This year, we have developed and introduced NOX (Neo-quOrum sensing-based Xpression biosensor platform), which provides a highly versatile and reliable platform for the detection of various molecules.

NOX stands out for its expandability, as its upstream genes can be modified to incorporate structural domains that bind to different small molecules, while its downstream genes remain fixed as a quorum sensing and fluorescence display pathway. This makes NOX a versatile platform that can easily adapt to different target molecules and be applied in various contexts.

This page showcases our considerations regarding the application scenarios, advantages, and potential usage risks associated with NOX. It outlines how we can effectively implement NOX in practical settings.

Background of Detection Industry

There are various instruments and techniques for detecting trace molecules, such as mass spectrometry, spectroscopy, electrochemical analysis, and chromatography, among others. These technologies have their own advantages and can rapidly detect target molecules in laboratory settings. In recent years, there has been a growing demand for small molecule detection in fields such as environmental monitoring and healthcare, which has brought the concept of small molecule detection into everyday life. For example, we undergo blood tests in hospitals to detect diseases, and factories perform quality inspections to check for excessive levels of small molecule additives.

However, what about in daily life?

We have observed that there is a lack of suitable products to meet the needs of individuals seeking specific small molecule detection in their daily lives. Taking commonly used additives like bisphenol A (BPA) and the liver disorder biomarker bile salts as examples, people have a demand for personalized molecule testing in various scenarios.

  • Bisphenol A

    • Bisphenol A (BPA), a plastic monomer and plasticizer, is widely recognized as one of the most extensively manufactured compounds on a global scale. It is employed in the manufacturing process of polycarbonate plastics and epoxy resins, which find extensive application in various consumer goods [1]. The Centers for Disease Control and Prevention (CDC) performed the 2003-2004 National Health and Nutrition Examination Survey (NHANES III), which revealed that 93% of the 2517 urine samples collected from individuals aged six years and older contained measurable amounts of BPA [2].

    The primary sources of exposure to BPA encompass food packaging and dust, dental supplies, healthcare equipment, thermal paper, toys, and goods intended for children and infants. BPA undergoes hepatic metabolism, resulting in the formation of bisphenol A glucuronide. Primarily, this metabolite is eliminated from the body through urinary excretion. The phenolic structure of BPA has been demonstrated to engage with estrogen receptors and exert agonistic or antagonistic effects through estrogen receptor (ER) mediated signaling pathways. Hence, it has been demonstrated that BPA contributes to the development of several endocrine disorders, encompassing female and male infertility, premature puberty, hormone-dependent tumors like breast and prostate cancer, as well as several metabolic disorders, including polycystic ovary syndrome (PCOS). Due to its persistent and regular exposure as well as its propensity for bioaccumulation, BPA appears to necessitate specific considerations, such as the use of daily biomonitoring measures [3].

  • Liver dysfunction

    • Approximately 844 million individuals worldwide are estimated to have chronic liver diseases, with a mortality rate of 2 million fatalities annually, which can be compared to other significant chronic disease-related public health issues like diabetes (422 million, 1.6 million deaths) [4]. In order to manage and treat liver dysfunction, there is an urgent need for effective worldwide activities, such as education, prevention, and early diagnosis.

    However, when people wish to quickly test for early signs of liver disease at home, they currently have to visit a hospital for a physical examination rather than being able to perform a simple test at home. In addition to liver diseases, any early disease detection and chronic diseases monitoring all contribute to lowering mortality and enhancing patients' quality of life, but those diagnostic methods are expensive, complicated, and dependent on experienced workers, which restricts testing to concentrated locations like hospitals [5].

Why NOX?

As demonstrated by the examples of BPA and liver dysfunction, when untrained individuals need to perform daily small molecule detection without access to laboratory conditions, sophisticated detection instruments are unable to meet their needs. This is where our product, NOX, comes into play.

