Three generations of students, two overthrows: the unexpected reversal of nanorobots

The truth becomes clearer the more it is debated.

Written by Wang Wei (Professor at Harbin Institute of Technology (Shenzhen))

Recently, our research group published two articles in succession in the top journal in the field of chemistry, Angewandte Chemie. There are some twists and turns behind the two articles, which are thought-provoking. A few days ago, I shared the birth of the first paper (From the paper stranded to the top journal in the field: the rebirth of a doctoral student). Today, I will talk about the second paper: Why the nanorobot unexpectedly walks in the opposite direction. (Paper link:
https://onlinelibrary.wiley.com/doi/10.1002/anie.202201018)

0 Wedge

More than two years ago, I wrote a popular science article about nanorobots, "Want nanorobots to be omnipotent? Let's see how much science there is here first." Because nanorobots are very small and slow, and even feel that water has become unusually viscous, to make them move, we need to develop different methods from those used for machines in the macroscopic world. And using the energy released when chemical fuels decompose is a very effective method.

Hydrogen peroxide is a classic fuel that can be decomposed into oxygen and water and release a large amount of energy, so it is widely used in rocket propulsion. In order to speed up this reaction, platinum metal can be used as a catalyst. More than a decade ago, scientists discovered that if platinum is coated on the surface of a nanoparticle, it can be made to swim quickly in a diluted hydrogen peroxide aqueous solution.

Structure, preparation and actuation of nanorobots covered with platinum (Pt)

This strategy is so simple and the manufacturing of the robot is also very convenient. Therefore, once this platinum-based micro-nano robot was launched, it was deeply loved by scientific researchers in many fields such as physics, chemistry, and materials. It became popular in the scientific research circle and became an absolute Internet celebrity product.

After using the popular products for a long time, some "experience" will naturally come into play. For example, many people (including myself) have always believed that the nanorobots made in this way will move away from the platinum side, and the reason for the movement is because of the metal platinum. This idea is very consistent with human intuition, so it has gradually become an unwritten "hidden rule" supporting many platinum-based micro-nano robot research.

Until one day...

1 Unexpected Discovery

In the second half of 2019, Lv Xianglong, a second-year graduate student in the research group, just completed his first SCI paper. Like other young academic stars, Xianglong is happy to try all kinds of strange ideas. One day, he wanted to try to see how the movement of the nanorobot would change if the thickness of the platinum coating was different.

As mentioned above, such nanorobots will catalyze the decomposition of hydrogen peroxide. Because the reaction occurs on the surface of the platinum film, the speed of the nanorobots obtained may be similar whether the film is thicker or thinner; or it may be because the thicker the platinum layer, the heavier and larger the ball, the greater the friction, and the slower it runs.

However, Xianglong's experiment obtained the opposite result: the thicker the platinum layer, the faster the nanorobots became. What's even more amazing is that the robots with thick platinum layers walked in reverse! To make a very inappropriate analogy: our discovery is like adding 2 more wheels to a 4-wheeled car and making it faster, while an 8-wheeled car moves in reverse! This doesn't make sense at all...

The robot with thin platinum layer moves in opposite directions to the robot with thick platinum layer.

Was the experiment done wrong? But Xianglong's sample preparation and video shooting were impeccable, and the results were clearly presented to us. But I have never seen or imagined such a result!

For a moment, Xianglong and I fell into silence, with many questions flashing through our minds, but the answers were vague. Since he couldn't figure it out for the time being, Xianglong went to work on other experiments. I also put this question behind my mind, and let it accompany other unsolved mysteries in the laboratory.

2x speed playback of 3 µm diameter polystyrene microsphere robot movement, each ball has a 20 nm thick platinum layer on it. Video source: Wang Wei's research group [Please go to the "Fanpu" public account to watch the video]

2 The student is better than the master

In the fall semester of 2019, the campus became bustling again. Xianglong continued his other projects, while Chen Jingyuan, a senior student in the School of Materials Science and Engineering, returned to Shenzhen after completing his summer study at the University of California, Irvine. Chen Jingyuan is from Guangzhou, tall and has the temperament of a fair-faced scholar; but when talking about the scientific research topics that interest him, the young man's sharpness and edge penetrate his shyness.

Jingyuan has been doing research in our research group since his sophomore year, so as soon as he came back from the United States, he came to the research group to report and prepare to start his senior year graduation project. It just so happened that I gave Jingyuan the problem of the robot inversion that bothered Xianglong and me, and asked him to do some exploration within his ability.

Since the junior year of undergraduate studies, Jingyuan has shown excellent scientific research literacy and is a promising prospect. Even so, objectively speaking, undergraduates' knowledge reserves and scientific research experience are slightly inferior to those of master's and doctoral students. So I just want Jingyuan to repeat Xianglong's experiment, maybe try new materials and new parameters, and make the experiment more systematic. After all, I dare not expect Jingyuan to make a big breakthrough in a topic that even the experienced Xianglong can't do.

