Single-cell manipulation technologies have become indispensable tools in modern biology, medicine, and bioengineering. Among various manipulation capabilities, controlled cell rotation is particularly important because it allows researchers to observe cells from multiple viewing angles, enabling three-dimensional reconstruction and detailed characterization of cellular morphology and dynamics. Controlled rotation can also facilitate studies of cell-cell interactions, mechanical responses, and intracellular processes.
Despite substantial advances in optical, magnetic, electric, and acoustic manipulation techniques, achieving programmable rotation of single cells around arbitrary axes remains a significant challenge. Most existing approaches rely on specially engineered beam structures, microfabricated mechanical components, or intrinsic asymmetries of the target objects. As a result, their flexibility is often limited, especially for spherical particles and cells whose rotational axes cannot be defined by geometry alone. Furthermore, dynamically switching between different rotation modes within a single platform has remained largely unexplored.
In a new paper published in Light: Science & Applications, a team led by Prof. Yuebing Zheng from The University of Texas at Austin has developed a programmable opto-thermo-osmotic platform capable of rotating single cells along arbitrary axes and dynamically switching between distinct rotational modes.
The platform is built upon a plasmonic substrate consisting of bovine serum albumin (BSA)-functionalized gold nano-islands (AuNIs). When illuminated by laser light, the AuNIs generate localized temperature gradients that induce strong thermo-osmotic flows at the solid-liquid interface. Meanwhile, polyethylene glycol (PEG) molecules in the surrounding solution produce depletion forces that confine cells near the substrate surface, where the thermo-osmotic flow is strongest.
Using a spatial light modulator (SLM), the researchers can dynamically project programmable laser patterns onto the substrate, thereby tailoring both temperature distributions and flow fields in real time. This capability enables highly flexible control of the forces and torques acting on individual cells.
The researchers first investigated the possibility of arbitrary-axis rotation using spherical polydimethylsiloxane (PDMS) particles. Because spherical particles possess complete geometric symmetry, their rotation axes cannot be determined by shape. Numerical simulations revealed that a single Gaussian laser spot positioned asymmetrically relative to the particle generates a highly non-uniform thermo-osmotic flow field. The resulting hydrodynamic torque can reach sufficient magnitude to drive stable rotation.
By simply changing the position of the laser spot, the direction of the generated torque can be continuously tuned, allowing the particle to rotate about different axes. Experimental observations confirmed the theoretical predictions and demonstrated arbitrary-axis rotation of spherical particles. These results establish that the rotation axis is defined entirely by the engineered flow field rather than by particle geometry.
The researchers then extended the concept to biological cells. Using yeast cells as a model system, they demonstrated two distinct rotational modes that can be selectively activated through optical pattern engineering.
Under a single Gaussian laser spot, the induced thermo-osmotic torque drives the cell to rotate around its major axis. When the laser pattern is reconfigured into a half-ring shape, the optical torque and thermo-osmotic torque act together to reorient the cell and drive continuous rotation around its minor axis.
One of the most remarkable features of the platform is its ability to switch between these rotational modes in real time. In the experiments, the researchers first maintained stable major-axis rotation using a Gaussian beam. When the illumination pattern was changed to a half-ring configuration, the cell rapidly transitioned into minor-axis rotation within less than one second. The entire process occurred without mechanical movement, sample repositioning, or physical contact, relying solely on optical reconfiguration.
To better understand the underlying mechanism, the team combined multiphysics simulations with electromagnetic calculations. Their analysis showed that major-axis rotation is predominantly driven by thermo-osmotic torque, whereas minor-axis rotation arises from the synergistic coupling of thermo-osmotic and optical torques. Together, these torques create a continuous torque landscape that sustains rotation throughout the entire cycle without trapping the cell in stable equilibrium states.
The demonstrated platform offers several important advantages. It operates at relatively low optical power, requires no labeling or modification of cells, and provides exceptional programmability through dynamic optical pattern generation. Unlike many conventional rotational manipulation techniques, it does not depend on complex beam shaping or specialized particle geometries.
The researchers believe that the technique could become a powerful tool for a broad range of biological and biomedical applications. By integrating with confocal microscopy and other advanced imaging modalities, the platform may enable label-free three-dimensional cellular imaging and reconstruction. It could also facilitate studies of cell mechanics, cellular interactions, developmental biology, and drug screening.
Looking forward, the team envisions combining opto-thermo-osmotic manipulation with emerging metasurface and integrated photonic technologies. Such integration could lead to compact, chip-scale platforms capable of high-throughput cellular manipulation and analysis, opening new opportunities for next-generation bioanalytical systems.
