As we went on with our projects, we tried to consider how our project will impact the world and took the time to create meaningful activities that will allow us to look at our projects from various aspects. By engaging with the potential stakeholders of our project including doctors, patients, and elderly, we were able to approach heart failure from both social and scientific aspects, ensuring our project was addressing the actual needs.

All of the activities were crucial in informing us about the overall direction of the project such as stressing the significance of the project, emphasizing the necessary parts, and overcoming minor lacks. Interactions with people who have a deep understanding of heart failure were very helpful throughout the project, constantly reminding us of ways to improve.

The following are our integrated human practice activities:

1. Webinar Hosted by Promega Corporation

There were several problems with cloning steps.

The problems were as follows.

• 1) Ligation vector sample was transformed to E. coli DH5-alpha. But no colonies were observed with high-efficiency cells.
• 2) We checked appropriate insertion of the construct in the vector by gel electrophoresis after reaction with XbaI and SpeI to verify the exact band scale. Insert DNA band was not observed or inappropriate size of insert band was observed.

To troubleshoot related problems, we asked for advice in a laboratory that conducts the cloning experiment frequently, and they provided various ways to solve the problem. They advised us to use large amounts of DNA in transformation or different rates of vector and insert during the ligation process.

Through participating in a webinar hosted by Promega with the help of iGEM, we were able to troubleshoot the issues related to inserting genes into the vector. The following is the screenshot of the webinar, a part where we found a solution to the problem.

Screenshot of the Webinar

This is a slide from Promega webinar. We were able to solve one of the problems we encountered in experiments through this webinar.

2. Doctors Interview

The project focuses on the detection of NT-proBNP as a means to diagnose heart failure. However, what’s more important is the amount of NT-proBNP present in the serum. I would recommend both qualitative and quantitative assessment. It would be great if the HAPPI chip could support a quick diagnosis. Then, HAPPI chip surely will affect heart failure mortality rate positively. Nonetheless, a potential drawback is that countries with inadequate infrastructure have no potential for huge investment and will not be able to adopt HAPPI chip into their medical infrastructure.

U-healthcare system-adopted heart failure diagnosis, which is the ultimate goal, will definitely benefit the diagnosis and treatment of heart failure. Heart failure is not a condition whose symptoms are evident. U-healthcare system will allow convenient detection of the condition at its initial stage and will be beneficial, but the meaningful criteria need to be considered is the patient’s mortality. If released in the future, the HAPPI chip would be beneficial to first-line medical care, i.e. emergency patients, Emergency Medical Services (EMS), and novice paramedics.

In my opinion, the project will be meaningful if the development of the HAPPI chip is feasible.

What we learned

Professor Jong-Wha Lee gave us great advices on the practical aspects of our project. Rather than just focusing on the beneficial aspects, he also shared his opinion on the weak aspects of our project. Our team realized some important clinical aspects, such as the practical utility of the fabricated chip and the importance of quantitative detection of the NP-proBNP as well as qualitiative assessment, because normal people also have it somewhat. Furthermore, we perceived that the development of a low cost biosensor that can be used for early diagnosis and monitoring of heart failure disease is important. As a result, we have tried to apply a simple and low-cost fabrication method for a small chip by using plastic substrates that are very cheap and the GBP-ProG fusion protein we have developled in this study. We also could confirmed that our project is very helpful to many people suffering from heart failure disease.

*All interviews were conducted at Ewha Womans University, Mokdong Hospital.

The 2017 ACC/AHA Focused Update Heart Failure Guideline for the management of heart failure recommends the diagnosis, progress monitoring, prognosis prediction, and prevention of heart failure with the support of a Randomized Clinical Trial research. The results show that the diagnosis using echocardiography of patients with no clear sign of cardiac malfunction but with a potential for heart failure development and also with high levels of NT-proBNP leads to a decrease in asymptomatic left ventricle malfunction. I think the HAPPI chip your team has been developing can be a meaningful device for heart failure patients. Moreover, it would be useful in not only early diagnosis of heart failure but also real-time monitoring with mobile phones. However, I concern the price of the diagnostic chip. You should consider if your proposed method would be more cost-effective than the NT-proBNP method which is currently used in clinics.

What we learned

Kyung-Jin Kim is a professor who has extensive knowledge in the field of clinical cardiology. She has provided us with detailed advices, citing a clinical heart failure guideline and comparing our project to the NT-proBNP method currently utilized in clinics. She has also raised meaningful questions on the applicability of HAPPI chip for us to consider. Thanks to the professor, Kyung-Jin Kim, our team was able to take some time to compare the specifications of our HAPPI chip with the conventional method. These considerations helped us to contrive our HAPPI chip in specific ways for its feasible implementation in clinics. Therefore, we have focused on a low-cost fabrication method of HAPPI chip in this study.

