phage

How can bacteriophage-based biosensors identify cancer quickly?

Estimated Reading Time: 12 minutes

This article comprehensively explores the recent advancements in bacteriophage-based biosensors for rapidly detecting cancers. It offers a detailed overview of these cancers, emphasizing the critical need for early detection and the role of innovative biosensor technologies. Furthermore, the article delves into clinical applications and provides a comparative analysis with traditional detection methods. It addresses current challenges and envisages future research directions in biosensor technology. This work highlights the potential of bacteriophage-based biosensors as a significant advancement in cancer diagnostics.

Author ID: 2024024866

1. Introduction Bacteriophage Endolysin-Based Biosensors

1.1. Bacteriophage

The use of bacteriophage biosensors in cancer detection represents notable progress in the accuracy and effectiveness of diagnosis. These biosensors use the specific nature of bacteriophages, which are viruses that infect bacteria and are cleverly modified to target cancer cells [1]. This innovation comes from the remarkable futures of bacteriophages, including the ability to detect specific markers on cancer cells with high affinity and selectivity, therefore recognizing different types of cancer [2]. This method dramatically improves the accuracy of detecting cancer, particularly in its early stages when it’s crucial to detect cancerous cells quickly for effective treatment and better patient outcomes.

Bringing bacteriophage biosensors into the cancer diagnosis process is a significant change from traditional methods, providing a quicker and more sensitive option. The technology in these biosensors is based on sophisticated genetic engineering, which allows them to identify a wide range of cancer markers with great precision. This precision reduces the possibility of false positives, a common issue with conventional cancer screening. As ongoing research and development progress, bacteriophage biosensors become a crucial part of oncology, potentially transforming how cancer is diagnosed and managed.

1.2. Endolysins protein

The science behind bacteriophage endolysins lies at the heart of their innovative application in cancer detection. Bacteriophage endolysins, which are enzymes to break down target cell walls, applied in cancer detection due to their remarkable abilities (Fig. 1) [3]. They are engineered to identify specific cancer cells, facilitating the release of markers critical for early cancer recognition and treatment.

Nowadays, developing endolysin-based biosensors that are highly sensitive and capable of rapid cancer cell identification leads to advancement in the phage sensor field. Integrating endolysins with biosensor technology creates a powerful tool for oncology diagnostics, offering a non-invasive and efficient alternative to traditional methods. The precision of these biosensors in identifying cancer markers ensures a high degree of accuracy, reducing the likelihood of false positives. As research continues to enhance the stability and efficacy of endolysin-based biosensors, their potential in transforming cancer diagnostics grows, promising a future where early detection and effective treatment of cancer are more attainable.

Fig.1. The schematic of Endolysin protein

2. The Critical Requirement for Early Cancer Detection

2.1. Overview of Cancer Progression and Diagnosis Challenges

The progression of cancer, a complex and multifaceted process, presents significant challenges in diagnosis and treatment. Cancer development typically follows a series of stages, beginning with the initial genetic mutation in cells, leading to uncontrolled cell growth and potentially metastasis, where cancer spreads to other parts of the body. Early detection is crucial as it significantly improves the chances of successful treatment. However, one of the primary challenges in cancer diagnostics is the identification of malignancies at an early stage when symptoms are often non-specific or absent. Traditional diagnostic methods, while effective in later stages, can miss early, subtle signs of cancer, highlighting the need for more sensitive and precise diagnostic tools.

The diagnosis of cancer is further complicated by its heterogeneity. Different types of cancers exhibit varied behaviors and responses to treatment, necessitating personalized diagnostic approaches. This requirement for specificity often makes it difficult to develop universal screening methods that are effective across all cancer types. Additionally, patients may experience dangers and discomfort from the intrusive nature of some diagnostic procedures, such as biopsies, emphasizing the need for reliable but non-invasive diagnostic methods.

Developing new diagnostic tools that can identify cancer early on is necessary to address these issues. Integrating advanced biosensors and molecular diagnostic tools promises a new era in cancer detection, offering the sensitivity and specificity needed to identify cancer in its early stages. These technologies hold the potential to transform cancer diagnostics, enabling timely and personalized treatment and ultimately improving patient outcomes. As research advances in this field, the goal of early, accurate, and non-invasive cancer diagnostics becomes more available.

