Grant: Project Grant

Cells in body release nanoscale particles called extracellular vesicles (EVs). These particles are 10 000-times smaller than a grain of sand and contain proteins and other biological molecules that can indicate the health or disease status of the cell that released them. EVs are constantly being released by cells and we, and others, have shown that they can be readily found in the blood. Just like healthy cells, diseased cells (e.g. cancer cells) also release EVs. The EVs released by diseased cells are different than those released from healthy cells, having their own unique 'barcode.' If there were a way to scan this barcode, we would be able to identify diseases such as cancer by simply scanning through the EVs in the blood. Cancer and other diseases could thus be diagnosed from a simple blood test. We have been working towards detecting diseased EVs by identifying a protein signature that gives them a unique barcode. We scan for this barcode using fluorescent antibodies that bind to the EVs and cause them to 'light up.' A challenge is that EVs may only have 20-30 copies of the proteins of interest, giving a dim signal that is difficult to detect. What is needed is new super- bright fluorescent materials that can bind the proteins of interest and give an easily detectable signal. At present, such methods are lacking. We propose to address this challenge in two ways: (1) the use of advanced fluorescent materials, called "quantum dots" and "polymer dots," to provide larger signals when analyzing EVs via current standard methods; and (2) the novel use of advanced microscopy technology and methods to enable analyses down to the level of just one biological molecule of interest per EV. By developing tools to detect as little as one molecule per EV, we will be able to maximize our ability to find EVs from diseased cells, and use them to diagnose and monitor different diseases from a simple blood test.