Human practices is a systematic work, from the origin of the project to it finally becoming a product, human practices will play an indispensable role. It is not a part of our project but a medium for the project to interact with the real world. A good project cannot be without excellent human practices work.
This year, we have guided our human practices in the form of problem orientation. How about the experience of conventional detection methods? We made questionnaires to investigate. What is the demand for new detection methods? We interviewed nurses in the hospital. We look for appropriate detection methods through a large number of literature, and obtain professional advice through consulting experts and professors. We share projects with other teams at various online exchange meetings, and they will raise our shortcomings. We collect data from testing equipment manufacturers to understand the status of industrial development. In addition, we also use online media to promote our project to expand its influence, and calculate the function and cost of the equipment to find its market position. We studied the safety regulations and environmental protection regulations, and formulated a reasonable equipment management plan to make it meet the standards of practical use.
1. Intuitive understanding (why we notice detection about coronavirus?)
1.1 An experience of misdiagnosis
Because of the outbreak, one of our team members was trapped in school and couldn't go home. In the lonely detention life, he developed some fever, cough and other symptoms, so he went to the hospital immediately. The hospital's initial test results told him he had COVID-19, which saddened him. After a short period of isolation, he was told after a second test that the previous test had been a misdiagnosis and that he did not have COVID-19. This led him to understand the shortcomings of existing detection methods, and he hoped to develop a more efficient detection method. When other iGEMers learned this, they decided to support his idea, so our team moved on to developing new detection methods.
1.2 Experience of volunteers
One of our team members became a volunteer during the epidemic and participated in many actions during the epidemic prevention and control phase. In her practice, she also noticed that the importance oftesting equipment and there were some defects in the current testing methods.
1.3 Media reports
Early media often reported the misdiagnosis and mutation of coronavirus. It has been reported that some people have been diagnosed after three tests, and there are also reports that the coronavirus has mutated into many new subspecies. These reports have different opinions, showing that there are many difficulties in the detection of coronavirus.
2. Information collection
(why a new detection method necessary?)
2.1 literature reading
We looked up a lot of literature to learn the principle of current nucleic acid detection. Combined with the actual performance and theoretical analysis, we found that the current detection method has flaws like low accuracy, long time cost, concentration of testing resource and so on. We also found some literatures discussing the site mutation of SARS-CoV-2, which tell us that mutation detection is necessary.
2.2 Public survey
To investigate the feasibility of our idea and the further direction of development, we sent a survey about the public’s awareness of COVID-19 and their willingness to detect COVID-19 nucleic acid in Feb, 2020. It turned out that most people have a basic understanding of COVID-19.
After that, we did another online investigation about the detection of COVID-19 in April, 2020, which finally showed that most people have not been tested for nucleic acids. But if there is a small, convinient testing device, most people are willing to support its development and testing. In addition, through the surveys, we found that the public’s demands for the COVID-19 detection products are high sensitivity, high accuracy, low price, wide popularity and easy to operate.
his is the exact same product that we want to develop.
2.3 Enterprise Investigation
The Beijing Genomics Institute, the leading domestic enterprise of nucleic acid amplification testing, reached 0.6 billion US $ in income from 2020.1.1 to 2020.3.30, which increased by 209.73--232.96% year-on-year. Its net profit reached 1.530 million to1630 million, an increase of 672.83 to 723.35% year-on-year. It is the sales of COVID-19 kits that lead to the high profit. Their products covers more than 180 countries and regions around the world, and its overseas sales have reached 35 million copies (data source BGI's 2020 semi-annual forecast).
In the mean time some other production companies' profit also rised because of the dramatically increased demand of testing kits. DAAN GENE has reached 620-800 million profit in the first half of this year, an increase of 924.57 to 1222.03 percents year-on-year. The company's daily production capacity of testing reagents has increased from 100,000 to 200,000, which has now reached 300,000 to 500,000. According to market demand, the production capacity may reach more than 1 million per day. Up to now, the company has produced more than 30 million copies of COVID-19 detection kits.
As of April 14th, more than 15 million people have been tested globally (not including China, and only 200,000 in India). In fact, the shipment of kits is far more than 15 million, because each person needs to be tested at least 2 times. If the diagnosis is confirmed, the whole process requires at least 6 to 8 tests. With the expansion of the testing population, including statistics on the number of asymptomatic patients, herd immunity measurement, and resumption of work screening, the conservative assumption is that the total demand of tests will reach 20 times the current confirmed number. That is, the number of people who need to be tested globally is 40 million. The next 25 million people need to be tested, that means the number of test kits required for the corresponding test may reach 100 million. Assuming the average price of 50 yuan per box, the scale will reach 5 billion.
These commercial data tell us that the market of testing equipment is expanding, and a new type of testing equipment will have enough commercial value.
