Langmuir 1993,9,2426-2429
2426
Surfactant-Stabilized Microbubbles as Ultrasound Contrast Agents: Stability Study of Span 60 and Tween 80 Mixtures Using a Langmuir Trough S. Singhal,? C. C. Moser,* and M. A. Wheatley'tt Department of Chemical Engineering, Drexel University, Philadelphia, Pennsylvania 19104, and Department of Biophysics and Biochemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 Received February 5, 1993. I n Final Form: July 12,199P The sonication of mixtures of two nonionic surfactants, Span 60 and Tween 80, produces stable microbubbles which are being investigated as contrast agents for use in diagnosticultrasound. The results of a previous unpublished study showed that stabilizationof microbubbles does not occur when only one type of surfactant is used. The work presented here involves a study of the molecular associations of the surfactants around the microbubble "skinmthat lead to stability. The resemblance of this system to a surfactant monolayer at an aidbuffer interface suggested the use of a Langmuir trough to provide insight intothe molecular parametersthat promote stability. Similaritybetween the P-A curve for the microbubbles and curves obtained for solutions of surfactants at a molar ratio of 0.63 indicates there are 1.7 molecules of Span 60 to each Tween 80 molecule. This is further supported by the values obtained for the collapse pressure and area per molecule of microbubbles (40mN/m and 32 A2/molecule)compared with the mixture at a 0.63 M ratio (50 mN/m and 31 A2Imolecule). In addition the same molar ratio was found to produce the highest yield of microbubbles during fabrication. The hypothesis of opposing forces was used to explain these interactions. The numbers suggest that incorporation of the correct proportion of Span molecules between the Tween molecules results in decreased head group repulsion, which lends stability to the microbubble. A molecular arrangement of these surfactant molecules around a microbubble is proposed.
Introduction Diagnostic ultrasound is a noninvasive and safe procedure, widely used by physicians in obstetrics and cardiology, to gain insight into the internal organs of the body. Despite such advances as gray scale imaging and color Doppler, the present images lack the precision to, for example, detect metastatic lesions in organs such as the liver. A novel contrast agent is under development in our laboratory which would improve the resolution of ultrasound imagesthereby enhancing the diagnosticpower of the physician. An ideal contrast agent is one which is safe, stable, small enough in diameter(
