Innovative Droplet Lenses for NextGen Light Sensors of Biomarkers of Inflammation

项目摘要/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可能会有随之而来的 过度强健的免疫反应，可能导致器官损伤、神经缺陷，甚至死亡。 在CAR T细胞治疗方面，据估计，大约20%到40%的患者经历了细胞因子 释放综合征(CRS)。鉴于其潜在的严重性，至关重要的是在治疗后对患者进行监测，以便 在过度的器官损害之前，可以采取措施治疗CRS。虽然每天的血液检测中有一种生物标记物 炎症(C-反应蛋白；CRP)在术后第一周在医院有效地进行 治疗，持续检测并不一致，尽管发病可发生在数周后，甚至 在治疗后几个月。需要一种护理点设备来监控已建立的生物标志物 发炎。我们有能力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，利用两相液滴作为大量微米级透镜来反射 折射光线。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，提供响应分子相互作用的强烈方向性光学变化。 具体地说，分子相互作用会影响透射光(类型1传感器)和反射光(类型2 传感器)。这种光线强度和方向的变化可以通过智能手机来感知，而不需要 昂贵而笨重的设备，最终实现了人与健康之间的联系 照顾者。我们的首要目标是开发类型1和类型2的传感器来检测 全血或血清中生理上相关水平的炎症。我们还建议测试一下 集成发射/吸附染料作为实现多路复用的一种手段。具体目标1是揭示 1型传感器检测C反应蛋白的有效性。具体目标2是确定第二类传感器的有效性 用于传感CRP的反射光。具体目标3是发展多路传输能力。拥有PoC传感器将 不仅用于监测已建立的炎症生物标志物，而且还将引起 纵向数据的深度史无前例。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反应数据更好地预测免疫相关的不良事件。这个 建议的“NextGen”POC传感器可提供精致的灵敏度、量化数据和 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.