Form

We had an interview with Doctor Yuan-Yen, Chang on March 20th at Chung-Shan Medical University. Doctor Chang is the professor of microbiology. His specialties are virology, Immunology, and biotechnology.

Purpose

As a professor of microbiology, doctor Chang knows well about the knowledge as well as the mechanism of respiratory disease. Through this interview, we would like to know more about the background knowledge of respiratory disease and the diagnosis of influenza. We drafted the questions below:

• How to detect influenza in a lab?
• What kind of sample does the professor recommend for influenza rapid test?
• Do you recommend using the blood to detect the flu directly?
• Do you recommend using swabs to detect flu directly?
• What are the current methods of influenza detection?
• Do you have any suggestions for our fast screening products?

Process

• Generally, a bacterial culture is performed in a lab, and the whole process takes about 3 to 7 days.
• The general influenza samples have two forms, blood, and swab. The advantage of a blood sample is a lot amount at one time. The advantage of the swab is non-invasive.
• Dr. Chang recommended swab as the sample of our influenza rapid test. Since taking a blood sample needs to penetrate patients’ skin with needles, it is more invasive than taking a swab sample and less accepted by patients. Besides, drawing blood can only be conducted by professionally trained people, it isn’t good for promoting simple use. What’s more, a blood sample is valid only when there are viruses in the blood or so-called viremia.
• Dr. Chang recommended that we design a kit that can test lots of pathogens and is user-friendly, which means everyone, even people who aren’t professionally trained, can use it. To know more about the technique he suggested we visit Adimmune Corporation.

Feedback

After the interview, we had a clearer idea of our product. We decided to take swabs as the sample of our device. Our device needs to be fast, accurate and easy-to-use. We can make our product as kits in the near future, and we can ask Adimmune Corporation for more details.

Form

On March 28th, we interview the doctor of the Medical Laboratory at Chung Shan Medical University Hospital.

Purpose

Our team wanted to know the opinions of the Medical Laboratory scientists for rapid influenza diagnostic test products and ask for some advice. We would like to know how laboratory scientists operate rapid diagnostic tests and if they have confronted any problem. Besides, we wanted to know the methods for testing our finished products and ask for opinions about our conception. To figure out these questions, we drafted the questions below and interview a laboratory scientist.

• Why are the control lines of rapid test kits designed by many companies different?
• Can we get patients’ samples from the Medical Laboratory in order to test our product? Or can we take our product to the medical laboratory to test it?
• How can we test our product?
• Why does the Medical Laboratory have to use a specific instrument to analyze the result of the rapid test? Can’t the result be read with naked-eyes?
• Why do they choose nasal mucus but serum as the sample for rapid influenza diagnostic tests?
• What is the mechanism of amplifying the signal of a sample in a rapid influenza diagnostic test?
• How high are the sensitivities of rapid influenza diagnostic tests nowadays?
• Is there anything of rapid influenza diagnostic tests that you want it to be improved?

