Timeline
What we do?
IHP
Through case studies, we proposed two project directions, one is biofuel cells, and the other is cancer detection using hairpin as a probe and circRNA as a biomarker
Mar 17
Tzu-Kang Sang
Should I choose a project on cancer screening or biofuel cell? Neither is feasible; there are too many variables.
Read more Mar 15
After team discussions, we have decided to focus on cancer screening as our project theme.
Mar 16
Kai-Ti Lin
What type of cancer should we choose as our research focus? We should look into cancers that are currently difficult to detect, such as liver cancer and pancreatic cancer.
Read more Mar 22Chun-Chao Wang
A detection method primarily based on hairpins is feasible, and sequence design is not too challenging, but we need to thoroughly study the mechanism
Read more
Hsing-Ying Lin
Inquiry about the project:
1. We need to amplify the signal for circRNA.
2. We need to confirm the method for purifying RNA from blood.
3. When selecting circRNA biomarkers, they should have significantly different
expression levels and high specificity.
Revised project focus on liver cancer
Hsing-Ying Lin
H1, H2, and H3 would be more complex, and coating them on nitro cellulose membrane could be challenging. It seems more feasible to use commercially available PCRD assays with Dig and FAM antibodies for testing.
Read more Apr 7
Hong-Yao Chen
Liver cancer may not be a suitable target for our detection method, considering that we aim to screen diseases through blood samples. If liver cancer could be detected through circRNA, it might already be at an advanced stage, and intervention may not be as effective. Therefore, doctors suggest that colorectal cancer or other cancers related to the digestive system could be better screening targets. Additionally, our screening method has significant advantages for early detection.
Read more Apr 22
After discussions, we have proposed two amplification
methods:
1. Amplifying circRNA with RT-RPA or RT-LAMP and using PCRD for detection. (The
specific
amplification method is yet to be determined.)
2. Amplifying circRNA with RCA and developing a custom cassette for visualization
using
a hairpin structure or using the redshift caused by self-aggregation of gold
nanoparticles for colorimetric detection. (The specific detection method is yet to
be
determined.)
And target disease focus on colorectal cancer.
Hsing-Ying Lin
1. We will use a tube of blood as the specimen, rather than
just a
drop of blood, as the concentration of circRNA in blood is likely to be low.
2. Our focus will be on colorectal cancer, and we will identify two or more
circRNAs
with high specificity and sensitivity to serve as biomarkers.
3. In the Dry Lab, we can train machine learning models to capture and recognize
the
color changes resulting from the aggregation of gold nanoparticles in photographs.
4. For detection after RCA, we will utilize the gold nanoparticle colorimetric
method but may not necessarily require hairpins.
Guo-Tai Hong
Since our samples are derived from blood, as opposed to fecal occult blood tests, our detection method has a significant advantage in detecting cancer at an earlier stage. The accuracy of our method will require step-by-step validation with clinical data.
Read more May 9
1. Searching for methods to synthesize circRNA independently
(in
vivo or in vitro).
2. Exploring the use of thiol-modified DNA to attach it to gold nanoparticles.
3. Researching and comparing primer design for RPA and LAMP.
Hsing-Ying Lin
1. LAMP primer design is more complex and requires too many
primers; let's start with RT-RPA.
2. Use thiol-modified DNA for attachment to gold nanoparticles.
Cheng-Yao Chen and Hsing-Ying Lin
1. Opt for in vitro synthesis of circular RNA.
2. Select T4 RNA ligase 2 as the enzyme for circularizing RNA.
3. Considering the challenges with a 300-bp circularization, it's advisable to
be
prepared for potential failures. It might be best to explore alternative methods for
initial testing of combination the gold nanoparticles and probes.
4. Due to the extensive experimental validation required, it's a good idea to
plan
experiments thoroughly and conduct multiple aspects simultaneously to expedite the
experimental process.
Chun-Chao Wang
1. To initially test the gold nanoparticle method, we can
start by
using insert ligation and then run gel purification to obtain large fragments of
ligation products. Subsequently, we've found that asymmetric PCR (AELA) can be
employed
to generate single-stranded long DNA fragments for probe-conjugated gold
nanoparticles
testing.
2. After performing cloning, it's crucial to send the samples for sequencing.
3. Confirm whether the reverse transcriptase will disrupt the DNA-RNA hybrid
during
the RCA process.
We fix our project and design following experiments
Mentor Varshiny G
If you cannot determine the concentration, you can try to identify the upper and lower limits of amplification instead.
Read more June 29
Check all detailed experiments for each part.
Start conducting gold nanoparticle experiments.
Jian-Ming Huang
1. Taq DNA polymerase can sometimes add an extra adenine (A)
base
to the 3' end of DNA fragments.
2. Using PFU DNA polymerase is a great choice, as it is a high-fidelity
polymerase
that is less likely to add extra adenine (A) bases at the 3' end of DNA fragments.
3. I can provide PFU DNA polymerase.
Jian-Ming Huang
I am willing to provide equipment and materials for running gels, including TAE buffer, agarose, and bacterial culture-related equipment.
Read more July 18
Hsing-Ying Lin
1. Confirming the Details of Each Part
2. Verifying All Medications/Chemicals
3. Providing Relevant Support for SEM Imaging
Chung-Yu Chou
1. You can add a bit more tetrachloroauric acid to directly
increase the optical density (OD) of gold nanoparticles.
