His name is Yang Chen, 33 years old, he graduated from the Department of Mechanical Engineering of Rutgers University, studying 4D printing, and graduated from the Hong Kong University of Science and Technology.
Unlike many doctoral graduation choices, after graduating from Beijing, he chose to come to Shenzhen, the "highland" of China's manufacturing industry, and became a mechanical design engineer.
Figure | Yang Chen (Source: Yang Chen)
Prior to his Ph.D., one of his papers was published in Advanced Materials under the title 4D-Printed Transformable TubeArray for High-Throughput 3D Cell Culture and Histology.
Developed TTA's 4D printing tool for batch processing of cell tissue section detection
The study used a 4D printed tool called Transformable Tube Array (TTA) to enable batch processing from three-dimensional cell culture to cell tissue section detection. This accelerates the research cycle of drug screening, new drug development, disease models, and personalized drugs related to three-dimensional cell culture.
Yang Chen said that compared with the traditional two-dimensional cell culture, three-dimensional cell culture is a way to study the extracted cells in vitro, and then better restore the state of the cells in the organism, so this field is highly valued.
Currently, bulk culture of three-dimensional cells has been achieved, most commonly through the use of 96-well plates. In the detection, cell tissue section detection (Histology) is a more commonly used means, which refers to the cell materialization, fixation, dehydration, embedding, sectioning, staining, and microscopic observation to restore the tissue and structural characteristics in the three-dimensional cell structure from different heights of sectioning.
The transfer of cultured three-dimensional cells from the 96-well plate generally needs to be done manually one by one, and the transfer of cell tissue requires a very delicate operation. In the subsequent steps after transfer, embedding, slicing, etc. also need to be carried out one by one.
The process of transferring from to assay is time-consuming and labor-intensive, and the batch processing technology for subsequent assays is significantly insufficient compared to batch cell culture techniques.
The main research direction of Yang Chen's laboratory is 4D printing, that is, 3D printing deformable devices or structures with variable performance, and achieving design changes in the fourth dimension (time). So they envisioned using 4D printing deformable 96-well plate nested devices and naming them TTA. For subsequent transfers and sections, let the TTA carry all the 3D cell samples with them for batch processing.
(Source: Advanced Materials)
Yang Chen said that the project was set up from a bidding project of a biological company, and the demand they put forward was to solve the problem that three-dimensional cell detection was too time-consuming and labor-intensive.
In the study, the solution they team solved by the 4D printing deformable tool TTA was approved by the company, and the project was approved. After having the project, Yang Chen and his mentor analyzed the key difficulties together.
In the mechanical design, the size of the 96-well plate is 3.6 times the size required for subsequent section inspection, so it is necessary to ensure that the layout of the 96-well plate is maintained during the incubation of the transfer, and the overall structure size is reduced by 70%. The three-dimensional cell tissue is then sliced with the TTA.
Materially, cell culture requires TTA to be biocompatible. In addition, the deformation of the TTA also needs to be controlled, when it needs to be mated to a 96-well plate, it needs to be maintained at a large size, and when it needs to be sliced, it needs to be small and maintained at a small size. And this controllability is determined by mechanical design and materials.
After finding the difficulty, it is time to find the direction to solve the difficulty. Dr. Yang Chen's main research direction during his time was 4D printing shape memory polymers, which are characterized by the ability to maintain deformation at low temperatures and restore the printed shape at high temperatures, which is very controllable.
After the general direction of the material is determined, it is necessary to consider how to design the material to achieve the required properties, which are determined by the application scenarios of the device, such as biocompatibility, the temperature of the trigger deformation (in order to ensure the shaping of the cell culture, the cell tissue structure must be ensured when the high temperature deformation is not damaged), the material strength (the operability of the nested device), and the elongation at break (no fracture occurs when the overall size is deformed by 3.6 times).
Material design is basically determined, the requirements of mechanical design are gradually clear, and the three-dimensional spiral structure designed in the paper is the result of combining various needs and limitations.
At this point, the TTA has a prototype, and the next step is to test the culture and subsequent sectioning of the cells. Since this was not Yang Chen's area of expertise, he began to cooperate with the biochemistry doctoral students in the team and pathologists.
At this point, Yang Chen's responsibility becomes to understand their existing processes and design a compatible use plan for TTA. During the period, of course, it is indispensable to improve and optimize the mechanical design, material post-processing and printing process.
Cross-disciplinary cooperation projects often also mean high difficulty, which he deeply feels.
