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

这个小企业创新研究（SBIR）第一阶段项目提议开发一种手持式亚细胞共聚焦显微镜，使用微机电系统（MEMS）技术，用于非侵入性和早期癌症检测。85%的癌症发生在上皮细胞，发生在组织最上面的200微米处，包括口腔癌、皮肤癌、宫颈癌和许多其他癌症。上皮性癌症，如口腔癌，在早期很少有疼痛感，如果没有侵入性活检或CT扫描等基于放射的成像，很难发现。该手持式显微镜由具有机械可调分辨率和视场（FOV）的共聚焦MEMS成像扫描仪组成，允许医生在没有机械切割的情况下在多个深度密切检查上皮层，并通过组织结构的形态变化和改变识别癌症的早期迹象。通过芯片上的主动微机械调节，实现了分辨率和视场的可调性。将建立一个手持式原型，通过利用离体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使用，以确定相对于组织病理学金标准的体内癌前病变。该项目的更广泛的影响/商业潜力是使一类新的临床微成像工具能够显著改善上皮性癌症的早期诊断，从而实现个体化、微创治疗并提高长期生存率。目前的诊断方法需要对良性病变进行反复的手术活检，而发现恶性病变往往为时已晚，无法进行恢复性治疗。该技术的关键创新之处在于，它将共聚焦显微镜转化为体内应用，使用微型光学、光纤、可调谐MEMS设计和强大的封装技术，为临床医生和研究人员提供组织细胞结构的实时3D视图，而无需移除组织。这项技术为非侵入性和无辐射癌症诊断提供了一个潜在的突破。手持扫描仪不仅可以在早期发现肿瘤并确定癌症的进展程度，还可以在治疗过程中监测肿瘤，并跟踪所采用的治疗效果，从而开辟了征服癌症的全新机会。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.