Collaborative Research: Plasmofluidic Nanoantenna-Superlens Biosensor for Single-Cell Functional Immunophenotyping

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Accurate and real-time analysis of the functions of different disease-fighting blood cells is very useful for monitoring the immune status of the human body, as well as evaluating the disease stage and drug efficacy. The objective of this research is to develop a new method that enables single-cell functional immune analysis from droplets of human blood. Such a platform would ultimately provide clinicians a new measurement for quantitatively characterizing the disease-fighting blood cells. The proposed educational plans will have broad impacts on students from various educational levels (K-12, undergraduate, and graduate), genders, and ethnicities. Accurate and real-time analysis of the functions of different immune cell subsets is needed for monitoring the immune status of patients, as well as for evaluating the disease stage and drug efficacy. In particular, quantitative and dynamic profiling of the cytokine secretions from individual immune cells is useful for determining the cellular functional immune phenotype in patients. However, the heterogeneity of the immune cells makes such quantitative characterization challenging especially when dealing with human blood samples. The objective of this research is to develop a new integrated plasmofluidic nanoantenna-superlens biosensing platform that enables single-cell, multi-subset, multiplex functional immune analysis from microliters of human blood. The approach combines an efficient on-chip single immune cell isolation technique and a parallel cell cytokine secretion assay based on the label-free plasmonic nanoantenna-superlens biosensor. The proposed research will be achieved by pursuing the following objectives. 1) development of plasmonic nanoantenna-superlens biosensing platform for rapid and sensitive on-chip cytokine detection; 2) development of microfluidic single cell isolation technique to achieve purification of leukocyte subsets from a heterogeneous mixture found in whole blood; and 3) demonstration of an integrated plasmofluidic nanoantenna-superlens barcode microarray biosensor for multiplex functional immunophenotyping of single immune cells. The analysis performed using the proposed platform for a large number of individual immune cells will establish a new approach that permits immunophenotypical screening of leukocyte subsets by detecting differences and time-dependent variations of their immune functions. Such a platform would ultimately provide clinicians a new tool for quantitatively characterizing the immunophenotypes of patients and would, therefore, allow precise disease diagnosis, monitoring, and risk stratification. The proposed educational plan will have broad impacts on students from different educational levels (K-12, undergraduate, and graduate), genders, and ethnicities. Technologies developed in the proposal will be used as effective vehicles for education and outreach activities. Extending research opportunities to K-12 students and undergraduates will expose them to the rewarding scientific discoveries and encourage them to pursue future studies and careers in engineering.