Current diagnostic tests in clinics for infectious disease states mostly rely on the variation in the innate immune cell count, which is not entirely predictive of the disease state. Neutrophils and other innate immune cells are multifaceted cells that have a vast array of phenotypes. By quantifying these immune cell phenotypes, we will have a more accurate description of the disease state. To address this, in our work, we engineer a microfluidic device to simulate the in vivo host-pathogen interactions, primarily focusing on Neutrophil-Pseudomonas interactions. Here, we aim to quantify the neutrophil phenotypes such as phagocytosis, swarming and release of NETs (Neutrophil Extracellular Traps) during the pathogen-mediated infection. Our overall goal is to develop a robust, high-throughput microfluidic assay in which the host-pathogen interactions can be quantified in real-time at single-cell resolution in precisely controlled conditions. These microfluidic assays are significant in the context of clinical samples, as they need reagents or samples only in the order of microliters. They are also cost-efficient and easy to set up, with the advantage of being able to monitor the device parameters precisely. Besides, there is a repertoire of signaling molecules or chemokines secreted by the cells in the extracellular matrix, epithelial cells and other leukocytes in vivo that play a significant role in the activation and recruitment of neutrophils to the site of infection. Seeing that traditional assays fail to address the in vivo tissue-specific cell responses, we aim to use this device further to co-culture epithelial cells and other cells in microenvironment such as fibroblasts and resident macrophages to simulate infection-on-chip. Future studies will include incorporating on-chip biosensors to quantify the key regulators triggering the neutrophil decision-making and to mathematically model the host-pathogen interactions with the help of empirical data.

Sharing my research story with the Warm Hearth retirement community in Blacksburg.