Microbubbles preparation

Thus, the use of gases that possess very low surface tension (e.g., perfluorocarbons) should reduce the pressure against bubble collapse such that the radius of the microbubbles formed would be small. Indeed, perfluorcarbon microbubbles prepared from perfluoropropane or perfluorobutane form bubble diameters on the order of 1 to 2 pm, which are ideal for passing through capillary beds. In addition, because of their extremely low solubility in aqueous media, the perfluorocarbon microbubbles would not dissolve in the venous blood and are therefore less prone to collapse. 

The use of ultrasonic (US) radiation (typical range 20 to 850 kHz) to accelerate Diels-Alder reactions is undergoing continuous expansion. There is a parallelism between the ultrasonic and high pressure-assisted reactions. Ultrasonic radiations induce cavitation, that is, the formation and the collapse of microbubbles inside the liquid phase which is accompanied by the local generation of high temperature and high pressure [29]. Snyder and coworkers [30] published the first ultrasound-assisted Diels-Alder reactions that involved the cycloadditions of o-quinone 37 with appropriate dienes 38 to synthesize abietanoid diterpenes A-C (Scheme 4.7) isolated from the traditional Chinese medicine, Dan Shen, prepared from the roots of Salvia miltiorrhiza Bunge. 

While the microbubbles with an albumin shell were already in development, other groups of researchers investigated the use of surfactants or fipid-stabilized microbubble shells. Pluronic-stabifized renografin-air bubbles were prepared, but their storage stability was unsatisfactory. It required sonication shear mixing immediately prior to administration into experimental animals [18]. Other materials fared considerably better. A combination of a hydrophobic Span and... 

The third chapter is dedicated to contrast agents for ultrasound imaging starting with the design, preparation and application of microbubbles. Additionally, the different presently available generations of contrast agents are... 

An effort was made to better quantitate this suggested preponderance of N-acetylglucosamine and/or N-acetylgalactos-amine in the carbohydrate portion of microbubble glycopeptide surfactant by performing direct HPLC analysis of the monosaccharides contained in the surfactant. This analysis began with the (carbohydrate) hydrolysis of a partially purified preparation containing approximately 30 pg of the proteinaceous microbubble... 

Fig. 4.3. High performance liquid chromatography (HPLC) of the monosaccharides obtained from a partially purified preparation of microbubble glycopeptide surfactant from forest soil. Following hydrolysis (in 2 N HC1 for 6 hr at 100°C) and filtration, the carbohydrate mixture was charged on a Bio-Rad HPX-87 cation exchange column. For comparison, part A shows the chromatogram (using the same HPLC column) of a standard solution, which contained 4 pg of each of three different monosaccharides (i.e., the last three peaks shown are glucose, xylose and fiicose, in the order of increasing retention times). Part B shows the chromatogram obtained from hydrolysis of the partially purified (see text) microbubble surfactant (approximately 30 pg). All other experimental conditions were identical in the two cases, i.e., water eluent, 0.5 ml/min flow rate, 85°C, refractive index detector attenuation -2x. (Taken from ref. 322.)...

The trough itself measured 20 x 12 cm, was milled from a block of Teflon, and held approximately 750 ml of liquid. Monomolecular films were prepared on a subphase of (ultrapure) distilled water or on aqueous subsolutions containing varying concentrations of either NaF, HC1, NaOH, thiourea, or dimethyl sulfoxide (DMSO). Aliquots, between 50 and 250 pi, of the ethanol-solubilized microbubble-surfactant mixture were applied slowly to the surface of the subsolution from a Hamilton microsyringe. It was found unnecessary to allow the films to stand for more than 2 min after spreading before taking measurements. Furthermore, following compression or expansion, the surface pressure was observed to remain constant for periods of up to at least 10 min. All measurements were made at 20.0 0.5°C. 

In summary, while the nonionic surfactant dimethyldo-decylamine oxide forms only spherical micelles even in 0.20 M NaCl (see above and ref. 498), micelles of dimethyloleylamine oxide are subject to a sphere-rod equilibrium in aqueous solutions of NaCl as dilute as 10 4 M and even in water alone (ref. 500). Thus, Imae and Ikeda (ref. 479) conclude the rodlike micelles are stabilized more, as compared with the spherical micelles, when the hydrocarbon chain of the surfactant molecule is longer. This conclusion is, therefore, consistent with the earlier-mentioned belief of these authors that the rodlike micelles are more stable when the polar head group of the surfactant molecule is smaller and the chain length of its hydrocarbon part is longer (ref. 473). Since the surfactants referred to all behave as nonionics, these findings of rodlike micelle production have direct relevance to the formation of artificial gas microbubbles (see Section 10.3) with either the earlier-mentioned surfactant mixture Filmix 3 (see Chapter 9 and Section 10.4) or another, related surfactant preparation (see Section 10.4). 

In conclusion, it is possible to prepare concentrated gas-inwater emulsions using various surfactant mixtures. The artificial, surfactant-stabilized microbubbles produced apparently undergo a cyclical process of microbubble formation/coalescence/fission/dis-appearance, where the end of each cycle is characterized by a collapse of the gas microbubbles into large micellar structures — only to re-emerge soon after as newly formed, gas microbubbles. This cyclical microbubble process is promoted by prior mechanical agitation of, and hence entrapment of macroscopic gas bubbles in, these saturated surfactant solutions. 

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