Process

• Each company designs a different control line because they use different kinds of mice to produce antibodies. Just to make sure the sample can combine with the control line. Usually, they design various control lines, test and check the result, and choose the best one for production.
• The Medical Laboratory doesn’t keep samples after testing, and can’t give samples to us for testing our product, either. Without patients’ consent forms, patients’ samples can only be used for diagnosis. Biotechnical companies usually mix two different kinds of viruses as a sample for product testing at an initial stage. Too many different kinds of virus used at once are not recommended because it becomes hard to analyze the effect factors of the results. Types of viruses that will affect results are noted in Instruction manuals for doctors and laboratory scientists.
• We have to apply for experimental plans in order to get samples from the Medical Laboratory.
• The experiments to test products with different kinds of viruses must be taken in biosafety level-3 laboratories.
• Different medical laboratories of hospitals use different rapid influenza diagnostic tests.
• As for the data analyzing instrument we saw in the lab, it is used when the amount of the influenza virus in the sample isn’t enough, or for some fluorescence-used products that are hard to read with naked eyes. By using the instrument, there will be a standard for if patients are infected by influenza.
• Rapid influenza diagnostic tests always use samples collected from nasal mucus but serum because it is more difficult and more invasive to draw a patient’s blood than doing swabs, and the amount of the virus in nasal mucus is more than in blood, too. That is the reason why products nowadays seldom use samples collected from patients’ serum.
• When doing swabs, doctors will get into the patient’s throat as deep as possible to make sure they collect enough samples. The products nowadays seldom have a mechanism to amplify sample signals but they improve sensitivities by getting rid of the impurity. Some products contain enzymes to break down other bacteria or viruses to reduce interference. However not every company does so.
• The sensitivities of the products nowadays are not so good. Besides, many factors affect accuracy, for example, the ways doctors collect samples, the false negativity of products, or the disease process of patients is still at an early stage.
• It is impossible for patients to use the rapid influenza diagnostic test by themselves because the procedure of collecting samples must be done by well-trained doctors. Also, after using rapid diagnostic tests, patients still need to go see doctors and get treatments. It is worthless to let patients do the rapid test by themselves.
• We can try some ways to get rid of the impurity of other viruses or improve the sensitivities of our rapid test. It will benefit clinical medicine.

Feedback

The Medical Laboratory scientists said there were always many samples in the lab waiting for them. He thought that our products would be able to help them save time. Through the interview, we found that swabs are a better way for our product. We then chose swab instead of blood as the method to get samples.

Form

Our team went to a medical exhibition called “ Medical Taiwan” on March 28th.

Purpose

In order to compare the concept of our products with those in the market, we would like to take references from other products and know the needs of the market to see what aspect we can apply to. Through the posters and the reports in the exhibition, we would like to know the opinions the government and the media held for infectious diseases.

Process

• We saw a product called “Redeye”, which can detect invisible blood in our urine. It helps people discover their diseases such as colorectal cancer, kidney disease, bladder cancer earlier. It gives people awareness and makes them go to hospitals earlier for appropriate treatments. We found that early detection is very important in every kind of disease. People can use the device at home, which avoids the inconvenience of going to hospitals or getting invasive examinations. The company which produced “Redeye” wanted to combine their product with smart toilets and helped people examine their health with excreta. The device can connect to smartphones through wifi to get data.
• We saw many companies emphasized that their devices can detect many kinds of diseases or abnormal body function index. There was a product called “MSA—Blood” which can detect problems with a very small amount of patients’ blood. It can detect diabetes mellitus, liver function, cardiac function, kidney function, metabolism function, etc. Because of its convenience and fast analyze time, it can be used in some specific places such as clinics, care centers, nursing houses, ambulances, community health centers, schools, or rural areas. With these advantages, it might be possible to use it in every single family in the future. The market strategies and applications of this device are similar to ours.
• Many posters and reports were talking about the development of medicine, we were very impressed by one of them. The report was about the history of the development of infectious diseases in Taiwan, from SARS to influenza. The next trend of influenza is often predicted by WHO. But what can we do if WHO doesn’t predict right? The president of Min-Sheng General Hospital—Chiung-Lang Wang pointed out that if there is a shortage of the supplement of vaccines, or WHO predicts the wrong subtype of influenza for us to make vaccines, clinical workers and senior managers in hospitals will be under great pressure. In this situation, what hospitals and the public need are the technique of rapid diagnostic tests to help them figure out whether the disease is serious or slight. He recommended that faster and more efficient rapid diagnostic tests need to be developed.

Feedback

Through visiting the exhibition, we saw many different kinds of diagnostic products. These products could be used not only in hospitals or clinics but also in some institutions which need more medical care, such as nursing houses, community centers, etc. Moreover, we found out the importance of more rapid and efficient rapid diagnostic tests which can help control epidemics.

Form

Dr. Feng-Yih Yu is the professor of the department of biomedical at Chung Shan Medical University who specializes in screening tests, protein chemistry, food microbiology and toxicology, and immunochemical techniques and so on. We had an interview with him on 2nd, April.

