One-Step Self-Organized Multifunctional Micromotors via Evaporative Liquid-Liquid Phase Separation

Technical Summary: One-Step Self-Organized Multifunctional Micromotors via Evaporative Liquid–Liquid Phase Separation

Problem Statement
Active microcarriers capable of transporting multiple functional components and navigating complex environments are critical for biomedical applications, such as autonomous targeted delivery and the construction of synthetic biomimetic systems. However, the fabrication of such multifunctional microcarriers typically relies on complex, multistep physicochemical processes to incorporate and spatially localize different functional units. These conventional methods often compromise biomolecular activity and introduce significant fabrication complexity, particularly when engineering shape anisotropy for magnetic steering. There is a need for simple, scalable strategies that can simultaneously incorporate diverse functional biomolecules with internal functional architectures, rather than relying on surface coatings or externally imposed structuring.

Methodology
The authors propose a one-step, bottom-up fabrication strategy utilizing evaporation-induced liquid–liquid phase separation (LLPS) in fully aqueous polymer and protein mixtures. The core mechanism involves the evaporation of sessile droplets containing multicomponent mixtures, specifically:

1. Polymer-Protein Systems: Polyethylene glycol (PEG) and Bovine Serum Albumin (BSA).
2. Polymer-Polymer Systems: PEG, Dextran (DEX), and Chitosan (CS).

During evaporation, phase separation occurs near the droplet edge, generating micron-sized condensates. The process is governed by Marangoni flows driven by interfacial tension gradients. These flows, occurring both within the microcondensates and in the surrounding fluid, facilitate the spontaneous encapsulation of biomolecules (enzymes, nucleic acids) and the asymmetric redistribution of nanoparticles. To stabilize the resulting microcondensates into functional particles, the authors employ crosslinking (e.g., glutaraldehyde for BSA/CS or calcium chloride for alginate).

Key Contributions and Mechanisms

• Spontaneous Asymmetry: Unlike traditional lithography or multi-step assembly, this method generates Janus-like internal architectures and shape anisotropy spontaneously. Marangoni-driven hydrodynamic flows capture nanoparticles and drive them to a stagnation point at the downstream pole of the condensate. Interfacial adsorption (Pickering effect) traps these particles, forming a dense, crescent-shaped cluster within an otherwise spherical matrix.
• Internal Magnetic Anisotropy: The asymmetric clustering of magnetic nanoparticles (e.g., magnetite) creates an internal magnetic anisotropy within spherical particles. This allows the particles to align with a uniform magnetic field and experience torque, enabling steering without the need for pre-fabricated anisotropic shapes (like rods or disks).
• Dual-Functionality: The platform simultaneously integrates catalytic propulsion (via enzymes like urease or catalase) and magnetic steering. The catalytic activity generates local concentration gradients for self-diffusiophoretic motion, while the magnetic anisotropy allows for directional control.

Results

• Fabrication and Characterization: The authors successfully fabricated stable microparticles, core-shell structures, and "particle-in-particle" architectures. In PEG-BSA systems, varying BSA concentrations allowed control over particle size and morphology (solid spheres vs. shells). In PEG-DEX-CS systems, the addition of chitosan stabilized the condensates, preventing coalescence and yielding uniform microcondensates (approx. 2.5 µm diameter).
• Encapsulation Efficiency: The system demonstrated high encapsulation efficiencies for various species. Urease and catalase showed efficiencies of 66% and 72%, respectively, while BSA encapsulation reached 87–85%. Nanoparticles and drugs (e.g., carboplatin) were also successfully encapsulated.
• Dual-Driving Dynamics:
  • Gradient-Free Steering: In a uniform magnetic field, the internal magnetic anisotropy suppressed rotational diffusion, allowing chemically propelled particles to maintain directional motion. The magnetic torque aligned the particles, enabling steering even without a magnetic field gradient.
  • Gradient Amplification: In the presence of a magnetic field gradient, the chemical propulsion amplified the magnetophoretic motion, resulting in significantly higher velocities (up to 23 µm/s) compared to magnetic or chemical driving alone.
• Versatility: The method was validated across various systems, including lysozyme, glucose oxidase, and alginate. It was also demonstrated for photocatalytic dye degradation (using graphitic carbon nitride) and drug release (carboplatin from chitosan particles).
• Theoretical Modeling: The authors provided theoretical models based on Langevin equations and hydrodynamic simulations. These models confirmed that Marangoni flows combined with interfacial trapping energy drive the asymmetric clustering of nanoparticles and that magnetic torque can effectively align active particles to suppress rotational diffusion.

Significance and Claims
The paper claims to present a versatile, scalable, and fully aqueous platform for engineering multifunctional active microcondensates. By leveraging simple evaporation-driven LLPS, the method eliminates the need for complex multistep fabrication, lithography, or patterned templates. The spontaneous emergence of internal asymmetry and magnetic anisotropy enables the creation of biocompatible micromotors capable of catalytic propulsion and magnetic steering. The authors assert that this approach offers a robust route for constructing next-generation active drug carriers, biomimetic microsystems, and adaptive synthetic cell-like structures that can navigate complex environments and perform multiple functions simultaneously.