Innovative Droplet Lenses for NextGen Light Sensors of Biomarkers of Inflammation

用于炎症生物标志物下一代光传感器的创新液滴透镜

• 批准号: 10381467
• 负责人: TIMOTHY M SWAGER
• 金额: $ 20.92万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10381467
• 关键词: Acute-Phase Proteins; Address; Adoptive Cell Transfers; Aftercare; Antibodies; Binding; Biological Markers; Blood; Blood Tests; C-reactive protein; CAR T cell therapy; Cancerous; Cause of Death; Cells; Cellular Phone; Cessation of life; Chronic; Clinical; Collection; Communicable Diseases; Complex; Coronavirus; Data; Detection; Development; Devices; Disease Outbreaks; Dyes; Equipment; Event; Fluorocarbons; Future; Goals; Health Personnel; Heart; Home; Hospitals; Hydrocarbons; Immune response; Immune system; Immunotherapy; Individual; Inflammation; Inflammatory; Laboratories; Lead; Light; Liquid substance; Malignant Neoplasms; Malignant neoplasm of lung; Measurement; Microscope; Monitor; Morbidity - disease rate; Morphology; Neurologic Deficit; Optics; Organ; Patient Monitoring; Patients; Persons; Physicians; Physiological; Positioning Attribute; Prognostic Marker; Proteins; Reaction; Reporting; Risk Factors; Serum; Severities; Skin; Surface; Symptoms; Technology; Test Result; Testing; Time; Toxic effect; Training; Water; Whole Blood; Work; base; cancer prevention; cancer therapy; cytokine; cytokine release syndrome; efficacy testing; experience; flu; home test; immune checkpoint blockade; immune-related adverse events; immunoreaction; innovation; lens; light intensity; liquid biopsy; novel; point of care; protein biomarkers; response; sensor; sensor technology; side effect; standard of care; treatment optimization

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.

项目摘要/摘要 虽然免疫疗法的效率可能令人震惊，但主要的副作用是可以确保 过度强大的免疫反应，可能导致器官损伤，神经系统缺陷甚至死亡。 对于汽车T细胞疗法，估计约有20％至40％的患者经历细胞因子 释放综合征（CRS）。鉴于其潜在的严重程度，监测治疗后的患者至关重要 可以采取步骤以治疗过量器官损坏之前治疗CR。而每日血液检查的生物标志物 炎症（C反应蛋白； CRP）在医院的第一周有效地进行 治疗，持续测试是不一致的，dospite的事实是，发病可能发生后几周甚至 治疗几个月。需要的是一个护理设备，以监视已建立的生物标志物 炎。我们可以在传感器开发中迈出大胆的一步来满足这一需求。我们有 开发了新型传感器，这些传感器利用双相液滴充当众多微米尺度镜头以反映 并折射光。具有抗体官能化表面的复杂多液滴可以改变形态 与分析物结合后，提供了强烈的方向光学变化，以响应分子相互作用。 具体而言，分子相互作用会影响传输光（1型传感器）和反射光（2型 传感器）。通过智能手机可以感觉到光强度和方向的这种变化，避免了需要 昂贵又繁琐的设备，并最终使人们与健康之间建立联系 护理提供者。我们的压倒性目标是开发1型和2型传感器，以检测 全血或血清的身体相关水平的炎症。我们还建议测试 集成的发射/吸附染料作为实现多重型的手段。特定目标1是揭示 1型传感器检测CRP的功效。具体目标2是确定2型传感器的效率 反射光，以获得灵敏度CRP。特定目标3是发展多重能力。拥有POC传感器会 不仅可以监测既定的炎症生物标志物，而且还会引起 纵向数据的空前深度。因此，拟议的传感器将向未来的研究打开大门 旨在利用详细的临时响应数据来更好地预测与免疫相关的广告事件。这 建议的“ NextGen” POC传感器为独家灵敏度，定量数据和数据提供了潜力 实时，增加了液滴传感器对癌症治疗和预防产生广泛影响的可能性。