Lab-on-a-Chip-Based System for Detection and Monitoring of Oral Cancer in Dental Settings

 描述（由申请人提供）：口腔癌和咽癌是最严重的癌症之一，全球约有40万例。在美国，5年生存率约为64%，是所有癌症中最低的。然而，当在早期诊断并局限于原发部位时，该比率急剧增加至约83%。此外，口腔癌是治疗费用最高的癌症之一，因为大约三分之二的口腔癌和咽癌在诊断时已经是晚期。到目前为止，手术刀活检一直是准确评估可疑口腔病变的唯一可靠方法。为了解决这些重大的临床差距，SensoDx将瞄准OraTechTM技术的开发和商业化，以用作诊断潜在恶性口腔病变的连续诊断辅助工具。这种新的方法将结合联合收割机的非侵入性口腔刷采样方法，微流控细胞捕获盒，分析平台和分析系统。这种最先进的自动化微型细胞学系统将用于揭示细胞形态学和蛋白质表达值（细胞表面标记物和细胞内标记物），以识别需要随访手术刀活检的潜在恶性口腔病变子集的患者。基于这些强大的基于芯片的工具获得的生物标志物数据的诊断模型，以及从定制的mHealth App获得的病变特征，将允许进行优雅的数据融合过程，从而病变特征，风险因素和众多细胞学因素为口腔癌患者提供迫切需要的临床见解。此快速通道SBIR提交将包括两个主要部分。在第一阶段，将定义可扩展检测盒的规格，并建立高重现性单细胞测量的方案。商业成像仪器和软件也将在此期间开发。在第二个主要阶段，将对耗材进行规模化，开发制造工艺，并使用库存标本对仪器和检测盒进行验证。 主要技术目标如下：1.设计和开发独特的基于微流体的检测盒，适用于捕获和完成由微创刷采样设备促进的单细胞测定。2.确定适用于高质量单细胞检测的最佳样本采集和运输方案。3.建立测试卡片的质量标准，并定义能够批量生产测试卡片、分析仪仪器和控制分析软件的制造方法。4.开发一种mHealth工具，允许刷检标本与病变照片的无缝配对，从而促进数据融合，增强这种非侵入性测试模式的性能。

 DESCRIPTION (provided by applicant): Cancers of the oral cavity and pharynx are among the most serious cancers, with approximately 400,000 incidents globally. In the US, the 5-year survival rate is approximately 64% among the lowest for all forms of cancer. Yet when diagnosed in the early stages with confinement to the primary site, the rate increases dramatically to about 83%. Further, cancers of the oral cavity are among the most expensive to treat due to the fact that approximately two-thirds of oral and pharyngeal cancers are advanced at the time of diagnosis. Until now, scalpel biopsy has been the only reliable means of accurately assessing suspicious oral lesions. To address these significant clinical gaps, SensoDx will target the development and commercialization of the OraTechTM technology for use as adjunctive diagnostic aids for the diagnosis of potentially malignant oral lesions. This new approach will combine a noninvasive oral brush sampling methodology, a microfluidic cell capture cartridge, an assay platform and an analyzer system. This state-of-the-art automated miniaturized cytology system will be used to reveal cell morphometrics and protein expression values (cell surface markers and intracellular markers) to identify the patients with a subset of potentially malignant oral lesions that require follow up scalpel biopsy. Diagnostic models based on biomarker data derived from these powerful chip-based tools, alongside lesion characteristics obtained from a customized mHealth App will allow for an elegant data fusion process to occur whereby lesion characteristics, risk factors and the numerous cytology factors yield the desperately needed clinical insights for patients suffering from oral cancer. This Fast Track SBIR submission will include two major segments. In the first phase, the specifications for the scalable cartridges will be defined and protocols established for high reproducibility single cell measurements. Commercial imaging instrumentation and software will also be developed during this time period. In the second major phase, the consumables will be scaled, manufacturing processes will be developed and the instrumentation and cartridges will be validated using banked specimens. The key technical objectives for the effort are as follows: 1. To design and develop unique microfluidics-based cartridges that are suitable for capture and completion of single-cell assays as promoted by a minimally-invasive brush sampling device. 2. To define optimal sample collection and shipping protocols suitable for high quality single cell assays. 3. To establish specifications for the cartridge and to define manufacturing methods that enable volume production of cartridges, analyzer instrumentation, and control-analysis software. 4. To develop a mHealth tool that allows for the seamless pairing of brush biopsy specimens with lesion photos thereby fostering a data fusion that enhances the performance of this noninvasive test modality.