2.2. Role of Biosensors in Transforming Cancer Diagnostics

The role of biosensors in cancer diagnostics is crucial, marking a significant advancement in the early detection and management of cancer [3]. These sophisticated devices are designed to detect specific biological markers associated with cancerous cells, offering a level of sensitivity and specificity that traditional diagnostic methods often lack. The ability of biosensors to identify minute quantities of cancer markers in biological samples, such as blood or tissue, facilitates the early detection of cancer, a critical factor in improving treatment outcomes. This early detection is particularly valuable in cancers that do not exhibit clear symptoms until advanced stages, allowing for interventions at an stage when the disease is more manageable and treatment more likely to be successful.

Biosensors also bring the advantage of non-invasive testing, which is less traumatic for patients compared to traditional methods like biopsies. This non-invasive nature not only enhances patient comfort but also encourages more frequent monitoring, which is crucial for tracking the progression of the disease or the effectiveness of treatment. Integrating advanced materials and technologies in biosensors, such as nanotechnology and microfluidics, further improves their accuracy and reduces the time needed for analysis, enabling faster clinical decision-making.

Moreover, the adaptability of biosensors to various cancer types makes them a versatile tool in oncology. Biosensors designed to detect specific types of cancer can be used in personalized medicine approaches, providing individualized diagnostic and monitoring solutions. As research and development in biosensor technology continue to advance, these devices are expected to become integral in cancer diagnostics, revolutionizing the way cancers are detected, monitored, treated and ultimately leading to improved patient survival rates and quality of life.

3. Clinical Applications of Bacteriophage Biosensors

3.1. Real-world Implementation in Cancer Diagnostics

The application of cutting-edge biosensors in cancer diagnostics represents an evolution in how cancer is identified and treated rapidly. Clinical trials and research studies demonstrate the efficacy of these biosensors, showcasing their potential to detect various cancer types with high precision and reliability. Such implementation in clinical settings is not just a theoretical advancement but a practical solution addressing the urgent need for early cancer detection. These biosensors, designed to identify specific biomarkers associated with cancerous cells, enable clinicians to diagnose cancer at earlier stages than traditional methods allow. This early detection is crucial in increasing the effectiveness of treatment and improving patient survival rates.

Moreover, incorporating biosensor technology into existing diagnostic frameworks reshapes the landscape of cancer care. Hospitals and diagnostic centers are gradually adopting these technologies, appreciating their accuracy, speed, and patient comfort benefits. The non-invasive nature of many biosensor-based tests, such as blood-based assays, makes them more patient-friendly and less risky than invasive procedures like biopsies. This aspect is particularly important in encouraging regular monitoring and follow-up, which is essential for patients with a high risk of cancer or those undergoing treatment.

As these biosensors are refined and validated for clinical use, their role in cancer diagnostics is set to expand further. Their flexibility for unique disease types makes them suitable for personalized medicine, aligning with the current trend toward more individualized cancer treatment approaches.

This real-world application of biosensor technology in cancer diagnostics represents a significant leap in medical science and offers hope for a future where cancer can be detected and treated more effectively, ultimately saving more lives.

3.2. Patient-Centric Advantages

The application of biosensor technology in cancer diagnostics creates a revolution and a new era of patient-centric advantages, significantly enhancing the patient experience in medical care. One of the primary benefits of these advanced biosensors is their non-invasive nature. Unlike traditional diagnostic methods such as biopsies, which can be painful and carry risks of complications, biosensors often require only simple, non-intrusive samples like blood or urine. This non-invasiveness not only reduces patient discomfort and anxiety but also lowers the risk of infection and other procedural complications. Patients are, therefore, more likely to follow screening and monitoring plans on a regular basis, which is essential for early cancer detection.

Furthermore, biosensor technology offers the advantage of rapid and accurate results, reducing the often stressful waiting period associated with cancer diagnosis. The ability of these devices to provide swift feedback is vital in fast-tracking the initiation of treatment, a critical factor in improving cancer prognosis. This timeliness also allows for more efficient and dynamic management of the disease, with the potential to adjust treatment plans in response to real-time changes in the patient’s condition.

In addition to these benefits, integrating biosensors into cancer care aligns with the growing trend toward personalized medicine. By modifying diagnostics and treatment to the individual’s specific cancer type and genetic makeup, biosensors contribute to more targeted and effective therapy regimens. This personalized approach enhances treatment efficacy and minimizes unnecessary side effects, improving the overall quality of life for patients undergoing cancer treatment. As biosensor technology continues to evolve, its role in fostering patient-centered care in oncology is poised to grow, offering a more compassionate, efficient, and effective approach to cancer diagnosis and management.