2. Recommendations for SEM preparation.
Jhong-Sheng Chen
This interview provides us with rapid screening technology, as well as professional advice from a biological science expert. This will help us gain a deeper understanding of this emerging field and achieve more breakthroughs in future research. Also, he recommends reinterpreting the actual Project steps to ensure the research is in the right direction. He mentioned a teacher Wang, Hong-jun who may have relevant expertise in rapid screening and cancer
Read more Aug 14
Ching-Hsuan Lin
Let us realize that we may not have organized our report logic properly, which makes it challenging to convince consumers to purchase our product. Also, he informed us that any medical equipment (including hardware and software) needs certification from the Taiwan Ministry of Health and Welfare, and the same applies to other countries
Read more Aug 20Chia-En Lien
He recommended accessing global-level disease data from the Global Burden of Disease (GBD) to support the project. This purpose outlines his intention to guide and enhance the project's foundation with relevant and reliable data.
Read moreSabrina Yao
After the discussion with Sabrina Yao, our team changed the way we presented and connected the whole project with a clearly focused storyline.
Read more
Start conducting all parts of experiments.
Aug 22
Ching-Hsuan Lin
1. We have observed that the structure of linear RNA is more
stable than circular RNA. However, when we refer to the stability of circular RNA,
we
mean that it is less prone to enzymatic degradation within the bloodstream, rather
than
just its structural stability.
2. The multiple peak of gold nanoparticles can be determined by calculating the
average.
3. Experimental results can be cloned and prepared for sequencing to confirm the
accuracy and integrity of the sequences obtained.
Jhong-Ren Wang
After the interview, we learned about the inconveniences patients face when suffering from colorectal cancer, and also reminds us that our research is not just an invention or a report; it requires a comprehensive understanding from top to bottom to fully grasp the real needs.
Read more Aug 29
Start designing 3D model of our hardware equipment.
Jeng-Fu You & Peng-Wei Hsu
Doctors raised economic
considerations, making us aware
that our product's impact may
vary depending on each
country's healthcare policies,
providing us with valuable
insights.
Furthermore, if successfully
commercialized in the future,
doctors expressed support for
collaborating with health centers
to make colorectal cancer
screening affordable for
underserved populations, aligning
with our goal of reducing
healthcare inequality
domestically (in line with SDGs 17
- Reduced Inequality).
Kuo-Chih Su
1. Since our hardware model requires a large printing
volume,
multiple 3D printers are provided here to help with printing. The main material
used
is
resin.
2. The first version of the model is printed for the first time
Make corrections to the shortcomings of the first version of the model, such as leaving gaps for fitting, and design models and components for automated equipment devices. Design the second-generation model.
Kuo-Chih Su
1. Provide recommendations for the resin's heat resistance
temperature.
2. Adjust issues regarding printing mirroring.
3. Offer a
second round of
3D printing.
Overview
Colorectal cancer ranks among the top three in incidence and mortality rates in Taiwan, and it also holds a top-five position globally. Early detection of colorectal cancer significantly improves chances of successful treatment. Addressing this unmet need, developing a fast, painless, and highly accurate screening tool or technology could effectively prevent the progression of colorectal cancer and increase early treatment rates.
To enhance our project, we sought advices from professors in various fields, continually adjusted our experiments, and interviewed startup companies to learn about entrepreneurship and promotion, making our product visible worldwide. We also engaged with gastroenterologists and patients to validate its alignment with market needs.
Professor
Tzu-Kang Sang
2023.03.15
Purpose of the Interview
Professor Sang is an expert in the field of neuroscience and neurodegenerative diseases research. He also has experience mentoring students in participating in the iGEM competition. Therefore, when we had a preliminary blueprint for our project, we consulted Professor Sang in hopes of determining the project's direction and feasibility with his assistance.
Key Insight
At the time, we found cancer screening and biofuel cells intriguing research topics. We had already gained a preliminary understanding and planning of the technologies to be used through case studies. Professor Sang accurately pointed out the challenges that developing cancer screening methods would face, including how to target specific biomarkers in cancer screening and the cost considerations when screening multiple sequences for the same disease. As for the biofuel cell, he suggested that we seek out more specialized experts.
Acquisition and Improvements
Through this consultation, we gained a clear understanding of the shortcomings in our experimental planning and literature support. We also became aware of practical considerations, such as funding, and therefore, after this consultation, we continued to search for relevant information and professional support for both topics.
Kai-Ti Lin
2023.03.22
Purpose of the Interview
When we were choosing the topic, we
asked Kai-Ti Lin, a professor in the Department of Life Sciences of our school. She is doing
cancer-related research, so we asked her the following questions.
1. Is choosing breast cancer a good topic for our project?
2. Is there a way to make gold nanoparticles more specific?
Key Insight
1. The professor mentioned that pancreatic cancer or ovarian cancer would be more promising
research projects than breast cancer. Despite the abundance of breast cancer research papers due
to its common occurrence, the public may not be very receptive to our reagents.
2. Check if it can be modified to become irreversible (covalent) in order to connect the
hairpin.
3. Determine how to implement irreversible covalent bonds.
Acquisition and Improvements
After this meeting, we learned that the focus of cancer screening targets may need to shift towards ovarian cancer, pancreatic cancer, or other challenging-to-detect cancers. Their detection is more complex, making them valuable subjects for study. Additionally, the professor advised us to explore methods for implementing irreversible covalent bonds, which is also a valuable suggestion for our future research.
