(People's ** Health Client Reporter Hou Jiaxin Wang Ning) "In 2023, Tupai's revenue will exceed 100 million yuan. The two major products, the ophthalmic global sweep OCT and the ophthalmic digital surgical microscope, let us stand at the forefront of the industry. Passing over the current achievements, Tupai's eyes are always fixed on the distance, looking at the other side of time. On the last night of 2023, at the R&D center of Topai in the Life Science Park of Changping District, Beijing, Wang Yingqi, co-founder of Topai Medical, and the founding team looked back on the past 7 years.
Tupai was incubated on the platform of Tsinghua Industrial Technology Research Institute. From four Tsinghua alumni to hundreds of R&D teams; From a quiet Tsinghua laboratory, it has developed into a R&D and manufacturing center of more than 10,000 square meters in many places across the country. Topai has become a pioneer in the high-end application of domestic medical equipment in the field of ophthalmology. The success of the company is not an isolated case, and the transformation of dozens of incubated enterprises on the platform of Tsinghua Industrial Technology Research Institute has also ushered in the dawn.
The intersection of medicine and engineering, that is, the cross-integration of medicine and modern engineering technology, is recognized as the key to breaking through the bottleneck technology of medicine. Jin Qinxian, president of Beijing Tsinghua Industrial Development Research Institute, told the people's health client reporter that the medical and health field has always been a key cultivation and incubation area of Tsinghua Industrial Technology Research Institute. Over the years, ITRI has adhered to innovation-driven development, relying on Tsinghua University's leading engineering advantages and Beijing's clinical research resources to promote the integration of medicine and engineering and promote the transformation of achievements.
the insurmountable valley of death".
From the laboratory to the clinic, from the clinic to the product, there are insurmountable valleys in the middle: insufficient investment in R&D resources and industrial resources leads to a low commercialization rate of scientific and technological achievements, and the lack of market maturity of the project leads to a low success rate, forming a "valley of death".
The cross-exploration of the integration of medicine and engineering in China arose in the late 80s of the 20th century. At that time, a new round of institutional reform was carried out in China's colleges and universities, and the engineering majors of comprehensive universities or science and engineering universities were merged with independent medical colleges, which contributed to the strong combination of non-medical colleges and medical colleges; Many key universities have established interdisciplinary research entities characterized by the integration of medicine and engineering.
However, the results of the exploration were not satisfactory. Jin Qinxian recalled that at first, the industry-university-research transformation chain of medical and engineering intersection had not yet been formed, and the research results could not be well connected with clinical needs, and many studies ended in vain. "More than ten years ago, it took at least 10 years to start the transformation of an innovative research results, which is a long and arduous process, with a large number of projects falling in each link of technology development, animal experiments, clinical experiments, approval and registration, etc. ”
According to the "Analysis of the Transformation of Scientific and Technological Achievements in China's Biomedical Field from 2011 to 2020" published by the Chinese Journal of Bioengineering in 2022, at present, the conversion rate of biomedical patents in China is low, and the transformation in some fields lags behind significantly. Taking the field of medical devices as an example, the number of patent applications from 2011 to 2020 was 296329, the number of conversions was 2,366, and the 10-year conversion rate was only 08%。In the fields of chemical drugs, biological drugs, and traditional Chinese medicine, the 10-year conversion rate is only about 3%.
Wang Yongjun, president of Beijing Tiantan Hospital and chief scientist of the Neurology Center, also felt deeply about this. More than a decade ago, when he chose to challenge the world's biggest problems in stroke with a new concept and paradigm – data-driven research – few understood his persistence. In a small conference room, Wang Yongjun faced this blank field alone, designing, calculating, overthrowing, and repeating.
Prior to this, innovation in the medical field was often knowledge-driven, that is, to find interventions through disease mechanisms and targets, and this model of developing new drugs has achieved many achievements in the past, but it has faced major challenges in major neurological diseases. Wang Yongjun said that the first challenge is to find targets, such as Alzheimer's disease, Parkinson's disease, etc., it is difficult to say that these diseases are caused by a single mechanism, so the development of drugs for a single mechanism approach does not seem to work.
