Team:DUT China B/Human Practices

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Contact lab with society

Introduction

We get our inspiration from MCU movie. We consider that micro-robots may have potential in medical applications such as micro-therapy and targeted drug delivery, but this is an innovative and cutting-edge medical tool. In the future, if it really has the feasibility and significance of the application remains to be proved. If the Chlamydomonas micro-robot is really applied in the future, can the public fully accept this treatment technology? In addition to the medical field, can the Chlamydomonas micro-robots also function in more fields? Guided by these problems, we will integrate feedbacks step by step during the project development process, promote in-depth investigation, and finally improve and demonstrate the possibilities and feasibilities of Chlamydomonas based micro-robot in society.

1. In the initial stage of the project, we have interviewed several medical research-related scholars and engineers from Dalian University of Technology, Shenzhen Institute of Advance Technology, and Shenyang Institute of Automation, Chinese Academy of Science in order to evaluate the feasibility of the micro-robots in the future and figure out exactly the practical application of our projects in the future society. We got their affirmation of the novelty and application feasibility of our project.

2. After clarifying the feasibility of the project and its significance to the society, we continue to promote the project. In the process, we have had many exchanges with the professors of Shenyang Institute of Automation, Chinese Academy of Science, and asked them about problems related to our measurement of Chlamydomonas’s movements. At the same time, we also considered a specific problem: if Chlamydomonas micro-robot is actually implemented in the future, can it be accepted by the public? We conducted a social survey to learn about the public's cognition degree of this technology and their acceptance level of its practical application from both online surveys and offline face-to-face interviews.

Through questionnaires and interviews, we learned that more than half of the people support the development of this technology in medical applications, and more than two-thirds of people can accept this medical technology.

3. During the investigation, some people have expressed the hope to bring such micro robots into other field. We have considered their suggestions carefully and believe that the micro-scale and mobility can give the cyanobacteria micro-robots advantages in many other fields. On the basis of these characteristics, we ask the relevant scholars in the field of microfluidics, physics and environment about their views in the application of micro-nano robots.

Scholars in different fields agree with the innovation of our project, but at the same time they also propose that the application of Chlamydomonas robots in different fields needs to consider its practical role, and to add downstream functional design. After careful consideration, we believe that Chlamydomonas can play a role in different fields, while single motion control cannot fully exert its function. Therefore, we took the advice of experts and selected three specific directions for the following design.

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I.We interviewed experts in the field of medical and robotics to explore the feasibility of future applications of Chlamydomonas micro-robot in medical fields.


In the literature review process, we learned that micro-robots will play an important role in the field of precision medicine in the future. With excellent features of strong motility, photoreceptivity and complex protein expression ability, Chlamydomonas will have good application prospects in precision medical treatment as micro robots. But what are the problems with our concept? How feasible is it, and how far is it to achieve its application in medical treatment? Will its excellent features solve the existing medical problems? We interviewed three professors in the field of medical research and professors in the field of robotics research to get the answers.

● Communication with Dr. Yang Yongliang

Introduction:
Dr. Yang Yongliang is an Associate Professor at Dalian University of Technology. His research interests include biomacromolecule simulation, bioinformatics (including artificial intelligence technology), chemical biology, drug design and medicinal chemistry to combine various in vitro and in vivo experimental techniques to study major diseases and important mechanisms of occurrence and development of life processes, discovery of relevant regulatory targets, design and development of innovative drugs, and advanced methods of diagnosis and treatment.

Dr. Yang is interested in the research status of micro-robots. He thinks that there are indeed limitations of targeted therapies in existing medical applications. It is believed that if the size of Chlamydomonas is appropriate, it can be used to encapsulate or mount drugs, and the light control help the doctors to get to the tumor treatment site where surgery is difficult to reach. For example, brain tumors now rely mainly on drugs for treatment, if the project can finally achieve the targeted effect, it will be very promising. However, the project also needs to consider whether there is an immune response in the human body. Whether it can be considered to apply the micro-robot to the human intestinal inflammatory system such as IBD, which does not require access to the human blood circulation system. Secondly, if the algae can add loading and adsorption functions in addition to the targeted movement, it will play its role better.