However, Jingyuan soon taught me what it means to be better than my teacher. After several years of scientific research training, plus a summer visit to the United States, Jingyuan's scientific research ability improved rapidly. After taking over Xianglong's platinum robot reversal project, he not only quickly reproduced the phenomenon done by Xianglong (this is not easy, many experimental results can no longer be done after changing hands), but also obtained very clear experimental laws through systematic experiments and careful data analysis.

It is not easy for an undergraduate student to do a better job than his master's student's experiment. What is even more admirable is that Jingyuan carefully read the relevant papers and studied several mechanisms of chemical fuel-driven micro-nano robot movement. Based on these, Jingyuan proposed a very feasible mechanism, so that robots with different platinum layer thicknesses can be driven by different mechanisms.

The new mechanism proposed by Jingyuan was beyond my expectation, but I was even more surprised. Before the winter vacation, Jingyuan's electrochemical test obtained high-quality data, which provided strong evidence for the reversal mechanism he proposed. After returning home for the Chinese New Year holiday, Jingyuan also learned simulation software with his senior brothers and sisters in the laboratory. In the spring of 2020, when he was locked at home by the epidemic, he further improved his proposed mechanism through numerical simulation.

From experiments to theories, from electrochemical tests to numerical simulations, in a few months, senior undergraduate Chen Jingyuan almost single-handedly solved the problem that even his supervisor couldn't figure out. While I was happy, I also felt a little regretful: such an excellent student is about to graduate in the summer and choose to study abroad, and can't continue to expand the boundaries of knowledge with me.

3 Xianglong "returns"

While Jingyuan was advancing, I was writing the paper. By April 2020, the paper and figures were basically finished, and I was really happy. For basic science researchers, when they have new discoveries and new insights, they always want to share them with friends and colleagues. Therefore, I immediately sent the draft of the paper to two foreign friends who were concerned about this issue, to listen to their suggestions and also to "show off" our findings.

However, before my friends could reply, trouble arose in the laboratory.

After Jingyuan graduated in the summer of 2020, the project was almost complete, but there was still some finishing work to be done. Since the project was started by master's student Lu Xianglong, it was natural for him to continue to take over.

After all, it has been a while since I touched this project. After returning to the project, Xianglong, like Jingyuan who had just taken over, first repeated the experiment. It just so happened that the school had just bought an imported precision coating machine, which was much more advanced than the domestic platinum coating machine in our laboratory. With the idea that foreign monks can chant sutras, Xianglong used the imported new machine to coat the nanorobot with platinum. But no matter how thick the platinum layer was, the catalytic performance was excellent, but there was no way to reverse the robot.

Vacuum sputtering coating machine. Left: Domestic coating machine in our laboratory; Right: Imported high vacuum coating machine purchased by the school (Picture from the Internet)

Xianglong and I were dumbfounded again. How come the project went wrong as soon as Jingyuan left? Was it a problem with the equipment, the experiment, the theory, or the people?

Fortunately, we didn't stay confused for too long this time. Xianglong soon discovered a key factor: the robot made with the domestic coating machine in the laboratory could be reversed, but the imported coating machine could not. Faced with this breakthrough, Xianglong had a brainwave: Could it be that the composition of "platinum" made by different machines is different?

My first reaction was: ridiculous. Both machines used four 9-purity platinum targets, and the coating process took place under our noses in a transparent glass cover. Where did the pollution come from? In addition, Baidu Encyclopedia tells us: "Platinum metal is extremely resistant to corrosion, very stable at high temperatures, and has very stable electrical properties. It will not oxidize at any temperature." Therefore, no other substances could appear in our experiment!

4 Dirty Milk

But is it possible that Xianglong's imagination is true? Is it possible that different coating machines can produce different "platinum"? Let's first understand how platinum film is plated.

Whether it is the domestic equipment in our laboratory or the imported equipment in the school, they are all machines called "vacuum plasma sputtering coater". This machine has a sealed cavity made of a glass cover, which contains pure metal sheets ("target materials") used to prepare thin films and the substrate on which the film is to be coated. When coating, the cavity is first evacuated, and then high voltage is passed. The gas molecules remaining in the cavity generate high-energy plasma, bombarding the target material, sputtering metal atoms from the target material, and depositing them on the substrate to form a thin film.

The process of sputtering deposition is a bit like smashing a glass bead into a pot of milk, and the splashing milk sprays onto the pot lid. The glass bead is the plasma, the milk in the pot is the platinum target, the pot lid is the substrate for growing the platinum film, and the splashed milk is the platinum film we want to plate. The pot is our sputtering instrument.

Vacuum sputtering deposition is a bit like throwing glass beads and splashing milk on the lid

Xianglong's idea essentially means that the same milk in different pots will have different compositions when splashed onto the lid. This does not make sense at first glance, but Xianglong has a reasonable guess: the vacuum degree of domestic coating equipment is not high, which will form a large amount of oxygen plasma; the sputtered platinum atoms will react with oxygen atoms and oxygen plasma to form platinum oxide, "polluting" the sample. The imported coating equipment has a high vacuum degree and uses inert gas argon for protection, so the plasma that sputters platinum is mainly argon. Argon does not react with platinum, so a purer platinum film will be obtained.