In a separate study, Han et al. developed an innovative phage-based sensor designed to detect cancer at its early stages. This advancement represents a significant leap in cancer diagnosis, emphasizing the potential of phage technology in medical applications. The early detection of cancer is crucial for effective treatment, and the introduction of such a sensor could greatly improve patient outcomes. However, while this novel approach holds promise, it may also face challenges in clinical implementation, such as ensuring accuracy and specificity in diverse patient populations, and navigating the regulatory landscape for new medical technologies. This balance of pioneering potential with practical considerations reflects the ongoing evolution and complexity of cancer research and diagnostics.

4. Detecting Different Analytes

Biosensors based on bacteriophages are not limited to the detection of cancer. They are also capable of recognizing other proteins and peptides, such as bacteria.

At the Interdisciplinary Research Institute of Grenoble (IRIG), scientists designed a cutting-edge method in the field of bacteriophage binding to gold nanoparticles for more bacterial capture. The study investigates how combining purification techniques with both covalent and physisorption methods enhances the attachment of bacteriophages to gold surfaces. By utilizing these approaches together, the research aims to maximize bacteriophage binding efficiency to gold, pushing the boundaries of geometric limits. This innovative approach has the potential to significantly improve various applications, such as biosensing and nanomedicine, by increasing the precision and effectiveness of bacteriophage interactions with gold materials [4].

SyntBiolab, a leading institution in biotechnology, has pioneered the use of bacteriophages to detect foodborne pathogens, notably Escherichia coli (E. coli), a common and potentially harmful bacterium found in food. This innovative approach leverages the natural targeting capability of bacteriophages, which are viruses that specifically infect bacteria, identify and quantify E. coli presence in food samples. By employing bacteriophages that have a high affinity for E. coli, SyntBiolab’s method offers a rapid, accurate, and non-invasive way to ensure food safety. This technology not only enhances the efficiency of detecting contamination in the food supply chain but also significantly reduces the risk of foodborne illnesses, demonstrating SyntBiolab’s commitment to employing cutting-edge science for public health advancements [5].

Z.Yousefniayejahromi et al. developed the novel Zeno phage sensor to identify Staphylococcus aureus in synovial fluid with a linear range from 101 to 104 CFU/ml with a detection limit of 6 CFU/mL [6].

Han et al. developed a label-free cytosensor technology that offers numerous advantages. This innovative approach employs specific peptides derived from a phage library to create a highly specific and sensitive electrochemical impedance cytosensor. Some key advantages include label-free detection, which eliminates the need for costly chemical labeling, high specificity towards target cells or molecules, sensitive detection of low concentrations, and versatile applications in biotechnology and diagnostics. However, there are challenges, such as the complexity of phage library selection, the importance of accurate sample preparation, initial setup and maintenance costs, and potential limitations in the target range [7].

5. Challenges and Limitations in Current Biosensor Technologies

The field of biosensor technology, despite its remarkable progress in cancer diagnostics, faces several challenges and limitations that need addressing for its full potential to be realized. One of the primary challenges lies in the accuracy and sensitivity of these devices. While biosensors shown promising results in detecting cancer markers, ensuring consistent accuracy across different types of cancers and stages of disease remains a hurdle. Variability in biomarker expression among patients can lead to false negatives, potentially delaying diagnosis and treatment. Moreover, in early-stage cancer diagnosis, biosensor sensitivity must be precisely calibrated to detect low amounts of cancer markers when biomarker levels may be low.

Another significant limitation is the reproducibility of biosensor technologies. Manufacturing biosensors that maintain consistent performance across large batches is a challenge, essential for their widespread clinical use. Ensuring that each biosensor device works with the same level of efficiency and accuracy is vital for their reliability and trustworthiness in clinical settings. Additionally, integrating these advanced technologies into existing healthcare systems poses logistical and infrastructural challenges. Adapting current diagnostic pathways to incorporate biosensor technology requires substantial investment, training, and systemic changes, which can be a barrier to widespread adoption.

Furthermore, the long-term stability and shelf-life of biosensor devices are areas of concern. The components of biosensors, especially biological elements, may degrade over time, affecting the device’s performance. Ensuring these devices remain stable and functional over their intended shelf-life is crucial for their practical use in clinical settings.

While biosensor technologies hold immense promise in revolutionizing cancer diagnostics, overcoming these challenges is key to their successful implementation. Addressing issues related to accuracy, reproducibility, scalability, stability, and regulatory compliance will be crucial in harnessing the full potential of biosensors in clinical practice, ultimately leading to improved patient care and outcomes in cancer treatment.