Reflection: Our project is feasible and innovative, but it should also be considered during the implementation of the project that what if the future of the algae micro-robots really changes the human body's immunity problem. The algae micro-nano robot should not just play the role of transportation, but also play more functions such as loading, expression and so on.

●Communication with Yang Guangrui

Introduction:
Professor Yang Guangrui is from Dalian University of Technology. His main research direction is the role of the biological clock in aging, behavior, and the development of major diseases. He received his Bachelor of Medicine (1999) and Ph.D. (2007) from the Second Military Medical University and Peking University, followed by the University of Utah (University of Utah, 2007/06-2009/12) and the University of Pennsylvania 2010/01-2011/10) After postdoctoral research, he served as Assistant Research Fellow at the University of Pennsylvania (2011/11-2014/10) and Assistant Professor of Research (2014/11-2017/03).

Professor Yang thinks our idea is interesting. The control and targeting in precision medical research and clinical application remain challenging. Our project provides an alternative strategy, which is novel and meaningful. He also expressed his concern that microalgae, as a living organism, may have a potential risk of entering the human body. It may be difficult for doctors and patients to accept.

Reflection: In the communication with Professor Yang Guangrui, he also mentioned the existence of immune response problems in the human environment. Secondly, in the realization of the technical problems, we consider that there are mainly control and targeting problems in precision medical research.

Whether the cost of solving these problems is lower and whether the treatment effect of this technology will be better than others by that time, are also necessary problems we need to consider in the development of cellular micro-nanobots. But if this technology and these issues can be well accepted by the public, then the development of this technology will also important to promote precision medicine. Therefore, we also hope to conduct public research on these technical attitudes on these issues.

●Communication with Shenyang Automation Institute, Chinese Academy of Science

Introduction:
The main research direction of Shenyang Automation Institute, Chinese Academy of Science is robotics, industrial automation and photoelectric information processing technology.

In the process of reviewing the literature, we found that the researchers such as Liu Lianqing, Wang Wenxue and Zhang Chuang of Shenyang Automation Institute, Chinese Academy of Science studied the cell movement of Chlamydomonas under blue light and white light. Therefore, we invited the professors from Shenyang to come to Dalian for a deep communication with us. We hope to know what opinions researchers in the field of robotics have on such a modified biological cell micro-robot.

Contents: On July 26, 2018, we invited Dr. Zhang to give us a lecture in Dalian. On August 17, 2019, we visited Shenyang and had a deep discussion with Prof. Liu Yangqing, Prof.Wang Wenxue, Dr.Zhang Chuang and their group members.Dr. Zhang introduced us his research results: the directional control of the Chlamydomonas movement, which used the self-made channel template and the diaphragm to achieve the captivity and precise directional control. In further communication with him, we also learned that although Zhang is engaged in the field of mechanical research, from the professional point of view of the mechanical field, rigid machinery can not easily reach the scale of micro-robots, and the cells are the finest in this scale. The cell system is the best alternative to mechanical micro-robots. Moreover, the use of cell-modified micro-robots also avoids problems such as difficulty in energy supply and low energy conversion efficiency. Therefore, they chose to use Chlamydomonas as a micro-robot for research on motion control. However, they also mentioned that the wild Chlamydomonas used by them have limitations such as being able to only experience blue light and weak light sensitivity. They have a strong interest in our project, affirming our idea of red light control transformation of Chlamydomonas and its future application in medical and other fields.

Reflection: Professors from Shenyang Institute of Automation, Chinese Academy of Science affirmed the high conversion efficiency and precision of biodynamics from a mechanical point of view. After we communicate with them, we also felt that cell life has more natural advantages over rigid machinery. In terms of actuators, Chlamydomonas, a highly mobile organism, is an excellent candidate, and the red light control transformation expands the application of this micro-robot to improve its performance.

●Communication with Dr. Jin Fan

Introduction:
Jin Fan, Researcher from Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences.

We were fortunate to listen to Professor Jin Fan's report when participating in the CCIC in Shenzhen Institutes of Advanced Technology,Chinese Academy of Science.Professor Jin Fan introduced the project he was studying - using red light to induce drug-loading Agrobacterium tumefaciens, which had a certain effect on the treatment of mouse lung tumor cells. We were in agreement without previous consultation because our team is devoting the project that targeted drug delivery through light control of Chlamydomonas reinhardtii, though there are differences in molecular mechanism. Professor Jin’s report has aroused our great interest, so we took this opportunity to further exchange with him.

