Nanorobots, which frequently appear in science fiction movies, are groundbreaking and essential tools for future medicine. These very small nanorobots are expected to perform various tasks such as entering the human body to detect and treat diseases. To advance innovative nanorobot technology, the Institute for Basic Science (IBS) Center for Nanomedicine Research Group, led by Director CHEON Jinwoo, has introduced the "Smart Clutch Nanorobot," challenging the paradigm of the convergence research field of nanomedicine that lies at the border of life and machines.

Unique properties hidden behind small size: nano

Self-diagnostic kits used for COVID-19 antigen tests or pregnancy tests utilize a red line to distinguish between positive and negative results. This red-colored sample consists of gold nanoparticles, where target materials of specific diseases bind or adsorb to the particle surface, appearing in the form of a line. Gold is typically yellow in our perception, so how does it turn red? The answer lies in the "nano" size of the particles.

The "nano" in nanoparticle represents a unit indicating one billionth, reflecting an extremely small size. Behind this small size lie hidden special properties and characteristics.

Metal particles like gold and silver, when reduced to nano-scale sizes smaller than the wavelength of light, exhibit colors different from what we commonly perceive. This phenomenon is due to the surface plasmon resonance effect. Metals possess free electrons, and when light shines on metal nanoparticles, the surface electrons resonate strongly with certain wavelengths of light, vibrating collectively as a group. At this point, the nanoparticles absorb that specific wavelength of light and exhibit a new, unconventional color. This color varies depending on the size or shape of the nanoparticle, leading gold nanoparticles to appear red. This altered color is then utilized in diagnostic kits.

[Figure 1] Gold nanoparticles used in self-diagnostic kits (left), surface plasmon resonance effect of gold nanoparticles (right).

Additionally, magnetic materials such as iron oxide exhibit unique properties called superparamagnetism as their size decreases to the nanometer scale. Nanoparticles with superparamagnetism become magnetized particles in the presence of a magnetic field but lose their magnetization rapidly when the surrounding magnetic field disappears, exhibiting a new property where they are no longer magnetic. In other words, even if they are magnetized by an external magnetic field, their direction of magnetization quickly changes back to a disordered state when the external magnetic field disappears. Magnetic nanoparticles are being applied in various fields based on these new characteristics. Especially in the medical field, magnetic nanoparticles are used to transport drug delivery vehicles to specific areas or to enhance imaging in magnetic resonance imaging (MRI). Moreover, in biological research, they are applied in various biological systems such as cell regulation.

[Figure 2] Magnetic nanoparticles behaving as magnetic particles in the presence of an external magnetic field (left), magnetic nanoparticles rapidly changing their direction of magnetization and behaving as non-magnetic particles in the absence of an external magnetic field (right).

Nanorobots turning imagination into reality

In science fiction movies, tiny nanorobots often appear to perform special tasks. They are depicted to locate and treat diseases inside the body or enhance bodily functions. The advancement of nanotechnology is making these imaginations a reality.

Indeed, various nanorobots are being researched and developed through the development of nanotechnology. Interesting design concepts and examples of nanorobots are being presented, which can be powered by external energy sources such as light, sound, electricity, or magnetic fields. Among these external energy sources, magnetic fields are particularly noteworthy in the medical field due to their high biocompatibility and harmlessness to the human body compared to other physical signals.

While nanorobots are still in their infancy compared to microrobots, microrobots larger than nanoscale have been actively developed with various shapes and functions over the past decade. For example, in 2018, Professor Peer FISCHER's team at the Max Planck Institute in Germany developed a micrometer-sized medical robot capable of drug delivery. This microrobot is composed of a head and a helical tail, similar to a tadpole. The head's nickel metal capsule can carry drugs, and the helical tail can propel itself forward under the force generated by an external rotating magnetic field.

[Source: "A swarm of slippery micropropellers penetrates the vitreous body of the eye," Science Advances, 2018]

While the field of nanorobots is still in its early stages compared to microrobots, it is advancing through continuous research and development. One of the most crucial aspects in the early stages of nanorobot development is establishing an engine to power the robot and a system to transmit that power.

Self-operating smart clutch nanorobot

Paper: A magnetically powered nanomachine with a DNA clutch, Nature Nanotechnology, 2024

One of the crucial components in a car, the clutch, is used to transmit power in the transmission system. By using the clutch, we can stop the car without turning off the engine each time, thus efficiently utilizing energy. Interestingly, it has been discovered that bacteria in nature also use biological clutches to control the movement of their flagella. If we can mimic the principles of such clutches, nanorobots could selectively operate and perform various complex tasks with high efficiency.

In 2024, led by Director CHEON Jinwoo (Underwood Distinguished Professor at Yonsei University), the Institute for Basic Science (IBS) Center for Nanomedicine introduced a smart clutch nanorobot with this clutch function. This clutch nanorobot, with a size of 200 nm and 500 times smaller than the thickness of a human hair, consists of an engine, rotor, and clutch. The engine, capable of generating force, is composed of magnetic nanoparticles that can be remotely controlled by an external magnetic field. The rotor is made of porous gold nano-membrane, enabling interaction with the external environment.

Lastly, the clutch made of DNA is programmable and detects various signals generated in the biological microenvironment to regulate the power transmission of the nanorobot. Depending on external environmental factors, the transition between the "off" state, where the engine blocks power transmission, and the "on" state, where the engine delivers power to the rotor, is reversible.

[Figure 3] Structure and operation principle of the smart clutch nanorobot. The clutch nanorobot consists of an engine, rotor, and clutch, with the genetic clutch composed of 20 base sequences capable of encoding nearly infinite (4 to the power of 20) amount of information.

Under the rotating magnetic field, the engine, which rotates according to the magnetic field, generates a torque in the piconewton range, a critical range for cellular stimulation. This force only transfers power to the external rotor in the "on" state, blocking power transmission in the "off" state in the absence of external environmental factors, allowing stimulation of specific cell environments.

The researchers confirmed that the clutch nanorobot's selective power transmission ability could mechanically regulate biological signals. In cases where specific microRNA genes corresponding to disease factors are present, the clutch nanorobot is activated, which causes the activation of gene expression in cells. The DNA clutch is composed of about 20 base sequences, allowing for nearly infinite (4 to the power of 20) programmability of information. Therefore, the newly developed clutch nanorobot can theoretically possess memory and computational functions, enabling intelligent detection of various genetic disease factors.

[Figure 4] Electron microscopy image of clutch nanorobot bound to cells. (Bottom) In the presence of disease factors, the clutch nanorobot generates force, inducing gene activation in cells (activated cells are shown in red fluorescence).

Nanorobots performing various tasks in biological environments

Through the achievements of the IBS Center for Nanomedicine, we can glimpse into the future where nanorobots perform various tasks in biological environments. Although small nanorobots still have a long way to go, their advantage lies in their ability to precisely manipulate at the level of single cells or molecules, making them highly valuable for research and development. By integrating the principles of various mechanical devices, such as the clutch system introduced earlier, it may be possible to perform even more complex tasks. Nanorobots capable of diagnosing and solving problems occurring in biological environments through the fusion of nanotechnology and modern medicine will become groundbreaking and essential tools in future medicine.