HAPPI chip will obviously have a positive impact on people, especially the elderly. Diagnosing heart failure isn’t easy because heart failure has a poor prognosis. Usually, within three years, 30-40% of patients with heart failure pass away. Furthermore, with the aging, heart failure patients may not be aware of the disease and miss the golden time for their appropriate treatment. For example, heart failure is common among the elderly, therefore they often think that the symptoms of heart failure are due to their age. From this point of view, HAPPI chip could be very meaningful as it gives people the opportunity to diagnose heart failure early.

However, the biosensor chip seems to be expensive. NT-proBNP levels are usually measured from about 50 to 100 US dollars. It would be much more expensive to invent this diagnostic device to a chip. If it is commercialized, the unit price will be lower, but it may become more expensive depending on the demand. However, I think it could be popular if a kit comes out in the market at an affordable price with high accessibility. If a low priced chip is developed, it could be used widely in developing countries.

The implementation of the U-healthcare system in the diagnosis of heart failure will be a great advantage to the current diagnosis and treatment of heart failure. Nevertheless, more research is needed to ascertain if it even affects mortality. It should be verified through scientific evidence as to tell whether the mortality rate is reduced.

What we learned

Overall, professor Wook Bum Pyun has provided invaluable advice on numerous aspects of our project. He has commented not only on the medical aspects of HAPPI chip but also on practical ones, such as economic and social perspectives. Moreover, his use of specific data in describing current heart rate mortality and pricing of NT-proBNP measurement allowed us to ground our project on reality. As a result, we were able to analyze some obstacles related to the practical aspects of our device, which helped us to improve our project. Thanks to professor Wook Bum Pyun, we were able to address both the medical and practical aspects of our device.

3. Heart Failure Patient Interview

The main purpose of our team’s project is an advanced diagnosis of heart failure. Therefore, it was essential for our team to hear from actual patients who have been suffering from heart failure. By doing so, we aimed to discuss the reasons why individuals acquire such diseases and to relate the difficulties they face in their daily lives.

Through a contact with a medical institution in Seoul, our team had an interview with a middle-aged, male patient who has been suffering from heart failure since 2016. The patient had been working as an office worker for nearly 30 years since his twenties and admitted that the main reasons for the disease he acquired were his lack of exercise and poor diet schedule. When we inquired about the symptoms that he had noticed before he was diagnosed as having heart failure, he said that the symptoms were the shortness of breath and swelling of his ankles and legs.

Through the interview we had, our team reinforced the main purpose of our project with the creation of the most effective heart failure diagnostic kit. Especially because not only its early diagnosis and treatment but also effective patient monitring are extremely important when heart failure occurs, our team was motivated once more to make a contribution into the world through making the diagnostic kit and in combination with mobile phones.

4. Heart Failure Campaign at Welfare Center

We have visited the Mapo Welfare Center to alert elders about the diagnosis and prevention of heart failure. Worldwide, despite the stark reality that heart failure has shown a high growth rate, unfortunately, Koreans are relatively less aware of the condition. Therefore, we conducted a Q&A session followed by a discussion on the topic of heart failure targeting Korean senior citizens (a high-risk group).

First, we explained the symptoms of heart failure and proper prevention methods. We prepared about seven large infographic boards for elders in order to make them understand the information easily. Elders whose acquaintances suffer from heart failure were particularly interested in prevention measures. We emphasized the steady exercise and a healthy diet as a necessary prevention method.

Our project of developing the HAPPI chip is based on the concept of Ubiquitous healthcare. U-healthcare is a healthcare service based on the combination of telemedicine and ubiquity. U-healthcare provides healthcare to patients regardless of age, location, and time, simultaneously increasing the quality of healthcare. U-Health Care System is a relatively new and unfamiliar concept even for the new generations. Particularly to the elders who have little exposure to the modern devices that enable the ubiquitous telemedicine, the U-Healthcare system would be even more difficult to understand. Therefore, we thought that the biggest challenge was explaining this concept to the seniors. We introduced this concept through a hypothetical U-healthcare system where the elders’ smartphones are equipped with our HAPPI chip. If the HAPPI chip gets developed and commercialized, doctors can easily monitor the patient’s conditions just with the elders’ effort as little as dropping their blood on the chip-linked mobile phones.

The activity at the Mapo Welfare Center was very successful. Even after the campaign, some seniors showed enthusiasm for our project. Finally, we concluded our campaign was useful for all of us and our audiences by volunteering at the center and assisting the elders with their meals.

After the campaign, we volunteered to serve lunch to the elderly at the welfare center.

5. Development of Education Materials for Campaign

We collected official documents and leaflets from The Korean Society of Cardiology (KSC), healthcare center, and hospitals. We selected useful contents and developed the materials for campaign of preventing heart failure in Mapo Welfare Center.

The materials included in the panel are listed below;

• What is heart failure?
• Current status of heart failure prevalence and the effect of heart failure
• Prevention method 1, 2, 3
• What are symptoms of heart failure?
• Action guideline for prevention of heart failure
• Why is early screening important?

We also handed out daily schedule for the elderly in effort to prevent heart failure. The following is the handout mataral.