Content: We gave an introduction of our project. Dr. Jin affirmed the possibility of C. reinhardtii as a micro-robot in the direction of targeted drug delivery. Meanwhile, He explained to us why to use microorganisms for the treatment of cancer. He raised a novel question. Is it really necessary to use drugs to completely kill tumor cells? With the continuous development of medicine, people began to find that the complete killing of tumor cells is not necessarily the best way. And if there is a kinetic balance on the killing of tumor cells, it may achieve better therapeutic effects. The human-modified microorganism can play a function similar to immune cells in the body, so as to better maintain the immune balance in the human body.

In the previous literature search, we also found a lot of articles to realize the directional control of micro-robot through magnetism. We also want to know what advantages the light control has over the more precise magnetron motion. Professor Jin’s opinion is that light control has its superiority in inducing expression over magnetic induction.

Reflection: In the communication with Professor Jin, we solved many doubts related to the project. For example, microbial targeted therapy has a significant advantage over other control measures on the controllable release of drug delivery. After the communication, we reconsider that despite the problems of immune response, photo-controlled microbial carriers for in vivo targeted therapy make full use of the characteristics of microbes themselves, and have irreplaceable advantages in specific disease application scenarios, so some existed problems can not hinder the development of this technology. In view of the characteristics of our algae micro-robot, we should also make full use of the advantages of light control and supplement the downstream design.

After communicating with above professors, we have summarized the following feedback: 1. Chlamydomonas micro-nano robot technology has novelty and applicability of targeted therapy in the future. Compared with mechanical robots, it has the advantages of complete control system at micro-scale and high energy conversion efficiency, but we should investigate the public acceptability. 2. In future applications, we should consider the issue of immune response in the human body, but it would not prevent the development of micro-robot technology. 3. The project should further develop its advantages and complement the downstream functional design for the light control and expression systems.


During the project development process, we built active communications with professors from Shenyang Institute of Automation Chinese Academy of Sciences and achieved suggestions about the technical problems of measuring the movement of algae. At the same time, we also carried out social research to understand the public's acceptance of the micro-robot technology.


● We consulted Dr. Zhang for movement measurement of Chlamydomonas several times.

1. In order to fully understand the instruments, measurement methods, and precautions for measuring the physical quantity of Chlamydomonas, on August 17, 2019, we went to Shenyang to visit the experimental apparatus for the measurement of Chlamydomonas. We need a gel channel specially tailored for the size of Chlamydomonas. The millimeter size of the channel can limit the number of algae, which is beneficial to the observation of Chlamydomonas,and the gel material prevents the adhesion of Chlamydomonas cells to the channel. Dr. Zhang provided with us millimeter-scale hydrogel channels that can be used to observe Chlamydomonas movements, and we have customized parallel and cross channel templates for different motion characteristics. This visit is very important because we have got ideas how to measure the movement of the algaes. After returning to the school, we designed and built a simple light measuring devices using microscopes, light-emitting diodes and optical power meters. (See our Demonstration)

2. In the measurement of Chlamydomonas movement, we also received many suggestions from Dr. Zhang Chuang and his group. They suggested us that for the measurement, at least 20 groups should be averaged at one time; in the dark room, there is no need of observation light source, and the experimental light source is enough to see the movement of algae. The objective lens can be used to converge the light source and achieve the effect of the point source. Since it is difficult to separate the individual Chlamydomonas cells, groups of algae can be used for the purpose of characterization; and for the measurement of the FM impact force, it is not recommended if the school does not have the conditions.

Reflection: With the help of Dr. Zhang, we built our method for the movement measuring of Chlamydomonas, which is suitable for our experimental conditions, and fully considered the accuracy of the data of Chlamydomonas.

● Conduct social research on the acceptability of cellular micro- robots in the social sphere The communication with Professors reminds us of the importance of the public's acceptance of this technology. The public's support attitude will greatly promote the further development of this technology and research. Will it be difficult for the public to accept the technology of micro-robots? Can these technical difficulties be solved? In what period can we finally achieve such a complete technology? Does this technology have an irreplaceable therapeutic superiority, effectiveness, or economy over other technologies? In response to these thoughts, we designed an online questionnaire for publication. At the same time, we selected random interviews at three locations: hospitals, schools, and plazas to understand attitudes of the patients who have medical needs, higher levels of knowledge and the general population.

