Background & Inspiration
Global Healthcare-Seeking Behavior: A Common Reluctance to Visit Hospitals
As a group of high school students from around the world, we have observed significant differences in healthcare-seeking behavior across regions, including China, the United States, Singapore, and Japan. Despite these regional variations, one common issue persists: when individuals experience discomfort, there is a reluctance to promptly visit a hospital (especially in China and the U.S.). This hesitation is largely due to concerns compounded by factors such as time consumption at hospitals, the complexity of healthcare processes, the travel required to reach medical facilities, fears related to hospital-acquired infections, payment willingness, insurance coverage, and varying levels of trust in scientific testing[1-2].
Questionaire data: Reasons for relactance to hospital
The Demand for At-Home Testing in Chronic Disease Management
Our comprehensive literature review reveals that early detection and monitoring of various diseases can substantially decrease morbidity and mortality rates, thereby reducing overall healthcare expenditures[3]. Furthermore, long-term management of many conditions can be effectively administered outside of clinical environments.
Meanwhile, through our observations, surveys with parents, teachers, and other adults, as well as background research, we identified that chronic conditions, including the so-called "four-highs" (hypertension, diabetes, hyperlipidemia, hyperuricemia), have a significant need for frequent monitoring[4]. This creates a strong demand for at-home testing rather than regular hospital visits and also holds the potential to be effectively managed through such methods[5].
Questionaire data:The demand for Home-based POCT
Initial Idea for a Home-Based POCT System Focused on Glucose and Uric Acid
Based on these global observations and research, we propose the development of a home-based Point-of-Care Testing (POCT) system and decided to take glucose and uric acid as our first two biomarkers for this system.
In conclusion, our initiative is inspired by our findings, which are substantiated by both qualitative and quantitative data, as well as existing literature on the subject.
Integrated Human Practice
"Human Practices is the study of how your work affects the world, and how the world affects your work."
——Peter Carr, Director of iGEM Judging
Our Integrated Human Practice (IHP) provided valuable real-world insights that informed our entire team, guiding both our bioengineering and hardware taskforces in their decision-making and product design.
IHP-Guided Project
We aim to ensure human practices were not only integrated into every phase of our project but also affects the real-world, aligning our goals and product design with real-world dynamics beyond the lab.
The following table illustrates the map of our IHP framework:
IHP Framework
Phase 1: Initial Goal Setting
Gaining Industry Insight: Understanding the IVD Landscape and Stakeholder Dynamics
Starting from our initial idea to build a home-based POCT (point-of-care testing) system, we first contacted Dr. Yue Ren, an IVD (in-vitro diagnostics) industry expert from ArcoBiosystem. He gave us a comprehensive lecture, which provided an understanding of the IVD industry landscape, including stakeholders, market dynamics, and technology trends. He especially clarified the role of stakeholders throughout the product lifecycle, both during development (e.g., regulatory bodies, companies, CROs, and doctors) and post-launch (e.g., patients, distributors, and end-users). His insights offered a detailed view of how these parties influence the IVD market, helping us gain a clearer perspective on the industry's structure and driving forces. Additionally, we gained an in-depth understanding of how to approach POCT product design, focusing on both the assay reagents and the engineering aspects of the hardware.
HP in ArcoBiosystems
Lecture from IVD expert Dr. Ren
Choosing Biosensors: The Optimal Solution for our Glucose and Uric Acid Meters
We conducted an in-depth investigation into existing home-use glucose and uric acid meters and identified that electrochemical testing is the predominant method. However, after further research and evaluation of available technologies, we ultimately selected the biosensor approach for our POCT system. Biosensors provide significant advantages, particularly their higher specificity, which results in enhanced accuracy, improved consistency, and reduced calibration frequency compared to traditional electrochemical methods. This makes biosensors the most suitable solution for our glucose and uric acid monitoring product[6-8].
In summary, through our Phase 1 IHP, our primary objective is to design and develop a home-based POCT system focused on glucose and uric acid monitoring, utilizing the biosensor method.
Phase 2: Stakeholder Analysis
Stakeholder-Driven Strategy for Designing a Home-Use POCT System
When designing a home-use POCT system, it is essential to first address the project strategy tailored for this specific scenario. By conducting a comprehensive listing, engagement, and analysis of stakeholders using an interest and influence matrix, we developed a strategy that considers the varying interests and influence of different stakeholders. This includes determining the weight of each stakeholder's influence during product design and deriving the overall objectives of our project based on these considerations.
We identified six key categories of stakeholders:
Subsequently, we mapped these stakeholders to specific positions within an interest-influence matrix based on their relative power and interest in the project.