6. Future Perspectives

6.1. Innovations on the Horizon

Significant innovations in biosensor technology are on the horizon, promising to revolutionize cancer diagnostics. The advent of nanoscale biosensors is a crucial development, enhancing the sensitivity and specificity of cancer detection. These nano biosensors, utilizing nanomaterials’ expansive surface area and unique properties, can detect cancer markers at exceptionally low concentrations, crucial for early-stage diagnosis. This advancement not only promises greater accuracy in identifying malignancies but also paves the way for detecting a broader range of cancer types at their nascent stages.

Another groundbreaking innovation is integrating artificial intelligence (AI) with biosensor technology. AI’s capability to analyze and interpret complex data patterns will significantly improve the diagnostic accuracy of biosensors. This fusion of AI and biosensors is expected to lead to smarter, more efficient diagnostic tools capable of providing real-time, actionable insights for clinicians. The potential for multiplexing, enabling simultaneous detection of multiple cancer markers, further underscores the transformative impact of these emerging technologies. As these innovations progress, they promise to usher in a new era in cancer diagnostics, marked by enhanced precision, efficiency, and a shift towards more personalized and proactive cancer care.

6.2. Path Forward for Bacteriophage-Based Biosensors

Bacteriophage-based biosensors for cancer diagnosis have a bright future ahead of them thanks to ongoing innovation and teamwork in research. The future development of these biosensors hinges on enhancing their specificity and sensitivity, ensuring that they can reliably detect a wide range of cancer types at early stages. This requires ongoing research into optimizing bacteriophage engineering, focusing on refining their ability to target and bind to specific cancer markers. Collaborative efforts between biotechnologists, oncologists, and engineers are essential in this endeavor, as they bring together diverse expertise to address the multifaceted challenges of cancer diagnostics.

Moreover, integrating these biosensors into clinical practice is a critical step in realizing their potential. This involves rigorous clinical trials to validate their efficacy and safety, followed by developing guidelines for their use in medical settings. A focus on these biosensors’ cost and scalability is also necessary to guarantee that various healthcare systems and patient populations can use them. Bacteriophage-based biosensors have the potential to be a key component in the early diagnosis and treatment of cancer, providing a novel approach in the ongoing battle against this widespread illness if certain obstacles are resolved.

7. References

[1] https://www.mri.bund.de/en/institutes/microbiology-and-biotechnology/research-areas/bacteriophages/

[2] www.creative-biolabs.com

[3] Le Brun, G., Hauwaert, M., Leprince, A., Glinel, K., Mahillon, J. and Raskin, J.P., 2021. Electrical characterization of cellulose-based membranes towards pathogen detection in water. Biosensors11(2), p.57. DOI: 10.3390/bios11020057

[4] O’Connell, L., Marcoux, P.R., Perlemoine, P. and Roupioz, Y., 2023. Approaching the Geometric Limit of Bacteriophage Conjugation to Gold: Synergy of Purification with Covalent and Physisorption Strategies. ACS Biomaterials Science & Engineering9(5), pp.2335-2346. DOI:10.1021/acsbiomaterials.2c00386

[5] https://syntbiolab.com

[6] http://www.societasim.it

[7] Han, L. et al. A Label-Free Electrochemical Impedance Cytosensor Based on Specific Peptide-Fused Phage Selected from Landscape Phage Library. Sci. Rep6, 22199. DOI: 10.1038/srep22199(2016)

COVID

How do Smart Electrochemical Biosensors control the COVID-19 pandemic?

Estimated Reading Time: 11 minutes

During the COVID-19 pandemic, there is an urgent need for the development of rapid and efficient detection systems. This article emphasizes the significance of biosensors in the context of COVID-19 control. It focuses on electrochemical methods for detecting COVID-19 and highlights biosensors’ unique advantages and limitations compared to other detection methods. The article also discusses recent advancements in biosensor technology, their integration with digital health technologies, and potential future applications. It delves into the challenges associated with biosensors, including technical and operational obstacles, as well as risk management strategies. This comprehensive review aims to serve as a critical reference for researchers and healthcare professionals in effectively managing the pandemic.

Author ID: 2024024866

1- Introduction

The COVID-19 pandemic, caused by the new coronavirus SARS-CoV-2, has become a significant worldwide health pandemic. This highly contagious virus caused a worldwide emergency, impacting millions and disrupting societies and economies. The quick spread and severe effects of COVID-19 have highlighted the urgent need for fast and accurate ways to detect the virus to control its spread. Understanding and identifying the virus is crucial in fighting this global threat [1].

