ERI: Developing an Impedimetric Immunosensor for Characterization of Phagocytosis

Every day, the human body generates waste such as damaged cells and cellular debris. The body is also challenged by invading germs from outside. Phagocytosis is an essential immune function where specialized cells (phagocytes) serve as scavengers, swallowing and clearing cellular waste and foreign invaders. The ability to measure phagocytic activity is important for understanding immune function and disease. Common laboratory and clinical methods to measure phagocytosis often rely on fluorescent labels, bulky equipment, and long processing times, which limit rapid testing and continuous monitoring. This ERI project will develop a compact, easy-to-use biosensing platform that measures phagocytosis. It will track small electrical changes in phagocytic cells as they recognize, engulf, and process targets. The long-term goal is a practical tool to help researchers and clinicians evaluate immune function and quickly compare how well natural or engineered phagocytes perform. The project will also provide training opportunities for undergraduate and graduate students at the intersection of biomedical engineering, microfabrication, microfluidics, and machine learning. It will include outreach activities for K-12 students and the public to show how engineering tools can improve healthcare. This EIR project will test the hypothesis that phagocytosis produces dynamic, detectable changes in the electrical/ dielectric properties of phagocytotic cells, particularly in the plasma membrane and cytosol, which can serve as quantitative indicators of phagocytotic activity and functional state. To achieve label-free monitoring, the team will develop an impedimetric immunosensor based on electrical impedance spectroscopy integrated with microfluidic bio-MEMS. Objective 1 will create two switchable sensing modules: (A) a microelectrode-array microfluidic platform for time-resolved, multi-site impedance monitoring during phagocytosis, and (B) an impedance-based microfluidic flow cytometer for single-cell measurements with synchronized optical capture. Signal features will be interpreted using equivalent circuit models to estimate membrane capacitance/resistance and cytosolic properties across phagocytic stages. Objective 2 will integrate electrorotation-enabled 3D cell imaging with impedance cytometry and apply machine learning for 3D reconstruction and phenotype classification, generating paired impedance–image datasets to map electrical signatures to morphology and internalized particle burden. Objective 3 will benchmark sensor performance against fluorescence-activated cell sorting (FACS) and evaluate diagnostic accuracy in blinded clinical samples from systemic lupus erythematosus (SLE) patients, where impaired phagocytosis is implicated, using monocytes/macrophages derived from PBMCs. Outcomes will include new quantitative insight into electrophysiological mechanisms of phagocytosis and a scalable, point-of-care–oriented platform for immunophenotyping, drug screening, and evaluation of engineered phagocytes (e.g., chimeric antigen receptor macrophages). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2550306 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Yuhao Qiang | Institution: University of Maryland Eastern Shore, PRINCESS ANNE, MD | Award Amount: $199,934 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2550306 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2550306.html