Purpose

After decided our project topic as rapid screening of influenza, we have been looking for a better way to enhance the correctness and accuracy of rapid screening and promoting the convenience of its usage. Later, we found several papers which concern aptamers acting the function as antibodies, hence came up with the idea that whether it is possible to develop our influenza rapid screening with aptamers. Therefore, we visited Dr. Yu to ask if our concept is feasible. We drafted the questions below:

• Are aptamers able to act as antibodies in screening tests?
• How to select aptamers and to apply them to our rapid test paper?

Process

• Dr. Yu was developing screening tests with aptamers
• Yes, aptamers can perform the function of protein antibodies. In fact, they perform even better than antibodies since they are smaller in size.
• We apply SELEX(Systematic Evolution of Ligands by EXponential enrichment) to select the aptamers that have high affinity with our target proteins.
• Since Dr. Yu specialized in the screening tests of toxicant molecules, which are smaller than our target, influenza proteins, he wasn’t 100% sure whether aptamers would fit protein or not. However, Dr, Yu indicated that since the principle is the same it is supposed to work, and encouraged us to take a try.
• Aptamers are easier to process. If we want to have the color changed we can add nanogold or other substrates to the tails of aptamers.

Feedback

After the interview, Dr. Yu confirmed that applying aptamers to screening is highly possible. Therefore, we decided to develop our influenza rapid screening test with aptamers.

Form

We had an interview with Doctor Rung-Tzung, Tsai on April 4th at Chung-Shan Medical University. Dr. Tsai is a professor of biochemistry. His specialty is molecular biology, biochemistry, biotechnology, and structures of proteins.

Purpose

As a professor of biochemistry, Dr. Tsai has been studying the structure of proteins for his whole career. He has a thorough understanding of viruses, bacteria, and even animal proteins. The purpose of this interview is to understand how to decide our protein biomarker of influenza. We drafted the questions below:

• We want to take the proteins of influenza as our target for SELEX. Could you give some advice to us?
• We find people often use HA and NP as influenza’s target proteins. If we want to produce them by ourselves, what recommendations or advice would you give us?
• How to produce proteins of high purification?

Process

• There are many complex chemical reactions in the human body fluid and it’s hard to predict. Aptamers have to bind to target protein when doing SELEX. Dr. Tsai recommended us using purified protein to do SELEX.
• Generally speaking, the water-soluble ability of HA is worse than NP. Dr. Tsai thought that to easily purify, using proteins that are better water-soluble and add His tag to the tail is a better choice. We can use Nickle columns to purify proteins.

Feedback

Through this interview, we have a better concept for our experimental direction. After discussed with teammates, we chose NP as our target protein. On one hand, we can use NP to distinguish between influenza type A and B; on the other hand, with the feature of better water-soluble, it’s easier to purify proteins. Last but not least, we invited Doctor Rung-Tzung, Tsai to be our instructor.

Form

Our team had an interview with Professor Yu-Ling Chen at Cheng Kung University Hospital on August 6th. Prof. Chen is the director of Cheng Kung University Graduate Institute of Medicine. She had written many papers about aptamer and SELEX, who is one of the authoritarian people in this field.

Purpose

We want to ask questions about our experiment. On one hand, we would like to explain to the professor about the difficulties that we had encountered during the experimental process, and asked the professor for possible reasons and solutions. On the other hand, we wanted to learn and improve our experimental process from the experience of the professor about SELEX experiments. We showed the data of our result (figure1 to figure5) to the professor and drafted the questions below:

• We have found through experiments that there was an unknown molecule with high molecular weight that appeared after SELEX. It seemed to be related to the template concentration, primer concentration, and the number of cycles. Why? How can we solve it?
• From our data, it is found that as the Template concentration or the number of PCR cycles increases, a by-product of about 100 bp would appear first and resulted in the ladder-like band. Then it evolved into a by-product with high molecular weight and resulted in the band gathering near the well that had a strong signal. How can we explain this situation?


