Innovative Droplet Lenses for NextGen Light Sensors of Biomarkers of Inflammation

项目总结/摘要 虽然免疫疗法的疗效可能是惊人的，但一个主要的副作用是， 过度强大的免疫反应，这可能导致器官损伤，神经缺陷，甚至死亡。 在CAR T细胞治疗的情况下，估计约20至40%的患者经历细胞因子治疗。 释放综合征（CRS）。鉴于其潜在的严重性，在治疗后监测患者至关重要， 可以在过度的器官损伤之前采取步骤来治疗CRS。虽然每天血液测试的生物标志物， 炎症（C-反应蛋白; CRP）在医院有效地进行后的第一周， 治疗，继续测试是不一致的，尽管事实上，发病可能发生在几周后，甚至 治疗后数月。所需要的是一种用于监测已建立的生物标志物的床旁设备， 炎症我们能够在传感器开发方面迈出大胆的一步，以满足这一需求。我们有 开发了新型传感器，利用双相液滴作为众多微米级透镜， 和闪烁的光。具有抗体功能化表面的复杂多液滴可以改变形态 在与分析物结合时，响应于分子相互作用提供强的方向性光学变化。 具体而言，分子相互作用可影响透射光（类型1传感器）和反射光（类型2 传感器）。光强度和方向的这种变化可以用智能手机来感测，从而避免了使用智能手机的需要。 昂贵和笨重的设备，最终使人们与他们的健康之间的联系 护理提供者。我们的首要目标是开发1型和2型传感器，以检测生物标志物， 在全血或血清中生理相关水平的炎症。我们亦建议测试以下药物的效用： 集成的发射/吸附染料作为实现多路复用的手段。具体目标1是揭示 1型传感器检测CRP的有效性。具体目标2是确定2型传感器的功效， 用于感测CRP的反射光。具体目标3是发展多路复用能力。使用POC传感器将 不仅可用于监测炎症的既定生物标志物，而且还将引起 前所未有的深度纵向数据。因此，拟议的传感器将为未来的研究打开大门 旨在利用详细的时间响应数据来更好地预测免疫相关的不良事件。的 提出的“下一代”POC传感器提供了精确的灵敏度，定量数据和数据， 实时，提高了液滴传感器对癌症治疗和预防产生广泛影响的可能性。

Project Summary/Abstract While the efficacy of immunotherapy can be staggering, a major side effect is that there can be an ensuing excessively robust immune response, which can lead to organ damage, neurological deficits, and even death. In the case of CAR T-cell therapy, it is estimated that between ~20 to 40% of patients experience cytokine release syndrome (CRS). Given its potential severity, it is critical to monitor patients after treatment so that steps can be taken to treat CRS before excessive organ damage. While daily blood tests for a biomarker of inflammation (C-reactive protein; CRP) are effectively performed in the hospital for the first week after treatment, continued testing is not consistent, despite the fact that onset can occur weeks after and even months after treatment. What is needed is a point of care device to monitor established biomarkers of inflammation. We are in a position to take a bold step in sensor development to address this need. We have developed novel sensors that exploit biphasic droplets that act as a multitude of micron scale lenses to reflect and refract light. Complex multi-liquid droplets with antibody functionalized surfaces can change morphology upon binding to analytes, providing strong directional optical changes in response to molecular interactions. Specifically, molecular interactions can impact transmitted light (Type 1 sensors) and reflected light (Type 2 sensors). Such changes in light intensity and direction can be sensed with a smartphone, avoiding the need for expensive and cumbersome equipment and ultimately enabling connections between people and their health care providers. Our overriding goal is to develop Type 1 and Type 2 sensors to detect biomarkers of inflammation at physiologically relevant levels in whole blood or serum. We also propose to test the efficacy of integrated emissive/adsorptive dyes as a means for achieving multiplexing. Specific Aim 1 is to reveal the efficacy of Type 1 sensors for detecting CRP. Specific Aim 2 is to determine the efficacy of Type 2 sensors of reflected light for sensing CRP. Specific Aim 3 is to develop multiplexing capacity. Having a POC sensor will not only be useful for monitoring established biomarkers of inflammation, but it will also give rise to unprecedented depth of longitudinal data. As such, the proposed sensors will open doors to future studies aimed at leveraging detailed temporal response data to better predict immune-related adverse events. The proposed “NextGen” POC sensors offer the potential for exquisite sensitivity, quantitative data, and data in real-time, raising the possibility for droplet sensors to have a broad impact on cancer therapy and prevention.