1. Online survey In response to the above considerations, the design questionnaire consists of 12 questions in order to understand the degree of cognition of cellular micro-robots, the attitudes toward the pros and cons of this technology, and the acceptable degree of the algae cellular micro-robot entering the body. Below is a detailed survey report. In this survey, the number of valid questionnaires was 394. The ratio of men to women filled out the questionnaire was 1:1.36, and the age of 85% or more was concentrated in 18-49 years old, from 22 different provinces in China.

1. Public awareness of micro-robots and cellular micro-robots

Have you heard of the concept of micro-robots?

Conclusion: The above results show that the public has a certain degree of understanding of micro-robots and cellular micro-robots, but the understanding of cellular micro-robots is less than that of micro-robots.

2. Public attitude towards the pros and cons of micro-robotics

What do you think about the application of micro-robots in medical and human body

Conclusion: Among the people participating in the survey, the proportion of people who do not agree that micro-nano robots enter the human body is only 3.55%, and over 95% support the medical application of micro-nano robots. Although more than 30% of them still have concern about the potential risks of technology, we can still see the public's support for this technology in the medical field. At the same time, cell micro-robots have the advantages of utilizing the characteristics of the cells themselves.

3 The public's view on the existence of problems in the development of cellular micro-robots

What do you think are the disadvantages of bio-microrobots compared to traditional mechanical micro-robots?

Do you think that the current technology of cellular micro-robots for medical functions is difficult?

How many years do you think these technical problems will be solved in the future?

Conclusion: In the development of cellular micro-robots, the public believes that transformation and control are the biggest problems in the development of technology, but also is optimistic about the solution of these technical problems, and believes that these technical problems can be solved in the near 30-50 years.

Summary: Through online surveys, we can know that most of the public can accept cell micro-robotic treatment methods, and have an optimistic view on the solution of problems during development. Therefore, the application of our projects in medical care is socially acceptable.

2. Offline interview We went to the hospitals, schools and plazas for random interviews to understand the public knowledge of biotechnology and the development of cellular micro-robotics among patients with medical needs, college students with higher levels of knowledge and ordinary residents.

● Second Hospital of Dalian Medical University
We interviewed 11 groups and 15 people. There are about one-third of people above age 50, and about two-thirds of people at around 30 years old.

Everyone interviewed had a limited knowledge of biological knowledge, but they all heard about technologies or products related to genetic manipulation such as genetic modification. Older people have a negative and unsupportive attitude towards such technology and products. We learned that they learned about genetically modified crops from news and internet media, and learned that these products are not beneficial. they also hope to get scientific knowledge from professionals.

Most young people are optimistic and supportive of synthetic biology and genetic manipulation technology, and believe that this is a beneficial development for human beings, but almost everyone has showed concern about the development of this technology, such as the disclosure of genetic modification.

Regarding these problems, some people expressed the belief that the development of science and technology is gradually finding problems and solving problems; others also said that the acceptance of technology among the public will take some time. At the same time, they suggested that the Chlamydomonas micro-robot can also be used in more fields, where it can make full use of its characteristics.

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We communicated with professors in different fields to understand the potential applications of red-light-controlled Chlamydomonas micro-robots in different fields.

In the investigation of the social acceptability of cell micro-robots, some people have proposed the application of Chlamydomonas micro-robots in more fields. We also believe that Chlamydomonas could show its good characteristics in more fields, such as the micro-scale size and movement. Therefore, we asked the relevant scholars in the field of microfluidics, physics and environment to view the application of micro-robots, hoping to explore the possibility of more applications.