Chun-Chao Wang
2023.03.24 & 2023.06.21
Purpose of the Interview
Professor Wang's research is primarily focused on understanding the mechanisms and regulatory aspects of gene expression and signaling networks in human breast cancer. Once we confirmed that our project was related to cancer screening, we engaged in extensive discussions with Professor Wang regarding the feasibility of our research ideas. We are honored to have him as our instructor, and during our interactions with him, we gained valuable guidance and insights to enhance our project's feasibility and success.
Key Insight
In the early stage of our project development, our team browsed through numerous pieces of literature to verify our design of the probe on gold nanoparticles but not sure if it's feasible to use RNA as screening target as most research use DNA-based target. Professor Wang expressed confidence in the feasibility of a detection method primarily based on RNA. He also emphasized that while sequence design is not overly challenging as there's already plenty of paper work , a thorough understanding of the underlying mechanism is essential.
To initiate testing of the gold nanoparticle method, Professor Wang proposed a stepwise approach. Starting with insert ligation and subsequent gel purification, this method allows for the generation of large fragments of ligation products. Additionally, it was suggested that asymmetric PCR (AELA) could be employed to produce single-stranded long DNA fragments suitable for probe-conjugated gold nanoparticle testing. These practical steps provide a clear path for experimental setup and validation. He further highlighted the importance of sending samples for sequencing after performing cloning. This step is crucial for confirming the accuracy and integrity of the cloned DNA sequences, ensuring that the project proceeds with reliable data.
Another significant consideration raised during the consultation was the potential impact of reverse transcriptase on the DNA-RNA hybrid during the RCA (rolling circle amplification) process. Professor Wang recommended a thorough examination to confirm whether reverse transcriptase might disrupt this process.
Acquisition and Improvements
In conclusion, the insights gained from the consultation with Professor Wang provide a robust framework for advancing the project's development. The feasibility of a hairpin-based detection method, a stepwise approach to testing with gold nanoparticles, the importance of sequencing for cloning confirmation, and the need to assess the impact of reverse transcriptase on DNA-RNA hybrids all contribute to a well-rounded and informed research strategy.
Hsing-Ying Lin (Principal Professor)
2023.03.24
Purpose of the Interview
As the primary advising professor, Hsing-Ying Lin specializes in the study of the development and application of IoT smart healthcare real-time sensing systems and analysis methods in translational medicine, as well as the development and clinical analysis applications of plasma resonance-enhanced sensors. Additionally, Professor Lin's expertise extends to cancer-related diseases, particularly brain tumors. To ensure Professor Lin comprehends the purpose of our project, our research direction, and our experimental design, we organized a meeting to provide a comprehensive explanation of our project and our potential goals for the competition.
Key Insight
Our team member explained the following thing of the project:
1. The necessity of signal amplification for circular RNA.
2. The need to validate the RNA purification method for blood samples.
3. When selecting circRNA biomarkers, they should exhibit significantly distinct expression
levels and high specificity.
Acquisition and Improvements
After the meeting, the primary advising professor, Hsing-Ying Lin, gained a clear understanding of the project's concept, the challenges we identified during our goal brainstorming session, and the objectives we aimed to achieve. She fully recognized our needs and provided relevant scientific research and papers to help our team further explore potential solutions to our challenges. further thoughts and find the solution to our struggles.
2023.04.27
Purpose of the Interview
In order to develop a more convenient and feasible method for detecting Colorectal Cancer, and given the uncertainties surrounding our current project, we requested a meeting with Professor Lin to inquire about the usability and ease of implementation of our methods.
Key Insight
Professor Lin expressed concern that our proposed methods involving H1, H2, and H3 could be overly complex, and the process of coating them onto a nitrocellulose membrane might present challenges during experiments. Therefore, it appears more feasible to consider using commercially available PCR assays with Dig and FAM antibodies for testing.
Acquisition and Improvements
In conclusion, after several days of discussions regarding various methods related to H1, H2, and H3, our team decided to change our approach and explore the use of PCR assays with Dig and FAM antibodies for testing.
2023.04.28
Purpose of the Interview
In order to provide an update on our current progress and maintain continuous communication with Professor Lin, our team held a meeting during which we discussed the entire process of detecting circular RNA in sample blood and the responsibilities of the Dry Lab.
Key Insight
The team reached a consensus regarding our primary research focus, which is Colorectal Cancer. We have decided to identify two or more circular RNAs with high specificity and sensitivity to serve as biomarkers. The Dry Lab will play a crucial role in training machine learning models and providing assistance to the Wet Lab for the utilization of gold nanoparticles.
Acquisition and Improvements
We used a tube of blood as the specimen rather than just a drop of blood, as the concentration of circular RNA in blood is likely to be low. Additionally, we aimed to identify two or more circular RNAs with high specificity and sensitivity to serve as biomarkers. In the Dry Lab, we trained machine learning models to capture and recognize color changes resulting from the aggregation of gold nanoparticles in photographs. For detection after RCA, we employed the gold nanoparticle colorimetric method, although it may not be the only method utilized.
2023.05.23
Purpose of the Interview
With the aim of finding a simpler method for primer design and experimentation, our team held a meeting with Professor Lin to explore the best approaches for our project.
Key Insight
Compared to the complex LAMP primer design, RT-RPA appears to be a more feasible option for our team, as it does not require as many primers. Thiol-modified DNA could be a valuable resource for attaching to gold nanoparticles.
