Author: Huang Tianyun (Researcher at the Department of Advanced Manufacturing and Robotics, School of Engineering, Peking University, China Key Laboratory of Micro-Nano Processing Technology, and State Key Laboratory of Turbulence and Complex Systems)

For humans, the microscopic world still has many mysteries - whether it is the water bear, the most tenacious microorganism on earth, or the micron-sized E. coli known as the "microbial factory", or even the nano-sized bacteriophage that can parasitize in E. coli, and the molecular gene encoding DNA that contains the mysterious origin of life, people know very little about them. For nearly half a century, people have been eager to create a micro robot that can enter the microscopic world, put on the "soft armor" of water bears, sneak into the "brain" of E. coli, listen to the "whispering" of bacteriophages, command genes to synthesize proteins, and work with cells to complete the evolution of life, and "see" what is happening in the microscopic world on behalf of humans. Perhaps in the near future, this wish can be realized - micro-nano robots.

A Unique Microscopic World

The microscopic world is a magical and unknown "blessed land" with many incredible and magical scenes. As the size decreases, the microscale space-time effect gradually emerges. Here, the ratio of the surface area of an object to its volume increases in inverse proportion, which means that in the microscale world, the dissipation of energy is more intense, the metabolism of living organisms is accelerated, and the life cycle is shortened; the low Reynolds number characteristics of the microfluidic environment show that the viscosity is dominant, the inertial force can be ignored, and the object is like being placed in very viscous honey. At the nanoscale, objects will also be subject to stronger intermolecular interactions, such as van der Waals forces. At this time, the gravitational force on the object can be approximately ignored, and at the same time, the mechanical collision of molecules is more significant, and the irregular Brownian motion is relatively more intense.

In this seemingly extremely harsh microscopic world, there are a wide variety of tiny intelligent bodies, which show tenacious vitality and strange functions. For example, water bears are a type of microscopic invertebrates with a body length of sub-millimeter. With their unique physiological structure and powerful gene repair ability, they can show their unique "unique skills" when the environment deteriorates, so as to withstand extreme environments such as extreme heat and drought, extreme freezing close to absolute zero, high altitude hypoxia, deep sea high pressure, and high dose radiation in outer space. In the microbial world that is difficult to distinguish with the naked eye, there are also an astonishing number of micron-sized single-cell organisms, such as protozoa, bacteria, fungi, mycoplasmas, chlamydia, etc. They are widely distributed in nature and are closely related to human production, life and survival. In addition, viruses, which are composed only of nucleic acid molecules and protein protective shells, are generally considered to be non-living things because they do not have a complete cell form and cannot complete metabolism independently without the host. However, they have the ability to selectively adsorb hosts and complete self-replication and proliferation with the help of raw materials provided by host cells after invasion, showing amazing collective intelligence and behavior.

Not only that, the operation of the microscopic world is highly organized. As we all know, cells are the basic units that make up organisms, and their interior is more like a complex, busy, but well-organized "micromachine factory". The cell nucleus is the control center of the factory, where DNA containing information coding is replicated and transcribed into mRNA under the catalysis of enzymes. After splicing and modification, mRNA enters the cytoplasm, is translated in the protein synthesis workshop-ribosome, and many single amino acids are assembled into long protein chains. These proteins are then packaged and modified, and transported to the designated area by the "freight locomotive" kinesin using microtubules as guides. The locomotive power is provided by the molecular fuel cell ATP produced by oxidative metabolism of the "power station" mitochondria in the factory. How the entire operation process of this micromachine factory can be so precise, controllable and efficient has always been the ultimate mystery of life that scientists hope to solve. This is of great significance to revealing the mysteries of microscopic life, improving the efficiency of biosynthesis, and improving the direction or path of biological metabolism, and can provide important technical support and material guarantee for the sustainable development of mankind in the future.

Micro-nano robots born to explore the microscopic world

Nature is so amazing that it can build such exquisite intelligent life forms as DNA, ribosomes, bacteriophages, E. coli, etc. at the micro-nano scale. In engineering, scientists are also trying to imitate the way of nature, creating similar artificial intelligent bodies at the microscale level, using them to enter the microscale, participate in regulating the growth and evolution of life at different stages in all dimensions, and finally achieve self-organization through the interaction and coordination between these artificial micromachines and organic life forms, and emerge controllable systematic macroscopic behaviors.