Second, the traditional knowledge-driven R&D model of new drugs takes a particularly long time, with an average of 15-17 years for a drug. Third, the success rate of traditional model research and development is very low, and it is difficult to cross the valley of translational death, such as neuroprotective agents for cerebrovascular disease, which have entered the clinical trial stage with more than 1,000 candidates, but none of them have been approved by the FDA.
It is precisely because he saw the limitations of knowledge-driven that Wang Yongjun resolutely embarked on the road of exploration of data-driven research. He hopes to find a solution to reduce the probability of stroke patients through bispecific antibodies through a data-driven approach.
Knowledge-driven is like a positive drive, and if this path doesn't work, we will try it backwards, which is what we call data-driven. Wang Yongjun said.
Wang Yongjun, President of Beijing Tiantan Hospital and Chief Scientist of the Neurology Center. Photo courtesy of the interviewee.
Break down that invisible wall."
After more than eight months, Wang Yongjun and his team "calculated" the answer in millions of data.
Mild stroke and high-risk TIA", "within 24 hours of onset", "aspirin + clopidogrel combined for 21 days", can reduce the risk of high-risk non-disabling cerebrovascular disease for 90 days** by 32%, and there is no increase in bleeding*** Its English abbreviation "chance" happens to be the same as the English word "chance", hence the name. At that time, Tsinghua Industrial Technology Research Institute also began to try new explorations on the transformation of medical innovation achievements.
Jin Qinxian mentioned that in view of the low conversion rate of medical innovation, Tsinghua Industrial Technology Research Institute has conducted a lot of analysis, and believes that the best solution is not to tackle common technologies, nor to raise a large amount of financing, but to build a "platform + ecosystem" system of medical and industrial integration, strengthen resource integration, optimize resource allocation, and expand the scope, quantity and efficiency of resource connection.
In 2017, Tsinghua ITRI initiated the establishment of the Global Health Industry Innovation Center (GHIC), a transformation platform dedicated to providing all-round support and incubation for mid-to-early stage medical device projects.
Tsinghua Industrial Technology Research Institute - Global Health Industry Innovation Center. Photo courtesy of the interviewee.
Also in this year, Topai Medical was established in a 20-square-meter office outside the east gate of Tsinghua University. The start-up team consists of only 4 people, in addition to Wang Yingqi, who graduated from the Department of Biomedical Engineering of Tsinghua University, Professor Huo Li of the Department of Electronic Engineering of Tsinghua University, and his two doctors, Xing Yanfei and Wang Xiao.
In fact, there were many hot 'outlets' in the market at that time, but we finally chose the 'unpopular' track of high-end ophthalmic instruments and equipment. Wang Yingqi recalled, "What we want to do is not only domestic substitution, not only low-quality and low-price, but to break the technical barriers in this field for decades and achieve a real "advantage substitution."
Along the way, they inevitably suffered setbacks after setbacks. Wang Yingqi said that they often say that "fail quickly, summarize quickly, and correct quickly". With high-frequency technical trial and error, the team found the best product technology path in the shortest time.
Many times, we are also involuntarily influenced by overseas products. To give you an example, we initially imitated an imported brand and gave the early prototype an English name; But we later found out that this kind of imitation is meaningless, and what Tupai really relies on is our core technology. ”
Based on strong technical confidence, we gave our first product a resounding 'Chinese style' name - 'Beiming Kun'. The word Beiming comes from Zhuangzi's "Wandering Away", which means broad, deep and mysterious, which also corresponds to the characteristics of our products, with an ultra-high scanning speed of 400,000 times per second, a large depth of field of field of 6mm, and a large field of view of 120°. Its "ultra-wide-angle OCTA" function has become the first domestic ophthalmic device to promote the innovation of China's ophthalmic clinical diagnosis guidelines.
After 3 years of technical research, "Beiming Kun" and "Yaoguang Xing" were released at the National Ophthalmology Academic Conference in November 2020. Since its listing, these two products have achieved the "first" of three Chinese markets for two consecutive years: the first in the industry in terms of sales amount, the first in the industry in terms of sales volume, and the first in the industry in terms of average bid.
In November 2020, Topai Medical (formerly known as "Topai Imaging") brought the world's first 400,000-times ultra-high-speed global ophthalmic scanning OCT "Beiming Kun" to the 25th National Ophthalmology Academic Conference of the Chinese Medical Association (CCOS 2020). Photo courtesy of the interviewee.