To continue with our milk analogy, it is like saying that different pots use different "glass beads" to smash the milk. The glass beads used in imported pots are very clean, and the milk that comes out is pure milk; in our low-end domestic pots, the glass beads have dirt on them, which makes the splashed milk deteriorate.

As a milk drinker, I immediately thought it made sense. To convince me, Xianglong also found evidence from the vast literature that someone had successfully obtained platinum oxide by bombarding platinum targets with similar high-energy plasma.

To prove the "dirty milk" hypothesis, Xianglong first confirmed through various material characterizations that our old domestic sputtering equipment does produce platinum oxide, and the thicker the film, the greater the content of platinum oxide; while the imported one is basically pure platinum. Secondly, he designed a series of sophisticated heat treatment experiments, which confirmed that as long as there is platinum oxide on the surface, the robot will reverse, and as long as the platinum oxide is removed, it will resume moving forward.

The above results are closely linked, strongly proving Xianglong's "dirty milk" conjecture. We suddenly realized that the reason why the nanorobot reversed was because platinum oxide was sputtered on the nanoparticles, instead of the myth that most of us had previously held: there can only be platinum on the platinum robot. This theory was also affirmed by collaborator and college colleague Professor Ma Xing.

This experience also taught me that scientific research cannot rely on Baidu Encyclopedia.

5 The Last Disaster

In the summer of 2021, Xianglong will go to Germany to study for a doctorate. After many ups and downs, the project, which has outlasted Jingyuan and Xianglong, has finally come to an end. After months of hard work by doctoral student Liu Jiayu, and with the great assistance of doctoral students Duan Shifang and Peng Yixin (yes, the male protagonist in the previous article), and after many revisions, this paper on understanding and controlling the reversal motion of platinum-based nanorobots was finally submitted.

Like the journey to the West, the paper experienced one last disaster before it was completed: a reviewer pointed out that our electrochemical test results were not accurate enough. This was not a big problem, and the error could be reduced by doing more tests. But the more the students measured, the more they found that the order of the results of several samples was jumping around without any pattern. On the other hand, in order to explain the mechanism by which platinum oxide would cause the robot to reverse, Xianglong had previously designed an ingenious experiment with gratifying results that matched the simulation results brilliantly; but the student who took over, Liu Jiayu, found that the experiment was difficult to repeat.

Faced with these less than ideal results, I hesitated. The reviewer's questions were actually easy to answer, but we "made trouble for ourselves" by doing a lot of experiments that the reviewer didn't ask, but got puzzling results. In order to get the article published smoothly, we could have kept these "bad" data from the reviewers or readers, and perhaps it wouldn't have much impact on the main point of the article. But I quickly dismissed this idea: I didn't want to publish results that I knew were wrong, and I didn't want to teach students to turn a blind eye to naked results in order to publish papers.

Therefore, for this little bit of persistence, we delayed the revision that was supposed to be returned in two weeks to two months, reluctantly deleted some of the reversal mechanisms, and frankly stated that we could not confirm all the speculations. It is regrettable that we cannot end a work with a strong rest, but the open-ended "answer" may also open a new door for subsequent research.

Fortunately, the revised paper was accepted by Angewandte Chemie in April 2022. To be honest, I don’t know if the editor or reviewer noticed the struggle behind our revision, but at least we have a clear conscience.

6 Ending

Good work always has a difficult fate. This work on nanorobots took two and a half years from the first discovery of the phenomenon to the final publication, and went through three generations of principals (undergraduate student Chen Jingyuan of 2016, master student Lv Xianglong of 2018, and doctoral student Liu Jiayu of 2020). The mechanism we thought was correct was overturned twice. Failures, joys, reversals, and accidents over and over again are really exhausting. But what kept us going was the desire to share our discoveries with the world, and also a belief in wanting to prove ourselves.

Three generations of students have devoted their efforts to the project: undergraduate student Chen Jingyuan 2016, master student Lv Xianglong 2018, and doctoral student Liu Jiayu 2020

However, desire and belief are only necessary conditions for success, but not sufficient conditions. We also need diligent, practical and patient students like Xianglong, Jingyuan and Liu Jiayu. If Xianglong had not keenly captured this abnormal phenomenon in 2019, Jingyuan had not made a series of breakthroughs based on solid theoretical and simulation skills, Xianglong had not made bold conjectures and systematic verifications, and Liu Jiayu and several other students had not provided assistance and careful error corrections regardless of fame and fortune, this project would no longer exist, and we would have lost an opportunity to unveil the secrets of science.

During these two and a half years, I have also been learning, growing, and reflecting on this topic. Looking back on this journey, I deeply agree with Jingyuan's words: the more you debate, the clearer the truth becomes.

In scientific exploration, when you discover a problem, you propose a hypothesis and design an experiment to verify it or refute it. Keep thinking about it and challenging it. Stand up from failure and continue to fight. Put aside personal feelings and continue to look for the truth from clues. After getting the result, let others challenge it. If it is wrong, start over again. Fight again and again until you are exhausted, and then draw a line on the ground with a battle flag. This is the boundary of our knowledge. Lick your wounds, make yourself stronger, and then try again.

The truth becomes clearer the more it is debated, and only through repeated tempering can steel be made.

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