Figure 1. Test of template conc. Condition



Figure 2. Test of template and dNTP conc. condition (Wash compared with Probe)



Figure 3. Experiment to find out the best template conc. condition of PCR.



Figure 4 & 5. Test of PCR cycle number.

Process

• Template concentration or a high number of Cycles may has confused the Template and the Primer, resulting in incorrect copying or an unexpected secondary structure.
• The number of PCR cycles was too high. The general PCR condition after SELEX is 15 cycles. After conducting SELEX for many times, the product was relatively pure, and the number of cycles of PCR could be increased. It is recommended that the PCR part be tested first to find the most suitable conditions.
• The band of the product that appeared at about 100 bp may be the result of the double-stranded PCR product which hadn’t denatured, so the position of the band was higher than 87 bp which we expected. If there was no band, it represented that there was no product for PCR.
• Although the ladder-like by-products had occurred in the past, it hadn’t occurred that all by-products gathered at the top. However, a strong signal should be caused by its high molecular weight, not its volume.
• The professor recommended that we conducted the SELEX experiment as follows:
  • Step: SELEX – PCR with Elution – Check by DNA page – Denature – Renature – Purify – Cryopreservation – Denature – Renature – SELEX
  • Control the number of PCR cycles, template concentration, and primer concentration during PCR to avoid the appearance of by-products.
  • Prior to each round of SELEX, using a Primer with beads to separate and remove the complementary sequence generated during the PCR process.
  • Quantify the PCR product before running SELEX to determine how much DNA is added to SELEX.
  • Increase the volume of PCR for subsequent testing and experimentation.
  • While denaturing, the recommended temperature is 95 degrees Centigrade and the recommended time is 10 minutes. While Renaturing (folding), it is recommended to slowly return the sample to room temperature from 95 degrees Centigrade instead of putting it on ice.
• The professor would start the specificity test after 5th round of SELEX. Under normal circumstances, the specificity will be enhanced successively. Usually, we can get the ideal result at the 7th to 8th round, and then we can conduct DNA sequencing. If conducting SELEX above 9-10 round, there may appear some impurities.
• Specificity test: Choose an unrelated protein (albumin) as a negative control, run the ELISA test with the proteins of the influenza A and B viruses, and confirm the result of DNA page after PCR.
• Affinity test: Conduct sequence dilution with Aptamer or Target. After getting a result of a binding curve, plot with Prism and get the KD value.
• The aptamer with good affinity should have a KD value below 10 nm, and an acceptable range for the value falls within 10-100 nm.

Feedback

Through this interview with Prof. Chen, we learned about better condition settings during the experimental process of SELEX, which coincided with the conclusions that we had gotten from the experiment. We were more confident to revise our experimental process. From the experimental process described by the professor, we obtained some experience and skills about the experimental process of SELEX, which could reduce the time of finding the solution just by ourselves.

Form

On August 7th, we came to visit the Department of Public Health of Taiwan. We had an interview with three government officials.

Purpose

In order to know about the prevention work of influenza nowadays and how our product will affect the government, we drafted the questions below:

• How does the government collect the data of the influenza subtypes every season? Which department collects and analyzes the data?
• What role does the rapid influenza diagnostic test play in the prevention work?
• How does the government know which subtype to make for vaccines next season?
• What is the countermeasure of the government for preventing influenza?
• In what situation should the clinic or hospital report the epidemic of influenza to the government? How do they report?
• Were the cases reported to the government diagnosed by using rapid influenza diagnostic tests, or according to their symptoms?
• Most of the rapid influenza diagnostic test nowadays have the problem of false negativities. Does it an issue for the government during the prevention works?
• Is the disease spreading map helpful for preventing influenza in Taiwan, or developing countries?
• Where are the influenza virus during the rest period between every outbreak? Is it possible to stop the spreading of the virus during the rest period?
• If there is a product which can detect influenza more rapidly, correctly, and even cheaper, what impact will it bring to the public or the government?