2.4 Doctor interview
In order to further integrate our projects and actual needs, we also conducted interviews with frontline nurses. We interviewed nurse Wang from affiliated Hospital of Jining Medical University from Shandong Province. Because he have experience in the treatment of the worst-hit areas of the pandemic and have a better understanding of the problems that need to be solved in the nucleic acid detection process, which helped us to design the POCT to match the actual detection more closely. Through interviews, we learned that throat swab nucleic acid testing is mainly used for the detection of suspected cases, and that the shortage of kits was very serious at the beginning of the outbreak. The detection kit has played a very important role in the entire treatment process, hence the necessity of the accuracy rate. Only accurate detection can facilitate our next treatment and other work. If possible, the kit is simpler, more convenient and better. Based on the results of this interview, we further improved the accuracy of our detection and enhanced the humanization of the equipment design.
3. In depth literature research and technical consulting (how to make our design)
We studied more literatures, including Zhang Feng's Sherlock technology, and finally found E-CRISPR as the detection method. However, at the beginning of the project design, we didn't know how to implement a POCT test, so we consulted the professors in our school and got a lot of suggestions. When we first wanted to use the traditional microfluidic platform, Professor Gu Zhen generously provided us with digital microfluidic technology and electrochemical workstations. We considered E-CRISPR in the design framework, and then found DNA Walker according to the literature. With regard to the design of DNA Walker, we want to add it to the framework of DMF. After consulting Dr. Ma Peiqiang, we changed the carrier from the original gold ball to magnetic beads, which solved the problem of solid-liquid separation.
4. Meet up (Where to exchange project)
On July 11th, we participated in the Eastern China Meetup hosted by Jiangnan University. At the meeting, we received many useful suggestions from Ambassador Zhang Nan on Human Practices. After that, we were honored to invite professor Wu, PI of last year’s Grand Prize winner——NCKU_Tainan team to comment on our work. On the Northeastern Coastal Areas Online Meetup, we were excited to find that teams from NEU_China and ZJUT_China were also developing new detection methods for the novel coronavirus. Then we held a seminar with them, learned about each other’s projects and exchanged our opinions. We created a chat group and shared some of our survey results. The data provided by ZJUT_China solved our problem of insufficient sample size of the lower and higher age groups.
After investigation, we found that the cost of nucleic acid detection in China can be controlled at 120 yuan(roughly 18$) per time, and the time from sampling to getting results is controlled within one day. Assuming that the accuracy is equivalent, d-e-detector will be able to detect 150 yuan(roughly 22.5$) each time, and control the time from sampling to getting the results within 2 hours. It seems the advantage of D-E-detector is not so obvious, but we shouldn’t forget that it is a POCT device. Its portability and ease of operation will make up for the cost defects. By changing the reagents and disposable consumables, D-E-detector will be able to achieve multiple tests. Moreover, D-E-tector can detect multiple viruses simultaneously, which means that a single test will produce multiple results for different viruses. We originally wanted D-E-tector to be used in the family or community, but now it seems that there is no need for the family to bear the cost of the entire equipment. The whole community testing needs can rely on only one D-E-tector to meet!
With the continuous improvement of the project, we need to calculate the advantages and disadvantages of our project compared with the traditional detection methods and other new detection methods. We investigated the current situation of conventional nucleic acid detection methods, as well as the new detection methods developed in the past eight months, and made a horizontal comparison with D-E-detector.
After investigation, we found that the cost of nucleic acid detection in China can be controlled at 120 yuan(roughly 18$) per time, and the time from sampling to getting results is controlled within one day. Assuming that the accuracy is equivalent, d-e-detector will be able to detect 150 yuan(roughly 22.5$) each time, and control the time from sampling to getting the results within 2 hours. It seems the advantage of D-E-detector is not so obvious, but we shouldn’t forget that it is a POCT device. Its portability and ease of operation will make up for the cost defects. By changing the reagents and disposable consumables, D-E-detector will be able to achieve multiple tests. Moreover, D-E-tector can detect multiple viruses simultaneously, which means that a single test will produce multiple results for different viruses. We originally wanted D-E-tector to be used in the family or community, but now it seems that there is no need for the family to bear the cost of the entire equipment. The whole community testing needs can rely on only one D-E-tector to meet!
6. Mutate detection (Is D-E-tector limited to simple detection?)
Through the characteristics of DMF, we can realize the simultaneous detection of multiple channels. Therefore, by setting the types of DNA Walker and E-CRISPR elements in different channels, we can detect different viruses and mutation sites. The D-E-tector designed for use in the community requires only a small amount of channels, and we plan to make a D-E-tector plus, sacrificing the portability of the device in exchange for higher throughput, so as to realize the rapid mutation of multiple mutation sites. This device will be suitable for research institutions, and we will conduct further investigation in this regard.