Here, let's roughly define "micro-nano robots": they are a kind of intelligent micromechanical system, usually with a size ranging from sub-millimeter to tens of nanometers, and are considered to be used to adaptively and autonomously complete controllable micro-operations in complex microscale environments.

The miniaturization of machines provides a new perspective and effective tools for exploring the microscopic world. The development of micro-nano robot technology is of great significance to exploring the mysteries of life. In terms of scientific research and exploration, as one of the important branches of advanced robotics, micro-nano robotics is an emerging interdisciplinary subject that integrates many major scientific issues and cutting-edge hot technologies, covering physics, chemistry, biology, mechanics, materials science, micro-nano manufacturing, micro-electromechanical systems, robotics, microdynamics, microelectronics, information and control, bioengineering, biomedicine, clinical medicine and other disciplines.

Speaking of the history of micro-nano robots, we can perhaps trace it back to the 1960s. Richard Feynman, an American theoretical physicist and Nobel Prize winner in physics, first mentioned nanotechnology in a speech at the California Institute of Technology on December 29, 1959. He described this magical technology as follows: "There is enough room at the bottom." This epoch-making statement not only laid the foundation for the concept of nanotechnology, but also foreshadowed the arrival of the era of micro-nano robots and nanomedicine.

According to Feynman, his doctoral student at the time, Albert Hibbs, first proposed the bold idea of "devouring surgeons" and pointed out that "perhaps some tiny machines can be permanently implanted in the body to assist certain organs with insufficient functions to work properly." This "crazy" idea was later adapted into a plot that used miniaturization technology to shrink submarines to the size of microorganisms and inject them into the human body to repair brain damage, and was made into the famous science fiction movie "Fantastic Voyage".

It is worth mentioning that this idea of entering the body in a miniature form had similar plots as early as the "Journey to the West" written in the middle of the Ming Dynasty in ancient China. For example, Sun Wukong transformed into a flying insect and drilled into the belly of Princess Iron Fan, and the Ruyi Jingu Bang could change the size at will. The "Legend of Immortals¡¤Hu Gong" written by Ge Hong in the Eastern Jin Dynasty of China also mentioned a similar spell of miniaturization of time and space: "(Fei Chang) Fang has a magic skill that can shrink the earth veins, and the existence of thousands of miles is clear at present."

Half a century later, in 2008, Feynman's wonderful idea was finally successfully realized by the research team of the Swiss Federal Institute of Technology in Zurich - artificial "magnetic mites". The size of this mechanical mite is sub-millimeter. Under the control of a high-frequency oscillating magnetic field, it converts the inertial impact generated by the collision of misaligned magnetic blocks into a forward thrust, thereby achieving precise control of tiny objects. In 2009, the team developed an artificial "bacterial flagellum" by mimicking the spiral motion of Escherichia coli. This three-dimensional micro-helix made by the self-curling technology of nano-heterogeneous films can achieve precise targeted drug delivery under the control of a low-field rotating magnetic field.

Early research focused more on exploring how to design micro-actuators that convert various forms of energy into mechanical energy, so they are often figuratively referred to as micro-nanomotors. In recent years, with the rise of soft matter materials, micro-nano additive manufacturing, and artificial intelligence, micro-nano robotics has begun to develop from the functionalization of a single structure to the intelligent direction of adapting machines to complex microscale environments and multi-task requirements.

Today, the research on micromachine intelligence has taken shape, including micro-power and precision operation, micro-mechanical gain, software adaptability, compliant continuum, modular reconstruction, information storage and processing, hybrid hybrid advantage, bionics and optimization, microsystem integration, self-organizing interaction and swarm intelligence, as well as molecular self-assembly/replication/growth and other hot directions. At present, the most cutting-edge work in this field is trying to explain or solve the core problem of how to give machines real intelligence at the microscale, which points to the ultimate goal and highest stage of micromachine functionalization: micromachine intelligence, or microscale artificial intelligence.