Acquisition and Improvements
Our team opted to use RT-RPA instead of LAMP primers. Additionally, we utilized thiol-modified DNA for attaching to gold nanoparticles.
2023.06.16
Purpose of the Interview
To gain a deeper understanding of how to conduct the entire experiment, our team met with Professor Lin. During the meeting, we learned about both in vitro and in vivo methods. Additionally, we discussed the challenges we encountered while attempting to circularize RNA and explored potential improvements for our experiment.
Key Insight
As outlined in the following four
points:
1. Opting for in vitro synthesis of circular RNA.
2. Selecting T4 RNA ligase 2 as the enzyme for circularizing RNA.
3. Acknowledging the challenges associated with a 300-bp circularization, we should be prepared
for potential setbacks. Exploring alternative methods for the initial testing of the combination
of gold nanoparticles and probes may be advisable.
4. Given the extensive experimental validation required, thorough experiment planning and
concurrent execution of multiple aspects can expedite the experimental process.
Acquisition and Improvements
We took into consideration what Professor Lin mentioned during the discussion and sought alternatives for the initial testing of the combination of gold nanoparticles and probes. Regarding circularization, we opted for T4 RNA ligase 2 as the enzyme for circularizing RNA. Furthermore, our team conducted experiments more carefully than before to improve the quality of our experiments and obtain better experimental data results.
2023.07.31
Purpose of the Interview
In alignment with our project requirements, our team aimed to ensure the accuracy of every detail in every experimental aspect. To achieve this, we scheduled a meeting with Professor Lin to review our direction, protocols, and seek her advice on project preparation.
Key Insight
The primary points discussed during
the meeting are as follows:
1. Confirmation of the Details of Each Experimental Component.
2. Verification of All Medications/Chemicals.
3. Ensuring Adequate Support for SEM Imaging.
Acquisition and Improvements
After the meeting with Professor Lin, our team successfully confirmed the details of all experimental components, verified the availability of all required medications and chemicals, and gained a clear understanding of the role of SEM imaging in assisting with experiments.
2023.08.10
Purpose of the Interview
We have observed that linear RNA structures exhibit greater stability than circular RNA structures. However, when referring to the stability of circular RNA, we specifically mean its resistance to enzymatic degradation within the bloodstream, rather than merely its structural stability. The purpose here is to analyze and understand the distinct stability characteristics of linear and circular RNA.
Key Insight
The determination of multiple peaks in gold nanoparticles can be achieved through average calculations. This insight holds significant importance in nanotechnology as it provides a method for deciphering complex nanoparticle spectra. Understanding the relevance of these peaks, whether related to size distribution or composition, is essential for advancements in materials science and catalysis research.
Acquisition and Improvements
Experimental results can be cloned and prepared for sequencing to confirm the accuracy and integrity of the obtained sequences. This methodology of cloning and sequencing represents an ongoing process of acquisition and refinement. It ensures that the acquired genetic sequences are not only accurate but also reliable, serving as the foundation for further analysis and interpretation across various scientific disciplines.
Ching-Hsuan Lin
2023.08.20
Purpose of the Interview
In addition to teaching courses in his research field at the university, Professor Ching-Hsuan Lin also teaches students in the fields of biotechnology internship and entrepreneurship, offering valuable insights into the biotech industry. After iGEM Taiwan Seminar, we took the opportunity to seek Professor Lin's views on our topic. As simulation competition judges, He primarily provided us with insights into the commercialization of our product and the narrative logic in presenting it.
Key Insight
We had a quick review of our project and presentation with Professor Ching-Hsuan Lin, and he mentioned some points that we needed to change before the competition.
Professor Lin ask us two questions first, which are “why it is necessary to simultaneously conduct experiments using two different testing methods” and “what the relationship between AUC and disease sensitivity and specificity is”. These two questions have made us realize that we may not have organized our report logic properly, which makes it challenging to convince consumers to purchase our product. Additionally, the professor informed us that any medical equipment (including hardware and software) needs certification from the Taiwan Ministry of Health and Welfare, and the same applies to other countries. This guidance provides us with the direction for further refining our research.
Acquisition and Improvements
Through our discussion with Professor Ching-Hsuan Lin, we were able to clarify the overall logic of our experiment. We also became aware of potential areas in our presentation that may not have been clear. Additionally, we also begun to collect related information on medical equipment legal regulations, making the entire project more likely to be achievable. Although our time for discussion was limited, Professor Lin's suggestions were extremely valuable, greatly benefiting us and helping us optimize our presentation.
Jian Ming Huang
2023.07.31 & 2023.09.10
Purpose of the Interview
After roughly finalizing the various experimental procedures, we engaged in discussions with Professor Jian-Ming Huang in the hope of further refining the overall experimental process. In addition, we need to perform gel electrophoresis to validate the experiment, so we asked the professor if we could borrow the necessary equipment and also learn from him how to operate it.
Key Insight
Professor Huang has been immensely helpful to our project, not only by providing gel electrophoresis-related equipment, including TAE and agarose but also by generously offering access to bacterial culture-related equipment. Additionally, he has granted us permission to use his laboratory facilities for conducting experiments and also remind us of the experiment's details to reduce the error rate in the experiments of our project. For example, he noted us that Taq polymerase tends to add an extra A at the 3' end, which can possibly affect our circularization.
Acquisition and Improvements
Thanks to the professor's guidance, we have learned how to utilize gel electrophoresis to validate our experimental results. In addition to providing equipment, he frequently met with us over few months to review our experimental findings and provided invaluable advice and guidance. His support has been instrumental in propelling our experiments forward and influencing the direction of our research.