Traditional diagnostic approaches, such as the Enzyme-Linked Immunosorbent Assay (ELISA), antigen tests, and Reverse Transcription Polymerase Chain Reaction (RT-PCR), have been the cornerstone of COVID-19 detection efforts. Each of these methods poses its own set of advantages and limitations. For instance, RT-PCR is highly sensitive and specific but requires sophisticated laboratory infrastructure, skilled personnel, and substantial processing time, which could lead to delays in diagnosis and subsequent intervention. ELISA and antigen tests, while useful for indicating the presence of the virus or antibodies against it, also face challenges in terms of cost, accessibility, and the time needed to deliver results.

Comparatively, electrochemical biosensors, which consist of biological bioreceptors, such as aptamer, DNA, antibody, bacteriophage, endolysin protein etc. and transducers to covert biological mechanism to electrical signals, present a revolutionary approach to addressing these challenges. These biosensors offer a more straightforward, cost-effective, and rapid testing method that does not compromise on accuracy. Their design allows for the direct detection of the virus or its markers in biological samples without the need for extensive sample preparation or sophisticated equipment. This makes electrochemical biosensors particularly appealing for use in point-of-care settings, including those with limited access to laboratory facilities.

In this review, we aim to showcase the development of electrochemical biosensors, highlighting their role in medical innovation. They are crucial in tackling public health challenges, offering hope and practical strategies to manage pandemics like COVID-19.

2-Electrochemical biosensors

Electrochemical biosensors detect viruses and bacteria, translating their identification into electrical signals. This approach addresses traditional diagnostic method limitations. These biosensors quickly detect specific viral markers with high sensitivity and specificity, enabling rapid responses crucial for contact tracing and patient isolation. Their portability and ease of use make them valuable in various settings, including resource-limited or remote areas. Electrochemical biosensors play a vital role in the global response to the COVID-19 pandemic by bridging the diagnostic gap and providing a practical tool to manage and resolve this unprecedented health crisis.

One of the most significant advantages of electrochemical biosensors in combating COVID-19 is their high sensitivity and specificity. They are engineered to detect specific viral markers, allowing for accurate identification of the SARS-CoV-2 virus. This precision is critical in reducing the incidence of false negatives or positives, which are common challenges in other testing methods like antigen tests.

The rapid response time of these biosensors is another critical factor in their effectiveness. Unlike conventional diagnostic methods such as ELISA, Antigen test, and RT-PCR tests, which can take hours to days to yield results, electrochemical biosensors deliver results in a significantly shorter time frame. This speed is essential for effective contact tracing and the immediate isolation of infected individuals, which are critical strategies in curbing the spread of the virus.

In addition, the simplicity and portability of electrochemical biosensors make them a versatile tool in the fight against COVID-19. These characteristics enable their use in various settings, not just in well-equipped laboratories but also in remote or resource-poor areas. This widespread applicability is vital in ensuring equitable access to testing, especially in regions where traditional diagnostic facilities are scarce.

The comparison between electrochemical biosensors and traditional detection methods in controlling the COVID-19 pandemic is a narrative of complementary strengths and weaknesses. Conventional methods are still reliable, but biosensors’ remarkable qualities, such as speed, specificity, and digital technology integration offer promising avenues for rapid, efficient, and widespread disease detection and control. The ongoing development and refinement of these biosensors will undoubtedly play a crucial role in organizing future pandemic response strategies (Table 1).

Table 1. Comparison of various approaches to recognize COVID-19

MethodAccuracySpeedCostEase of UseScalabilityApplicationSample TypePoint-of-Care Testing
RT-PCRVery highHours to daysHighRequires trained personnelChallengingLaboratory-basedRespiratoryLimited
Antigen TestModerate, prone to errors15-30 minutesLower than RT-PCRMinimal training neededEasier than RT-PCRField settingsRespiratoryHighly suitable
ELISAHigh for antibodiesSeveral hoursModerateLab expertise neededScalable with lab capacityLaboratory-basedBloodLimited
Electrochemical BiosensorsHigh with calibrationMinutesLower, especially in scaleUser-friendlyEasier to deployVarious, including remoteVariousHighly suitable

3. Advances in Electrochemical Biosensor Technology

The field of electrochemical biosensor technology is rapidly changing, driven by innovations that are revolutionizing their use in managing pandemics, particularly COVID-19. This progress is marked by several key developments demonstrating biosensor technology’s transformative impact in healthcare.

