何将光谱微型设备集成到现有诊断仪器中的知识和策略;和（iii）实现用于生化测定和微创医学诊断和手术的先进的、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体系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应用的广泛领域中起着关键作用。这里提出的进展，使用微制造技术，允许建设集成的光谱微型设备能够实时荧光测量组织和细胞。这将使微型多功能仪器和诊断技术的协同作用的进步。例如，将这种装置集成到内窥镜、活检探针和手术/监测装置中，将同时提供关于被调查侧的生化和功能变化的信息，从而在不改变其功能和基本形式的情况下增强这些仪器的诊断能力。我们建议开发一种MOEMS设备，包括一个微制造的色散系统和光电倍增管，将取代传统的单色器和检测器的荧光光谱仪，并允许稳态和时间分辨（寿命）测量。具体目标包括：（1）设计、微加工、集成和测试微单色器（MMC）。这将是一个多芯片系统，包括一系列的关键要素（压电驱动悬臂与衍射光栅，镜子和透镜）。(2)设计、微加工并验证多通道板光电倍增管（MM-MCP-PMT）的功能。该R21应用的结果将是足够的知识基础，以允许在未来的R 01应用中继续将所提出的MMC和MM-MCP-PMT集成到紧凑型MOEMS器件中。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，并开发最佳MM-MCP-PMT的设计解决方案。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设备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内核。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中。

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.