Scientists Turn Immune Cells Into Light-Controlled Robots

Chinese researchers have developed a new type of microrobot that transforms ordinary immune cells into precision-guided warriors using nothing more than focused light beams.

The “phagobots”—macrophage cells that can be awakened and steered with near-infrared laser light—represent a major advance in biomedical robotics by combining the natural power of immune cells with robotic controllability. Published in Light: Science & Applications, the research demonstrates how these light-powered immune microrobots can hunt down and destroy various threats including bacteria, cancer debris, and plastic nanoparticles both in laboratory settings and inside living zebrafish.

The breakthrough addresses a fundamental challenge in medical robotics: how to create controllable microscopic machines that won’t be rejected by the body’s immune system.

Waking Up Cellular Warriors

“We wanted to find a way to control immune cells with the same precision as machines, but without taking away their natural strengths,” said Professor Hongbao Xin from Jinan University, the study’s corresponding author. “With this dual-mode optical control strategy, macrophages remain completely natural, yet they can be precisely instructed to move, seek, and phagocytosis of bio-threats both in vitro and in vivo.”

The process begins by focusing a tightly controlled near-infrared laser beam onto resting macrophages—the immune system’s natural cleanup crew. Within minutes, the localized heating effect triggers temperature-sensitive ion channels in the cell membrane, causing calcium to flood into the cell.

This calcium surge activates the cell’s energy production and leads to a burst of reactive oxygen species, transforming the dormant macrophage into an active predator complete with flexible “arms” called pseudopodia.

Light-Guided Precision Navigation

“It’s like flipping a biological switch with light,” said Xing Li, the paper’s first author and PhD student at Jinan University. “The light doesn’t just move the cell. It turns the cell into a warrior.”

Once activated, the researchers can control the phagobot’s movement by manipulating its extended pseudopodia with gentle optical forces. Unlike other bio-microrobots that push entire cells around using magnetic or acoustic fields, this approach works at the subcellular level.

“Other bio-microrobots that rely on magnetic or acoustic fields to push entire cells, which may inevitably disturb cell activity and immune state. On contrast, this method works at the subcellular level, guiding only the pseudopodia,” explained co-corresponding author Associate Professor Ting Pan. “This keeps the rest of the cell undisturbed, mimicking how immune cells naturally migrate in tissue.”

Hunting Down Multiple Threats

Laboratory tests revealed the phagobots’ remarkable versatility in targeting different biological threats. The controlled immune cells successfully engulfed Staphylococcus aureus bacteria, yeast cells, plastic nanoparticles, and tumor cell debris with impressive precision.

The speed of engulfment depended on target size—smaller particles like bacteria took about 2 minutes to consume, while larger targets like yeast cells required around 10 minutes. In one demonstration, researchers programmed a single phagobot to sequentially hunt down and destroy six different bacterial cells within 10 minutes.

Key Capabilities Demonstrated:

• Activation within 3 minutes using focused 1064-nm laser light
• Controllable steering with rotation speeds up to 8.7 × 10⁻³ rad/s
• Navigation speeds reaching 4.3 μm/min in living tissue
• Successful targeting of particles from 500 nm to 5 μm in size
• Sequential elimination of multiple threats in programmable patterns

The Calcium Connection

What makes this approach particularly sophisticated is its exploitation of the macrophages’ natural activation pathway. The research reveals that the laser-induced heating specifically targets TRPM2 channels—temperature-sensitive calcium channels that macrophages use to detect environmental changes.

The controlled temperature increase (from 37°C to approximately 51°C at the laser focus point) opens these channels without damaging the cell. The resulting calcium influx triggers a cascade of cellular changes: increased mitochondrial activity, enhanced ATP production, and the generation of reactive oxygen species—all hallmarks of an activated immune cell ready for action.

This biological authenticity represents a crucial advantage over traditional microrobots that rely on artificial materials or genetic modifications, both of which can trigger immune rejection or raise safety concerns.

Living Proof in Zebrafish

The most compelling demonstration came from experiments in living zebrafish larvae, where researchers successfully activated and controlled native macrophages without any prior modification. Using the transparent fish as a natural laboratory, they showed phagobots navigating through complex tissue environments including intestinal walls, mucus, and luminal spaces.

The in-vivo phagobots actually performed better than their laboratory counterparts, achieving higher speeds and more efficient targeting. This enhanced performance likely stems from the more natural 3D tissue environment that supports optimal macrophage function.

Importantly, the laser powers used (up to 80 milliwatts) showed no adverse effects on the zebrafish, with heart rates returning to normal after light exposure ended.

Beyond Simple Movement Control

What distinguishes this research from typical coverage is the sophisticated mechanism underlying phagobot activation. The study reveals that successful activation requires a precise balance of multiple cellular processes occurring simultaneously.

The researchers discovered that mitochondrial membrane potential increases by approximately 42% following laser activation, while ATP levels rise by up to 25% depending on laser power. Reactive oxygen species production jumps by 17.5%—creating the perfect cellular storm for enhanced immune function.

This multi-parameter optimization ensures that phagobots aren’t just mobile—they’re metabolically primed for maximum efficiency in their search-and-destroy missions.

Medical Applications on the Horizon

The implications extend far beyond laboratory demonstrations. These light-controlled immune robots could revolutionize treatment of infections, cancer, and inflammatory diseases by providing unprecedented precision in immune system deployment.

“This approach overcomes the two major bottlenecks in the field of bio-microrobots: external driving systems can only drive the cells to move and the need for synthetic or genetic modifications,” the scientists noted. “It provides a non-genetic platform for in vivo immune intervention, offering promising applications in targeted therapy and precision immunomodulation.”

Current challenges include light penetration in deep tissues, which limits applications to accessible body regions or may require advanced optical delivery systems like fiber optics. However, the researchers suggest that combining optical control with other actuation methods could enable rapid long-distance navigation while preserving the precision benefits of light-guided control.

The ability to turn the body’s own immune cells into controllable microscopic robots represents a fundamental shift in how we might treat disease—not by introducing foreign materials, but by giving our natural defenses the guidance they need to work more effectively.

As the research team continues refining their light-powered phagobots, we may be witnessing the early stages of a new medical paradigm where immune cells become our most sophisticated allies in the fight against disease.