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

 描述（由申请人提供）：龋齿是地球仪上最常见的疾病，影响着24亿人。目前识别龋齿的过程包括在常规检查中通过肉眼或X光检查龋齿形成。一旦确定，牙科修复程序被用来钻掉牙齿的腐烂部分，并用合成材料填充。这种“钻孔和填充”的牙科护理方式非常无效，每年在美国损失超过430亿美元。美国牙科协会提倡“早期发现和预防性治疗”的模式，这可以大大减少人类的痛苦和与疾病相关的高昂费用。传统的广谱化合物，如洗必泰和木糖醇是有效的，但更有前途的是物种特异性抗生素，使“健康”的肠道细菌完好无损。为了使这些预防性治疗有效，至关重要的是在对牙齿造成结构性损害之前预测龋齿的形成。我们建议通过检测变形链球菌（S。变形菌），其唾液浓度与将来的龋齿形成强烈相关的主要致龋细菌。目前，能够检测S.相关浓度的变异蛋白检测都是基于实验室的，如PCR或ELISA，由于成本高和获得结果的时间长，很少使用。本项目的主要目标是开发新一代快速、廉价、简便的检测沙门氏菌的方法。使用新的三维纸传感器（3PS）技术的变形。该3PS装置包括一个使用双水相系统（ATPS）的样品预浓缩步骤和一个用于检测的快速侧流免疫测定（LFA）。传统的LFA对S.相关浓度下的变异体。为了克服这一障碍，使用ATPS的浓缩组件可以在LFA检测之前将目标病原体浓缩几个数量级。通过使用纸微流体，我们证明了我们的3PS设备可以同时无缝地浓缩和检测目标病原体，仅使用轻便且廉价的纸材料。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，以可靠地预测椅侧的龋齿形成。通过这种诊断，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：“低挂水果”两阶段平台和“高风险，高回报”一阶段平台。这些目标的成功执行将导致可以预测龋齿发展的诊断测试，允许牙科保健专业人员使用预防性治疗，而不是目前的“钻孔和填充”方法。这将大大降低龋齿治疗的成本，提高护理质量。这种“早期检测和预防性治疗”组合的简单性和成本效益有机会在工业化和资源贫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.