Paper-based Rapid Diagnostics for Early Dental Caries Prediction at the Chairside

 描述(申请人提供)：龋齿是全球最常见的一种疾病，影响着24亿人。目前识别龋齿的过程包括在常规检查中用肉眼或X光检查龋齿形成。一旦确定，手术修复程序被用来钻出牙齿的腐烂部分，并填充合成材料。这种“钻填”式的牙科护理非常无效，在美国每年花费超过430亿美元。美国牙科协会提倡“早期发现和预防性治疗”模式，这可以极大地减少人类的痛苦和与疾病相关的高昂成本。传统的广谱化合物，如洗必泰和木糖醇是有效的，然而更有希望的是特定物种的抗生素，它让“健康的”共生细菌保持不变。为了使这些预防性治疗有效，在牙齿受到结构性损害之前预测龋齿的形成是至关重要的。我们建议通过检测变形链球菌(变形链球菌)来实现这一点，变形链球菌是一种主要的致龋菌，其唾液浓度与未来的龋病形成密切相关。目前，能够检测相关浓度的变形链球菌的方法都是基于实验室的，如PCR或ELISA法，由于成本高和结果时间长，这些方法很少使用。本项目的主要目标是利用新型三维纸张传感器(3PS)技术开发新一代快速、廉价和简单的变形链球菌检测方法。3PS装置包括使用双水相系统(ATPS)的样品预浓缩步骤和用于检测的快速横向流动免疫分析(LFA)。传统的LFA不够灵敏，无法检测到相应浓度的变形链球菌。为了克服这一障碍，使用ATPS的浓度成分可以在LFA检测之前将目标病原体浓缩几个数量级。通过使用纸张微流控芯片，我们展示了我们的3PS设备可以同时无缝地浓缩和检测目标病原体，只需使用轻而便宜的纸张材料。一旦完全开发，3PS设备将是一种快速(10分钟)、廉价和一次性的诊断工具，牙医可以在办公室使用它来可靠地预测主席的龋齿形成。有了这种诊断，龋齿形成的预防性治疗成为牙科保健专业人员的实用解决方案。在第一阶段，我们将使用两种方法开发3PS设备的原型：一种是“低挂果”的两级平台，另一种是“高风险、高回报”的一级平台。这些目标的成功实现将导致一种能够预测龋齿发展的诊断测试，使牙科保健专业人员能够使用预防性治疗，而不是目前的“钻孔和填充”方法。这将大大降低龋齿治疗的CST，并提高护理质量。这种“早期发现和预防治疗”组合的简单性和成本效益有机会在工业化和资源匮乏的环境中彻底改变龋齿的医疗保健。

 DESCRIPTION (provided by applicant): Dental caries is the single most common affliction across the globe, affecting 2.4 billion people. The current process of identifying dental caries involves examining caries formation by naked eyes or X-ray during routine checkups. Once identified, surgical-restorative procedures are used to drill out the decay portion of the tooth an filled with synthetic material. This style of 'drill & fill' dental care is highly ineffective and osts more than $43 billion in the United State per year. The American Dental Association promotes the "early detection and preventive treatment" paradigm, which could dramatically reduce human suffering and the high cost associated with the disease. Traditional broad spectrum compounds such as chlorhexidine and Xylitol are effective, however even more promising are species-specific antibiotics which leave the 'healthy' commensal bacteria intact. For these preventive treatments to be useful, it is crucial that caries formation is predicted before structual damage is done to the tooth. We propose to achieve that by detecting Streptocauccus mutans (S. mutans), a major cariogenic bacteria which its salivary concentration strongly correlates to future caries formation. Currently, the only methods capable of detecting S. mutans at relevant concentrations are all lab based, such as PCR or ELISA, which are very rarely used due to the high cost and long time-to-result. The main goal of this project is to develop the next generation rapid, inexpensive and simple test for the detection of S. mutans using the novel 3-dimensional Paper Sensor (3PS) technology. The 3PS device incorporate a sample pre-concentration step using aqueous two-phase system (ATPS) and a rapid lateral-flow immunoassay (LFA) for detection. Traditional LFA is not sensitive enough to detect S. mutans at relevant concentrations. To overcome this barrier, a concentration component using ATPS can concentrate the target pathogen by several orders of magnitude prior to LFA detection. By using paper microfludics, we demonstrated our 3PS device can simultaneously and seamless concentrate and detect target pathogen using only light and inexpensive paper materials. Once fully developed, the 3PS device will be a rapid (<10 mins), inexpensive, and disposable diagnostic that dentists can use in the office to reliably predict caries formation at the chairsid. With this diagnostic, preventative treatment of caries formation becomes a practical solution for dental healthcare professionals. In Phase I, we will develop the prototypes of the 3PS device using 2 approaches: a "low-hanging fruit" two-stage platform, and a "high-risk, high-reward" one-stage platform. The successful execution of these aims will result in a diagnostic test that can predict caries development, allowing dental healthcare professionals to use preventive treatment rather than the current "drilling & filling" approach. This will drastically reduce the cst of dental caries treatment and improve the quality of care. The simplicity and cost effectiveness of this "early detection and preventive treatment" combination has the opportunity to revolutionize healthcare of dental caries both in industrialized and resource poor settings.