Interest-Influence Stakeholder Analysis
Based on our stakeholder analysis, our stakeholder strategy for designing the POCT product is as follows:
In summary, our stakeholder analysis has guided the development of a targeted strategy for designing the home-use POCT system. By categorizing stakeholders based on their interest and influence, we actively engage key players like manufacturers and doctors, while focusing on user-friendly designs for end-users such as patients and pharmacy personnel. Government and experts are kept satisfied through compliance, and lower-influence stakeholders are monitored as needed. This approach ensures that the product meets both technical standards and practical user needs.
Project Principle: Ongoing Integration of Human Practices Throughout Bioengineering and Hardware Development
From this point onward, our Human Practices (HP) efforts are integrated throughout the entire design and development process of the bioengineering and hardware components. HP work led the strategy formation and interest-influence analysis, and continues to ensure that the Bioengineering and Hardware Taskforces align their goals with real-world needs, incorporating stakeholder feedback at every stage of development.
Phase 3: Initial Product
Goal Specificity
Based on our research into relevant stakeholders and our strategy for how stakeholders influence product design, we have identified the following key performance specifications.
We focus our efforts on both bio-engineering design and hardware design to be employed to ensure that these specifications can be achieved on home-use scenarios. Through workshops with our team's bioengineering and hardware taskforces, we have made the following breakdown of strategy and assignments accordingly.
Key Performance Specification and Breakdown of strategy & assignments:
The refinement of these key performance specifications comes from our Integrated Human Practices with stakeholders of POCT manufactures, IVD experts, doctors, researchers, and end users. For detailed information, please refer to our "Investigations & Reflections" section.
IHP Cycle in Initial Product Development
HP-Driven Validation of Biosensor System for Glucose and Uric Acid Detection
After defining the specifications for our initial product, our bioengineering team began conducting experiments to validate our biosensor system for detecting the two biomarkers, glucose and uric acid. These experiments involved testing across various concentration gradients to verify the effectiveness and stability of the reagent reaction system within our test kits. The design of these concentration gradients was informed by the HP taskforce’s review of data on normal and abnormal levels of glucose and uric acid, with primary references from organizations such as the World Health Organization (WHO), Chinese Diabetes Society, Chinese Medical Association, American Diabetes Association (ADA), and the American College of Rheumatology (ACR).
HP-Facilitated Collaboration and Workshops Shaping Hardware Design
Simultaneously, the hardware taskforce initiated concept development and broke down engineering modules based on research from POCT-related papers and patents. During this process, the HP taskforce facilitated discussions between the hardware taskforce and engineers from Baidu's smart hardware division, Xiaodu, as well as organized a workshop with TagetingOne, a leading POCT manufacturer in China. At the workshop, they disassembled several devices for us, revealing the internal structures of optics, temperature control, electronic circuits, and mechanical controls. They also introduced us to the user interface and reagent-related components.
Workshop with TagetingOne
Revealing the internal structures of a POCT
Their hardware, software, electronic circuit engineers, and microfluidic chip engineers provided valuable insights into our hardware engineering solutions, which inspired the framework for our hardware design. For detailed hardware design, please refer to our team's hardware page.
Throughout the initial product phase, HP efforts have been integrated continuously into the design and development process.
Phase 4: Product Evolution
Goal Expansion
As our bioengineering taskforce approached the completion of validation experiments for biosensors targeting uric acid and glucose, and the hardware taskforce advanced the hardware design, our Human Practices efforts remained ongoing. Through consultations with experts, we identified the necessity for modularity [Event 5] and recognized opportunities for expanding our project. This led to the further standardization of our plasmid design, incorporating standardized interfaces and structures to support compatibility with multiple biosensors, thus enabling the detection of a range of biomarkers. Lactic acid was selected as a validation target to demonstrate the system’s versatility. However, our Human Practices consultations revealed that lactic acid holds limited clinical significance [Event 2]. Subsequently, tryptophan was identified as an additional biomarker [Event 4], and we successfully validated the generalizability of our system.
On the hardware front, the need for simultaneous detection of multiple biomarkers emerged as a common requirement, prompting us to enhance the system’s expandability. Consequently, we developed the hardware as a POCT system capable of concurrently detecting three biomarkers, addressing optical crosstalk challenges inherent in multi-indicator detection. Our design encapsulates the optical, fluidic, and temperature control systems into standardized modules, facilitating future use by other research teams.
These jobs reflect the iterative evolution of our product.