Cheng-Yao Chen
2023.06.16 & 2023.08.21
Purpose of the Interview
We conducted an in-depth interview with Professor Cheng-Yao Chen, a DNA synthesis expert, and the founder of SourcePoint Biotech, a biotechnology startup dedicated to developing novel enzyme-based DNA synthesis technology and platforms. During our interviews, Professor Chen not only provided us with valuable experimental suggestions but also shared insights into the company's background, motivations, and the challenges encountered on their entrepreneurial journey.
Key Insight
Wet Lab
First, when embarking on the in vitro synthesis of circRNA, Professor Chen strongly recommends selecting T4 RNA ligase 2 as the enzyme for circularizing RNA. This enzyme has proven effective in facilitating the circularization process, making it a favorable choice for researchers in the field. He also emphasized the importance of acknowledging the challenges associated with circularizing RNA strands as long as 300 base pairs. Therefore, it might be best to consider alternative methods for the initial testing of the combination of gold nanoparticles and probes. Finally, given the extensive experimental validation required, he stressed the need for a well-thought-out experiment plan and conducting multiple aspects of the experiment simultaneously to expedite the process.
Entrepreneurship
First and foremost, he emphasized the necessity for unwavering passion in the entrepreneurial process. Professor Chen initially worked in the biotechnology industry in the United States, where he realized the potential of his skills in cross-disciplinary integration and the amalgamation of knowledge from diverse fields. This realization fueled his desire for innovation and entrepreneurship, and he stressed the importance of young individuals discovering their passions, believing in themselves, and fearlessly pursuing ambitious goals. Upon returning to Taiwan, Professor Chen founded SourcePoint Biotech, guided by a vision that transcended mere financial pursuits. He believed in providing a new realm of opportunities for the future by making DNA recombination and modification more accessible.
In the process of founding the
company, Professor Chen encountered numerous challenges and reminded us that facing rejections
is a normal part of the journey. He highlighted the need for extensive cross-disciplinary
knowledge integration after venturing into entrepreneurship. Developing a product requires
collaboration among technical experts, marketing professionals, packaging specialists, legal
experts, and more. Therefore, he encouraged us to diversify our knowledge. When it comes to
commercializing a project, Professor Chen provided the following recommendations:
1. Clearly define the product to ensure compliance with relevant regulatory requirements.
2. If the product requires clinical trials, seek out clinical trial specialists and create a
detailed timeline for that.
3. Understand that stabilizing and optimizing technology is key to commercializing a product and
requires substantial human resources and financial investment.
Acquisition and Improvements
In summary, our key takeaways include the importance of refining our screening methods, effectively securing funding, and ensuring compliance with relevant regulations when bringing a product to market. Professor Cheng-Yao Chen's wealth of experiences and insights serve as invaluable resources as we navigate the path to successfully commercialize our project.
Doctor
Jeng-Fu You & Peng-Wei Hsu
Purpose of the Interview
Doctors are our most important future partners, and in order to ensure that our product can truly assist doctors in diagnosing colorectal cancer, we conducted an interview at Chang Gung Hospital with Dr. Peng-Wei Hsu and Dr. Jeng-Fu You. We discussed the current state of colorectal cancer screening methods, related challenges, and the significant impact our product may have on this crucial field of medicine.
Key Insight
Current Colorectal Cancer Screening Methods and Challenges
Traditionally, colorectal cancer screening methods include the following:
Fecal Occult Blood Test (FOBT):
This method is widely used and typically recommended every two years for individuals aged 5.0 to
70. Positive results usually lead to a colonoscopy. It is cost-effective but has a sensitivity
of around 80%, potentially missing early-stage cancers.
Colonoscopy:
Known for its effectiveness but has drawbacks such as invasiveness, the need for anesthesia, and
higher costs. Additionally, the preparation process before the procedure can be cumbersome,
requiring dietary restrictions, bowel cleansing, and fasting.
Carcinoembryonic Antigen (CEA):
This blood test has lower sensitivity than FOBT and is primarily used for post-surgery
monitoring and recurrence tracking, not suitable for early detection, and its rate of increase
varies among individuals.
CT-Colon Imaging (less common):
Uses CT scans to visualize the colon, and it is relatively uncommon.
Despite these screening options, there are still significant challenges, including invasiveness, discomfort, and economic burdens that sometimes discourage people from undergoing screening.
Recommendations for Current Colorectal Cancer Screening
In our interview, doctors expressed concerns about current screening methods:
Family History:
Patients with a family history of colorectal cancer may develop colorectal polyps more
quickly,
making prediction challenging using current methods.
FOBT:
The accuracy of fecal occult blood testing is relatively low, leading to potential false
positives or false negatives.
Colonoscopy Preparation:
Besides invasiveness, the dietary restrictions before colonoscopy are inconvenient, especially
for patients with underlying conditions such as diabetes. Patients may need to adjust their
medication, increasing the risk of hypoglycemia. Doctors and patients need to make additional
adjustments to address these medication-related challenges, ensuring the health and safety of
patients before and after the examination
Cost Issues:
The cost of colonoscopy varies significantly depending on the level of anesthesia. In Taiwan,
where there is universal healthcare coverage, the government subsidizes healthcare costs for the
population. If promoting colonoscopy to the public, its cost would put pressure on Taiwan's
healthcare system.