● Communication With Fujian Agriculture and Forestry University

When participating in CCIC, we had the opportunity to communicate with students from Fujian Agriculture and Forestry University. They proposed whether it is possible to use different light control to achieve the sorting of different Chlamydomonas, so as to better improve the light-receiving and growth efficiency of Chlamydomonas. After discussing the actual incubator conditions with them, we think it is somewhat difficult, but it also stimulates us: the sorting and enrichment of Chlamydomonas may play a role in the concentration of pollutants in the environmental field, and will make Chlamydomonas as the pollutant adsorption carrier sorted and enriched by different light control. Therefore, we first went to consult a professor of environmental engineering to understand the application possibilities of Chlamydomonas in the treatment of environmental pollutants. At the same time, we also consulted the microalgae production related companies to understand the growth of Chlamydomonas in the actual production process and to find the potential application of light-controlled algae movements.

● Interview with Prof. Wang Jing, School of Environment, Dalian University of Technology

Content:In the interview, we asked Prof.Wang about the possibility of using the algae micro-robot for environmental pollutant treatment. He made the following suggestions for us: 1. Because environmental applications often require an open outdoor environment, it is difficult to strictly control the wavelength conditions of light in such a big space. Therefore, we should broaden the absorption wavelength range of Chlamydomonas and make it close to natural light. 2. There are many catalyst applications in the environmental field. We can use different wavelengths of light to induce algae to produce different kinds of catalysts, or to activate the activity of the catalyst or poison the catalyst. 3. Water quality monitoring can be carried out in water bodies. It is recommended to add a sensor molecular device or a light-controlled induction device to Chlamydomonas.

Reflection: After talking with professor Wang Jing, we learned that the control of light is more challenging in the environmental field, so the use of specific wavelength light to control the algae in the environmental field has greater inaccuracy and inconvenience. Therefore, we hope to interview relevant professors in the field of physical optics to understand the special application fields of red light to find a feasible application direction.

● Communication With Professor Sun Changsen, who engaged in biomedical engineering and optical related research

Content: For our red-light control of the sports celestial micro-robot, the professor mentioned that the red light is quite friendly to human beings. The Chlamydomonas micro-robot can carry information or drugs to the designated location, and use optical cable and micro-mirror technology to guide the air into the trachea and the stomach. The corresponding role has once again proved its more application prospects in the medical field.

● Microalgae production company

Knowing the actual production of microalgae could help us to explore whether our robot can be used in the actual production of microalgae, thus we conducted a telephone interview with the staff of Shanghai Guangyu Biotechnology Company. The interviewer is a staff who engaged in the work related to the cultivation of algae aquaculture bait. After listening to our introduction of project, he proposed that in his work, compared with the directional control of light, they pay more attention to the influence of light on the accumulation of algae biomass, that is, how to prevent the microalgae from being dead and how to cultivate algae bait containing more biomass. As for our light control system, the staff proposed whether to separate the beneficial algae and harmful algae according to the characteristics of light control, so as to achieve environmental control. This confirms our desire to use different light control for algae sorting

For our proposed use of Chlamydomonas as a drug-loading platform for drug delivery, the staff suggested that Chlamydomonas without a porous structure is not suitable for direct drug loading, but can be achieved by light-induced expression. The controllable expression of algae at specific sites to achieve real-time controlled targeted administration has affirmed our application ideas.

● Microfluidics field

Introduction:
Professor Liu Junshan is mainly engaged in the application of polymer micro-nano manufacturing. Lu Yao focuses on single cell analysis, microfluidic chip related biotechnology research and development and biomedical applications.

Content: Prof. Liu Junshan introduced us enthusiastically. The microfluidic chip is manufactured by tiny chip structure, which provides a micro controllable reaction chamber for biochemical experiments, which not only improves the experimental reaction flux, but also reduces the demand for experimental consumables. The microfluidic chip is customized according to special experimental and research requirements, and greatly expands the experimental reaction flux on a small reaction platform, which lays a foundation for other research and basic work. Dr. Lu Yao mainly focuses on single cell analysis, microfluidic chip related biotechnology research and development and biomedical applications. Both professors have suggested for us that in the microbiological experiment chip we should first consider the particularity of these experiments and the subsequent experimental programs. The microfluidic chip only provides an experimental reaction platform, and we should design downstream expression according to different application scenarios of microalgae.

Summary 1. Chlamydomonas micro-robots are more suitable for applications in the medical field, but also have the possibility of being applied to the direction of sensing and environmental pollutant treatment. 2. The application of the Chlamydomonas micro-robot should be further designed according to the specific scene to achieve complete functions.


Contact lab with society
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