Microengineered Lollipop for Patient-Centric Saliva Collection

项目摘要/摘要 口腔样本对于呼吸系统疾病的诊断是必不可少的，因为某些细菌和病毒感染会导致 如果不治疗，就会出现严重的长期疾病。然而，在某些情况下，访问这些示例是具有挑战性的 例如，在幼儿和远程病人中，远程医疗是必不可少的。目前，口腔样本 收集依赖于传统的鼻咽拭子，这对年轻人来说是困难、痛苦和创伤的 这可能会导致延迟获得诊断结果，从而导致负面结果。我们 设计了一个新颖的、微工程的、受棒棒糖启发的平台(LolliTest)，以改进家庭口腔样本 收集能力。LolliTest的设计具有两个关键特征：(1)功能化开放微通道 用于病原体捕获和浓缩以及(2)时间控制的香料释放，使平台更多 以病人为中心。使用开放式微流体(即，没有天花板的微制造通道)是有利的 因为它允许最佳的唾液交换和进入捕获区，同时防止机械磨损 舌头或口腔的其他表面，可以驱逐捕获的细菌。时控调味料 Release使用户能够直观地知道LolliTest设备需要使用多长时间，不需要复杂的 居家环境中的使用说明。为了建立这个平台，我们提出了两个具体目标。目标1将优化 LolliTestPlatform捕获健康受试者的已知口腔共生微生物。这使安全成为可能 测试和开发周期，可轻松接触具有多种细菌的人类受试者 唾液中的浓度。我们将具体调整和优化LolliTest的关键功能，例如 开放式流体功能化捕获通道和时间定制的风味释放功能，使捕获成为可能 所选微生物的浓度与典型病原体相称。这一目标还允许 基于用户调查改进易用性和主题体验的迭代。Aim 2将演示 LolliTest平台捕获和检测A组链球菌(GAS)的功能 大规模临床研究，以证明该平台在从儿童身上采集样本的潜力 诊所。我们将比较LolliTest抽样(随后进行实时聚合酶链式反应)的结果与 常规咽拭子和临床分析，验证LolliTest确定患者是否 气体是阳性还是阴性。通过精心设计，最大限度地提高唾液采样的收集性能， 我们的长期愿景是，我们的LolliTest平台将获得比以往更好的灵敏度和特异度 使用当前的生物样品收集技术获得，同时提供患者首选的平台 并且在家庭环境中可用。最终，LolliTest有可能使唾液样本成为新的黄金 呼吸系统疾病诊断标准。

PROJECT SUMMARY/ABSTRACT Oral samples for respiratory disease diagnosis are essential as certain bacterial and viral infections can lead to serious long-term conditions when left untreated. However, accessing these samples is challenging in some cases, such as in young children and remote patients where telemedicine is essential. Currently, oral sample collection relies on traditional naso- and pharyngeal swabs that are difficult, painful, and traumatic for young children and potentially result in delayed access to diagnostic results, leading to negative outcomes. We designed a novel, micro-engineered, lollipop-inspired platform (LolliTest) to improve on at-home oral sample collection capabilities. The LolliTest was designed with two key features, (1) functionalized open microchannels for pathogen capture and concentration and (2) time-controlled flavoring release to make the platform more patient-centric. The use of open microfluidics (i.e., microfabricated channels without a ceiling) is advantageous as it allows optimal saliva exchange and access to the capture areas while preventing mechanical abrasion by the tongue or other surfaces of the mouth, which could dislodge captured bacteria. The time-controlled flavoring release enables the user to intuitively know how long to use the LolliTest device, eliminating the need for complex instructions in a home setting. To establish the platform, we propose two specific aims. Aim 1 will optimize the LolliTest platform to capture known oral commensal microorganisms in healthy subjects. This enables safe testing and development cycles with simple access to human subjects who have a range of bacterial concentrations in their saliva. We will specifically adapt and optimize key features of the LolliTest, such as the open-fluidic functionalized capture channels and the time-tailored flavor-release function, to enable the capture of a selected microorganism in concentration commensurate with typical pathogens. This aim also allows iteration to improve ease-of-use and subject experience based on user surveys. Aim 2 will demonstrate functionality of the LolliTest platform to capture and detect Group A Streptococcus (GAS) in vitro and in a small- scale clinical study to demonstrate the potential of the platform for acquisition of samples from children in the clinic. We will compare results of the LolliTest sampling (followed by real time-polymerase chain reaction) with conventional pharyngeal swabs and clinical analysis, validating the ability of the LolliTest to determine if a patient is positive or negative for GAS. With deliberate design to maximize collection performance from saliva sampling, our long-term vision is that our LolliTest platform will achieve better sensitivity and specificity than can be obtained with current biospecimen collection techniques, while providing a platform that is preferred by patients and usable in home settings. Ultimately, the LolliTest has the potential to make saliva sampling a new gold standard for respiratory disease diagnostics.