Flow as a Control Strategy to Promote Biomolecule Nucleation

Area of Science:

• Biophysics
• Chemical Engineering
• Materials Science

Background:

• Biomolecular crystallization is crucial for structure determination and pharmaceutical production.
• Understanding nucleation and growth dynamics in solution flow is key to process optimization.
• Mass transfer, influenced by diffusion and convection, dictates crystal quality and purity.

Purpose of the Study:

• To explain biomolecular crystallization results in solution flow for process optimization.
• To review nucleation and growth in forced and natural convective flows, including microgravity.
• To analyze mass transfer modalities and their impact on depletion zones.

Main Methods:

• Theoretical analysis of diffusion vs. convection-dominated mass transfer.
• Experimental investigation of forced flows (air pressure, pumping, mixing, stirring, shearing).
• Review of studies on natural convection, sedimentation, and microgravity effects.

Main Results:

• Solution flow influences mass transfer, creating biomolecule-depleted or self-purifying zones.
• Flow velocities exceeding buoyancy-driven convection favor heterogeneous nucleation.
• Lower flow velocities lead to predominant bulk nucleation; impurities affect nucleation type.

Conclusions:

• Flow-utilizing strategies can be tailored for specific biomolecular crystallization needs (e.g., X-ray crystallography, XFEL, pharmaceutical production).
• Optimizing flow parameters for nucleation, growth, and cessation stages is feasible.
• Expanding the range of proteins studied in flow crystallization experiments is recommended.