One major advancement is the use of nanotechnology in biosensors. This has dramatically improved their sensitivity and specificity, allowing for the detection of pathogens at much lower levels. This increased sensitivity is key for early disease detection, such as COVID-19, leading to faster isolation and treatment.

Another important innovation is wearable biosensors. Worn on the body, these devices continuously monitor various biological markers. During a pandemic, they can provide real-time health data, helping to quickly identify signs of infection.

It is significant that the integration of biosensors with digital health technology. Smart biosensors connected to digital devices like smartphones can send data directly to healthcare providers, leading to faster responses and the prevention of illnesses like COVID-19.

Miniaturization is another advancement. Smaller, portable biosensors enable testing in various settings, not just labs. This is crucial for testing in remote areas or where immediate results are needed, such as at airports.

Electrochemical biosensors are also being used beyond detecting pathogens. They now monitor physiological parameters, like oxygen levels and breathing rates, important for managing COVID-19 patients.

Nonetheless, there are still issues, especially with large-scale manufacturing and standardization. One of the biggest challenges is making sure these cutting-edge biosensors are broadly accessible and consistently effective.

In disease detection and management. These innovations are not only useful now but are shaping future applications. The experiences from using biosensors in the COVID-19 pandemic guides research for better diagnostics in future health crises.

4. Limitation of biosensor development

Although using electrochemical biosensors is remarkable to manage COVID-19. It brings several challenges and risks, from technical issues to concerns about reliability and risk management. These challenges need strategic solutions for biosensors to be effective in public health.

A key technical challenge is ensuring biosensors work accurately in different environments. Factors like temperature and humidity can affect their performance. This reliability is hard to achieve but crucial.

Another biggest problem is calibrating and maintaining biosensors. Like all precision tools, they need regular calibration, which can be logistically tough, especially in areas with limited resources or in large public health efforts where many devices are used.

Integrating biosensors with current healthcare systems also poses challenges. They must be compatible with other health technologies, which is not always easy, particularly in less equipped healthcare settings.

Training users correctly is vital. As biosensors become more complex, educating healthcare workers and users on their proper use is essential.

Data privacy and security are major concerns with smart biosensors that transmit health data. Ensuring strong data protection is crucial to keep patient trust and meet privacy laws, especially when sharing data globally.

Scalability is another issue. Producing biosensors in large quantities, especially during a pandemic, is a huge task. This includes manufacturing and supplying the components and materials needed.

Risk management for biosensor use needs to cover these challenges comprehensively. This means not just technical solutions but also policies and standards for using, maintaining, and handling data from biosensors.

Planning for contingencies is key. This includes having protocols for device failure, data breaches, and other issues that could affect biosensor-based public health strategies.

While electrochemical biosensors have great potential in pandemic management, especially for
COVID-19, their deployment faces many operational challenges and risks. Addressing these requires combining technical innovation with strategic policy and planning to maximize their benefits in public health.

5- Literature review

The Max Planck Group’s research in Nanobioengineering research used the electrochemical biosensors for detecting COVID-19 biomarkers focuses on personalized medicine. Their study analyses various biomarkers to diagnose and forecast the disease’s progression. Emphasizing the biosensors’ role in understanding SARS-CoV-2’s structure and infection mechanism, this research also considers their diagnostic and prognostic potential. Furthermore, it explores integrating these biosensors with emerging technologies, advancing personalized medical approaches [2].

Biosensors, like those created by SD Biosensor for COVID-19 detection, typically use biological elements for virus identification. These elements, such as antibodies or nucleic acid probes, are designed to specifically bind to the virus’s antigens or genetic material. This binding is then translated into a measurable signal, providing quick diagnostic results. This innovative technology plays a crucial role in rapidly testing and managing the pandemic effectively [3].

Yakoh et al. developed paper-based electrochemical biosensor, designed for diagnosing COVID-19, effectively detects SARS-CoV-2 antibodies and antigens, offering a swift and precise method for identifying infections. The advantages of this sensor include its low cost, ease of use, and rapid results, making it highly beneficial in resource-limited settings. However, there are some disadvantages, such as potential variability in sensitivity compared to more complex laboratory tests and a reliance on correct sample collection [4].

Lomae et al. designed the label-free electrochemical DNA Biosensor for COVID-19 diagnosis in biological samples. Its main advantage lies in its speed and simplicity, enabling faster results than traditional RT-PCR tests. However, its accuracy can be affected by sample quality and external substances, potentially leading to false results. While easier to use than some methods, it still requires technical know-how and equipment, limiting its applicability in less-equipped settings [5]​.

