Goal

We wanted to understand the clinical landscape in which AD is currently diagnosed and gain a foundational understanding from an expert clinician's point of view. In detail, we also wanted to: (1) identify gaps and unmet needs in the current diagnostic toolkit; (2) confirm societal and medical need for a new early detection method; and (3) gain an understanding of operational challenges to introducing a new point-of-care test.

Expert Profile

Experts' Insights

In the meeting with Dr. Li, she shared her review of Alzheimer's Disease from the clinical perspective, which allowed us to understand the problem from the following aspects:

• The size and nature of the AD problem: Clinical definition: AD is a slowly progressive neurodegenerative disease, leading to cognitive impairment, behavioral disorders, and social dysfunction. (Insidious, progressive, neurodegenerative). Pathology: Brain atrophy, senile plaques (amyloid beta proteins), and neurofibrillary tangles (hyperphosphorylated tau proteins) – this will support the biomarker-driven rationale for diagnostics.
• Limitations of the existing diagnostic toolbox: We proceeded to discussed about details of the available options for clinical testing (with some of them to be used in combination), all of which are burdened with a major flaw, leaving the space for improvement:

1. Neuropsychological testing: MMSE, MoCA (standard procedure) – not objective (highly subjective, education-dependent, clinician-dependent – experience) and does not provide molecular-level information (biomarkers).
2. CSF testing: Biomarker testing (measure the levels of Aβ42 and Tau proteins in the CSF) is the existing gold standard for biomarkers; however, the clinical utility is extremely low due to high invasiveness (lumbar puncture), cost, which leads to poor acceptance.
3. Blood tests: Direct blood tests (for direct detection of denatured proteins) have a poor specificity and are not yet at the level of being used as a diagnostic.
4. Brain imaging: MRI – can be used to prove brain atrophy. Advanced PET-scans – amyloid plaque deposition in the brain can be seen visually; however, this method is expensive, not universally available, and used as a confirmatory method rather than a general, non-selective method.
5. Genetic testing: Only certain familial types of AD (mutations in APP, PSEN1, PSEN2, etc.) respond to genetic testing, leaving the rest of AD-affected patients unaffected.

• Future directions and unmet clinical needs: As per Dr. Li, there is a clinical trend towards biomarker-driven diagnostics. One of the top priorities in the field, as Dr. Li pointed out, is an ongoing international effort to develop non-invasive means to detect biomarkers such as Aβ and tau in the human body. Dr. Li also confirmed that a simple, low-cost, non-invasive test would be a major unmet clinical need.
• Societal barriers: The major societal obstacle identified by Dr. Li is the lack of public awareness of AD, as it often leads to patients (or their relatives) not seeking medical attention until it is too late and the illness is at an advanced stage. Effective medication is hard to come by in later stages of AD; thus, a need for societal intervention and education exists, in parallel to the need for technological breakthrough.

Figure 5. Interview with Dr. Qingli Li

Reflection & Improvement:From Hypothesis to a Grounded Strategic Direction

This initial interview with Dr. Li served as the cornerstone of our problem investigation phase. It helped us transform our project from a theoretical concept into a clinically-grounded mission. The insights we gained were not merely informative; furthermore, they were formative and fundamental for our project's strategic direction, technical design principles, and even overall philosophy.

• Validating Our Core Mission: From a "Good Idea" to a Clinical Imperative

Before this interview, we were concerned about to help people, especially elderly citizens diagnose AD in an early stage with an innovative solution may provide them with more time and opportunities for treatment, and hence enhance their post-diagnosis life quality. Non-invasiseness, combined with blood-based test was somehow a hypothesis—an idea we believed had merit.

Dr. Li's testimony provided the expert validation that converted this hypothesis into an imperative. By systematically analyzing the clinical utility of current methods—particularly the high patient burden of CSF testing and the subjectivity of neuropsychological assessments—she implied that a huge gap in the existing diagnostic pathway.This validation was crucial, reassuring us that our scientific endeavors were aimed at a genuine, pressing and well-recognized problem in modern medicine. It gave us the "why" which would propel our entire project forward.

• Establishing Critical Design Constraints and Key Questions for Society

In addition to being validation, Dr. Li's critique of the diagnostic toolbox actually provided the essential design constraints for our project. We moved from the ill-defined objective of "making a new test" to a specific set of design requirements that our solution had to satisfy to be successful.

1. Objectivity: To overcome the subjectivity of psychometric tests.
2. Accessibility & Affordability: To provide a viable alternative to costly and specialized imaging techniques.
3. Patient-Centricity: To address the low acceptance rate of invasive procedures by prioritizing a non-invasive approach.

Dr. Li's observation about the "low acceptance rate" of invasive methods was a crucial piece of clinical insight. But it also left our team with an important question. But it also posed an important question for us: is this fear of invasive procedures a universal public opinion, or is it confined to a clinical setting? If we were to build a truly human-centered product, we had to verify it with the general public.

• Expanding Our Scope: Formulating a Hypothesis for Public Investigation

In many ways, the biggest "take-away" from the interview was a very simple, but important, one: how to widen the scope of our project beyond the bench. In Dr. Li's professional, clinical opinion, a significant societal challenge was lack of public awareness, resulting in late diagnosis, and this message hit home. It was evident to us, in no uncertain terms, that no matter how innovative a technology we developed, it would not be enough on its own.

It was at this point that we decided that wanted to make a hypothesis that could only be directly validated by society: if lack of public awareness is a critical factor contributing to the lack of early diagnosis, then any successful solution must include both a technology AND public education. Before we could design a successful public education effort, we needed numbers: how significant of a problem are we talking about? We needed to be able to answer a few questions:

1. How significant is the knowledge gap regarding AD in the general public?
2. What are the public's primary attitudes and fears surrounding the disease?
3. Would the public be receptive to early screening if a non-invasive, accessible option were available?

• Our Next Step: A Bridge from Clinical Insight to Public Data

The interview with Dr. Li gave us an expert-informed map of the problem. It gave us a clinically validated mission and a set of core design principles. But it also raised important questions about the broader societal context which we couldn't answer from the inside of the hospital. To validate our hypotheses and answer these questions, the next immediate and logical step was to zoom out from a single expert's point of view to a wide-angle, data-informed perspective. We designed and executed a large-scale public survey to validate Dr. Li's societal insights and deeply understand the community we were about to serve.

Goal

After we interviewed experts who provided a strong clinical rationale for the need for non-invasive diagnostics, but also the problem of low public awareness, we set out to test this logic on data directly from the public. The questionnaire below was aimed at 3 major goals:

• Gauge the public's baseline knowledge of AD and detection
• Measure the demand and preferences for a new, non-invasive early screening solution
• Uncover the primary product attributes (accuracy, price, convenience) that would drive public adoption

Instrument and Respondents

Questionnaire: 17 questions ranging from basic awareness/knowledge/experience to basic opinion on current vs. future diagnostic technology, with acceptable price range and decision-making factors (see below for full questions)

Distribution Channels: Social media (WeChat, Xiaohongshu, TikTok, etc.)

Sample: 224 Validated Responses: The respondent demographics span a wide range of age (largest two age groups are 18-30: 30.4% and 31-50: 34.4%), with one extremely important signal: a 45.5% having direct experience of AD patient (family/friend/neighbor), which indicates the issue bears extremely high relevance for almost half of our respondents.

Key Findings

Our analysis is broken down into 3 main segments: (1) a straightforward descriptive analysis which confirms our hypothesis, (2) a deeper dive into what is the public's ideal product attributes, and (3) a correlation analysis to infer more granular findings on user motivation:

Figure 6. Data Visualization of Public Survey on AD Awareness and Diagnostic Needs

• Descriptive analysis: A mandate for our non-invasive technology plus education

This survey has generated a powerful and highly actionable motive for our dual mission of scientific technology and public education.

