1
Introduction

Robot is a multifunctional machine that can perform tasks such as work or movement through programming and automatic control. In 1920, Karel Capek, a Czech writer, published the science fiction script "Rossum's Universal Robots," a classic of the world's science fiction literature. In the play, the writer changed the Czech word "robota," which originally meant "slave," into "robot," which is the origin of the word "robot." The play tells the story of a company called Rossum that introduced robots to the market as industrial products produced by human beings and let them act as labor instead of human labor, and predicts the tragic impact of the development of robots on human society, and has attracted extensive attention.

The invention of robots is to let human beings free their hands and better improve and enjoy life. With the deepening of people's understanding of the intelligent nature of robot technology, it began to penetrate into all fields of human activity. However, there is no unified standard for the classification of robots in the world, and there can be different classifications from different definition standards. Among them is a micro- and nanorobot defined according to the size of the robot, which has attracted more and more interest of researchers in many disciplines. It may completely change the application fields, including biomedicine, information storage, environmental detection and repair, and micro-/nanoengineering. Especially in the biomedical field, biomedical micro- and nanorobots may become an important driver for the development of this field.

1.1 Origin of Biomedical Micro- and Nanorobots

The story of biomedical micro- and nanorobots can be traced back to the famous speech "There's plenty of room at the bottom" in 1959 (Figure 1.1). It is well known that the Nobel Prize-winning theoretical physicist Richard Feynman first proposed the idea of "nanotechnology" in his classic speech. Although he did not use the word "nano," he actually expounded the basic concept of nanotechnology. In addition, he said, "A biological system can be exceedingly small. Many of the cells are very tiny, but they are very active; they manufacture various substances; they walk around; they wiggle; and they do all kinds of marvelous things - all on a very small scale. Also, they store information." His smart brain began to flash, "Consider whether it's possible: we can also make a little thing under our command; we can also make a thing to act according to plan on the above-mentioned small scale!" [1].

Figure 1.1 Richard Phillips Feynman (11 May 1918 to 15 February 1988), American physicist, Professor of Physics at Caltech, winner of the 1965 Nobel Prize in Physics.

"Under our command" and "small scale," yes, this is the initial description of mini machine. In his subsequent speech, he continued, "A friend of mine (Albert R. Hibbs) suggests a very interesting possibility for relatively small machines. He says that, although it is a very wild idea, it would be interesting in surgery if you could swallow the surgeon. You put the mechanical surgeon inside the blood vessel and it goes into the heart and 'looks' around. (Of course, the information has to be fed out.) It finds out which valve is the faulty one and takes a little knife and slices it out. Other small machines might be permanently incorporated in the body to assist some inadequately-functioning organ." This is the most absurd and great idea of "swallowable surgeon".

One might ask, does this "swallowable surgeon" idea come from Albert R. Hibbs or Richard Feynman? We can't find the right answer now. But Richard Feynman praised this idea, "I can hardly doubt that when we have some control of the arrangement of things on a small scale we will get an enormously greater range of possible properties that substances can have, and of different things that we can do."

At the end of the speech, Richard Feynman offered an attractive reward of 1000 dollars to researchers who can prepare miniature books (can be read by an electron microscope) and working electric motors (only 1/64?in. cube with 1/64?in. side length) in future. The last sentence is "I do not expect that such prizes will have to wait very long for claimants".

However, he did not offer a reward to researchers who could prepare "swallowable surgeons" in the future. Maybe it's because he can't afford it, because at the critical moment, the value of a surgeon may be far more than a miniature book or a miniature electric motor. After all, who doesn't cherish life? The "swallowable surgeon" mentioned by Richard Feynman or Albert R. Hibbs is the protagonist of our book - biomedical micro- and nanorobots.

1.2 A Long Journey

The wings of artistic spirituality always lead the heavy steps of science and technology. In 1966, a novel entitled "Fantastic Voyage", written by Isaac Asimov, the most famous popular science writer and science fiction novelist in America, was published by Houghton Mifflin Harcourt [2]. This novel described the fantastic adventure of shrinking human beings to the size of cells through scientific means. In August of the same year, Richard Fletcher served as the director and used miniature technology to go deep into the human body to shoot the science fiction film Fantastic Voyage of the same name. It described, how under the background of the Cold War between the United States and the Soviet Union, five American doctors boarded a submarine reduced to a micron scale and entered the blood of a wounded Soviet diplomat. Although the blood fluctuation caused by each heartbeat kept the submarine on the verge of overturning at any time, and the antibodies in the body also took the submarine as the source of infection and madly attacked it, the heroic protagonists were still able to manipulate the submarine to avert danger in the blood and destroy life-threatening thrombus. They succeeded in saving the diplomat's life. After the final task was completed, they escaped through the eye of the diplomat. This film had a novel idea and created a new vision for the theme of science fiction films. Therefore, it won two Golden Awards, the 39th Academy Award for best art direction and best visual effect in 1967. Politics and war aside, the film has successfully triggered more imagination about micro machines (microrobots) all over the world.

The realization of dreams ultimately depends on the development of science. It has been more than 60?years since the micro- and nanorobot was developed and applied to the research of in vivo treatment of major diseases. The major events in the research history of micro- and nanorobots are listed in Figure 1.2 [3]. From the swimming of microscopic organisms observed by Sir Geoffrey Taylor in 1951 [4], and the bacteria swimming by rotating their flagellar filaments observed by Howard C. Berg in 1973 [5], these belong to the movement of organic organisms, but they are also concerned by researchers about their internal rotating machines [6].

Figure 1.2 Major events in the history of micro- and nanorobot research (1951-2022).

Source: Wang [3]/John Wiley & Sons.

Researchers turned their attention to smaller molecules, which may be caused by the random motion of the molecules driven by environmental heat. At the time of Feynman's speech, chemists did not master enough synthetic technology and analytical means to create artificial molecular machines. From the 1970s to the 1980s, the rapid development of synthetic chemistry and supramolecular chemistry (which won the Nobel Prize in chemistry in 1987) provided reliable synthesis templates and strategies for the construction of artificial molecular machines. In 1991, Fraser Stoddart published an article entitled "A Molecular Shuttle," which described the earliest rotaxane-based molecular machine synthesized with a receptor template [7]. He believed that the early molecular machines only limited the random movement to a certain dimension and space. For example, the molecular shuttle limited the random movement of the macrocycle to two equivalent binding sites on one axis. Jean-Pierre Sauvage and Fraser Stoddart independently introduced the stimulus response mechanism into the design of molecular machines in 1994, realizing the control of external conditions on molecular machines [8, 9]. In 1999, Ben L. Feringa proposed the light-driven monodirectional molecular motor and described how the first molecular machine designed by him experienced two cis/trans-isomerizations of alkene and two thermal relaxation processes to realize 360° of unidirectional rotation under light. The carefully designed olefins with large steric hindrance and skillfully arranged steric hindrance groups make the thermal relaxation an irreversible unidirectional process, ensuring the unidirectional rotation of the molecular machine under light [10].

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