Patient Compliance:
Despite recommendations for FOBT, some individuals still refuse screening, further reducing its
effectiveness.
Emerging Technologies:
Emerging technologies under research often come with higher development costs and do not
necessarily significantly improve detection rates.
Potential of NanoCircDx
We also introduced our product, NanoCircDx, to the doctors, which is based on the detection of
circular RNA (circRNA) in blood and has the potential to become a cancer biomarker. Doctors saw
several advantages in NanoCircDx:
Ease of Use:
NanoCircDx aims to provide a simpler and less invasive screening method. Blood samples eliminate
the need for bowel preparation and anesthesia.
Enhanced Sensitivity:
Initial research suggests that NanoCircDx may offer higher sensitivity than traditional methods.
Cost-Effectiveness:
As the technology matures, NanoCircDx could become affordable, making screening accessible to a
broader population.
Significantly Reduced Testing Time:
Compared to FOBT, which requires taking test tubes home to collect samples and then returning
them for analysis, which takes at least a day, NanoCircDx's estimated testing time of 2.5 hours
is much faster.
However, challenges include regulatory approval, further technical refinement, and how to ensure cost-effectiveness in a clinical setting.
Acquisition and Improvements
Through this interview, doctors recognized the tremendous potential of our research to provide a simpler, faster, more accurate, and cost-effective method for colorectal cancer screening, addressing the challenges of current screening methods. It may also have future applications in cancer tracking, boosting our confidence in the research. Additionally, doctors raised economic considerations, making us aware that our product's impact may vary depending on each country's healthcare policies, providing us with valuable insights.
Furthermore, if successfully commercialized in the future, doctors expressed support for collaborating with health centers to make colorectal cancer screening affordable for underserved populations, aligning with our goal of reducing healthcare inequality domestically (in line with SDGs 17 - Reduced Inequality).
Guo-Tai Hong
Purpose of the Interview
We inquired Dr.Guo-Tai Hong about the feasibility of using circRNA for colorectal cancer detection and whether our plan aligns with the medical system.
Key Insight
The current fecal occult blood test utilizes immunofluorescence to detect red blood cells (RBCs) in feces. If there is no bleeding, it cannot detect colorectal cancer (the test result is negative). However, with our NanoCircDx, colorectal cancer can be detected at an early stage even in the absence of bleeding.
Acquisition and Improvements
Since our samples are derived from blood, as opposed to fecal occult blood tests, our detection method holds a significant advantage in detecting cancer at an earlier stage. The accuracy of our method will require step-by-step validation with clinical data. Lastly, the product's cost may be too high, so we have decided to conduct the experiment first and then consider cost reduction.
Hong-Yao Chen
Purpose of the Interview
Our department has a tradition of alumni returning for a communication meeting among alumni of the department. During this gathering, our iGEM team presented our planned project to the alumni, hoping they would provide suggestions and financial sponsorship.
Hong-Yao Chen, one of our alumni and a hepatobiliary gastroenterologist, offered valuable suggestions after the communication meeting. This was a pivotal moment in our decision to focus on colorectal cancer as the detection target.
Key Insight
Liver cancer may not be a suitable target for our detection method, considering that we aim to screen diseases through blood samples. If liver cancer could be detected through circRNA, it might already be at an advanced stage, and intervention may not be as effective. Therefore, doctors suggest that colorectal cancer or other cancers related to the digestive system could be better screening targets. Additionally, our screening method has significant advantages for early detection.
Acquisition and Improvements
1. The disease targets the digestive tract organs and detects early cancers.
2. Recognize that current screening tests for colorectal cancer are flawed.
Chia-En Lien
Purpose of the Interview
Dr. Chia-En Lien's role as a judge in the Taiwan iGEM Seminar mock competition serves a specific purpose. He had abundant experiences in medical and biological field, and he also engaged in many medical activities. Due to the reason that our product is related to medical use, so we interviewed Dr. Lien in order to get all-round aspect of our project .This purpose outlines his intention to guide and enhance the project's foundation with relevant and reliable data.
Key Insight
Dr. Chia-En Lien's feedback on the
presentation content is a key insight gained from the interview, and he provides specific
guidance on how to improve the project's communication strategy and overall effectiveness as the
following points:
1. He recommended accessing global-level disease data from the Global Burden of Disease
(GBD) to support the project to be more realistic and impactable.
2. He mentioned about the words we used for presentation in the power point slides should
considered the positive impact or negative impact, for instance, importance is an positive word
and should be used on positive things instead of disease which commonly considered an negative
thing.
3. On the slides of our presentation power points, using more visualization could help the
audience to gain more understanding on the project.
Acquisition and Improvements
The interview process itself represents a crucial aspect of acquisition and improvement. By incorporating Dr. Chia-En Lien's recommendations, the team can enhance their project significantly. This iterative process of gathering feedback, refining strategies, and implementing improvements is fundamental to the project's development, ensuring it evolves to meet the highest standards set by the competition.
Entrepreneur
Cheng-Yao Chen
2023.06.16 & 2023.08.21
Purpose of the Interview
We conducted an in-depth interview with Professor Cheng-Yao Chen, a DNA synthesis expert, and the founder of SourcePoint Biotech, a biotechnology startup dedicated to developing novel enzyme-based DNA synthesis technology and platforms. During our interviews, Professor Chen not only provided us with valuable experimental suggestions but also shared insights into the company's background, motivations, and the challenges encountered on their entrepreneurial journey.