IHP Cycle of Product Evolution
Our realization of the need for modularity and the potential for project expansion emerged through a series of expert consultations. Initially, in our discussions with Professor Jiancheng Xu, we explored various testing methods for biomarkers, such as uric acid, lactic acid, tryptophan, and glucose. Professor Xu, an expert in clinical laboratory diagnostics, provided critical feedback on our biomarker selection. His insights into the complexities of lactic acid testing, which requires arterial blood, highlighted its impracticality for home use. As a result, we decided to exclude lactic acid from our testing panel for practical reasons [Event 2].
Simultaneously, Professor Xu’s expertise helped us refine our biomarker selection, shifting our focus towards indicators more suitable for patient self-administration and aligning with the goals of our POCT system. We also engaged with Professor Zheng Li, whose extensive experience in mental health led us to explore tryptophan as a potential biomarker. His explanation of the metabolic interplay between tryptophan, serotonin, and phenylalanine broadened our understanding of its biological relevance and the technical challenges associated with its detection [Event 4].
Furthermore, Song Jie, a synthetic biology and bioinformatics expert, reinforced the importance of modularity in our system design. His support validated our decision to further standardize our project plasmid, creating interfaces compatible with multiple biosensors and enabling the detection of various biomarkers. Song Jie’s perspective on modularity in synthetic biology inspired us to develop standardized interfaces and structures, allowing our system to accommodate future expansions and integrate emerging technologies [Event 5].
These expert consultations collectively shaped our decision to adopt a modular, multi-biomarker detection system. We incorporated lactic acid as a validation marker to demonstrate system versatility, but ultimately replaced it with more medically relevant biomarkers, such as tryptophan. The feedback we received from these experts directly influenced both the evolution of our bioengineering and hardware designs, ensuring that our system was both practical and adaptable.
For detailed information on the design and implementation of the product's evolutionary development, please refer to our bioengineering and hardware pages.
Investigation & Reflections
Learnings from Interaction/Visit HP:
- Preliminary Design and Questions:
Before the visit, we had a preliminary design for a home-use POCT device, focusing on blood glucose and uric acid as the initial biomarkers. However, we had many technical questions regarding the feasibility of this detection method.
- Engagement with AcroBiosystems:
We reached out to AcroBiosystems for a visit and technical input to gain a better understanding of the industry and technology. We compiled a list of specific questions based on internal discussions.
- Industry Overview from Dr. Ren:
Dr. Ren provided a comprehensive overview of AcroBiosystems’ business areas, covering key aspects like protein and antibody provision, reagent kits, analytical testing services, and clinical diagnosis products. During the discussion, we focused primarily on reagent kits and analytical testing services. He emphasized important aspects of In-vitro Diagnostics (IVD) development, including the balance between efficacy and risk, and the importance of accuracy, scalability, and affordability in IVD products.
Takeaways (Reflections and Decisions):
- Clearer Understanding of Reagent Kits and Analytical Testing Services:
The visit clarified the critical role of reagent kits and analytical testing services in diagnostics. These tools are essential for the development and validation of our POCT system.
- Feasibility of Detection Methods:
Many of our technical questions were addressed, especially concerning the application of molecular assays like qPCR for detecting biomarkers such as glucose and uric acid. This discussion helped refine our approach to detection methods for the POCT device.
- Refined Product Development Path:
The insights provided by Dr. Ren, particularly regarding IVD product development and the technological platforms (immunoassays, qPCR, and multiplex assays), guided us towards a clearer path for product development. This included focusing on utilizing reagent kits and considering advanced analytical methods.
Learnings from Interaction/Visit HP:
- Professor Jiancheng Xu's Expertise:
Professor Jiancheng Xu, a clinical laboratory diagnostics expert and director of the hospital laboratory at Norman Bethune Medical University, specializes in diabetes pathogenesis, big data analysis, and establishing reference intervals for test items. He provided us with critical feedback on the feasibility of our project.
- Detailed Explanation of Testing Methods:
Professor Xu expressed great interest in our project and introduced various testing methods for biomarkers such as uric acid, lactic acid, tryptophan, and glucose. He also explained the collection of different blood samples for these tests, which helped us identify challenges in our initial design.
Takeaways (Reflections and Decisions):
- Realization of Limitations in Testing Lactic Acid:
One of the major insights we gained was that lactic acid testing requires arterial blood, which is not practical for home use or self-administration by patients, as we had initially envisioned. Based on this realization, we decided to exclude lactic acid from our testing panel for practical reasons.
- Refinement of Biomarker Selection:
This discussion prompted us to focus more on biomarkers that are feasible for home testing and patient self-administration, aligning better with the goals of our POCT device.