At the Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf e.V. (HZDR), deploying electrochemical biosensors for COVID-19 detection reflects their commitment to advanced diagnostic technologies. Utilizing techniques like electrochemical impedance spectroscopy and gold nanowires, these biosensors mark a significant step in precisely detecting SARS-CoV-2 antigens and antibodies. This method boosts the efficiency of COVID-19 testing and showcases the institute’s dedication to developing innovative solutions for critical medical challenges, including the pandemic [6]​.

Sengupta, J., and Hussain designed the Graphene-Based Electrochemical Biosensors based on identifying SARS-CoV-2 with different electrochemical approaches such as amperometry and impedance spectroscopy methods. This biosensor was sensitive and fast, which helped detect the virus earlier than usual methods. However, they need to be carefully set up and can be affected by the environment. Despite these challenges, these biosensors are a big step in fighting COVID-19, as they offer a faster and more efficient way to test for the virus [7].

AT RISE, researchers also carry out verification tests on diagnostic point-of-care analyses. A current assignment includes verification of rapid tests for measuring SARS-Cov-2 specific antibodies [8].

Meridian’s antibodies detect SARS-CoV-2 various rapidly with high sensitivity. Their monoclonal antibodies specifically target the S1 protein in saliva, effective regardless of its shape. This approach, focusing on a stable region of S1, is key for diagnostics and vaccine development, offering substantial potential for neutralizing antibody production in patients [9].

5. Integration of artificial intelligence (AI) with electrochemical biosensor

Merging artificial intelligence (AI) with electrochemical biosensor data revolutionizes in managing health, especially during crises like the COVID-19 pandemic. This means we can get quicker, smarter insights from the health data collected, helping spot disease outbreaks faster and making personalized healthcare a reality. AI can sift through many biosensor data, spotting health trends or disease markers that humans might miss, leading to early warnings and tailored health plans.

However, privacy concerns are a major topic of discussion when discussing the use of AI with health data. Ensuring the safety and security of patient information is imperative. A wide range of data must be used during training to ensure that the AI does not prefer any particular group over another. We also need to ensure that these AI systems function well everywhere and in various environments.

Recently, the potential for AI and biosensors in health is enormous. They could help us monitor our health in real time, catch diseases early, and fit into a bigger picture of digital health. But, as we move forward, we’ll need to tackle the big questions about privacy, fairness, and reliability head-on to ensure these tech advances benefit everyone.

6. Electrochemical biosensors in point-of-care devices: future trends

Advanced electrochemical biosensors become more popular approach in the fight against COVID-19, indicating the potential of cutting-edge technologies to revolutionize public health. These biosensors enable rapid disease detection, providing crucial data for managing infectious diseases and facilitating quicker responses to outbreaks. Their ability to deliver real-time insights into infection rates and trends has proven invaluable for public health decision-making, especially in controlling the spread of viruses and managing healthcare resources efficiently.

In patient care, electrochemical biosensors offer immediate diagnostics, reducing the burden on healthcare facilities and improving access in under-resourced areas. The forward-looking applications of these technologies extend into personalized medicine, where biosensors could tailor treatments to individual patient profiles, and the development of global health networks that leverage biosensor data for early warning systems, potentially averting future pandemics.

The integration of artificial intelligence (AI) with biosensor data holds promise for transforming public health through advanced data analysis, enabling predictive modeling of disease spread and enhancing public health planning. This synergy could lead to more informed and proactive health strategies, emphasizing the importance of continuous research and development to keep pace with evolving health challenges.

However, realizing the full potential of electrochemical biosensors in public health requires overcoming significant hurdles, including data privacy concerns, the need for technology standardization, and ensuring equitable access to these advancements. Addressing these challenges is critical for harnessing the transformative power of biosensors in healthcare, indicating a future where data, efficiency, and proactive measures drive public health strategies.

