Production of uniformly sized serum albumin and dextrose microbubbles

Abstract

Uniformly-sized preparations with average microbubble (MB) diameters from 1 µm to 7 µm were produced reliably by sonicating decafluorobutane-saturated solutions of serum albumin and dextrose. Detailed protocols for producing and size-separating the MBs are presented, along with the effects that changing each production parameter (serum albumin concentration, sonication power, sonication time, etc.) had on MB size distribution and acoustic stability. These protocols can be used to produce MBs for experimental applications or serve as templates for developing new protocols that yield MBs with physical and acoustic properties better suited to specific applications. Size stability and ultrasonic performance quality control tests were developed to assure that successive MB preparations perform identically and to distinguish the physical and acoustic properties of identically sized MBs produced with different serum albumin-dextrose formulations and sonication parameters. MBs can be stored at 5°C for protracted periods (2 weeks to one year depending on formulation).

Temperature is key to yield and stability of BSA stabilized microbubbles

“…Sonication is normally used for the production of these microbubbles (Borrelli et al, 2012;Cavalieri, Ashokkumar, Grieser, & Caruso, 2008;TchuenbouMagaia et al, 2011TchuenbouMagaia et al, , 2010Zhou, Cavalieri, & Ashokkumar, 2011).…”

“…The initial protein concentration, the pH and ionic strength of the solution, the preheating temperature, the sonication time, sonication intensity and the storage temperature are claimed to play a role (Borrelli et al, 2012;Cavalieri et al, 2008;Zhou et al, 2011). reported that an increase in protein concentration from 0.5% (w/v) to 5.0% (w/v) resulted in an increase in microbubble yield and stability after 14 days.…”

“…reported that an increase in protein concentration from 0.5% (w/v) to 5.0% (w/v) resulted in an increase in microbubble yield and stability after 14 days. According to Borrelli et al (2012), the protein concentration influences the size of the microbubble, with a constant diameter for concentrations between the 3% and 10% and a larger diameter at higher protein concentrations (without specification of the sizes obtained under these conditions). Furthermore, Borrelli et al (2012) claimed that an increase in protein concentration results in higher storage stability.…”

“…According to Borrelli et al (2012), the protein concentration influences the size of the microbubble, with a constant diameter for concentrations between the 3% and 10% and a larger diameter at higher protein concentrations (without specification of the sizes obtained under these conditions). Furthermore, Borrelli et al (2012) claimed that an increase in protein concentration results in higher storage stability. According to , the highest number of microbubbles, when using BSA as shell material, can be obtained at pH 5.…”

Intelligent controlling microbubble radial oscillations by using Slave–Master Feedback control

“…UCAs are constituted from microbubbles filled with gas by a stabilizing layer such as albumin, polymer or lipids, only a few microns in diameter (1-to 10-lm diameter) usually administered to a patient by intravenous injection [1][2][3]. One of main applications of UCAs is to develop the imaging or the blood flow [4].…”