Process

• Taiwan Centers for Disease Control (CDC) will collect the data from laboratories engaged by special arrangement. These laboratories in every city cultivate the virus and report the data to the CDC. After CDC collects and analyzes the data, they announce the subtypes of influenza viruses that are prevalent each week. If there’s a rapid diagnostic test with higher accuracy and efficiency, it would help the government for the statistics of epidemiology.
• Most of rapid influenza diagnostic test products nowadays have up to 50% of false negativities. Doctors will take the result of these products as a reference, and consider other factors such as individual symptoms.
• There are many subtypes of influenza viruses, so it is hard to combine all of the subtypes in one rapid influenza diagnostic test. If only some common ones, it might be possible. It might have an impact on the type of influenza vaccine the government buys.
• WHO announces the subtype of influenza vaccines every season, and the government will take reference from it. Biotechnical companies provide vaccines globally, so it is hard to get specific types only for certain regions.
• The Department of Public Health monitors crowded places such as prisons, nursing houses, nurseries, schools. These places have to report if a cluster infection happened. A so-called cluster infection means that there are two or more infected cases each day. The reporting system is online and opens 24/7. After then, the Department of Public Health will conduct environmental disinfection and urge people to put on masks and even prescribe preventive medicine. Besides, the Department of Public Health will send propaganda to non-government institutions, reminding them to carry out preventing measures such as keeping windows open. The Department of Public Health will provide them a checklist to help them make sure that they are prepared for the upcoming outbreak.
• For general non-government institutions, the cases reported have to be diagnosed by doctors. Doctors take the results of rapid influenza diagnostic tests as a reference, combined with patients’ symptoms to make diagnoses.
• The disease spreading map is not useful for the prevention works in Taiwan. For the one-day-life circle in Taiwan, the virus could spread around Taiwan in a very short time. For the developing countries which their traffic is inconvenient or with broad territories, it may be helpful.
• During the rest period between each outbreak, influenza viruses don’t disappear. However, they exist in human bodies. It is hard to find all of the influenza viruses during the rest period and eliminate them.
• If there is a product that can detect influenza more rapidly, correctly, and even cheaper, the clinics will be willing to buy so they can know if the patients are infected by influenza more efficiently. The government can also start their prevention works earlier and additionally prevent the widespread of influenza viruses.

Feedback

During the interview, we found that the rapid diagnostic test products nowadays are of low sensitivities. Although doctors make diagnoses combined with patients’ symptoms, they aren’t confident if they are always right. While the government has the responsibility to prevent the spread of influenza, it is vital that influenza being diagnosed earlier and correctly to help the government promote preventing work smoothly. Besides, we found that our product could help the statistic of epidemiology. The officials encouraged us to develop our product and it might help prevent influenza. Last but not least, we learned what exactly the works the government does to fight against influenza.

Form

Our team had an interview on August 10th with Taiwan Centers for Diseases Control Dengue Vector virus and Rickettsia Laboratory, which launched a new type Virus Serotyping rapid test kit this year.

Purpose

While searching for factories which produce rapid diagnose test product, we saw the information of the first reagent produced in Taiwan on the webpage of Taiwan Centers for Diseases Control. We found the laboratory that developed the technology. This time, we hope to get to know more about issues we have to be aware of while developing our rapid diagnose test product. Also, the plan after the production is very important, so we drafted the questions below.

• Rapid diagnose tests could hardly avoid the problem of false negativities. In this situation, what is the position of clinical application?
• What kinds of certification should a successfully developed product get before it is launched in the market?
• How do general laboratories manufacture and market outsource?

Process

• Dengue fever is a major project for the prevention of infectious diseases in Taiwan every year. AsiaGen Corporation developed the product “Dengue fever NS1 rapid diagnose test” and it is the only product certificated in Taiwan now. The product can detect 4 types of dengue fever at the same time. While using RT-PCR, it needs 6 hours to get the result, this product only takes 30 minutes to examine dengue fever. It is a very convenient product, consuming little time and saving spaces. The product has 98-99% of sensitivity and has low false negativities. However, it is only for front line examination use. Dengue fever has to be confirmed by rTP—ELISA.
• We asked them about how they confirm the sensitivity. They said they have tested it by the dengue virus in their laboratory. Besides, they suggested we test our product with the whole influenza virus.
• They suggested we visit the Innovation Incubation Center of our school, for the questions such as applying for patents.