The Awareness Paradox: AD awareness is low at the technical level, but relatively high at the public level. On one hand, the survey shows that almost all people have heard of AD (98.2%), 73.7% of which reported to have "some understanding" of AD; on the other hand, when probed on deeper technical concepts like "biomarker detection", a combined 83.5% reported being "not familiar"or "heard of it, not sure". These results clearly confirm our diagnosis in the need for public education and translation of complex scientific terms into simple and understandable words.

Confirmation of the need for non-invasive technology: the clinical need for more practical and less invasive detection methods is also fully shared by the public. To the question, "if a non-invasive AD detection method, say in saliva/blood, becomes available, would it be socially valuable", an overwhelming 96.4% of our respondents said it would be "helpful". This translates into an extremely actionable mandate of our technology being fully aligned with the public's clear and strongly felt needs.

The current status quo is unmet: Public perception seems to largely align with clinical reality that the current detection methods are far from meeting public need. To the question "How would you rate the current AD detection methods in general in terms of accessibility (availability of test site, time to wait for results)?", a combined 74.1% of our respondents reported it as being "somewhat limited" or "very limited". This underscores the great need for a more practical solution.

• Descriptive analysis: What is the ideal product for public adoption?

The public survey provided critical insights on key attributes that can make an ideal new diagnostic tool a success.

Accuracy is the top priority: To the question "If there are multiple factors to consider, which is the single most important factor in making you decide to use a new AD detection method?" (multiple choice from 8 options provided), Accuracy was the clear winner at 35.3%, followed by Price (26.8%) and Safety (22.3%), indicating that although the public is price sensitive and would care for convenience, they would not trade off with accuracy, and our technical team should design for the highest sensitivity/specificity.

Price sensitivity and market size: In response to a wide range of provided price points (Question 11), most of our respondents preferred a price under ¥500, but yet a large segment of them (21%) also consider a price over ¥2000 to be acceptable. This can hint at a potential market segmentation between a lower-cost routine screening product vs. a higher-priced, more definitive product for medical use, which perfectly matches the product strategy of developing a 2-product solution (chip, test kit) that we later proposed.

• Trust in Clinical Settings: While there is growing interest in at-home testing, a majority of respondents (54.5%) still place higher trust in tests conducted in a hospital setting. This suggests that our initial go-to-market strategy should focus on partnerships with clinical institutions to build credibility and trust.
• Correlation analysis: The power of personal experience

In addition, based on our survey results, we can infer a highly strong correlation between the number of personal AD experience and the corresponding willingness to solve or preempt the risk through early AD screening tests.

Experience correlates with risk awareness: We infer that the 45.5% (Q2) having personal experience with AD (family/friend/neighbor) is the primary driver of the extremely high perceived future risk, a combined 60.7% of our respondents are "likely" or "very likely" to develop AD in the future for them or a family member (Q12), turning the risk from a remote statistic to a present and concrete personal threat.

Awareness drives the urgency to act: As a result of the strong perceived risk, which is driven by the personal AD experience, the willingness to adopt a new solution is also extremely high, with 90.2% of our respondents stating that they "definitely would try/use" or "recommend" an accurate AD detection method (Q9). Thereafter, we can infer that a significant addressable market exists among individuals and families directly affected by Alzheimer's, who demonstrate a strong predisposition for early detection solutions.

From Data to Empathy: The Need for a Human Perspective

After we finished that public survey, we felt a lot more grounded. The data gave us a huge boost of confidence; it was like society was giving us a clear signal that people want a non-invasive diagnostic method. It also showed us that most people's understanding of AD is pretty surface-level.

These data tell us what people are thinking, but we can't really know how they're feeling. And when we saw that almost half the people we surveyed had a personal connection to the disease. We knew that behind that statistic were actual people, real families suffering from the disease. The survey could tell us that a family member was sick, but it couldn't tell us what that's even like. The day-to-day challenges, the helplessness of watching memories slip away and the real financial burden.

The numbers gave us the "what," but we were desperate to find the more human "why."

So, we just felt like we couldn't stop there. We knew right then that we had to go and listen to a real story. We needed an actual person to connect those cold, hard stats to a living, breathing family.

The survey results painted a picture of the problem, but we felt we were still looking at it from a distance. To truly understand the human cost of Alzheimer's, we needed to get closer. Our goal for this interview was to listen to a firsthand account of a family's journey with the disease. We wanted to understand the lived reality behind the statistics: the day-to-day struggles, the emotional landscape, and the practical challenges that no questionnaire could ever capture.

Insights from Mr. Wang's Story

We got the opportunity to speak with Mr. Wang, whose grandmother has been living with an AD diagnosis for over 6 years. He was incredibly generous in sharing his family's story, and his perspective was, frankly, transformative for our team.

Figure 7. Interview with Mr. Wang

He walked us through the whole 6-year timeline. It all started with those small, almost unnoticeable things—forgetfulness, a change in mood—that were easy to brush off as just "getting older." The journey to getting a real, definitive diagnosis was long and frustrating, filled with uncertainty. That was a huge takeaway for us: the initial stage isn't a clear medical event, but a confusing and anxious time for the whole family.

We learned a few really crucial things from him:

• The Slow, Unfolding Nature of the Disease: Mr. Wang described how the symptoms evolved . It wasn't a sudden decline but a slow erosion of memory and personality. This meant the family was constantly having to adapt their caregiving, their communication, and their own emotional expectations. It's not one battle; it's a thousand small ones, every single day.
• A Sense of Helplessness with Current Treatments: He spoke about the different medications and therapies they tried. While some seemed to help for a little while, he described an overarching feeling of inadequacy—that current medicine is more about managing the decline than truly stopping it. This really underscored the urgency for a breakthrough, starting with much, much earlier detection.
• The Hidden Burden of Stigma: This was something we hadn't fully grasped. Mr. Wang shared how some friends and even extended family became distant. The social stigma and widespread misconceptions about AD created this invisible wall, isolating his family at a time when they needed support the most.

When we asked him what he wished for, looking back, his answer was simple but powerful. He wished for an earlier, clearer answer. He wished for tools that could have helped them track the small changes, to feel a little less in the dark.

Reflection & Improvement: Redefining Our Project's Purpose

The interview has made us feel how urgent and important the problem is. The difference between reading the problem in the report and listening to Mr. Wang's voice, so tired but full of love, determined that our project must do more than just be technically precise.

• From "Tool" to "Support System": We came to realize that we were not simply building a diagnostic "tool," but rather something that must become an integral, and as seamlessly functional and empathetic as possible, part of the family's life at their most vulnerable times. We started to wonder if the solution we are working on could be more than just a test result, but a part of a larger support system. What if we could also provide them with educational resources and give families a way to participate in the process? Mr. Wang's simple desire for "simpler symptom tracking" could be the key.
• The "Why" of Our Education Mission: Mr. Wang's story of his family's isolation only strengthened our resolve to pursue our public education. It is not only about explaining the science behind AD, but also about helping to break down the stigma and build a community that is empathetic and supportive of families like Mr. Wang's instead of judging them.
• Responsibility Felt Even Deeper in Our Hearts: After this interview, we started to feel different. The project became more special. The responsibility we felt was no longer just for achieving a positive result in the lab. It was for families like Mr. Wang's, who needed our help. We have to do our best to make sure that we not only do scientific research well but also deliver real help to the society we live in.

In a word, this interview not only further encouraged our determination to proceed with our project for developing an early detection method, which should be both accurate and convenient, for individuals who may be affected by AD, but also pushed us to design and implement public educational activities to enhance people's awareness of AD, ranging from its pathology, to possible prevention methods, to early symptoms, to detection methods and to popular therapy. (For details, please visit our Education Page)

Goal

we began to transition from understanding the problem to actually designing a solution, we knew our first step shouldn't be in the lab, but in learning from those who had walked this path before us. Our goal was to connect with an experienced iGEMer—specifically one who had tackled the immense challenge of AD diagnostics. We wanted to gain a real-world, "behind-the-scenes" perspective on the entire iGEM journey: the scientific pitfalls to avoid, the strategic best practices for the competition, and the general mindset needed to succeed.