Like Ophthalmology OCT, the "Artificial Bone" project incubated on the Tsinghua platform is also one of the typical cases of achievement transformation.
The so-called 'bionic artificial bone' refers to a highly biomimetic artificial bone material in terms of chemical composition, hierarchical assembly structure, and mechanical properties. Wang Xiumei, a researcher at the School of Materials Science and Technology of Tsinghua University, one of the main members of the R&D team, told the Health Times reporter that we have prepared highly biomimetic mineralized collagen fibers at the micro-nano scale for the first time in vitro in the world. Recently, we proposed a strategy of "multi-scale cascade control", and successfully obtained centimeter-scale bionic large wood-based plate laminar bone (ALB) at room temperature, which can be used for bone defect repair at the bearing site.
Wang Xiumei observed an operation at the Department of Neurosurgery at Yuquan Hospital at Tsinghua University. "At the scene, we saw more realistically the special problems and difficulties in the repair of large-scale skull defects in children, which also made me realize that we must learn to break through our own professional limitations and strengthen the interaction between 'doctors' and 'workers', so as to truly break down professional barriers and achieve the ultimate goal. ”
Wang Xiumei said that innovative research in the medical field has its own particularity, such as high technical barriers and industry barriers, in this process, the intersection and integration of medical engineering is very important and indispensable, whether it is medical basic research or product research and development has a strong complementarity. The integration of medicine and engineering is not just a simple 1+1, the key is to achieve the effect of 1+1 2 in the integration process.
The intersection of medicine and engineering is difficult in "cross-border" communication, but it is valuable in the common value pursuit behind the technology.
The integration of medicine and industry leads industrial upgrading.
In the process of medical-industrial integration, it is not only the R&D and product ends that have benefited, but also the industrial chain and the first chain have been upgraded.
The OCT products developed by Topai involve thousands of components, and the number of components of microscope products has reached nearly 3,000. Since 2017, Topai has developed thousands of low-level components in more than 30 categories and more than 200 subcategories. Wang Yingqi introduced that at present, most of the parts used in Tupai OCT products have been localized: in terms of quantity, more than 95% have been localized; In terms of value, 70% of them have been localized.
Wang Yingqi introduced that such as high-speed data acquisition cards, interferometers, photodetectors, 4K-CCD, microscope optical zoom, precision optical imaging systems and other core modules and components inside the modules are independently designed by us and jointly developed and manufactured by domestic manufacturers, which helps us break through the performance limit of the standard chain and reduce the dependence on imported devices.
In the past seven years, Topai has integrated almost all the optoelectronic industry chain resources related to ophthalmic instruments and equipment in China.
In the past, we always said that Germany and Japan are manufacturing powers, but in fact, we found that after 30 years of development, China's optoelectronic industry chain has quite strong technical strength. The reason why it seems that the output of high-end devices is lacking is that it is often "stuck" in the downstream of the ** chain - the demand side. Although the business has technical reserves, it lacks the continuous and stable technical cooperation demand for downstream products, and it is difficult to achieve the upgrade to the level of cutting-edge technology. ”
Topai has worked together with China's optoelectronic chain manufacturers to manufacture high-end devices that exceed the import level, which has promoted the continuous upgrading of the industrial chain.
In fact, whether it is internal medicine or surgery, traditional Chinese medicine or Western medicine, the development of medicine has never left engineering technology, and all the revolutions and innovations of medical technology are inseparable from the advancement of engineering technology.
Industry, academia, engineering, research and medicine should be put on a table, so that the integration of medicine and engineering can be better realized. In Wang Yongjun's view, clinical demand is the source of innovation, industrial development is the driving force of innovation, and it is possible to achieve twice the result with half the effort by complementing each other's advantages. In Tiantan Hospital, not only do we often hold exchanges of industry-university-research and medical talents, but also a special office for the transformation of scientific and technological achievements, in order to promote the development of medical and engineering integration.
Talking about the impact of medical-industrial integration on the industrial chain, Wang Yongjun introduced that in the field of cardiovascular and cerebrovascular diseases, medical-industrial integration has a strong leading role in the upgrading of domestic related industrial chains. Taking cerebrovascular disease thrombolytic drugs as an example, 60% of the world's manufacturers are now in China.
