SBIR Phase I: Sub-Cellular Tunable Confocal MEMS Scanner for Early Cancer Detection

这个小型企业创新研究(SBIR)第一阶段项目计划开发一种手持式亚细胞共聚焦显微镜，采用微电子机械系统(MEMS)技术，用于非侵入性和早期检测癌症。85%的癌症发生在上皮细胞中，发生在最上层200微米的组织中，包括口腔癌、皮肤癌、宫颈癌和许多其他癌症。早期的上皮性癌症，如口腔癌，如果没有侵入性活组织检查或CT扫描等基于辐射的成像，很少出现疼痛和难以发现的情况。拟议的手持显微镜由具有机械可调分辨率和视场(FOV)的共焦MEMS成像扫描器组成，允许医生在不进行机械切割的情况下密切检查多个深度的上皮层，并通过形态变化和组织结构的变化识别癌症的早期迹象。通过片上微机械主动调节，实现了分辨率和视场的可调性。将建立一个手持原型，通过利用体外组织样本和测量组织形态来测试诊断能力，并在未来的临床试验中用于相对于组织病理学的黄金标准来识别体内的癌前病变。该项目更广泛的影响/商业潜力是使一类新的临床显微成像工具能够显著改善上皮癌的早期诊断，从而实现个体化、微创治疗并提高长期存活率。目前的诊断方法需要对良性病变进行反复的手术活检，而且往往发现恶性病变时为时已晚，无法进行恢复性治疗。这项技术的关键创新在于，它利用微型光学、光纤、可调谐MEMS设计和坚固的封装技术将共焦显微镜转化为活体应用，为临床医生和研究人员提供组织细胞结构的实时3D视图，而无需切除组织。这项技术在非侵入性和无辐射癌症诊断方面提供了潜在的突破。手持式扫描仪不仅可以在非常早期的阶段发现肿瘤，确定癌症进展的程度，还可以在治疗过程中监测肿瘤，跟踪所采取的治疗效果，从而为征服癌症开辟了一个全新的机会。这项核心技术建立在发达的半导体行业的优势之上，有可能为癌症成像带来更多的智能，并降低医疗成本。

This Small Business Innovation Research (SBIR) Phase I project proposes to develop a handheld sub-cellular confocal microscope using Micro-Electro-Mechanical systems (MEMS) technologies for non-invasive and early detection of cancers. 85% of cancers arise in epithelium and occur in the topmost 200 microns of tissues, including oral, skin, cervical, and many other cancers. Epithelial cancers such as oral cancer at early stages are rarely painful and hard to detect without invasive biopsy or radiation-based imaging like CT scan. The proposed handheld microscope, consisting of confocal MEMS imaging scanners with mechanically tunable resolution and field-of-view (FOV), allows doctors to closely exam epithelial layers at multiple depths without mechanical cutting, and identify early signs of cancers through morphologic changes and alternations in tissue architectures. The tunability of the resolution and FOV is achieved by active micro-mechanical adjustment on-chip. A handheld prototype will be built to test the diagnostic capabilities by utilizing ex vivo tissue samples and measuring tissue morphology and used in future clinical trials to identify pre-cancer in vivo relative to the gold standard of histo-pathology. The broader impact/commercial potential of this project is to enable a new class of clinical micro-imaging tools that can significantly improve early diagnosis of epithelial cancers leading towards individualized, minimally invasive treatment and improves long-term survival rates. Current diagnostic methods require recurring surgical biopsy of benign lesions and often detect malignant change too late for restorative treatment. The key innovation of this technology is that it translates confocal microscopy into in vivo application using miniature optics, optical fibers, tunable MEMS design and robust packaging technologies to provide clinicians and researchers a real-time 3D view of tissue cellular structure, without removal of tissue. This technology offers a potential breakthrough in non-invasive and radiation-free cancer diagnostics. The handheld scanner can not only be used to spot tumors at a very early stage and determine how far the cancer has progressed, it also can be used to monitor the tumor during treatment, and track the efficiency of therapy adopted, thus opening up a whole new opportunity to conquer cancers. The core technology builds on the strengths of the well-developed semiconductor industry and can potentially bring more intelligence to cancer imaging and lower healthcare cost.