Expert Profile

Expert's Insights

Our conversation with Rashik felt less like a formal interview and more like getting a map of the road ahead from a seasoned traveler. He shared not just technical knowledge, but a whole philosophy for approaching an iGEM project.

• A Philosophy of Preparedness and Rigor:

Rashik really drove home the point that in iGEM, things will inevitably go wrong. His core advice was to plan for this from day one.

1. On Experimental Robustness: He stressed that our wet lab experiments had to be absolutely solid. This meant using multiple replicates, critically analyzing all results (especially the unexpected ones), and thoroughly documenting every single step so that our work could be reproduced.
2. The Importance of a "Plan B": He shared the challenges of working with aptamers and biomarkers in a complex medium like blood. His key strategic advice was to always have fallback plans. What if our primary aptamer doesn't work? What if our detection method isn't sensitive enough? Thinking through these "what-ifs" early on, he explained, is the difference between a stalled project and a resilient one.

Figure 10. Interview with Dr. Rashik Chand

• The Nitty-Gritty: Practical Science for AD Biomarkers:

Drawing from his ADx project, Rashik gave us a masterclass in the practical challenges of our chosen topic.

1. The Power and Promise of SELEX:
   Rashik went on and on about using SELEX to screen and isolate high-affinity aptamers to AD biomarkers. He was honest about its problems—it's a painstaking and exacting process—but also talked about its astonishing power. Hearing him go through how they successfully used this technique to develop a working biosensor gave us a huge shot of confidence. Validated SELEX as a solid, powerful core to our wet lab work.
2. The Challenge of Blood: He was very candid about how difficult it is to detect low-concentration biomarkers like beta-amyloid and tau in blood plasma. He even noted that tau might be a more sensitive early-stage marker. This insight was invaluable for our own biomarker selection process.
3. A Spark of Inspiration: Using a Proven Method for a Novel Target: Here's where the conversation got really exciting for us. Seeing that Rashik's team could so effectively target an AD biomarker with SELEX made us think: what if we didn't have to follow their exact path? What if we could take their proven methodology and apply it to an even more promising, cutting-edge biomarker?This sent us straight into the literature. We were looking for a target that could offer even greater specificity for early-stage AD than general beta-amyloid or tau. That's when we came across recent, groundbreaking research on Brain-Derived Tau (BD-tau). Studies were beginning to show that BD-tau in the blood is more directly linked to the brain's neurodegenerative state, making it a potentially more accurate biomarker for early detection than other forms of tau that can originate from outside the brain (Nam et al., 2023). It felt like a gamble, but a smart one. Rashik's success gave us the confidence to take that leap.

• Beyond the Bench: Navigating the iGEM Ecosystem:

1. Rashik emphasized that iGEM is much more than just a lab project.The Wiki is Your Identity: He advised us to start working on our wiki early. It's not just a final report; it's the living story of your project. He suggested having a dedicated design team to ensure consistency and a professional look.
2. Strategy and Judging: He repeatedly told us to "consult the Judge's Handbook." Understanding the medal criteria is essential for focusing your efforts on what is most impactful.
3. Community is Everything: He encouraged us to be active in the iGEM community, to join the Slack channels, and to collaborate with other teams. iGEM, in his view, is a network, not just a competition.

Reflection & Improvement: Translating Wisdom into Action

This interview didn't just give us advice; it gave us a whole new direction and the confidence to pursue it.

• From Imitation to Innovation: Our initial thinking was, perhaps, a bit conservative. We might have just targeted the same well-known biomarkers. This conversation shifted our entire mindset from imitation to innovation. Rashik's success with SELEX became our methodological springboard, empowering us to aim for a more novel and potentially more impactful target in BD-tau.
• Confidence in the Method, Flexibility in the Target: The biggest takeaway was this separation of method and target. We became firmly committed to the SELEX process as our core technique. This unwavering confidence in the "how" gave us the creative freedom and scientific courage to be more ambitious with our "what."
• The Birth of Our "Plan A / Plan B" Strategy: Rashik's mantra of preparedness was the final, crucial piece of the puzzle. We translated his advice directly into our experimental design.

1. Plan A: Our primary, high-risk, high-reward goal. We would dedicate our main efforts to using SELEX to screen for and isolate a novel, high-affinity aptamer specifically for Brain-Derived Tau (BD-tau).
2. Plan B: Our safety net. To ensure we would have a functional system even if the novel BD-tau approach faced unforeseen challenges, we would run a parallel track using SELEX to develop an aptamer for the more conventional, well-understood pan-Tau protein.

This two-track strategy, born directly from this conversation, made our project both more ambitious and more resilient. We were now aiming for a true innovation, but we were doing so with a responsible and well-thought-out backup plan.

Goal

Our chat with Rashik left us incredibly energized. We had a bold "Plan A" (developing a biomarker for the novel BD-tau) and a solid "Plan B" as a safety net. We felt like we had a good experimental design, and a clear strategy for the project overall. However, But a strategy is only as good as the science it's built on.

So it was time to transition from the theoretical world of iGEM strategizing into the light of neurobiology. We needed a seasoned professional to really guide us on the scientific details of our proposal. When we spoke with Dr. Lu, we wanted to put our experimental design through its paces: Was our strategy for detecting BD-tau in blood plasma actually realistic? What unacknowledged biological/clinical barriers could be lurking around the corner? And how could we make our laboratory work as robust and clinically relevant as possible?

Expert Profile

Experts' Insights

Dr. Lu's feedback was incredibly sharp and exactly what we needed to hear. He immediately moved past the general concept and dove into the hard questions of scientific and clinical execution.

Figure 12 Interview with Prof. Lu

• Hardening the Science: The Three Pillars of a Reliable Test Dr. Lu emphasized that for a diagnostic test to be meaningful, it has to be built on three pillars:

1. Sensitivity: Can it detect the biomarker when it's there, even at incredibly low concentrations?
2. Specificity: Can it only detect the target biomarker (BD-tau) and not be dispurted by other, similar proteins in the blood?
3. Reproducibility: Can you get the same, reliable result every single time you run the test?

He also gave us a critical piece of practical advice: a test that works in a clean, simple buffer solution is one thing, but blood is a completely different beast. He stressed that we had to simulate a realistic blood plasma environment in our experiments. Blood is a complex soup full of proteins like fibrinogen that could interfere with our test and cause false positives. He suggested using commercially available artificial plasma to make our results far more reliable.

• Confronting the Real World: The "Diagnostic Paradox" This was a huge moment for us. Dr. Lu pointed out a fundamental challenge in early AD diagnostics that we hadn't fully considered. He called it the "diagnostic paradox": the people who are most motivated to get tested—those who are already showing symptoms or have a strong family history—are often the ones who are already past the true "early" stages of the disease.

The real challenge, he explained, is getting healthy, asymptomatic people to screen for AD as part of a routine health check-up. To do that, you have to overcome several major hurdles:

1. Cost: It has to be affordable enough to be included in a standard check-up.
2. Accessibility: The procedure needs to be simple, requiring a minimal amount of blood.
3. Psychological Acceptance: People need to be emotionally prepared for what a potential positive result might mean.

Reflection & Improvement

Honestly, this discussion was tough, but in the best way possible. It pushed us to see the gaps in our own thinking. When Dr. Lu started asking pointed questions about our target users and the final form of our product, we realized our answers were a bit… fuzzy. We were so focused on the science that we hadn't thought through the end-to-end reality of its use.

