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.
Innovative Droplet Lenses for NextGen Light Sensors of Biomarkers of Inflammation
Year of Award:
Molecular & Cellular Analysis Technologies
SWAGER, TIMOTHY M
MASSACHUSETTS INSTITUTE OF TECHNOLOGY