Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3835_Библиотеки_им_академика_М_И_Перельмана

applications (Hettiarachchi et al. 2009; Dixon et al. 2013; Chen et al. 2014). Microflu­idics devices produce microbubbles which have a number of unique characteristics. The foremost positive characteristic is that, when operated in a stable regime, they are capable of producing essentially monodisperse (single size) microbubbles. This characteristic has driven the majority of interest in these devices. Unfortunately, microfluidics devices have limited production rates—typically possessing an upper limit in the hundreds of thousands of microbubbles per second range. Since a human intravenous dose may be of the order of several hundred million microbubbles, this presents a practical production challenge. Additionally, and particularly unfortunate when coupled with the previous limitation, the microbubbles have relative low sta­bility (typically tens of minutes). Finally, at least until the present, it has been feasible to produce microbubbles that are generally on the upper bound of what might be tol­erated for intravenous use—i.e., it is challenging to produce microbubbles smaller than approximately 6–8 µm in diameter. However, the limited stability, low produc­tion rate and large diameters are of lesser importance when the device is placed on a catheter tip and the microbubbles are intended to be used in conjunction with applied ultrasound within seconds of dispensation. It can also be argued that relatively large microbubbles can also be better tolerated if the rate of disintegration off-target is suf­ficiently high (e.g., disintegrated within 30 s). Taken together, the characteristics of relatively large microbubbles and rapid off-target disintegration, makes the approach particularly well suited to sonothrombolysis where an aggressive bioeffect mediated by the combination of ultrasound, large microbubbles and thrombolytic drug (typ­ically tissue plasminogen activator), combined with minimal off-target effects, is desired (Dixon et al. 2016). A 1.5 mm diameter prototype microfluidic catheter device has been developed and tested in vitro for the same application (Dixon et al.