NOX has developed a trace chemical detection platform. We have designed a fixed downstream gene pathway, such as the quorum sensing pathway, and by replacing the upstream genes with structural domains that are specific to the target small molecule, we can achieve detection with a desirable limit of detection (LOD). Compared to other similar instruments for small molecule detection, NOX has the following advantages:

  1. Expandability

    2. As a detection platform, NOX can leverage nearly identical gene pathways to achieve detection for different small molecules. This provides a significant advantage in the market. Once the upstream binding structural domains are identified for different small molecules, NOX can quickly release products and cover a wide range of applications. Additionally, if there are improvements in the downstream gene pathway, it can be applied to all NOX products. This demonstrates NOX's great potential for future development and innovation.

  2. Versatility

    3. NOX is extremely compact, with a housing that measures just 4 cm on each side. Its detection method utilizes fluorescence, which makes it easy for users to understand how to use it. Its portability and user-friendly nature make NOX suitable for a wide range of applications. It can be conveniently carried around and used in various settings, and it can cater to a broad user base, including individuals without specialized training. Furthermore, as a versatile detection platform, NOX has a vast potential for detecting a wide range of small molecules.

  3. Low Cost

    4. We have designed the hardware of NOX to be as compact and cost-effective as possible. The NOX kit utilizes low-cost and easily accessible components, resulting in hardware costs of less than $0.8 per unit. This extremely low price gives NOX a significant advantage in the market and makes it accessible even in economically disadvantaged areas.

  4. Environmental Friendliness

    5. NOX emphasizes environmental sustainability in its design and operation. The compact size and low power consumption of NOX contribute to its overall eco-friendliness. NOX incorporates the use of environmentally friendly materials. It is chosen for its ability to meet the desired performance requirements of NOX while minimizing negative effects on the environment. By utilizing environmentally friendly materials, NOX aims to reduce its ecological footprint and contribute to a more sustainable future.

Compass

To keep abreast of the market and industry demand, we achieved human practices to ask advice from several enterprises. More information please click "Human Practice-Integrated Human Practices" page.

  1. From the aspect of production – Beijing Hotgen Biotech

    2. Beijing Hotgen Biotech is a company specializing in selling detection instruments. They gave us advice from the aspect of production.

    Key points:

    • Without conducting large-scale production, it is challenging to achieve precise accuracy measurements. Therefore, quantitative detection should not be considered, and the focus should be on addressing "yes or no" detection questions in daily use.
    • The product should be simplified as much as possible, making it visually interpretable and easy for the general population to use.
    • It is important to compare the product with international standards to determine the level at which LOD should be achieved.
  2. From the aspect of investors – CAS Delta Capital

    3. CAS Delta Capital is a company focused on facilitating the translation of scientific achievements into practical applications. They provided advice from an investor's perspective.

    Key points:

    • Understand why the public would need our project and identify the target audience.
    • Assess the ability to produce the product in large quantities with consistency. While chemical and semi-chemical processes have achieved significant advancements in terms of scalability and consistency, biological systems inherently carry the risk of mutations, which can lead to inconsistencies.
    • Determine the extent of the price advantage offered by the product. Market size calculations are necessary to assess the potential pricing advantage.

Conclusion -SWOT Analysis

Based on the aforementioned information and an in-depth evaluation of the merits and demerits of NOX, we did a SWOT analysis.

  1. Strength
    • Expandability, modifying the target molecule and optimizing can be accomplished without difficulty;
    • Versatility, portable and user-friendly;
    • Low cost;
    • Environmental friendliness.
  2. Weakness
    • Safety especially needs to be considered for bio-products.
    • The product needs to achieve standardization and consistency in its production process, while biological systems may undergo mutations.
    • NOX only achieves qualitative detection and is unable to provide quantitative measurements. Further confirmation through detailed medical examinations at a hospital is necessary for scenarios such as the detection of disease biomarkers.
  3. Opportunities
    • A market gap in daily small molecule detection, where it is difficult to find products that offer portable detection of substances like BPA and bile salts.
    • With the increase in societal education levels, people's awareness and understanding of chemical molecules are rising, leading to an increased demand for body health monitoring.
  4. Threat
    • Security and accuracy in practical examination.
    • Other portable molecular detection products, such as COVID-19 test kits, can achieve smaller sizes.
    • The market supervision of synthetic biology products is not well-established.

