Releasing genetic biomarkers from cells and tissues with ultrasound

Ultrasound sonoporation has long been investigated as a means of enhancing therapeutic delivery into cells. More recently, however, ultrasound has been explored as means to liberate biomarkers out of cells. I will discuss our past efforts to enhance ultrasound biomarker release using microbubbles and nanodroplets both in vivo and ex vivo. Our recent in vivo work has demonstrated that ultrasound and nanodroplets can enhance extracellular vesicles and tumor DNA/RNA in the blood by 100-1000-fold. Because we can compare post- sonication blood biomarker levels to a pre-sonication blood draw baseline, and because any increase in biomarkers must be due to ultrasound treatment, this approach is a powerful alternative to biopies with much less tissue damage. In a different paradigm, we are exploring contrast-agent-free ablative acoustic mechanisms on a micro-scale to enhance biomarker release even further. Our group is further exploring novel avenues to detect circulating tumor cells in blood samples, where ultrasound treatment is applied to a separated blood fraction. By detecting biomarkers released from circulating tumor cells but primarily absent in blood cells, our approach is sensitive to single cells. Ongoing work in prostate cancer patients suggest promise for sensitive and specific detection of clinically significant prostate cancer. Ultrasound for biomarker release is a promising avenue of research which could lead to many important clinical applications given additional work and validation.