This conversation forced us to mature our project in two fundamental ways:

• A Rigorous Redesign of Our Experimental Protocol: We took his advice as a direct command. We immediately went back to our experimental plan and integrated the "three pillars" as our core metrics for success. We stopped our initial tests in simple buffer and began sourcing commercial artificial plasma to simulate the complexity of real-world samples. Our experiments became harder, but we knew the results would be far more meaningful.
• Grappling with the "Who" and "How": The "diagnostic paradox" was a wake-up call. It forced us to confront the fact that having a great test isn't enough if you can't get it to the right people at the right time. This sparked a whole new line of inquiry for our Human Practices work. We knew we had to start thinking seriously about our business model, our go-to-market strategy, and how we could partner with healthcare providers to make early screening a viable reality.

In the end, Dr. Lu pushed us to evolve. We went into the meeting with a strong scientific plan. We came out of it with the beginnings of a credible product blueprint, one that was not only scientifically rigorous but also far more attuned to the practical challenges of the real world.

Goal

Dr. Lu's interview set an incredibly high bar for us. We now knew that for our project to have any real-world value, our diagnostic test had to be ultra-sensitive, highly specific, and consistently reproducible. This was a daunting challenge, and honestly, we weren't entirely sure what technology could even get us there. Our core problem was clear: we needed a powerful signal amplification method to detect the tiny traces of BD-tau in a blood sample.

So, our team dove into the literature, searching for a potential "engine" for our test. That's when our research led us to the CRISPR-Cas12a system. We learned about its unique "collateral cleavage" activity, where target binding triggers the indiscriminate shredding of nearby single-stranded DNA, creating a powerful amplification effect (Chen et al., 2018). This principle had already been successfully harnessed in diagnostic platforms like DETECTR, and we saw its immense potential as the built-in biological amplifier we were looking for (Li et al., 2019).

But this was all just a concept from a paper. We had to ask ourselves: was this idea just a cool theory, or was it a truly viable path forward for a high school iGEM team? Before we invested months of work, we needed to consult an expert. Our goal in meeting Dr. Hu was to get a critical, expert validation of our core idea. Was our choice of engine a good one, and if so, what was the real-world roadmap to actually building it?

Expert Profile

Expert Insights

This was a dense, incredibly practical conversation that took our rough idea and started shaping it into a real plan.

• The "Engine" - A Green Light for Cas12a:

The first thing Dr. Hu did was confirm that our hunch about Cas12a was a good one. He explained that its collateral cleavage activity was indeed a powerful tool for diagnostics, providing the signal amplification we were looking for. This validation was a huge moment for us; it felt like our research had pointed us in the right direction.

• The "GPS" - A Rigorous Roadmap for Aptamer Screening:

With our "engine" choice validated, Dr. Hu immediately pivoted to what he saw as the biggest practical challenge: finding a high-quality aptamer (our "GPS"). He laid out a non-negotiable, hardcore technical plan for us:

1. Rigorous SELEX: He recommended an exhaustive screening process of at least 17 rounds of SELEX to ensure we isolate aptamers with the highest possible affinity and specificity.
2. The Validation Trilogy: After screening, he told us we had to validate our chosen aptamer using three different methods: Flow Cytometry (FACS), ELISA, and Surface Plasmon Resonance (SPR). This tripartite validation would provide definitive, quantitative data on how well our aptamer actually binds to its target.

Figure 14 Interview with Prof. Hu

• The Practicality Plan - Making It Affordable and Usable:

Connecting perfectly with the cost and accessibility concerns raised by Dr. Lu, Dr. Hu offered concrete, practical solutions:

1. Drastic Cost Reduction: He pointed out that commercial Cas12a protein is incredibly expensive. His top tip was to bring the purification in-house. By producing and purifying the protein ourselves, we could slash the cost to a fraction of that.
2. Simplifying the Output: He strongly supported the idea of moving away from lab-based fluorescence readers. He suggested exploring lateral flow test strips (like a pregnancy test) as a simple, low-cost, point-of-care output.

• A Crucial Shift in Perspective:

Perhaps his most profound piece of advice was about storytelling. He told us, "Don't just focus on the coolness of your tool (CRISPR). Focus on the difficulty of the problem you're solving." He urged us to frame our project not as "a CRISPR project," but as a solution to the incredibly difficult challenge of low-cost, high-sensitivity, portable detection of Tau protein.

Reflection & Improvement: From a Concept to a Concrete Blueprint

This interview was, to put it simply, a massive sigh of relief and a huge jolt of excitement all at once. It took our promising but fuzzy idea and turned it into a high-fidelity, actionable blueprint.

• From a Literature Idea to a Battle-Ready Plan: We went into this meeting with a good idea from a research paper. We came out with our first real, detailed experimental plan. We immediately rewrote our wet lab protocols to incorporate the 17+ round SELEX screening process and the mandatory three-part validation, making our entire approach far more robust.
• The Birth of Our Point-of-Care Vision: Dr. Hu's practical suggestions for cost reduction and test strips were a lightbulb moment. It connected the dots between the clinical need for accessibility (from Dr. Lu) and a tangible, low-cost product format. This discussion solidified our pivot towards designing a point-of-care device.
• Refining Our Project's Narrative: His advice on how to frame our project was transformative. We realized our initial pitch was probably a little too focused on the "wow" factor of CRISPR. This insight forced us to mature our narrative, shifting our focus to our project's true innovation: providing an accessible and affordable solution to a critical diagnostic challenge. It helped us understand that the tool serves the problem, not the other way around.

Goal

After our meeting with Dr. Hu, our project finally felt scientifically rigorous. We had our engine. We had our GPS. We had our game plan for how to build both. But as every iGEM team knows, our project does not exist in a vacuum. As our group met to discuss the next steps for our project, we were very aware of the many other teams working on the same challenge as us: Alzheimer's Disease (AD), only from other angles.

The goal of this meeting was to break out of that bubble of our own group and have a conversation with our peers. We came across from Xiaohongshu that our fellow iGEM team from Nankai University (NKU) also committed to tackling AD, then we decieded to set up a video conference to stay connected. We wanted to level up the conversation and speak horizontally to a team that was on the same journey as us. We wanted to benchmark our project against NKU's. We also wanted to hear about their challenges and successes, as they did with ours.

Insights

The conversation with NKU was fascinating. It was two very different and very complementary approaches to the same disease. The NKU team was approaching early AD with a therapeutic focus, based on engineering bacteria and a "gut-brain axis," while we were all about early diagnostics. The whole conversation was a striking reminder of how multidisciplinary the war on AD truly is.

Figure 15 Collaboration Meeting with NKU iGEM Team

• The Tale of Two Projects: Diagnostic vs. Therapeutics

NKU's Therapeutic Approach: NKU's project was incredibly exciting. They were engineering bacteria to produce butyrate in the gut, and then the butyrate would move through the "gut-brain axis" to treat neuroinflammation. They had even designed a genetic switch that would respond to AD biomarkers like TMA and ROS and control the dose.

Our Diagnostic Approach: We showed them our "TauTrack" project and walked them through our plan for using SELEX to discover aptamers for the novel biomarker BD-tau, which would then be coupled with the Cas12a system for read-out.

• The Modeling Masterclass: A Huge Inspiration for Our Dry Lab Work

This was by far the most impactful part of the meeting for us. We were completely blown away by the level of sophistication and depth of the modeling work that NKU was doing. They were not just using computational models as an afterthought to a wet lab result: they were using them to predict, inform, and optimize their entire project.

They showed us:

1. Pharmacokinetic models that predicted the behavior of biomarkers in the body. Deep learning models that predicted the permeability of their therapeutic compound across the blood-brain barrier.
2. Metabolic pathway models that calculated the output of their engineered yeast under different conditions.

