Cancer is among the leading causes of morbidity and mortality worldwide, yet about 46% of patients forsake routine screening because of the invasive nature of such procedures, including tissue biopsy. Therefore, there are significant efforts in basic and clinical research to develop a liquid biopsy, a minimally invasive paradigm for the detection of circulating biomarkers from biofluids. Among circulating biomarkers, exosomes, small particles released by cells that help cells communicate with each other, have drawn a great deal of attention. Exosomes are highly abundant in all biofluids including blood, saliva and urine, and they can provide crucial information to the type of cell, such as a tumor cell, that released them. However, using exosomes as biomarkers for cancer and other diseases has been challenging due to the lack a technology that can reliably isolate and characterize exosomes in a cost-effective and timely manner. This research will lead to a rapid and accurate micro-fabricated device that can quickly and cheaply purify and characterize exosomes from biofluids based on their electrical properties. The immediate focus of this project is to isolate and characterize exosomes related to cancer; however, exosomes are associated with many other diseases, including diabetes, cardiovascular disease, infectious diseases and neurodegenerative disorders. Thus, this novel device could be utilized for a wide range of medical diagnoses and biomedical research, potentially providing frequent, affordable, and early testing for patients. Furthermore this interdisciplinary project crosses the traditional boundaries between electrical engineering, micro/nanofluidics, biology and physics, which will provide students with a unique educational experience during their academic training. This project will expose K-12 students to the field of biomedical microsystems through memorable and exciting hands-on projects and active learning experiences. The education plan will broaden the participation of students from underrepresented groups by recruiting and training female scientists and engineers through the Women in Science and Engineering (WISE) program. These undergraduate students will work closely with graduate students to conduct this research, and they will be mentored by the principal investigator. This project will also educate the public about how micro-nanotechnologies can advance medicine through a YouTube channel and “ThinkTV†program, which will be broadcast in Southwest Ohio.
Exosomes (30–150 nm) are released from many cell types into the extracellular space, are distributed in all biofluids. Their compartmental composition and function depend on the originating cell type and they play an important role as a molecular cargo in cell-cell communication. Tumor-derived exosomes have potential use as circulating biomarkers in liquid biopsy for early stage diagnostics and routine clinical monitoring of cancer progression in difficult to access tumor sites. However, rapid and efficient detection of exosomes is challenging owing to their heterogeneity and the complexity of biological samples. The ultimate goal of this CAREER project is to investigate the use of indirect dielectrophoresis (DEP) and impedance probing to purify and identify circulating cancer-derived exosomes from biofluids. This research will employ a novel DEP device on chip to isolate exosomes from biofluids and measure their electrical impedance over a wide frequency spectrum (500 KHz-50 MHz) to establish their dielectric properties. The dielectric properties of the exosomes will then be correlated with their molecular content, biochemical properties, and functionalities in terms of pro-inflammatory responses. This research could ultimately enable minimally invasive liquid biopsies in a clinical setting. It could also open a new avenue for diagnostics and personalized therapeutics based on the ability to quickly isolate and analyze exosomes based on their dielectric properties.
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.