Learnings from Interaction/Visit HP:
- The engineers provided a detailed explanation of the principles and technical details of the nucleic acid detection integrated machine they designed. The innovation lies in integrating the traditional PCR amplification process into an automated system, which significantly improves detection efficiency and accuracy.
- In the discussion, we explored how to achieve efficient biological fluorescence detection through the design of sophisticated microfluidic chips and optical modules.
- We also discussed the feasibility of using flushable reagent kits. The engineers expressed concerns that this could lead to cross-contamination, compromise operator safety, and potentially contaminate the equipment.
- We learned about the advantages and implementation methods of using Peltier technology for thermostatic control, which can provide stable temperature management for our device.
Takeaways (Reflections and Decisions):
- We ultimately decided to abandon the dry powder storage solution and chose to embed liquids instead, which helped reduce the technical complexity and cost.
- For data display and user interaction, we opted to forgo using a built-in display on the integrated machine and decided to transmit data via Bluetooth to a mobile app. This decision allowed us to minimize the device size, making it more suitable for home-use scenarios.
- We abandoned the reagent flushing solution and instead adopted a disposable reagent kit design to avoid cross-contamination and enhance the safety of the equipment.
- The insights gained from Peltier-based temperature control provided valuable guidance, and we decided to incorporate this technology in future iterations of our device design.
Learnings from Interaction/Visit:
- Professor Zheng Li’s Expertise:
Professor Zheng Li, a psychiatrist with extensive experience in pediatric clinical work, particularly in autism, ADHD, and developmental delays, showed great interest in our project, specifically in the detection of tryptophan. He has a deep understanding of the roles that serotonin, phenylalanine, and tryptophan play in mental health, particularly in relation to conditions like autism.
- Discussion on Tryptophan Detection:
Professor Li provided us with valuable insights into the detection methods of tryptophan. He explained the complex relationship between serotonin, phenylalanine, and tryptophan and how these interactions can influence both mental and physical health. This broadened our understanding of the biological importance of tryptophan and the technical challenges associated with its detection.
Takeaways (Reflections and Decisions):
- Challenges of Detecting Tryptophan:
One of the key takeaways from this discussion was the difficulty of detecting tryptophan alone due to its metabolic interactions with other compounds. This realization prompted us to reconsider our approach and explore alternative methods that can provide more accurate detection in practical applications.
- Effective Testing Methodology:
Professor Li's advice led us to consider more comprehensive methods for detecting tryptophan, focusing on broader metabolic pathways rather than isolating tryptophan. This has provided us with a more effective direction for testing, aligning our project with real-world clinical applications.
Learnings from Interaction/Visit:
- Song Jie's Expertise in Detection Techniques:
Song Jie, with his background in bioinformatics and synthetic biology, introduced us to commonly used chemical detection techniques in the industry. He emphasized the importance of high precision and the reliance on detecting a single signal to ensure accuracy.
- Future of Biological Detection:
Song Jie highlighted biological detection as the future trend in diagnostics, though he noted technical challenges such as isolating peptides in complex samples and improving the strength of responses. He also introduced us to emerging technologies capable of designing systems with multiple molecular responses, which promise to significantly reduce experimental time and costs for researchers.
- Support for Modular Approach:
As a synthetic biology researcher, Song Jie appreciated our bioengineering approach, which focuses on modularity, interchangeability, and componentization. He noted that this approach would be highly advantageous for future researchers looking to build upon our work.
Takeaways (Reflections and Decisions):
- Refinement of Detection Methodology:
Song Jie’s insights on the technical demands of chemical and biological detection have reinforced the need for high precision in our POCT device. His emphasis on minimizing signal noise while ensuring accuracy is crucial as we refine our detection methods.
- Adoption of Emerging Technologies:
His introduction to emerging multi-response molecular systems has inspired us to explore how these technologies could potentially be incorporated into our project, aiming to reduce experimental costs and time while improving accuracy.
- Validation of Modular Design:
Song Jie’s support for our modular, interchangeable approach in synthetic biology further validated our design direction. His feedback reassures us that this framework will not only benefit our current project but also offer a strong foundation for future research advancements in the field.
Learnings from Interaction/Visit:
- Introduction to Advanced Microfluidics:
During our discussions with Digifluidic, Dr. Wu demonstrated their advanced electronic microfluidics technology. While we chose not to adopt this technology, the insights provided were valuable for understanding different approaches to fluid control in point-of-care testing (POCT).
