Author: Huang Tianyun (researcher, Department of Advanced Manufacturing and Robotics, State Key Laboratory of Micro-nano Machining Technology, State Key Laboratory of Turbulence and Complex Systems, Peking University Institute of Technology)
For human beings, there are still many puzzles in the micro world — — Little is known about water bear worm, the most tenacious micro-organism on the earth, micron-scale Escherichia coli known as "microbial factory", even nano-scale phage that can parasitize in Escherichia coli, and DNA encoded by molecular genes containing mysterious origin of life. For nearly half a century, people have been eager to create a micro-robot that can enter the micro-world, put on the "soft hedgehog armor" of water bears, sneak into the "brain" of E.coli, listen to the "whisper" of bacteriophages, direct gene synthesis of protein, cooperate with cells to complete the evolution of life, and "see" what happened in the micro-world instead of human beings. Maybe in the near future, this wish will come true — — Micro-nano robot.
The microscopic world with a unique hole in the sky
Micro-world is a magical and unknown "land of bliss", and there are many incredible magical scenes. With the decrease of size, the micro-scale spatio-temporal effect gradually appears. Here, the surface area of an object increases in inverse proportion to the volume ratio, which means that in the micro-scale world, the energy dissipation is more intense, the metabolism of living beings is accelerated, and the life cycle is shortened; The low Reynolds number characteristics of microfluidic environment show that viscous force is dominant, inertial force can be ignored, and the object seems to be placed in very viscous honey. At the nanometer scale, objects will be subjected to more intense intermolecular interactions, such as van der Waals force. At this time, the action of gravity on the object can be approximately ignored, at the same time, the mechanical collision of molecules is more obvious, and the irregular Brownian motion is relatively more intense.
In this seemingly extremely harsh micro-world, there are many kinds of tiny agents, which show tenacious vitality and strange functions. For example, the water bear worm is a kind of submillimeter-long micro invertebrate. With its unique physiological structure and powerful gene repair ability, it can show its unique hidden "stunts" when the environment deteriorates, so as to withstand extreme environments such as extreme heat and drought, extreme cold and freezing near absolute zero, high altitude hypoxia, deep-sea high pressure and high-dose radiation in outer space. In the microbial world, which is difficult to distinguish with naked eyes, there are still a surprising number of micron-sized single-celled organisms, such as original vivid plants, bacteria, fungi, mycoplasma, chlamydia and so on. They are widely distributed in nature and are closely related to human production, life and survival. In addition, viruses composed only of nucleic acid molecules and protein’s protective shell, because they do not have complete cell morphology and are separated from the host, can not independently complete metabolism, and are usually considered as nonliving. However, they have the ability to selectively absorb the host and complete self-replication and proliferation with the help of the raw materials provided by the host cells after invasion, showing amazing swarm intelligence and behavior.
Moreover, the operation of the micro-world is highly organized. As we all know, cell is the basic unit of organism, and its interior is more like a complex and busy but well-organized "micro-machine factory". The nucleus is the control center of the factory, where the DNA encoded by information is copied and transcribed into mRNA under the catalysis of enzymes. After splicing and modification, the mRNA enters the cytoplasm and is in the synthesis workshop in protein — — Translation is carried out in ribosomes, and many individual amino acids are assembled into protein long chains. These protein are packaged and decorated, and the protein driven by "freight locomotive" is transported to the designated area with microtubules as guide rails. The locomotive power is provided by the molecular fuel cell ATP produced by oxidative metabolism of mitochondria in the "power station" in the factory. How to make the whole operation process of this micro-machine factory so accurate, controllable and efficient has always been the ultimate mystery of life that scientists hope to solve. It is of great significance to reveal the mystery of micro-life, improve the efficiency of biosynthesis and improve 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 for exploring the micro-world.
Nature is ingenious, and it can build such exquisite intelligent life bodies as DNA, ribosome, phage, Escherichia coli and so on on the micro-nano scale. In engineering, scientists are also trying to imitate the way of nature, create similar artificial agents at the micro-scale, use them to enter the micro-scale, participate in regulating the growth and evolution of life in different dimensions and stages, and finally realize self-organization and emerge controllable systematic macro-behavior through the interaction between these artificial micro-machines and organic life.