"In fact, the testing process is the most time-consuming and difficult stage of the project, because everyone has to solve a lot of problems that have not been faced before and innovate on the basis of what they have," he says. ”
As a simple example, how to post-process a printed TTA to achieve biocompatibility and not affect the culture of cells at all, is a problem that neither he nor his collaborators have faced. After the treatment, TTA causes a large number of cells to die, a small number of deaths, the first few days are fine and then the cells suddenly die, and there have also been cases where TTA causes excessive cell growth.
"We also studied experiments for a long time to find a suitable post-treatment method." Yang Chen said.
Since starting the collaborative experiment, he has been running around in three places every day.
You have to go to the laboratory of the biochemistry doctoral student, observe the use of TTA and the response of the cells, and discuss the solution according to the observation; then, you have to go to the pathologist, take the TTA and cultured cells, and study the batch processing in the relatively mature cell tissue examination process.
During this period, Yang Chen and his collaborators need to understand each other's professions, and they also need to try their best to solve the problems they encounter from all angles.
Later in the project, due to the epidemic, the school was closed for about half a year. Later, even if you can go back to school to do experiments, the working time, efficiency and mobility are very limited, which makes cooperation much more difficult. Yang Chen recalled: "At that time, there were still some experiments in this project that made the TTA test results more complete and convincing, and there were some regrets. ”
It can accelerate the cycle of drug screening and new drug development
At the same time as the paper was published, Yang Chen and the team also applied for a patent, and if there is a suitable opportunity in the future, the TTA can be made into a product.
As mentioned earlier, the effort is to accelerate the research cycle for drug screening, new drug development, disease models, and personalized drugs related to three-dimensional cell culture. The acceleration of the research cycle has positive significance for the overcoming of various diseases and the rapid response to pandemics.
Yang Chen is a native of Beijing and was born in 1988. He studied mechanical engineering at the Hong Kong University of Science and Technology for another year and obtained a Master of Science degree in Mechanical Engineering. After studying in the United States, he has been studying at Rutgers University.
He said: "During my PhD, I was still a bit tortuous, and I changed a group in the middle. I was working on a new zero-loss coating process using centrifugal force in the first group, and I was still very interested at first, and I finished my first project and published a paper. But when planning the follow-up direction, I felt that it was not very attractive to me to continue to do it further. After a period of research and thinking, I changed to the group that did 4D printing, and then I studied it all the time and got a doctorate. ”
In recent years, 4D printing is a very popular research direction, he also remembers the mentor (Howon Lee) said that this direction is hot, it is easy to improve the influence of research results, at the same time there are many competitors, do not do well it is easy to be eliminated.
Fortunately, in recent years, it has not been eliminated, but it has also experienced several times when I just had an idea and experimented, and other research groups with similar ideas were published.
When I joined the 4D printing research group at that time, Yang Chen's supervisor was an assistant professor in the second year, and the laboratory was also in the initial stage. In the first few years, the whole group spent a lot of time on construction and exploration, and also under a lot of pressure.
Later, Yang Chen slowly realized that 4D printing seems to be a mechanical category, but it also involves a lot of materials and organic chemistry knowledge. After the previous trial and error, he finally made some achievements.
For example, the 2019 paper "4D printing reconfigurable, deployable and mechanically tunablemetamaterials",[2] published in Materials Horizons was rated Materials Horizons 2019 Outstanding Article。
Figure | Related papers (Source: Materials Horizons)
After graduating with a doctorate, Yang Chen returned to China to Shenzhen, obtained the recognition of overseas high-level "Class B" talents in Shenzhen and joined Shenzhen Mofang New Material Technology Co., Ltd. as a mechanical engineer for equipment research and development. Mofang mainly does projection micro stereolithography (PμSL) 3D printers, 3D printing materials, and terminal product research and development. The company has the world's leading ultra-high printing accuracy, high-precision processing tolerance control capabilities.
He said: "PμSL is a micro-nano-precision 3D printing technology that I have been studying and using during my PhD, so I am still very optimistic about the development prospects of this technology and want to contribute to the development and promotion of this technology." ”
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reference:
1、Yang C, Luo J, Polunas M, et al. 4D‐Printed TransformableTube Array for High‐Throughput 3D Cell Culture and Histology[J]. Advanced Materials, 2020, 32(40): 2004285.
2、Yang C, Boorugu M, Dopp A, et al.4D printing reconfigurable, deployable and mechanically tunablemetamaterials[J]. Materials Horizons, 2019, 6(6): 1244-1250.