- Guidance on Pneumatic Fluidic Chip Design:
Dr. Wu provided specific feedback on our pneumatic fluidic chip design, offering valuable insights into optimizing fluid handling. He also shared advice on chip coatings, hydrophobic surface design, and how these elements impact fluid dynamics, which was particularly useful for refining our existing design.
Takeaways (Reflections and Decisions):
- Refinement of Pneumatic Chip Design:
Although we decided not to adopt electronic microfluidics, Dr. Wu’s guidance on chip coating, hydrophobic design, and fluid control has led us to make important refinements to our pneumatic fluidic chip. These improvements will enhance the precision and reliability of fluid manipulation in our system.
- Focus on Practical Enhancements:
The discussion highlighted several practical improvements for our current design, allowing us to focus on pneumatic fluid control and the importance of surface properties, such as coating and hydrophobicity, to achieve better performance without the need for electronic control.
Local Engagement
Our local engagement efforts focused on education and active participation in the China iGEMer Community Conference (CCiC).
For our education efforts, we developed a card game and a WeChat mini-program game to popularize synthetic biology concepts. Additionally, we organized a poster campaign aimed at enhancing public health awareness, contributing to a broader understanding of home health-indicator monitoring in the community. For more details on our educational activities, please refer to the Education page.
During CCiC, we presented our project and received constructive feedback from judges and other teams. The event provided us with insights into refining our presentation style, such as focusing on key project aspects and reducing the content on slides to make them clearer for the audience. Additionally, we had meaningful exchanges with other iGEM teams, gaining knowledge from university-level projects and improving our own approach.
Our team presentation on CCiC
Through these engagements, we strengthened both our project and our community connections, fostering a deeper understanding of synthetic biology.
Document Sharing
One of the most helpful contributions throughout the HP process was the insightful sharing from Dr. Ren Yue of ArcoBiosystem regarding the medical diagnostics industry. With permission, we have shared this content with the iGEM community on our wiki. You can download it here.
Value Discussion
Potential Impact of a Home-Use POCT System and the Value of Data Stream
If this home-use POCT (Point-of-Care Testing) device becomes widely adopted, and users can purchase reagent kits to monitor multiple health indicators, the generated data will accumulate over time. This aggregation will result in a demographically significant big data set, holding immense value for various sectors.
Data Stream Value: The Future Importance of Health Data
For Doctors:
Our POCT system is designed to accurately track patients' health changes over extended periods. This continuous monitoring capability allows healthcare providers to observe precise trends in an individual’s health, thereby enabling more accurate diagnoses and personalized care.
For Insurance Companies:
The system provides detailed health data across a broad demographic spectrum, enabling insurance companies to gain deep insights into individuals' health profiles.
For Governments:
The ability to collect and analyze real-time health data provides governments with an invaluable tool for public health management.
Reference
- Wang, Y., Zeng, Y., Gao, K., & Fu, W. (2023) ‘The implications of the U.S. DRG payment reform process for the reform of China's medical insurance payment system’, Chinese Journal of Hospital Administration, 39(2), pp. 93–96. doi: 10.3760/cma.j.cn111325-20220920-00818.
- Yin, P., Liu, Y. & Ren, J. (2016) ‘Comparison of general practice systems in China and abroad’, Chinese General Practice, 19(1), pp. 8–11.
- Ornelas-González, A., Ortiz-Martínez, M., González-González, M. & Rito-Palomares, M. (2021) ‘Enzymatic methods for salivary biomarkers detection: Overview and current challenges’, Molecules, 26(22), p. 7026. doi:10.3390/molecules26227026.
- Thottam, G.E., Krasnokutsky, S. & Pillinger, M.H. (2017) ‘Gout and metabolic syndrome: a tangled web’, Current Rheumatology Reports, 19(10), p. 60. doi:10.1007/s11926-017-0688-y.
- Krouwer JS, Cembrowski GS. A Review of Standards and Statistics Used to Describe Blood Glucose Monitor Performance. Journal of Diabetes Science and Technology. 2010;4(1):75-83. doi:10.1177/193229681000400110
- He, Zhike, et al. "An Analytical Comparison Between Point-of-Care Uric Acid Testing Meters." Expert Review of Molecular Diagnostics, vol. 16, no. 3, 2016, pp. 245-252.
- Smith, Kenneth A., et al. "Commercial and Scientific Solutions for Blood Glucose Monitoring—a Review." Sensors, vol. 22, no. 2, 2022, pp. 425-438.
- Zhang, Yujie, et al. "Minimally Invasive Electrochemical Continuous Glucose Monitoring Sensors: Recent Progress and Perspective." Biosensors and Bioelectronics, vol. 52, no. 3, 2023, pp. 123-145.