Methods of Implementation

Based on the consultations with the two companies and the analysis of NOX's strengths and weaknesses, we have developed a preliminary implementation plan for NOX.

  1. NOX Improvements
    • Upstream: Explore additional structural domains suitable for different small molecules to expand the range of detectable molecules.
    • Downstream: Continuously improve the group sensing--fluorescence gene expression pathway to enhance the accuracy, sensitivity, and detection parameters such as LOD of the detection system, making the platform more effective.
    • Mutation prevention: To ensure consistent production and biosafety of the product during formal applications, it is important to design methods for preventing mutations. For example, incorporating a self-destruct switch in the mutated bacteria to prevent their survival.
  2. Marketing
    • Study more about the target market: while we aim at building a platform, we should also investigate more about the needs of what kinds of molecule have potential marker. Understand the needs, preferences, and behavioral characteristics of potential customers in these fields.
    • Figure out the target audience: We aim to establish NOX as a daily-use, affordable, and portable detection method for various small molecules. The target audience for detecting different small molecules varies. For example:
      • Detecting BPA (Bisphenol A): The target audience for BPA detection would be individuals exposed to plastic products extensively, such as those using plastic water bottles, food containers, and individuals, including newborns and infants, who may be more vulnerable to the potential effects of BPA.
      • Detecting bile salts: The target audience for bile salts detection would include individuals with a family history of genetic diseases related to bile metabolism or liver function impairment, as well as individuals who may be at risk of liver function damage due to factors like work fatigue or exposure to hepatotoxic substances.
    • Conduct marketing activities: Execute marketing strategies and engage in marketing activities to increase product visibility and appeal. We should participate in relative exhibitions and conferences, hosting seminars in realm of daily molecular detection, utilizing social media marketing, and advertising.
    • Regular evaluation and adjustment: Regularly assess the effectiveness of marketing strategies and make necessary adjustments and optimizations based on market feedback and competition. Maintain flexibility and adaptability to ensure the ongoing effectiveness of marketing strategies.
  3. Policy Advocacy
    • Especially in China, the policies related to synthetic biology products are not yet well-established. In order to promote the adoption and utilization of NOX and other synthetic biology products, it is important to advocate for the development of comprehensive policies that address the specific considerations and challenges associated with these products. This can be achieved through the following actions:
    • Engage with regulatory authorities: Initiate dialogues and engage in discussions with relevant regulatory authorities to raise awareness about the potential benefits of synthetic biology products like NOX.
    • Collaborate with synthetic biology associations and organizations: Gather our competencies to advocate for policy reforms and regulations that support the development and commercialization of synthetic biology products.
    • Educate the public: Conduct awareness campaigns and educational initiatives to inform policymakers, stakeholders, and the general public about synthetic biology, its applications, and the potential benefits it offers. Highlight the safety measures and ethical considerations in the development and use of synthetic biology products.
    • Foster international collaboration: Engage in international collaborations and exchanges to learn from best practices and experiences of other countries in regulating and promoting synthetic biology products.

References

[1] Laura N. V., Russ H., Michele M., Nicolas O., Wade V. W., (2007). Human exposure to bisphenol A (BPA). 24(2), 139–177. doi:10.1016/j.reprotox.2007.07.010

[2] Bisphenol A(BPA) -National Institute of Environmental Health Science. Accessed October 11, 2023. https://www.niehs.nih.gov/health/topics/agents/sya-bpa/index.cfm

[3] Konieczna A., Rutkowska A., Rachon D. Health risk of exposure to Bisphenol A (BPA). Roczniki Państwowego Zakładu Higieny, 2015, 66(1).

[4] Marcellin P., Kutala BK. Liver diseases: A major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int. 2018 Feb;38 Suppl 1:2-6. doi: 10.1111/liv.13682. PMID: 29427496.

[5] Lee S., Huang H., Zelen M.. Early detection of disease and scheduling of screening examinations. Statistical Methods in Medical Research. 2004;13(6):443-456. doi:10.1191/0962280204sm377ra

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