Cell disruptions using ultrasonic energy transmitted through a flexible int
erface into a liquid region has limitations because the motion of the vibra
ting tip is not completely transferred into the liquid. To ensure that some
degree of contact will be maintained between the ultrasonic horn tip and t
he flexible interface, the liquid must be pressurized. The pressure conditi
ons that yield consistent coupling between the ultrasonic horn tip and the
liquid region were explored in this study by using an analytical model of t
he system and test fixture experiments. The nature of the interaction betwe
en the horn tip and the flexible interface creates pulses of positive press
ure rises, increase in temperature, streaming flow, and almost no cavitatio
n in the liquid. There was sufficient energy to create a cloud of microsphe
res, or beads, that maintain a consistent pattern of ballistic motion in th
e liquid. The sonication was found to be repeatable by studying video recor
dings of bead motion and was shown to be statistically consistent using mea
surements of temperature rise. Sonication of bacterial spores to obtain mea
surements of released nucleic acid and SEM images of damaged spores were us
ed to verify the effects of liquid pressure on the horn-interface-liquid co
upling.