Key Insight
Wet Lab
First, when embarking on the in vitro synthesis of circRNA, Professor Chen strongly recommends selecting T4 RNA ligase 2 as the enzyme for circularizing RNA. This enzyme has proven effective in facilitating the circularization process, making it a favorable choice for researchers in the field. He also emphasized the importance of acknowledging the challenges associated with circularizing RNA strands as long as 300 base pairs. Therefore, it might be best to consider alternative methods for the initial testing of the combination of gold nanoparticles and probes. Finally, given the extensive experimental validation required, he stressed the need for a well-thought-out experiment plan and conducting multiple aspects of the experiment simultaneously to expedite the process.
Entrepreneurship
First and foremost, he emphasized the necessity for unwavering passion in the entrepreneurial process. Professor Chen initially worked in the biotechnology industry in the United States, where he realized the potential of his skills in cross-disciplinary integration and the amalgamation of knowledge from diverse fields. This realization fueled his desire for innovation and entrepreneurship, and he stressed the importance of young individuals discovering their passions, believing in themselves, and fearlessly pursuing ambitious goals. Upon returning to Taiwan, Professor Chen founded SourcePoint Biotech, guided by a vision that transcended mere financial pursuits. He believed in providing a new realm of opportunities for the future by making DNA recombination and modification more accessible.
In the process of founding the
company, Professor Chen encountered numerous challenges and reminded us that facing
rejections is a normal part of the journey. He highlighted the need for extensive
cross-disciplinary knowledge integration after venturing into entrepreneurship. Developing a
product requires collaboration among technical experts, marketing professionals, packaging
specialists, legal experts, and more. Therefore, he encouraged us to diversify our
knowledge. When it comes to commercializing a project, Professor Chen provided the following
recommendations:
1. Clearly define the product to ensure compliance with relevant regulatory
requirements.
2. If the product requires clinical trials, seek out clinical trial specialists and create a
detailed timeline for that.
3. Understand that stabilizing and optimizing technology is key to commercializing a product
and requires substantial human resources and financial investment.
Acquisition and Improvements
In summary, our key takeaways include the importance of refining our screening methods, effectively securing funding, and ensuring compliance with relevant regulations when bringing a product to market. Professor Cheng-Yao Chen's wealth of experiences and insights serve as invaluable resources as we navigate the path to successfully commercialize our project.
Jhong-Sheng Chen
Purpose of the Interview
In modern medical science, researchers continually seek faster and more accurate testing methods for early disease detection. This time, we interviewed a retired consultant from a biotech company who graduated from the Department of Biological Sciences at National Chung Hsing University. He conducted research at the National Institutes of Health and Kaohsiung Medical University, focusing on target drugs and anti-toxic proteins. Additionally, he worked on rapid screening technology, providing us with in-depth professional knowledge.
Key Insight
Reasons for entering this industry(Biology)
We asked our consultant why he
chose to enter the field of rapid screening technology. He mentioned that in the early days
when he was working in northern Taiwan, he realized that the job market in the south was not
ideal. Consequently, he decided to change careers and acquire new skills, considering his
background in biological science. He believes that rapid screening technology is a
challenging and promising field.
Suggestions for our project
The consultant provided some
important suggestions and insights for our Project. He reminded us that people may have some
questions about our Project that we need to answer, such as
Why do you use two different methods (one using gold
nanoparticles
and the other using PCRD detection)?
Because the two methods employ different detection mechanisms, and when we are uncertain
about which one is the more accurate detection method, we conduct both experiments
simultaneously. Ultimately, we will select the most suitable method.
Are circRNAs always present in the body? How could circRNA
suddenly appear in the body and then cause disease?
Yes, circular RNAs are always present in the body, but their concentration varies between
diseased and healthy states.
Are circRNAs related to other diseases?
Yes, there are connections, but our goal is to identify circular RNAs that are unique to our
target disease and not associated with other conditions.
He also mentioned some issues related to modifiers, such as how to determine the sequence and how to synthesize primers to prevent false positives.
We believe that these are complex issues requiring in-depth research and consideration, and we currently lack specific design tools for addressing them. Therefore, they will also be included in our future work.
Feasibility of our project
Regarding the feasibility of
the Project, the expert mentioned that there are many unknowns that need to be considered.
This shows that the development of rapid screening technology still faces many challenges,
but there are also opportunities for success.
Acquisition and Improvements
Regarding how to improve the Project, the consultant said that it is difficult to provide specific suggestions because of a limited understanding of circRNA. He recommends reinterpreting the actual Project steps to ensure the research is in the right direction.
Finally, we asked the consultant if he knew anyone who was an expert in the relevant field or could provide information. He said that because circRNA is relatively new, no large-scale professional network has yet been established. However, he mentioned a teacher Wang, Hong-jun who may have relevant expertise in rapid screening and cancer.
This interview provides us with valuable insights into circRNA rapid screening technology, as well as professional advice from a biological science expert. This will help us gain a deeper understanding of this emerging field and achieve more breakthroughs in future research.
Patient
Jhong-Ren Wang
Purpose of the Interview
In addition to seeking advice from medical professionals, we were also curious about the perspectives of patients. As the saying goes, “Technology has always been driven by human nature.” We are aware that our product will ultimately be used by colorectal cancer patients, and understanding their thoughts on the screening methods is crucial for the development of our project. Therefore, we reached out to cancer survivor Mr. Jhong-Ren Wang through the Taiwan Cancer Foundation. He has been battling colorectal cancer for 18 years since his diagnosis at the age of 49 and continues to inspire others with his resilience.
