Chinese researchers have developed a new type of micro-robot that transforms ordinary immune cells into precise guided warriors, nothing more than a focused beam of light.
By combining the natural power of immune cells with robotic controllability, a “phagocytator” that can be awakened and guided with a near-infrared laser – a giant cell that can be awakened and guided with a near-infrared laser. The study is published in Science and Applications: How these lightly driven immune microbots look for various threats including bacteria, cancer fragments and plastic nanoparticles in laboratory environments and inside living zebrafish.
The breakthrough solves the basic challenge in medical robotics: how to create controllable microscopic machines that are not rejected by the body’s immune system.
Awakening Cell Warrior
“We wanted to find a way to control immune cells without eliminating their natural advantages,” said Professor Hongbao Xin of Jinan University, the corresponding author of the study. “With this dual-mode optical control strategy, macrophages are still completely natural, but can accurately indicate that they move in vitro and in vivo, seeking and phagocytic threats.”
The process starts by focusing a tightly controlled near-infrared laser beam onto the stationary macrophages – a natural cleaning staff of the immune system. Within a few minutes, local heating effects trigger temperature-sensitive ion channels in the cell membrane, causing calcium to flood the cells.
This calcium tide activates the energy production of cells and causes a series of reactive oxygen species that converts dormant macrophages into active predators and has flexible “arms”, called pseudoworms.
Lightweight and accurate navigation
“It’s like flipping a biological switch with light,” said Xing Li, the first author and doctoral student at Jinan University. “Light is not just moving a cell. It turns a cell into a warrior.”
Once activated, the researchers can control the movement of the phagocytosis by manipulating its extended pseudo-animals with a gentle optic force. Unlike other biological microorganisms that use magnetic or acoustic fields to push the entire cell, this method works at the subcellular level.
“Other biological microorganisms rely on the magnetic field or the acoustic field to push the entire cell, which may inevitably interfere with cell activity and immune state. Instead, this approach works at the subcellular level, guiding only pseudopods,” said Ting Pan, an assistant associate professor of writers at colleagues. “This leaves the rest of its cells undisturbed, mimicking the way immune cells migrate naturally in tissues.”
Hunt for multiple threats
Laboratory testing reveals the significant versatility of Phagobots in targeting different biological threats. Controlled immune cells successfully ate up Staphylococcus aureus, yeast cells, plastic nanoparticles and tumor cell debris for precise accuracy.
The rate of phagocytosis depends on the target size – small particles of bacteria (such as bacteria) take about 2 minutes to consume, while larger targets (such as yeast units) take about 10 minutes. In a demonstration, the researchers programmed a single phagocytator to capture and destroy six different bacterial cells in sequence within 10 minutes.
Key features displayed:
- Activate in 3 minutes using focused 1064 nm laser light
- Rotating controllable steering speed up to 8.7×10⁻³RAD/S
- Navigation speed in living tissue reaches 4.3μm/min
- The size of successful targeting particles ranges from 500 nm to 5μm
- Remove multiple threats in programmable mode
Calcium connection
What makes this approach particularly complicated is its exploitation of the natural activation pathways of macrophages. The study shows that laser-induced heating is specifically targeted at the TRPM2 channel-macrophages used to detect environmental changes in temperature-sensitive calcium channels.
Controlled temperature rises (from 37°C to about 51°C at the laser focus) open these channels without damaging the cells. The influx of calcium produced triggers a series of cellular changes: increased mitochondrial activity, enhanced ATP production, and the production of reactive oxygen species, all the markers of activated immune cells.
This biological authenticity represents a key advantage of traditional micro-robots that rely on artificial materials or genetic modifications, both of which can trigger immune rejection or cause safety issues.
Zebrafish’s life proof
The most compelling experiments from living zebrafish larvae, the researchers successfully activated and controlled natural macrophages without any prior modification. They used clear fish as a natural laboratory, showing that phagocytators navigate in complex tissue environments, including intestinal walls, mucus and intraluminal spaces.
The performance of the in vivo phagocytator is actually better than the laboratory counterpart, achieving higher speeds and more effective targeting. This enhanced performance may stem from a more natural 3D tissue environment that supports optimal macrophage function.
Importantly, the laser capacity used (up to 80 mm) has no adverse effect on zebrafish, and the heart rate returns to normal after exposure to light.
Beyond simple motion control
The difference between this study and typical coverage is the complex mechanisms of phagocytosis activation. The study shows that successful activation requires precise balance of multiple cellular processes simultaneously.
The researchers found that mitochondrial membrane potential increased by about 42% after laser activation, while ATP levels rose by as much as 25% based on laser power. The production of reactive oxygen species increased by 17.5% – creating the perfect cellular storm to enhance immune function.
This multi-parameter optimization ensures that the phagocytator is not only moving, but also metabolized, to improve its search and disruption tasks efficiency.
Medical applications are coming soon
These implications go far beyond laboratory demonstrations. These light-controlled immune robots can revolutionize the treatment of infections, cancers, and inflammatory diseases by providing unprecedented accuracy in the deployment of the immune system.
“This approach overcomes two major bottlenecks in the biological-microbial field: external driving systems can only drive cells to move and require synthetic or genetic modification,” the scientists noted. “It provides a non-genetic platform for in vivo immune interventions, providing promising applications for targeted therapies and precise immune regulation.”
Current challenges include light penetration in deep tissues, which limits applications to accessible areas of the body, or may require advanced optical delivery systems (such as fiber optics). However, the researchers believe that combining optical control with other driving methods can enable long-distance navigation to be fast, while retaining the precise benefits of light control.
The ability to turn the body’s own immune cells into controllable micro-robots represents a fundamental shift in how we treat diseases, rather than introducing foreign bodies, but by giving us natural defense capabilities, they need to work more effectively.
As the research team continues to refine its light phagocytator, we may be witnessing the early stages of a new paradigm where immune cells become our most mature ally in the fight against disease.
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