Enhancing In Vitro Stability of Albumin Microbubbles Produced Using Microfluidic T-Junction Device

Area of Science:

• Biomaterials Science
• Microfluidics
• Chemical Engineering

Background:

• Microfluidic synthesis of microbubbles offers precise control over size and monodispersity.
• Microbubbles synthesized via microfluidics often exhibit limited stability due to rapid core gas dissolution in aqueous environments.
• Enhancing microbubble stability is crucial for various applications, including medical imaging and drug delivery.

Purpose of the Study:

• To develop highly stable, monodispersed albumin microbubbles using microfluidic T-junction devices.
• To investigate the efficacy of combined thermal and chemical cross-linking methods in improving microbubble stability.
• To analyze the structural and dissolution properties of cross-linked albumin microbubbles.

Main Methods:

• Monodispersed albumin microbubbles were generated using a microfluidic T-junction device with bovine serum albumin (BSA) and nitrogen gas.
• Microbubbles underwent chemical cross-linking (CC) with glutaraldehyde and thermal cross-linking (TC) in hot water.
• Dissolution studies in air-saturated water, circular dichroism (CD) spectroscopy, scanning electron microscopy (SEM), and high-speed imaging were employed.

Main Results:

• Combined thermal and chemical cross-linking (TC & CC) resulted in significantly longer microbubble dissolution times compared to CC alone, TC alone, or non-cross-linked microbubbles.
• CD spectroscopy indicated a greater reduction in BSA alpha-helices with TC & CC, suggesting enhanced protein structural changes.
• SEM micrographs showed the thickest shell for TC & CC treated microbubbles, and high-speed imaging revealed shell detachment rather than complete dissolution.

Conclusions:

• Combined thermal and chemical cross-linking is an effective strategy to produce highly stable albumin microbubbles.
• The enhanced stability is attributed to increased shell thickness and altered protein structure, leading to higher resistance to gas permeation.
• These findings pave the way for more robust microbubble formulations for advanced applications.