Here, let’s roughly define "micro-nano-robots": they are intelligent micro-mechanical systems, usually ranging in size from submillimeter to tens of nanometers, and are considered to be used to adaptively and autonomously complete controllable micro-operations in complex micro-scale environments.
The miniaturization of machines provides a new perspective and an effective tool to explore the micro-world, and the development of micro-nano robot technology is of great significance to explore the mysteries of life. In terms of scientific research and exploration, as one of the important branches of advanced robotics, micro-nano robotics is a new interdisciplinary subject with many major scientific problems and cutting-edge hot technologies, covering physics, chemistry, biology, mechanics, materials science, micro-nano manufacturing, micro-electromechanical systems, robotics, micro-dynamics, microelectronics, information and control, bioengineering, biomedicine, clinical medicine and many other disciplines.
Speaking of the history of micro-nano robots, we may date back to the 1960s. Richard feynman, an American theoretical physicist and Nobel Prize winner in physics, first mentioned nanotechnology in a speech delivered at California Institute of Technology on December 29th, 1959. He described this magical technology as follows: "There is enough space at the bottom". This epoch-making exposition not only established the concept of nanotechnology, but also heralded the arrival of micro-nano robots and nano-medicine era.
According to Feynman, Albert Hibbs, his doctoral student at that time, first put forward the bold idea of "devouring surgeons" and pointed out that "it may be possible to permanently implant some tiny machines in the body to help some organs with insufficient functions work normally". This "crazy" idea was later adapted into the plot of reducing the submarine to the size of microorganisms and injecting it into the human body to repair brain damage through miniaturization technology, and it was made into the famous sci-fi movie Fantasy Voyage.
It is worth mentioning that this idea of entering the body in miniature had a similar plot as early as in The Journey to the West, a book written in the middle of Ming Dynasty in ancient China. For example, the Monkey King turned into a flying insect and drilled into the belly of an iron fan princess, and he could change his size as he pleased. The fairy tale Hu Gong written by Ge Hong in the Eastern Jin Dynasty in China also mentioned a spell similar to miniature space-time: "(Fei Chang) The room has magical power, which can shrink the pulse of the earth and exist thousands of miles away, but it is now natural."
Half a century later, in 2008, Feynman’s wonderful idea was finally successfully realized by the research team of Swiss Federal Institute of Technology in Zurich — — Artificial "magnetic mite" The size of this mechanical mite is in the sub-millimeter level. Under the control of high-frequency oscillating magnetic field, the inertial impact generated by the collision of dislocated magnetic blocks is transformed into the forward driving force, so as to realize the precise control of tiny objects. In 2009, the team developed an artificial "bacterial flagella" through the spiral motion of bionic Escherichia coli. This three-dimensional micro-spiral made of nano-heterogeneous film self-curling technology can complete accurate targeted drug delivery under the control of 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 it is often called micro-nano motors figuratively. In recent years, with the rise of soft materials, micro-nano additive manufacturing and artificial intelligence, micro-nano robotics has begun to develop from a single structure to an intelligent direction to adapt machines to micro-scale complex environment and multi-task requirements.
Nowadays, the research of micro-machine intelligence has taken shape, including micro-power and precise operation, micro-mechanical gain, software adaptability, flexible continuum, modular reconstruction, information storage and processing, hybrid hybrid advantages, bionics and optimization, micro-system integration, self-organizing interaction and swarm intelligence, and molecular self-assembly/replication/growth. At present, the most advanced work in this field is trying to explain or solve the core problem of how to give machines real intelligence at the micro scale, which points to the ultimate goal and the highest stage of micro-machine functionalization: micro-machine intelligence or micro-scale artificial intelligence.
It has broad application prospects.
