Sonochemically produced hemoglobin microbubbles

Research output: Contribution to journalArticlepeer-review

Abstract

Using high-intensity ultrasound, we have developed a method for the synthesis of air-filled hemoglobin (Hb) microbubbles (≈2.5 μm in diameter). Transmission electron, scanning electron, and optical microscopy show spherical particles with a shell thickness of approximately 35 nm, or roughly six protein molecules thick. The mechanism of microbubbles formation has been determined to involve both the dispersion of gas into micron-sized bubbles and the chemical cross-linking of cysteine residues between protein molecules. The primary oxidizing agent is superoxide (HO2), which is sonochemically produced from oxygen and water during acoustic cavitation. The Hb microbubbles possess many of the desired characteristics of a blood substitute. The microbubbles are smaller than red blood cells and will not block capillaries. The microbubbles are air-filled and provide a large O2 carrying capacity. The hemoglobins of the microbubbles retain their ability to bind oxygen reversibly. In addition, the oxygen affinities are similar to those of native Hb. Even more surprisingly, microbubbles show extensive cooperativity, as indicated by Hill coefficients as high as 18, which means that in the microbubble shell, there is communication between several of the crosslinked Hb tetramers upon binding oxygen. The Hb microbubbles show minimal degradation (<25%) after storage for six months at 4 °C.

Original languageEnglish (US)
Pages (from-to)89-94
Number of pages6
JournalMaterials Research Society Symposium - Proceedings
Volume372
StatePublished - 1995

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials

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