<p dir="ltr">Cancer diagnosis has been at the forefront of research for decades. Current methods, such as tissue biopsy, are effective at detecting cancer but can be invasive and are often not performed until the cancer has progressed to a mid or late stage. Extracellular vesicles (EVs) are promising novel biomarkers secreted by cells that carry the molecular signatures of their cell of origin, including cancer-associated DNA mutations. These EVs circulate throughout bodily fluids, such as blood, making them strong candidates for minimally invasive and routine disease detection, including cancers. However, there is currently no established method to holistically isolate EVs from serum and extract their nucleic acids for the detection of pathological signals. Here, an innovative microfluidic device is presented that purifies EV-derived DNA (EV-DNA) in situ directly from plasma. The device features an anatase titanium dioxide-coated vertically aligned carbon nanotube (α-TiO<sub>2</sub>:VACNT) structure, which is highly efficient at capturing EVs. The metal oxide coating enables in situ DNA purification, allowing downstream disease detection via digital droplet polymerase chain reaction (ddPCR). The device successfully detected pancreatic cancer using EV-derived DNA directly from clinical patient plasma. This platform is a versatile, minimally invasive diagnostic tool with the potential to enable routine and early disease detection, addressing critical needs in healthcare and improving clinical outcomes.</p>