• Honest Feedback: NKU as a Critical Partner

The NKU team gave us two key pieces of constructive suggestions that we found to be extremely impactful:

1. The Narrative Is Too Diluted: They told us that in our presentation we might have been getting lost in the exciting details of the CRISPR system we were using. We needed to sharpen our story and refocus on the "core problem" that we were solving: low-cost, non-invasive, early detection.
2. The Evidence Isn't Convincing Enough: They rightly pushed back on us to make sure we had robust literature and experimental evidence to support our claim that BD-tau was a viable biomarker for use in our diagnostic.

Reflection & Improvement: The Next Steps for the Group

The meeting with NKU was so energizing. It is one thing to get advice from your professor: it is another to be inspired and challenged by your peers. We left the meeting feeling like we had a strong project, but that we could and should be doing so much more. We went back to our own group meeting and talked about what we wanted to improve.

• A Catalyst for Our Modeling Strategy: This was the most significant and immediate change. We were completely inspired by the depth and predictive power of NKU's dry lab work. It pushed us to think beyond our wet lab results and consider how we could use computational tools to further validate and strengthen our project. Inspired directly by this exchange, we decided to formally integrate a two-pronged modeling strategy into our project plan for the first time.

1. We decided to use a molecular docking model. This would allow us to computationally simulate and visualize the interaction between our top aptamer candidates and the BD-tau protein. The goal was to gain a deeper, molecular-level understanding and to provide a strong theoretical validation of the binding affinity we were observing in our wet lab experiments.
2. More ambitiously, we decided to develop a machine learning algorithm. We planned to use the raw absorbance data generated from our detection system as input. Our goal was to train a model that could learn to accurately and automatically distinguish between positive (AD) and negative (healthy) samples, adding a powerful, quantitative, and analytical layer to our diagnostic tool.

For a detailed look at the execution and results of these computational efforts, please see our Modeling page.

• Sharpening the Project's Story: We took their advice about our project's story to heart. We immediately set to work rewriting our presentations and documentation to first present the problem, and then introduce our technology as the solution. This made our project's value proposition much clearer and more compelling.
• The iGEM Community: The Power of Sharing and Learning Together

Above all, this meeting was a powerful reminder of the value of the global iGEM community. The generosity, collaborative spirit, and intellectual curiosity of the NKU team was inspiring. We are committed to being active, engaged members of this global community, and being as generous with our own knowledge and experience as the NKU team was with theirs.

Goal

After the inspiring exchange with the NKU team and the deep technical dives with our other experts, our project felt more ambitious and scientifically sound than ever. We had our core technology, a clear experimental plan, and a growing confidence in our approach. But we had to ask ourselves a tough question: was this just a great iGEM project, or could it ever be something more?

To answer that, we needed a completely different kind of expert. We needed someone who could look at our project not just as a scientist, but as a judge, a regulator, and an investor all at once. Our goal in speaking with Dr. Li was to get a candid, no-nonsense evaluation of our project's real-world viability. We wanted to understand the long, hard road from a lab prototype to a clinically approved, commercially successful product.

Expert Profile

Expert's Insights

This conversation was a masterclass in product development and strategic thinking. Dr. Li immediately zeroed in on the practical challenges and opportunities we hadn't fully considered.

Figure 17. Interview with Dr. Shiyuan Li

• The "Big Picture" View: Accuracy and Convenience Trump Cost

This was his first and most surprising piece of advice. We, like many teams, were obsessed with making our test as less costly as possible. Dr. Li completely flipped our perspective. He argued that for a disease like Alzheimer's, where downstream treatment costs are enormous, the market's willingness to pay for an accurate and convenient early test is actually quite high. Our primary focus, he stressed, should be on making the test incredibly reliable and simple to use, not just inexpensive.

• The Hard Reality of the Path to Market

Dr. Li laid out the long and non-negotiable path to getting a medical device registered.

1. The Stability Gauntlet: He warned us that technical stability is the single biggest challenge. We would need to prove our test works consistently across different batches of reagents, across a wide range of temperatures, and without being compromised by things like aerosol contamination. Every single detail would need to be meticulously documented.
2. The Clinical Validation Mountain: To get a registration certificate, we would need to validate our test with at least 1000 clinical samples (500 patients, 500 controls) and compare its performance against a gold standard. This, he noted, is a 2-3 year process.

• The User Experience: From a Lab Concept to a Simple Kit

He gave us incredibly valuable feedback on our product's physical form.

1. On Microfluidics: He was very positive about the idea of using a microfluidic chip, noting its potential for automating steps and amplifying signals.
2. The "Test Strip" Ideal: He advised that the final user experience should be as simple as a pregnancy test. The user should ideally just add a drop of their sample to the chip, with no complex steps. This meant we needed to think about things like pre-filtering the blood sample on the chip itself to remove interfering substances like lipids.

• A Judge's Advice on Storytelling

Putting on his iGEM Judge hat, he advised us to make sure our Wiki clearly highlights our project's key innovations (early detection, convenience) while also honestly discussing the challenges we've faced and the optimizations still needed. This, he said, shows the judges a mature, comprehensive understanding of the project.

Reflection & Improvement:

This conversation was a dose of reality in the best possible way. It forced us to mature our thinking and see our project not just as a series of experiments, but as the first step in a much longer journey.

• A Pivot in Product Design: From a "Strip" to a "Kit"

This was our most immediate and tangible change. We went into the meeting with the simple idea of a "test strip." Dr. Li's validation of the microfluidic chip approach gave us the confidence to think bigger. We realized a simple strip wouldn't be able to handle the necessary sample preparation. This conversation was the direct catalyst for our pivot to designing a more sophisticated, user-friendly kit with a built-in microfluidic chip. This fundamentally changed our product design path.

• Embracing the "Hard Problems" of the Real World

Hearing about the intense stability and validation requirements wasn't discouraging; it was clarifying. It gave us a new set of problems to solve. We immediately began designing experiments to test our system's resilience to temperature changes and its ability to resist interference from other substances in the blood. We started treating our lab work with a new level of rigor, documenting everything as if it were for a future regulatory submission.

• Thinking Like an Innovator, Not Just a Student

Honestly, this interview changed our team's entire mindset. We started to see our project through the eyes of a judge, an investor, and a regulator. We now have a much clearer, more realistic understanding of the long road ahead. We know that our current project is just the beginning, but Dr. Li gave us the map and the vocabulary to talk about that future with confidence and clarity.

Goal

Our meeting with Dr. Li, who had served as CRISPR-Cas12a researcher, diagnostic tool inventor, iGEM judge, and industry investor, was a great encouragement for the development of our vision. The fact that he found the use of the microfluidic chip "an excellent approach" assured us that we were on the right track towards realizing a concrete and feasible product. However, as rising scientists and researcher, we were well aware that an elegant business idea is worthless without a supporting technical development.

Before we would immerse ourselves into product design, business model innovation and market expansion, we felt that we first had the obligation to step back, to do our homework, to have a third party, unbiased specialist's verification. Was a microfluidic chip really the most suitable technical choice for our particular application, at this time? To find this out, we approached Dr. Han, a pioneer researcher on the use of microfluidics in biomedicine, and requested for an entirely honest and frank assessment of the technology, its unappreciated traps and true potential, as well as the engineering and manufacturing realities.

Expert Profile

Dr. Han gave us a brilliantly balanced and deeply insightful "scorecard" on microfluidic technology, grounding our ambitious ideas in scientific and practical reality.

Figure. 19 Interview with Prof. Xin Han

1. The "Pros": The Case For Microfluidics

The Holy Grail of POCT (Point-of-Care Testing): At the very start, he confirmed our intuitions that the single biggest advantage of microfluidics is its potential for POCT—delivering on-the-spot results in a low-cost format. Check!

Closer to Reality: He elaborated that a "microfluidic organ-on-a-chip" system could mimic more closely the complex, multifaceted environment of the human body, with results more reliable and directly applicable than current lab-based methods.

2. The "Cons": The Hard Realities and Hidden Hurdles

The Wild West of Standards: Dr. Han was very clear that a major challenge is that there are very few, if any, standardized benchmarks and guidelines for many of these microfluidic applications. This means the burden of proof for accuracy and sensitivity for any new device is very high.

