Acoustic holograms for homogeneous hyperthermia over several tumor spheroids

In this work we use 3D printed holographic lenses to enlarge the natural focus of a curved transducer with the aim of producing a uniform region of iso-thermal dose. With this system, we exposed several U87-MG glioma cell spheroids, located inside an IEC tissue mimicking phantom, to a uniform and real-time monitored temperature. Spheroids were exposed with this system until different thermal iso-effective doses (7.5, 30, 60, 120 CEM43) (TIDs) were reached. Also, the effects of ultrasound-delivered hyperthermia on the response of these spheroids were compared with heating using a polymerase chain reaction (PCR) thermal cycler in terms of viability and growth measured on a 10-day schedule. Using acoustic holograms designed to deliver iso-thermal doses, we observe a 6 mm wide uniform region of hyperthermia over the three targets, with temperature differences of less than 3%. In addition, tumor spheroid responses show that ultrasound delivered hyperthermia is more damaging than PCR heating for TIDs ≥ 30 CEM43. This system could help in future in-vitro studies of hyperthermia delivered with ultrasound.