Feedback

Through the interview, we were recommended to test our product with the whole influenza viruses. After then, we discussed this and decided to test our product by conducting TCID50 assay and serological test.

Form

Our team had an interview with Ph.D. Chih-Ming Chen, who is the Senior Director of the Business Development of TaiGen Biotechnology.

Purpose

hrough the interview, we would like to know if it’s possible to develop a medicine with aptamers and understand the market of influenza medicine nowadays. We drafted the questions below:

• What is the mechanism of your(TaiGen) new influenza medicine—TG1000? How does it function as a medicine and a vaccine at the same time?
• In the industry of influenza medicine, what aspect do the biotechnology companies focus on? What is the present situation of the influenza market? Why does TaiGen choose influenza as the subject to develop?
• How do biotechnology companies estimate the potential and prospect of a newly developed product? What aspect should be noticed?
• Can aptamers be applied to medicine?

Process

• Mr. Chen said that the mechanism of their new medicine—TG-1000 is Cap-snatching. It inhibits the duplication of influenza viruses and has shown well result on animal tests. It resists Type A and B and avian influenza H7N9 infection. Moreover, the validity period of the medicine lasts for 72 hours, which is better than Tamiflu. There isn’t only one molecule of the virus in one cell, so medicines have to reach a certain concentration to have a function. The viral molecules will combine with the medicine through random collision. By measuring the medicine's inhibition constant (IC50) or so-called binding constant can let us know their affinity to viruses.
• The influenza virus often infects lung cells, however, the concentration of the medicine in the blood doesn’t represent the same as in the lung. It is important to prove that the concentration in both places is proportional. Also, confirming that whether the medicine can exactly achieve the goal is very important.
• The product is design as an oral medicine for easier taking in. Different diseases have different consideration, for example, intravenous injection make medicine spread faster in body but oral medicine is more convenient for patients to take in.
• Besides providing community immunity, the advantage of their product is its slow metabolism rate. It keeps the effect even longer than a week, so it doesn’t need to be taken earlier before infection like a vaccine, and the effect is also much better than the vaccine.
• The limitation of the medicine is that the safety range of the dosage is narrow. If a child showed resistance to some other flu medicine, doctors can’t increase the dosage for the concern of safety. Although TG100 hasn’t passed a human test, the result of an animal test showed that the dosage can be increased.
• The reason why they choose to develop influenza medicine is that there are 3 to 5 million people affected by influenza annually, and Tamiflu, the flu medicine most commonly used, has many limitations needed to be improved.
• If technology advanced more in the future, it is possible to design an antibody by just knowing the structure of the protein of a virus. With gene sequencing, we are able to compare the similarity between different viruses similar and apply the same medicine to similar ones, which reduces the cost of the process to develop new medicines.
• As for applying aptamer to medicine, Mr. Chen agreed with our idea. He said medicine is not restricted to only a specific type. He emphasized that collecting data is very important.

Feedback

Through this interview, we got a lot of information about developing medicine. Besides, we knew more about the defects of influenza medicine nowadays. The importance of developing better medicine for influenza is worth noticing. Mr. Chen gave us a positive answer to our concept of applying aptamer to treatment. We then came up with the idea of applying aptamers to preventive medicine.

Form

We visited “TRANS Conference”, which was the biggest conference in biotechnology in Asia. The topic of the conference is “Transforming Healthcare, Transcending Limit”. We had conversations with the entrepreneurs in this conference.

Purpose

We would like to know other newly developed biotechnology products. We wanted to learn from those products and found how we could modify our products.