The Sensitivity Challenge: He also warned that the sensitivity required to detect the extremely low levels of AD biomarkers, especially at an early stage, was a significant technical challenge. AD's causes are multifactorial and a successful product would have to be extremely precise.

3. The Nuts and Bolts: Materials and Cost

Plastic is the Path to Scale: When we asked about what materials he would recommend for a low-cost microfluidic chip, his answer was unequivocal. Plastic is the only way to go. It's cheap, easy to work with, and most importantly, highly scalable.

The Economics of Production: He went into a bit of detail about the economics of plastic chip production: the one-off cost of a mold for a chip is quite high, but after the initial setup, if you're in the mass-production phase, you can get the cost per chip down to just a few RMB. The reagents are likely to be the driver of the final product cost, not the chip itself.

Reflection & Improvement:

How We Got Our "Dual-Product" Strategy

This was the "fork in the road" conversation that really made our product strategy come into focus. This single conversation from Dr. Han was the Rosetta Stone that finally made our idea make sense, by providing the missing context, and the perfect counterweight to our adolescent overconfidence. It didn't dishearten or demotivate us; it made us smarter.

The "Aha!" Moment: Embracing the Gap. During this conversation, we finally had a true "aha!" moment. We realized that trying to start at the perfect, optimized, low-cost, high-sensitivity microfluidic chip, from day 1 of iGEM, was probably counter-productive. It was putting the cart before the horse and the technical challenges he outlined were non-trivial.

The Birth of the "Dual-Product" Strategy: This conversation was the direct catalyst for the single most important strategic choice in our entire project: the decision to split our work into two distinct product lines.

The "Immediate-Goal Product Line": The Magnetic Bead Reagent Kit. As an immediate, most feasible goal for this iGEM season, we chose to focus on creating a fully functional, highly reproducible magnetic bead-based reagent kit. This would let us nail down our core biochemistry—the aptamer binding and the CRISPR-Cas12a detection—in a format that we fully understood and controlled, without the additional complexity and validation hurdles of an integrated microfluidic device. This became our "low-end" product line.

The "Long-Term-Vision Product Line": The High-End Microfluidic Chip. We didn't throw the baby out with the bathwater: we enshrined the microfluidic idea as our "high-end", long-term vision. With Dr. Han's insights, we now have a concrete, plausible plan for its future development, and we began to think seriously about pursuing different materials for different market niches. The ultra-precise glass chips could find a home in a higher-end, clinical market, where the absolute highest sensitivity and recyclability are non-negotiable, while more rugged plastic chips would be the way to go for mass-market products.

This single conversation gave us a much clearer, more coherent product strategy. It made us calibrate our product development plan to a realistic and achievable level, even as we kept our eyes on the future, for the high-end microfluidic product.

Goal

After previous two stages, we had a sound scientific plan and a smart, two-tiered product strategy. But everything we had designed so far, our reagent kit, our future microfluidic chip-existed only on paper and in the lab. We were well aware that there was an entire world between a successful prototype in a well-controlled lab, and a real manufacturable product that can be reliably, legally and consistently produced at scale.

To see how this was done in reality, we needed to visit the factory floor. To see how things were actually launched, we needed to experience life at the regulator's desk. Our goal for this visit was simple: to get as close as possible to the full lifecycle of a professional Point-of-Care Testing (POCT) company. To see the nuts and bolts of the whole process from design, manufacturing and production to that long and costly march to the endgame of regulatory approval.

Company Profile

Figure 21 Genome Logo

• Name: Beijing Genome Biotechnology Co., Ltd.
• Founded: 2011
• Qualifications: A comprehensive high-tech enterprise that integrates the R&D, production, and service of laboratory analytical instruments, and an ISO9001 and medical GMP-compliant company with the good credentials of having obtained medical registration for their own real-time fluorescence quantitative PCR instrument, as an instrument manufacturer with both deep manufacturing and regulatory expertise.
• Specialty: The company has a highly experienced team with in-depth expertise in optics, mechanics, electronics, software, and biology, and a core focus on developing innovative, homegrown high-tech instruments.

Industry Insights

The full company tour and in-depth interview we were given by Genome's general manager Mr. Qiyue Chen and deputy general manager Mr. Peng Wang, was a comprehensive journey across the entire productization landscape, from factory floor to regulator's desk.

• The Manufacturing Blueprint:

The "Airtight" World of GMP: One of the first things we noticed was the extreme rigor. Walking into a world of HEPA-filtered air, white coats, and cleanroom booths that wouldn't look out of place in a sci-fi movie, was a potent lesson in the exacting attention to detail that's demanded in the medical device industry.

The Golden Triangle of POCT Design: The experts distilled the core of the POCT design challenge down to a constant tradeoff between three critical factors: Accuracy, Cost, and Usability. It was a crucial insight: for a lab product to succeed in the field, simplicity and user-friendliness are not just important, they're essential.

The "Sample In, Result Out" Philosophy: A perfectly designed POCT device, they explained, would require minimal effort from its end-user-it should allow them to get a result with the push of a button, essentially turning the complex analytical process into "sample in, result out." This philosophy of handling all complex steps inside the device to avoid user error and mistakes became our guiding principle.

The Magic of Freeze-Drying: They also showed us the industry standard for making reagents that remain stable for years during shipping and storage is lyophilization, or freeze-drying. This was a simple yet vital nugget of practical information that our own product would need to take into account.

• The Regulatory Marathon: A 2-3 Year Journey to Market

Building the perfect product, it turns out, is only half the battle. Our experts also gave us a sobering, hard-to-digest realistic view of the long and winding road of product registration.

Phase 1: The Stability Gauntlet. Before we could even think about larger scale clinical testing, we would have to prove that the stability and quality of our kit is absolutely rock-solid, batch-to-batch, over an appropriate range of temperatures and environmental conditions.

Phase 2: The 1,000-Sample Mountain. The meat of the process is a large-scale clinical validation trial. We would need to test at least 1,000 human samples (e.g. 500 patients, 500 controls) and demonstrate that our test is at least as good as the relevant "gold standard" method that it is benchmarked against.

The Realistic Timeline: With the pre-clinical work, the clinical trial, and the final submission, our expert sources were candid in advising us to expect a 2 to 3-year timeline from a finalized prototype to an approved, market-ready product.

• The User & Market Perspective:

The final key insight, which we only thought to ask about on the way out the door, was a brilliant piece of advice on getting end-user buy-in. To overcome the stigma around Alzheimer's Disease and our diagnostic product, our contacts recommended we should position our product less as a "disease test" and more as a health management and routine monitoring tool.

Figure 22 Company Tour at Genome Co.,Ltd

Reflection & Improvement:

This experience was a rite of passage from our world of academia to the real world. It was the moment when our project truly matured in our minds, evolving from the concept of a 6-month iGEM competition entry into a long-term, sustainable product vision.

• Concretizing Our Product Design: The "sample in, result out" philosophy was the guiding principle our experts handed down. This visit, and the detailed, boots-on-the-ground perspective on POCT manufacturing we were given, gave us the practical justification to make a microfluidic chip our final design target for our high-end line, since its core value proposition is automation. And the insight about freeze-drying was a revelation; we started right away to dig into how to incorporate lyophilized reagents in our future kit design.
• A Reality Check on Our Timeline and Strategy: But as importantly, this much-needed dose of reality reshaped our entire concept of our project's timeline and purpose. It was not discouraging, it was a clarification of what we were getting into. We now see that our iGEM project is the crucial "proof-of-concept" step, that all the big companies have already passed, the very first step in a long process. This shifts our business strategy to the key being to develop a technology that can stand up to the validation marathon and attract the investment and partnership needed to survive it.
• Sharpening Our User-Centric Narrative: Finally, the advice to frame our product as a "preventive health" tool, rather than a diagnostic test, was a powerful idea. We immediately retooled our messaging to focus on a proactive health monitoring approach. This is not only more marketable, it also better serves our human-centered mission of making AD less stigmatizing and frightening for those who face it.