The integration of medicine and engineering is not only conducive to original innovation, but also promotes the upgrading of related industrial chains. Wang Yongjun said that the trend of medical-industrial integration has brought unprecedented development opportunities for the development of medical-industrial integration industries such as medical robots, AI medical diagnosis, telemedicine, medical big data, biochips, and bio-3D printing. If we can overcome these difficulties, we will not only be able to transform more research results, but also enable the industrial chain behind it to complete industrial upgrading, so as to make our medical industry system more competitive in the world.
The integration of medicine and engineering has become a new wave of development.
In recent years, the integration of medicine and engineering in China has been highly valued. Jin Qinxian said that many documents issued by the state have relevant plans for the integration of medicine and engineering.
In September 2020, the General Office of ** issued the "Guiding Opinions on Accelerating the Innovation and Development of Medical Education", which requires giving full play to the comprehensive advantages of comprehensive university disciplines and establishing a "medicine + X" multidisciplinary cross-integration platform and mechanism. In February 2023, the Ministry of Education and other five departments issued the "Reform Plan for the Adjustment and Optimization of the Discipline Setting of General Higher Education", which clearly aims at the forefront of the development of medical science and technology, vigorously promotes the deep cross-integration of medicine and science, engineering, liberal arts and other disciplines, and cultivates emerging disciplines such as "medicine + X" and "X + medicine".
Nowadays, the integration of medicine and engineering has gradually changed from a policy call at the national level to a conscious action in the field of innovation.
Jin Qinxian said that the integration of medicine and engineering in China started late, but the development speed is relatively fast, and there have been many successful explorations. From the perspective of development direction, there are mainly two kinds of import substitution and original innovation. In the early stage of the cross-development of medicine and engineering, import substitution was the main direction chosen by most researchers, but with the continuous improvement of China's technological innovation level, there are more and more researchers who are committed to original innovation.
Innovation in the medical field is like a "crown jewel", and behind the high technical difficulty, there are also broad market prospects.
According to the "2019 Annual Report on the Transformation of China's Scientific and Technological Achievements (Universities and Research Institutes)", in 2018, the contract amount of 3,200 universities and institutes in China to transform scientific and technological achievements in the form of transfer, licensing and investment reached 177300 million yuan, a year-on-year increase of 522%, of which there were 32 units with a total conversion contract amount of more than 100 million yuan, a year-on-year increase of 143%。
It is worth mentioning that among the 32 projects exceeding 100 million yuan, 12 are medical projects, which can foresee the great value of the transformation of medical scientific research achievements in the future.
At the same time, Jin Qinxian also mentioned that China's medical-engineering integration has made a good start, but it still faces problems such as low conversion rate and lagging innovative ideas, which need to be further explored and planned.
To promote original innovation, it is necessary to strengthen the integration of medicine and engineering. In Jin Qinxian's view, the following three aspects need to be done.
First, continue to improve or clarify the policy of integration and transformation of medical engineering. The integration of medicine and engineering is characterized by knowledge-intensive, multidisciplinary, long cycle of achievement transformation and high risk. The specificities of the biomedical field should also be taken into account as much as possible when formulating relevant policies;
Second, strengthen the training of interdisciplinary talents and discipline construction of medical and engineering. At present, the interdisciplinary disciplines of medicine and engineering in China are usually classified into the category of engineering, and there is a lack of in-depth integration of medicine. To open up the development channel of interdisciplinary talents in medicine and engineering, it should be promoted in many aspects such as discipline setting and talent selection;
Third, strengthen forward-looking prediction and increase R&D-related equipment. There is still a lack of forward-looking innovation direction guidance in the field of medical-industrial integration in China, and relevant institutions need to further give a clear direction. In addition, the construction of research wards in hospitals is still lagging behind, and relevant equipment needs to be further strengthened.
Clinically-oriented medical innovation transformation and medical-engineering integration have gradually become everyone's consensus, and innovative elements such as government, industry, academia, research and funding are forming a joint force, and a new era is slowly opening. Jin Qinxian said.
References: Dong Wu, Feng Xiao, Min Yuan, Yubao Chen, Hongxiang Zhang. 2011 Analysis of the transformation of scientific and technological achievements in the field of biomedicine in China in 2020. Chinese Journal of Biotechnology, 2022, 42(1 2): 191-201 doi:10.13523/j.cb.2111046.