Process

We recorded the process of our observation and listed out the features of some products below:

• eNano Health Limited--Kiss & Tell—1st ever Saliva-Based Glucose Monitor: The product takes saliva as a sample instead of blood to examine glucose.
• eNano Health Limited--Manage Health Risk Before Feeling Sick: The product lets users know their eating conditions through convenient testing tools. If there is a risk of their health (such as a high-risk group of diabetes), the users can eat the food developed by the company “eNANO P4 Food”. Users can use the App to share data with physicians and track their physical condition at any time to achieve health management.
• Helios Bioelectronics Inc. --Disease detection platform: The probe is coated on an electronic wafer, and the sample is reacted with the wafer, and then an electronic sensor is used to know whether a disease is present or not. The sample can be nucleic acids, proteins or cells. Through real-time digital results, combined with big data analysis, it can assist clinical diagnosis to achieve precise medical goals. The probes are coated on the electronic wafer by using covalent bonds, and they are well designed and were highly specific. Because the cost of the wafer is high and the entire wafer can’t be full of probes, so a dot distribution is required. In addition, the wafer is currently not reusable. The product directly relies on the change of the electrical signal to know the result (coloring is more troublesome).
• Papivax Biotech Inc.--HPV therapeutic vaccine: The HPV vaccine currently on the market is a preventive vaccine. However, the incubation period of HPV is long. If the abnormality is detected but not reach the level of becoming cancer, the patient will have to endure this unknown suffering for a long time (about 5~10 years). Therefore, the newly developed therapeutic vaccine, using prime-boost therapy, can break into the DNA fragment of HPV, activate T cells through cellular immunity, attack infected cells, and prevent infection from spreading. We asked the researchers of the company some questions about how to avoid DNA degradation. They said it is difficult to know and they have observed through the amount of virus in the course of treatment. Then we asked how to confirm that the DNA injected to human bodies won’t become another pathogen. They said these DNAs do not enter cells but only induce T cells.
• La Vida Tech—WaCare: The product plays a role in preventive medicine. It helps users connect with friends and relatives, hospitals and health education units by entering various indicators of a body to form a network of care. If there are any abnormalities, the users’ friends, relatives or physicians can immediately know the situations and remind them. As for online health consultation and remote medicine, if users have health-related concerns, they can get professional and correct information through consultation with dietitians, pharmacists, and doctors.
• Studio1labs—Smart Sheet: Through the sensing elements inside the sheets, the heartbeat, breathing, posture changes of a patient lying on it are detected. Chronic disease and the condition of a postoperative patient can also be tracked.
• Guzip Biomarkers Corporation—Cervical cancer detection paper: By detecting the methylation of DNA on the uterine surface, the product can determine whether there is a potential risk of cervical cancer.

Feedback

We documented how these products and the conversations with the entrepreneurs inspired us:

• eNano Health Limited--Kiss & Tell—1st ever Saliva-Based Glucose Monitor: We started to think of the possibilities of developing our product as using saliva as the sample.
• eNano Health Limited--Manage Health Risk Before Feeling Sick: The idea of this product is very interesting and could be a business model for a combination of atypical forced marketing kits. In addition, the idea of App management seems to be applicable to our influenza detecting product.
• Helios Bioelectronics Inc. --Disease detection platform: We discussed the possibility of applying aptamer to an air purifier, the researchers of the company thought it an interesting idea. We could apply an electronic wafer to our air purifier design.
• The principle is that when the target substance in the sample is attached to the probe (aptamer), it changes the electronic arrangement of the wafer and further changes the electrical signal. In order to make the wafer reusable, we then think about whether there is any way to get the attached object to fall off the probe. The probe is connected to the target by hydrogen bonding, and the probe and the wafer are connected by covalent bonds. There should be other methods.
• Papivax Biotech Inc.--HPV therapeutic vaccine: We came up with an idea of applying our product to a therapeutic vaccine. The company's products correspond to the concept of our therapeutic vaccine. The therapeutic vaccines of our works also include the part of injecting DNA (aptamer) into bodies, but the principle is different. Our concept is inhibiting viruses to infect cells by binding to the viruses. Their product injects DNA into human bodies. It helped us figure out the problem that whether aptamer will degrade in human bodies and whether it will become another risk of infection. After the interview, we started to study how to stabilize the DNA injected into human bodies and how to enhance the signal.
• La Vida Tech—WaCare: We asked the possibility of introducing our product to their App. The results of our product can be determined by naked eyes and it doesn’t require special equipment. Small-scaled hospitals, clinics, and even kindergartens can use our product and get results directly. However, since the accuracy of influenza screening is not very high, there may be false-negative results. If our product integrates with the app, users can get diagnosed through the results of our product and symptoms. They can also get medical advice and information. We thought it a great opportunity to cooperate with the company and develop an App.
• It was a precious opportunity to know different products in the market. There were many inspiring ideas at this conference. We came up with more concepts that we can apply to aptamers after attending this conference. We not only inspected and studied from other newly developed products but we also confirmed some of our idea through the discussion with the entrepreneurs.

