The objective of the proposed research is a biosensor platform to quantify the innate ability of human blood cells to combat pathogens (a phenomenon known as phagocytosis). Knowing phagocytic activity of blood cells is critical to determine the effectiveness of our immune system (body’s natural defense) to kill the pathogens potentially leading to stratify the high-risk individuals. Current clinical instruments are inadequate to perform phagocytosis monitoring in a rapid, automated way and requires extensive staff training, manual sample processing, long wait times, and huge cost per test. To address this unmet need, this project will design and fabricate a biosensor capable of quantifying phagocytosis requiring only a drop of blood. The project is at the nexus of micro-nano sensing, biomedical engineering, bioelectronics, microfluidics, machine learning and disease diagnostics. In proposed microfluidic biosensor, blood cells will interact with the functionalized microbeads (mimicking pathogens) and perform the phagocytosis. Different magnetic field configurations within microfluidic device will modulate the cells fluidic behavior accordingly which will in turn be identified and quantified using micro electrodes built on chip. The proposed biosensor will advance biomedical and device research and will have great potential to benefit human healthcare. This project will train undergraduate and graduate students in the fields of bioelectronics, microfluidics, and machine learning. The project will also enable the integration of proposed research into PI’s educational efforts. Further, PI’s outreach activities will include engaging K-12 students, the local health-care industry, and the general public through educational lectures and making them available online for broad dissemination of knowledge.
The proposal will enable the development of a next generation in-vitro diagnostic platform equipped with Electronic-Sensing & Magnetic-Modulation (ESMM) modules integrated in a microfluidic chip to quantify the human blood cells ability to kill pathogens. The heterogeneity of the immune system activation in response to pathogenic infections is critical to strategize the correct clinical response to treat the patients. Quantifying blood cells natural ability to kill pathogens i.e., phagocytosis is critical to demonstrate the effectiveness of individual’s response in combating pathogens. Further, the ability to engineer/ modulate the phagocytic activity will tremendously improve the therapeutic outcomes for the infected patients. This project aims to develop a novel personalized biosensor capable of not only quantifying the phagocytic ability but also will determine appropriate therapeutics to improve phagocytes ability to kill the pathogens. The biosensor is equipped with microfluidics, microelectrodes for electronic sensing, and quadrupole magnetic configuration to modulate the blood cells behavior on-chip. Blood cells will interact with antibody conjugated magnetic particles and will perform phagocytosis on-chip. Furthermore, the proposed biosensor will be equipped with real-time data analysis using machine learning to improve the sensor performance. The proposed sensor will enable stratification of immune response of infected patients requiring only a drop of whole blood with a rapid time to result (TOR). Sensors will be benchmarked with patient clinical samples. Sensor will have the capability to be used at the point-of-care at multiple health-care settings.
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.