In recent years, the emerging advanced materials and nanotechnology have promoted the rapid development of micro-nano-science. The research involves many frontier directions, such as controllable self-assembled molecular motors and DNA origami at molecular level, composite mechanical transmission devices at micro-nano scale, reconfigurable flexible variant micro-machines, hybrid electromechanical systems, integrated micro-electronic micro-machines, interactive nano-brain-computer interfaces, and millimeter-scale micro-robots such as flapping-wing mechanical insects. These artificial micro-machines have the unique advantages of small size, non-destructive and minimally invasive, ultra-light and portable, accurate control, high functional integration, easy to manufacture on a large scale, and micro-scale performance such as ultra-high sensitivity and responsiveness, enhanced stability and robustness, and extremely low energy consumption, which has an irreplaceable role in promoting 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 medical fields such as minimally invasive intervention, targeted delivery, rapid treatment, early diagnosis and tissue repair, such as using micro-nano robots to enter liver and kidney tumors, cerebral aneurysms, peripheral tissues and organs, embolizing and removing thrombi from micro-blood supply arteries, entering and accurately manipulating the central nervous system through subarachnoid space, realizing pain control in the treatment of advanced cancer, and monitoring physiological signs in vivo using implantable multi-sensor systems.
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, biodegradation and catalysis. Driven by the external field, these micro-agents can organize themselves to move in groups, so as to accurately control the local flow field micro-disturbance, make a directional response to specific environmental conditions, and selectively identify pollutants by carrying, transporting and releasing biological enzymes or catalysts, so as to speed up the reaction process and greatly improve the efficiency of capturing, removing, degrading or repairing pollutants such as organic molecules, toxins/nuclides, marine oil pollution, pathogenic microorganisms, microplastics, heavy metals and radioactivity.
Because of its small size, micro-nano robots have high spatial freedom and super-redundant dexterity, and can dive into the limited space that traditional robots can’t reach to complete fine operations. They have unique advantages in high-end equipment manufacturing fields such as complex three-dimensional metamaterial processing, microelectronic circuit assembly and packaging, and detection and maintenance in micro-cavities. It is particularly noteworthy that whether human beings can build an intracellular "protein synthesis factory" on a micro scale depends on how to construct a highly recognizable DNA code for the controllable assembly of amino acids to accurately guide the orderly synthesis of protein. Previous studies have shown that nano-magnetic editing technology can embed multi-modal variant information into micro-machines with nanometer precision, and its more important value lies in that base pairing similar to DNA double helix can be constructed by using nano-magnetic coding. Therefore, organizing the division of labor for micro-nano robots can efficiently and orderly assemble all kinds of functional micro-units, and it is expected that this technology will be used to truly realize the "micro-machine factory" from "machine manufacturing machine" in the micro-scale.
Of course, the stage of micro-nano robot is far from this, and it has unlimited potential for various practical applications. We can’t find ideal answers to many questions now, but each question is so fascinating: can DNA molecular computers surpass quantum computers? What is the minimum size of a micro air vehicle, micron or even nanometer? What is the physical limit of artificial intelligence? Is the smallest agent unit a single molecule of hydrogen and oxygen? Nano-doctor and long-term in vivo implantation, nano-brain-computer interface and precise manipulation of single nerve, and how to realize cross-scale interaction … … The resulting revolutionary subversion technology will be the potential development direction of micro-nano robots in the future.
Micro-nano robots have not only existed in science fiction movies, but scientists from all over the world are actively pushing them from basic research to real practical application scenarios. People are full of reverie and expectation that it will benefit mankind and transform the world one day. Nevertheless, we need to be soberly aware that the field of micro/nano robots has just started, and the extensive interdisciplinary will bring more thorny problems of integration and innovation. It is also necessary to actively guide scientists in the forefront of different disciplines to tackle key problems in depth and rapidly promote the high-quality development of micro/nano robots at the national level. In order to develop advanced micro-nano manufacturing and robotics for the next generation of intelligent micro-machines, we should be guided by the major national demand, incite the intellectualization and miniaturization of machines, equipment and systems, focus on exploring the basic theory and key technologies for the intelligent realization of micro-machines, promote the rapid development of micro-nano robots, seize the commanding heights of science and technology, and safeguard the core interests of the country.
Guangming Daily (16th edition, November 16th, 2023)