Form

Our team had an interview with Ph.D. Victor Tang, who is the Senior Research Chemist of New Product Research & Development Department of Eternal Materials Company on August 27th.

Purpose

The researchers of the Vector virus and Rickettsia laboratory introduce us to the company whom they transferred their technology—External Material Company. We would like to know more about technology transfer, or so-called transfer of technology(TOT), so we drafted some questions below.

• What roles do technology transfer companies play while producing rapid diagnose test products? What is the characteristic of External Material Company?
• How to distribute the profit of technology transfer? How to assign a different type of technology transfer (exclusive license or not)?
• How long does it take from receiving the technology and producing the final product?
• We would like to introduce our research and the issue we have confronted and ask for recommends.

Process

• External Material Company can meet the clients’ requirements, providing monoclonal antibodies in a specific way. The company is now developing antibodies for detecting vector viruses and infectious diseases. Using their product--Serotype-specific Dengue NS1 Antigen Rapid Test Strips, which is easy to use, can detect NS1 protein in whole blood. It gets correct and detailed information with only a little amount of sample, which helps the government and medical institutions to identify the virus and provide more information about dengue fever. The product can also distinguish four types of dengue fever, which can be used for data statistics and assists airport customs to know whether passengers are infected by dengue fever in a faster way. Traditional methods can’t distinguish the subtypes of dengue fever. The sample has to be sent to laboratories to analysis, which might take one day. The product shortens the processing time to only 30 minutes.
• Because the technique was provided by the government, and the government doesn’t give an exclusive license, so what External Material Company gets was a non-exclusive license. It means that if other companies want to use this technique, they can also get it.
• In fact, aside from the antibody, the key point of producing a rapid diagnostic test is the formulation of the buffer. How to avoid cross-reaction is very important.
• As for distributing the profits, the External Material Company paid money for the technique to the laboratory first. If the company gets the certification, they would give a reward. If they sell the product to other countries, they have to pay a proportion of money back to the laboratory.
• External Material Company could have accomplished the designation of the product in one year since they had made similar products before and applied the experiences to the Dengue fever test kit. Without related experiences and professionals, it may take at least 3 years.
• The characteristic of External Material Company is they provide antibodies by themselves, which reduces cost and they don’t need to worry about the shortage of antibodies in the market.
• About the issue of DNA sequencing that our team is confronting, Tang Ph.D. gave us some suggestions. The first is about how to make confirmation after DNA sequencing. Generally, antibodies and antigens can be amplified with ELISA, but the signal of the aptamer is very small which is closed to the background level. Tang Ph.D. suggests we use some simulation software such as Gene Duck, Auto Duck®, and Discovery Studio. We can put the aptamer sequences in these softwares and simulate if the aptamer can combine with the protein. Some laboratories thought that SELEX is hard to conduct so they simply use softwares to find our the aptamers they want and synthesis the sequence.

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Through the interview, we knew more about TOT which is important for our entrepreneurship. Besides, we got to know that simulation softwares are useful for simulating whether aptamers are able to combine with the protein. We then tried to use the softwares to simulate our aptamer sequences.