Goal

While our visit to the POCT company helped us visualize the manufacturing and regulatory marathon that lay ahead of us, we left with a pragmatic 2-3 year time frame in mind and a good idea of how to design a user-friendly product. But, an approved, great product is worthless if you can't find the right customers for it. Our next goal was to pivot from the "how" of product creation to the "who" and "where" of commercialization. What are the business parameters we should be aware of? How does one practically launch a new medical device in a market as large and complex as China? What are the distribution channels? The financial barriers? The regulatory shortcuts?

Expert Profile

Expert's Insights

Figure 24 Interview with Mr. Zhang

Mr. Zhang provided us with an extremely practical, step-by-step playbook for success in the Chinese healthcare market.

• The Go-to-Market Blueprint: Channels and Partnerships

The first thing he discussed was the go-to-market strategy or the product distribution channels we should be looking at in order to market our product. We often had tunnel vision and only considered one end-user at a time. But, he introduced a multi-channel/multi-partner strategy to penetrate the market from several different sides:

1. Hospitals/Medical Examination Centers: The most traditional and most credible channel for a product like ours
2. Insurers: Collaborate with insurance companies to provide the test as a part of a preventive package
3. Elderly Care Facilities: A very high-concentration target market which is also highly motivated. He also gave us very useful insights into financial instruments that a startup like ours could utilize such as leasing equipment instead of buying it to minimize the initial capital investment.

• The Regulatory Shortcut: Class II vs Class III

This was the most important part of his advice. He was very specific about a huge strategic difference that we should consider:

Class III vs Class II registration for medical devices in China

1. Class III: This is the route for a high-risk, ground-breaking diagnostic (something which claims to be a definitive AD diagnosis). This would take 3-5 years with a clinical trial and cost millions of dollars
2. Class II: This is for a lower-risk and an auxiliary diagnostic device/tool. This process is much more streamlined and quick (1-1.5 years).

His very strong recommendation was that we should frame our product to start off as a Class II auxiliary diagnostic tool for a Tau protein test, not a definitive AD diagnosis tool. He pointed this would be our "foot in the door."

• Acknowledging the Urban-Rural Differences

He also reminded us that there is a very large gap in the level of care and affordability of care between tier 1-2 Chinese cities (major urban cities) and rural areas or under-resourced cities. We should not make a product which is a one-size-fits-all.

Reflection & Improvement: Forging a Pragmatic Business Strategy

This conversation brought us to the final step of our product design and framed a full-fledged business plan around it. It connected our technology to an actionable roadmap.

• A Shift to Even More Accessible Samples: His focus on user-friendliness and wide-market accessibility led us to push for even less-invasive samples than blood. This conversation was the major driving force behind us starting the research for even less-invasive samples like urine or saliva which would be a gamechanger for the elderly care facilities and routine check-ups.
• Adopting a Smart Regulatory Path: We have adopted his advice on a Class II registration strategy as a major decision shaping our project's immediate focus and narrative. We are no longer building a definitive diagnostic tool; we are building an extremely useful and accessible screening tool instead. This is much more realistic for an iGEM project in its truest sense.
• Solidifying Our Dual-Product Strategy for a Diverse Market: Mr. Zhang's point on the urban-rural divide gap gave us the final and most resounding rationale for our dual-product line idea. Our high-end and high-precision microfluidic chip would be a perfect fit for top-tier urban hospitals while our simple and low-cost magnetic bead kit would be ideal for mass-screening and less-resourced settings.

Goal

We had a product concept, a manufacturing plan, a regulatory path, and a business strategy. It was like putting together a puzzle and we had all the pieces. For our final step in this stage, we wanted to put it all together and present our complete vision to someone who had successfully done this entire journey from start to finish—a scientist, a clinician, and a successful biotech CEO. Our goal was to get a final, holistic "go/no-go" verdict on our strategy from Dr. Mark Kotter. Was our dual-product line commercially feasible? And what were the absolute, non-negotiable next steps to prove our technology's worth?

Expert Profile

Expert's Insights

This was the final stress-test for our strategy, and Dr. Kotter's insights were extremely clarifying and validating.

Figure 26. Interview with Dr. Mark Kotter

• The "Yes" Vote: Commercial Feasibility of the Dual-Product Line

This was a moment of elation for us. We had laid out our two-tiered strategy to Dr. Kotter and after hearing us out he confirmed that it was a commercially feasible and an intelligent strategy. He also strongly suggested the "get a foot in the door" method of first launching the low-cost, simple version (our magnetic bead kit) and then see if there is market interest and use that as a litmus test for a large investment in the more complex and expensive high-end microfluidic chip.

• The Ultimate Mantra: "Verify, Verify, Verify"

While he was positive about our strategy, he was absolutely adamant on one thing: generating data. He was extremely clear that before any commercial success, we had to prove our technology works. This meant:

1. Technical Verification: We need to do our own rigorous testing for sensitivity, specificity, and repeatability.
2. Clinical Validation: The final and most important step. We had to test our system on real patient samples from specialized Alzheimer's research centers and prove that the system works and is clinically useful.
3. Startup Strategy: The Road to "Proof of Concept"

He also gave us some extremely useful startup advice. He suggested that our immediate goal should be to raise a seed round of funding ($1-2 million) to get us to "proof of concept." This could be done through academic funding, forming a strong scientific advisory board, and then using the funds for the initial clinical validation with real samples.

Reflection & Improvement: A Clear Mandate for Our Final Plan

This final interview was the perfect capstone for our Implementation Scenario stage. It took all our disparate plans and synthesized them into a single clear path forward.

Solidifying the Dual-Product Line Strategy: Dr. Kotter's endorsement gave us the last confidence we needed to fully commit to our dual-product line strategy. This was no longer just an idea, this was a plan that had been confirmed to be commercially valid.

• Defining Our Immediate and Most Critical "Next Step": His laser-focus on clinical validation above all else has clarified our path for the project's "immediate next steps." We know that the culmination of our iGEM project cannot just be a report; it has to be a plan to actually generate real-world data. This led us to our final decision to make the immediate year after the competition entirely focused on testing of our products using actual samples on the premise of generating absolutely zero revenue. We have decided to shift our sole mission to the single goal of getting that initial critical clinical data.
• Building the Foundation for the Future: His advice on forming a scientific advisory board and raising seed funding has now become the long-term plan we are committed to building towards. This was a direct "Next Step" from this meeting and in a follow-up post-mortem meeting we have already started the process of identifying experts and outreach for our future advisory board.

This final conversation gave us our ultimate marching orders. It provided the perfect logical bridge between our investigation and design phases and our final, concrete implementation plan.

Goal

The deeper dives into manufacturing, business, and clinical path to market questions had left us with the feeling that our approach to implementation was robust and comprehensive. But as we discussed for our final step, there was still one essential question that we had yet to ask ourselves as part of implementation planning: "What is the ultimate impact of our project?"

Product innovation is never just a responsible question but rather, a responsible innovation is both productively viable and socially and environmentally "net positive." As such, we didn't want to simply list a couple of related UN SDGs in our business plan, without understanding the true economic, social, and environmental footprint of our work.

In this final conversation, we wanted Professor Liu's guidance as an expert on SDGs, to learn how to properly "think globally" about the impact of our work and to double-check our approach.

Expert Profile

Expert's Insights

The primary thing we learned from Professor Liu is that one should not (and in fact cannot) simply "check a box" on a few SDGs they can justify ticking off the list. Rather, we should think critically about the project in a systematic way, analyzing its impact across three different (but related) dimensions: economic, environmental, and social.