Key Insight
Through the interviews, we learned about the inconveniences patients face when undergoing colonoscopy: Mr. Wang mentioned that before a colonoscopy, patients need to fast for an extended period, which can be especially burdensome for those with concurrent conditions such as diabetes. Furthermore, colonoscopy is highly invasive, discouraging many individuals from undergoing regular colorectal cancer screening.
Mr. Wang also highlighted the severity of delays in seeking medical attention. He mentioned that cancer patients often experience the challenge of pain during their treatment journey, including post-surgery wound pain, discomfort from artificial orifices (such as the anus), and bodily pain following chemotherapy and radiation therapy. In his case, a pre-surgery examination revealed that the tumor was located near the anus. The lingering side effect of chemotherapy and radiation therapy, namely diarrhea, continues to cause occasional anal pain to this day, sometimes even disrupting sleep with night-long episodes of diarrhea. “Many patients, due to their concerns about unbearable pain, are inclined to forego treatment, "said Mr. Wang.
In addition to technical improvements, he also reminded us to address the concerns and feelings of actual users. He suggested that we should study more colorectal cancer cases and understand their stories. 'Asking more questions and seeking more information can enhance the reliability of your research,' he said. Regarding whether there's a genuine need for a liquid biopsy screening platform, he provided us with his actual observation: “Currently, the government is actively promoting relevant screenings, but many people are still reluctant to get tested due to the high cost and invasiveness. However, the key issue is that many people don't believe they will get cancer, and it's even more crucial to address this on a psychological level.”
Acquisition and Improvements
This interview once again reminds us that our research is not just an invention or a report; it requires a comprehensive understanding from top to bottom to fully grasp the real needs.
Special Thanks
Mentor Varshiny G
Purpose of the Interview
In order to address the current challenges faced by each group, our team applied for assistance from the iGEM mentorship program to learn from experienced mentors and improve our work.
Key Insight
We had an online meeting with our mentor, Varshiny G, during which we discussed our progress, improvements, and the issues we were currently unable to resolve. We provided a comprehensive explanation of our project and followed up with questions and concerns that our team was struggling with.
For example, our wet lab members inquired about how to enhance protocols, purify samples, and design sequences for experiments. Our dry lab members sought advice on simulating the functions of circular RNA docking and complementary sequences. The human practice group had questions about competition standards, criteria, and schedules.
Acquisition and Improvements
After the meeting and a few subsequent email exchanges, our team gained a better understanding of how to optimize sequence design and prepare for the competition. While modeling was not Varshiny's primary area of expertise, she suggested that discussing with other iGEM teams could be beneficial to our progress. We collaborated with more iGEM teams and benefited from diverse perspectives. Working with mentor Varshiny was a rewarding experience, and we appreciated the opportunity to reflect on our project.
Sabrina Yao
Purpose of the Interview
Sabrina Yao was the team leader of the 2019 NCKU (National Cheng Kung University) iGEM team and led the team to win the Special Prize. Moreover, she has been a judge in the iGEM competition and has hosted the Taiwan iGEMers league. Communicating with Sabrina Yao meant a lot to us in terms of improving our project and finding the best way to present it to audiences and judges.
Key Insight
We had a quick review of our project and presentation with Sabrina Yao first, and she mentioned some points that we should change before the competition.
For example, Sabrina Yao taught our team how to go through the process from patients' blood to the final step of the project during the presentation. Moreover, she discussed how to make the presentation more attractive to the audience and focus on the primary objective instead of getting lost in minor details. Also, the timeline of the story and engineering cycle were essential for us to understand. Plus, not only did our team have to focus on the structure of the project, but we also had to ensure that we emphasized the main points and ended the report with a strong sense of closure.
Acquisition and Improvements
After the discussion with Sabrina Yao, our team changed the way we presented and connected the whole project with a clearly focused storyline. In addition to having a better way to report, our team members discussed many times and finally found the best way to engage the audience. We invited our seniors and the NYCU_Formosa iGEM team to check if the results matched what we wanted, and they gave us positive feedback. Taking Sabrina Yao's advice into consideration was a big success for our team in terms of presentation and showcasing the advantages of our project. We learned a lot from Sabrina Yao, and it turned out to be an awesome result!
Chung-Yu Chou
Purpose of the Interview
Gold nanoparticles synthesis is a crucial component of our project, and Chung-Yu Chou , our senior colleague, has played a pivotal role in assisting us in this regard. His support has encompassed various aspects, including conducting gold nanoparticles synthesis experiments, discussing future experiment planning, and analyzing the results obtained.
Key Insight
Through our interactions with him, we continuously fine-tuned our experiments and gradually honed the centrifugation conditions for gold nanoparticles synthesis. He also suggested us that we can use SEM (Scanning Electron Microscope) to confirm the status of gold nanoparticles synthesis. Additionally, Peter guided us in analyzing XPS (X-ray Photoelectron Spectroscopy) data, teaching us how to interpret the significance of various numerical values.
Acquisition and Improvements
Through discussions with him, we have become increasingly familiar with the gold nanoparticles synthesis experiment. We have also learned how to validate the synthesis results by the collected data, enabling us to independently conduct the entire experimental process and be more aware of the details for adjustments. His meticulous guidance has been instrumental in our laboratory work, significantly contributing to our project's success.