With broad application prospects

In recent years, emerging advanced materials and nanotechnology have promoted the rapid development of the field of micro-nano science, and the research involves many cutting-edge directions, from controllable self-assembly molecular motors and DNA origami at the molecular level to composite mechanical transmission devices at the micro-nano scale, reconfigurable flexible variant micromachines, hybrid biomechanical systems, integrated microelectronic micromachines, interactive nano brain-machine interfaces, and millimeter-scale microrobots such as flapping-wing mechanical insects. These artificial micro-machines have unique advantages such as small size, non-destructive minimally invasive, ultra-light and portable, precise control, high functional integration, and easy large-scale manufacturing. They also have micro-scale properties such as ultra-high sensitivity and responsiveness, enhanced stability and robustness, and extremely low energy consumption. They have irreplaceable driving force for technological innovation and scene expansion in many fields such as precision medicine, environmental engineering, intelligent manufacturing, life sciences, and artificial intelligence.

In medicine, micro-nano robots have great potential in precision medicine fields such as minimally invasive intervention, targeted transportation, rapid treatment, early diagnosis, and tissue repair. For example, micro-nano robots are used to enter liver and kidney tumors, brain aneurysms, and peripheral tissues and organs to embolize and remove blood clots from tiny blood supply arteries, enter and precisely control the central nervous system through the subarachnoid space, achieve pain control in the treatment of advanced cancer, and use implantable multi-sensor systems to monitor physiological signs in vivo.

In addition, micro-nano robots can also play an important role in environmental engineering fields such as river and sea sewage purification, air pollution prevention and control, and biodegradation and catalysis in the future. These tiny intelligent bodies can self-organize and cluster under the drive of external fields to precisely control the local flow field micro-disturbance, respond to specific environmental conditions, and selectively identify pollutants by carrying, transporting and releasing biological enzymes or catalysts, accelerate the reaction process, and greatly improve the capture, removal, degradation or repair efficiency of organic molecules, toxins/nuclides, marine oil pollution, pathogenic microorganisms, microplastics, heavy metals and radioactive pollutants.

Due to their small size, micro-nano robots have extremely high spatial freedom and super-redundant dexterity. They can sneak into confined spaces that traditional robots cannot reach to complete refined operations. They have unique advantages in high-end equipment manufacturing fields such as complex three-dimensional metamaterial processing, microelectronic circuit assembly and packaging, and micro-cavity detection and maintenance. It is particularly worth noting that whether humans can build a "protein synthesis factory" similar to that in cells at the microscale depends on how to construct a highly recognizable DNA code for the controllable assembly of amino acids to accurately guide the orderly synthesis of proteins. Existing studies have shown that nanomagnetic editing technology can embed multimodal variant information into micromachines at nanoscale precision, and its more important value lies in the fact that nanomagnetic encoding can be used to construct base pairing similar to the DNA double helix. Therefore, the organized division of labor of micro-nano robots can efficiently and orderly carry out the controllable assembly of various functional micro-units. In the future, it is expected that this technology will be used to truly realize the "micromachine factory" where "machines make machines" at the microscale.

Of course, the stage of micro-nano robots is far from limited to this, and it has unlimited potential for various practical applications. We now have many questions that we cannot find ideal answers to, but each question is so fascinating: Can DNA molecular computers surpass quantum computers? What is the minimum size of micro-aircraft, micrometers or even nanometers? What is the physical limit of artificial intelligence? Is the smallest intelligent unit a single hydrogen and oxygen molecule? Nano doctors and long-term in vivo implantation, nano brain-machine interfaces and single nerve precision control, how to achieve cross-scale interaction... The resulting revolutionary subversive technologies will be the most promising development direction of micro-nano robots in the future.

Micro-nano robots no longer exist only in science fiction movies. Scientists from all over the world are actively promoting them from basic research to real practical application scenarios. People are full of imagination and expectation that it will one day benefit mankind and transform the world. Despite this, we need to be soberly aware that the field of micro-nano robots has just started, and extensive multidisciplinary cross-border will bring more thorny problems of integrated innovation. It is also necessary to actively guide scientists in the most cutting-edge fields of different disciplines at the national level to deeply collaborate and tackle key problems, and quickly promote high-quality development in the field of micro-nano robots. To develop advanced micro-nano manufacturing and robotics technology for the next generation of intelligent micromachines, we must be guided by major national needs, leverage the intelligence and miniaturization of machines, equipment, and systems, and focus on exploring the basic theories and key technologies for the realization of intelligent micromachines, driving the rapid development of the field of micro-nano robots, seizing the commanding heights of science and technology, and safeguarding the core interests of the country.

Guangming Daily (16th edition, November 16, 2023)

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