Figure 28 Interview with Prof. Liu

• The Economic Dimension (SDGs #9 & #10)

1. Innovation & Infrastructure (SDG #9, Target 9.5) & Reducing Inequalities (SDG #10, Targets 10.2 & 10.A): While it is "automatic" that our innovation contributes to scientific and technological progress, the Professor guided us to think about it at a more global scale.
2. The economic potential of the project is linked in an obvious way with social dimensions like education (#4) and health (#3), but another economic effect to consider is on the other side of the spectrum, i.e., job losses, from workers whose jobs are replaced in industries making older, less efficient, and less precise diagnostic tools.

• The Environmental Dimension (SDG #12 & #15)

1. Responsible Consumption and Production (SDG #12) & Life on Land (SDG #15): These two SDGs involved brainstorming different ways we could design our kits to have as little environmental impact as possible (electronic vs. paper manuals; recyclable components of the kit; ensuring waste is appropriately classified and recorded, etc. ).
2. The Innovation Paradox: Our technology, while low-cost and disposable, is still a technological improvement on the no-test baseline. As such, it's an unfortunate but difficult truth that the amount of resources used (hence, ecological impact) will be greater in a world with our test compared to a world without it. In other words, our technology is an improvement, but the type of improvement isn't straightforwardly "environmental."

• The Social Dimension (SDG #3 & #4)

1. Good Health and Well-being (SDG #3): Professor Liu helped us to pull out a synthesis of all of our above learnings about the project into three pillars of good health: convenience, accuracy, and affordability, to be taken together as the central improvements our test will ultimately provide in terms of enabling earlier AD diagnosis.
2. Quality Education (SDG #4): While technology can be game-changing, it will be useless without public education to shift the perception of AD as untreatable. In short, this conversation provided a formal argument for our public education mission which we had, until this point, been feeling in an intuitive sense was important. Now, in addition to a deep personal conviction that our technology needs to be understood by the public, we have both an academic and economic argument for a "dual mission" of technology and education.

Reflection & Improvement: Checklists vs. Frameworks

As with the prior steps, the conversation with Professor Liu in this step provided us with essential insights on our approach, but also solidified our learning in more comprehensive, complete ways.

• A Systematic, 3D-Framework: Our most significant insight in this step was the tripartite Economic/Environmental/Social structure of the SDG discussion, and it's the framing we will use (instead of a simple SDG checklist) in our final project documentation.
• Embrace Complexity and Accept Trade-offs: One of the more humbling lessons of this conversation was that innovation and "doing good" are not simplistic endeavors with simple metrics for impact, but rather (theoretically, at least) fully comprehensive, quantifiable accounting statements. In practice, this means our technology (as well as any technology) has potentially negative impacts that we have not yet fully considered (disrupting existing market; creating ecological waste, etc.). Acknowledging that our innovation and project have trade-offs was a difficult but important part of our development as responsible members of the HP community, and we are now cognizant of the fact that we must be aware of this in the future too.
• A Formal Rationale for our "Dual Mission": Last but not least, our discussion with Professor Liu and the connection to SDG #4 (Education) provided a near-formal requirement for a "dual mission" of our organization, providing academic/technical/clinical content to the public to ensure our efforts will result in the uptake and usage of our innovation and that it would achieve its ultimate goal of improving public health.

For a more detailed analysis of our project's relationship to each of the discussed SDGs, please consult our Sustainable Development Goals page.

Toward the end of our project development and while our work plan was really beginning to take shape, we had the unique opportunity to meet up with several high school iGEM teams at Beijing National Day School. It was truly amazing to see so many high caliber, young minds gathered under one roof to work on such innovative and audacious projects.

Figure 30 BNDS High School Team Meet-up

The experience of sharing ideas, challenging one another, and celebrating each other's successes with such like-minded people was truly special. It is really invigorating to hear what other teams are doing, it gives you a much broader view of the landscape of what people our age are capable of in the space of synthetic biology. But more importantly than anything else, it was very much a powerful reminder to each of us that we are all in this together as a growing and evolving community. This meet-up and community cultivation activity will definitely help to make that a reality for all of us, and has inspired us to do much more of this community and educational outreach work in the future.

The iGEM high school meet-up was of course a living example of the third and final pillar of our three-pillar strategy. Please visit our Education page to read more about this activity and our other community focused initiatives.

Pulling everything we have heard, every datapoint we have collected, and every story we have learned, we have condensed our desired future for the project into the following three-part strategy:

• A Two-Product Line: A Solution for Every Need

To meet the diverse needs of our market, we will offer a two-tiered product line:

The Standard Kit (Magnetic Bead-Based): The short-term and accessible solution. This low-cost reagent, non-invasive kit will be used for broad and mass screening applications for AD in settings such as community health check-ups and elderly care facilities.

The Advanced Kit (Microfluidic-Based, please visit ourhardware for prototype information): The long-term and high-precision solution. This more advanced kit will be used for clinical diagnostics and settings where quantitative accuracy and higher sensitivity are needed.

• A Phased Go-to-Market: A Pragmatic Approach to Market Entry

To take on the long and arduous journey to market, we will follow a realistic, step-wise strategy:

Phase 1: Clinical Validation (Zero Revenue). The short-term and most important priority. Spend year one of our work plan forming partnerships with clinical institutions to test our kits against real patient samples and generate the data necessary to demonstrate the sensitivity and specificity of our technology.

Phase 2: Launch the Standard Kit. Following successful validation, apply for a Class II regulatory approval and bring to market our Standard Kit in partnership with check-up centers, insurers, and elderly care facilities.

Phase 3: Launch the Advanced Kit. With the Standard Kit established in the market, then form partnerships with diagnostic institutions and apply for the more rigorous approvals needed to launch our high-precision Advanced Kit to the clinical diagnostics market.

• A Pillar of Education & Accessibility: Our Social Mission

A product is only as good as the community's willingness to accept it. In addition to this technical plan, we will also be running parallel and in support of it our social mission:

Public Science Communication. We will be continuing our education outreach work in the community to build trust, break down stigmas, and ensure that this solution is available to and accessible by all.

The three-pronged strategy above is the culmination of all the pieces of our iGEM experience. It is our final work plan and project implementation strategy, ambitious in its vision, realistic in its details, and human in its purpose.

Please visit our Entrepreneurship page to see our business model canvas, our market analysis, cost breakdowns, and our vision for the long-term.

Reference

Alzheimer's Disease International. (2023). World Alzheimer Report 2023: Reducing dementia risk: Never too early, never too late. https://www.alzint.org/resource/world-alzheimer-report-2023/

Jia, L., Du, Y., Chu, L., Zhang, Z., Li, F., Lyu, D., Li, Y., Zhu, M., Jiao, H., Song, Y., Shi, Y., Zhang, H., Gong, M., Wei, C., Tang, Y., Fang, B., Guo, D., Yin, P., Xu, J., & Wang, F. (2020). Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study. The Lancet Public Health, 5(12), e671–e681. https://doi.org/10.1016/S2468-2667(20)30185-7

World Health Organization. (2023, March 15). Dementia. https://www.who.int/news-room/fact-sheets/detail/dementia

Nam, H., Lee, M., Kim, M., Lim, H., & Lee, Y. (2023). Plasma brain-derived tau as a promising biomarker for Alzheimer's disease. Brain, 146(5), 1813–1824. https://doi.org/10.1093/brain/awac465

Chen, J. S., Ma, E., Harrington, L. B., Da Costa, M., Tian, X., Palefsky, J. M., & Doudna, J. A. (2018). CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity. Science, 360(6387), 436–439. https://doi.org/10.1126/science.aar6245

Li, Y., Li, S., Wang, J., & Liu, G. (2019). CRISPR/Cas systems towards next-generation biosensing. Trends in Biotechnology, 37(7), 730–743. https://doi.org/10.1016/j.tibtech.2018.12.005