7. References

[1] https://www.csiro.au

[2] https://www.mpg.de

[3] https://www.sdbiosensor.com

[4] Yakoh, A., Pimpitak, U., Rengpipat, S., Hirankarn, N., Chailapakul, O. and Chaiyo, S., 2021. based electrochemical biosensor for diagnosing COVID-19: Detection of SARS-CoV-2 antibodies and antigen. Biosensors and Bioelectronics176, p.112912. DOI:10.1016/j.bios.2020.112912

[5] Lomae, A., Preechakasedkit, P., Hanpanich, O., Ozer, T., Henry, C.S., Maruyama, A., Pasomsub, E., Phuphuakrat, A., Rengpipat, S., Vilaivan, T. and Chailapakul, O., 2023. Label-free electrochemical DNA biosensor for COVID-19 diagnosis. Talanta253, p.123992. DOI: 10.1016/j.talanta.2022.123992

[6] https://www.hzdr.de

[7] Sengupta, J. and Hussain, C.M., 2023. Graphene-Based Electrochemical Nano-Biosensors for Detection of SARS-CoV-2. Inorganics11(5), p.197. DOI: 10.3390/inorganics11050197

[8] https://www.ri.se/en

[9] https://www.meridianbioscience.com/

A Game Theory Model of Opportunism Behavior in Auctions

A Game Theory Model of Opportunism Behavior in Auctions

Estimated Reading Time: 19 minutes In this study, readers examined the use of the game theory model for opportunistic behavior in auctions. Additionally, the agreement between the project owner (employer) and the contractor and the mathematical range of this agreement were discussed.

ion-selective-electrode

How do Ion-Selective Electrodes Regulate Diseases? A Comprehensive Review

Estimated Reading Time: 13 minutes

This review discusses the increasing application of nanomaterials in ion-selective electrodes for public health, emphasizing their role in healthcare, pharmaceuticals, and the food industry. It addresses the use and challenges of carbon-based nanoparticles in wearable devices for better patient monitoring and preventative healthcare. Additionally, it contrasts these electrodes with traditional medical methods, highlighting their cost efficiency, accessibility, and real-time capabilities. The review also looks forward to the evolution of sensor technology and nanoparticle research, underlining the importance of interdisciplinary collaboration to advance health monitoring by integrating nanomaterials with ion-selective electrodes.

Author ID: 2024024866

1. Fundamentals of Wearable Ion-Selective Electrodes

Wearable ion-selective electrodes represent a groundbreaking advancement in health monitoring technologies. At their core, these devices utilize the principles of ion-selective electrodes (ISEs), traditionally used in laboratory settings to measure ion concentrations in various solutions precisely. It is significant that the transition of this technology into a wearable format opened new horizons in personal healthcare, enabling continuous, real-time monitoring of physiological parameters.

The basis of wearable ion-selective electrodes lies in their ability to selectively respond to specific ions in the body [1]. This sensitivity comes from a special membrane in the electrode that reacts mostly to certain types of ions. When it touches a liquid like sweat or blood, the electrode’s potential changes based on how much of the specific ion is present. This electrochemical reaction forms the foundation for ion concentration analysis, providing crucial data on the wearer’s health status. Furthermore, an ion-selective electrode is considered the most important device in the food industry to regulate the level of ions to prevent illnesses.

Integrating nanomaterials plays a crucial role in enhancing the performance of these electrodes. Nanoparticles, particularly carbon-based materials like graphene, carbon nanotubes, and fullerene, revolutionized the sensitivity and selectivity of these devices. Their unique properties, such as high surface area, excellent conductivity, and chemical stability, make them ideal for biosensing applications. The devices achieve higher sensitivity, faster response times, and greater miniaturization by incorporating these nanomaterials into the electrode’s sensitive membrane, which is essential for wearable technology.

In wearable applications, the ion-selective electrodes are typically part of a more extensive system that includes a signal processing unit and a wireless transmitter. This system collects and analyzes the electrode’s data, translating the electrochemical signals into understandable health metrics. The data could be transmitted to a smartphone or a remote healthcare provider, enabling quick medical help.

However, developing these electrodes for wearable use is not without challenges. Ensuring long-term stability, maintaining consistent performance in varying environmental conditions, and minimizing interference from other bodily substances are ongoing research areas. Integrating these sensors into comfortable, user-friendly wearable formats requires innovative engineering and design solutions.

Incorporating nanomaterials enhances wearable ion-selective electrodes and significantly advances health monitoring technology. They offer the promise of personalized health care, with potential applications ranging from fitness tracking to early detection and management of medical conditions. As this technology continues to evolve, it holds immense potential for transforming healthcare by providing insights into our body’s ionic composition in real-time, paving the way for more proactive and preventive health management strategies.

2. Comparative ion-selective electrode with Traditional Medical Techniques

In this comparison, we look at the benefits of cost-effective ion-selective electrodes over traditional methods for monitoring various ions in the body, environment, and food safety. Conventional techniques such as titrations, spectroscopy, etc., are often expensive and complex, involving lab analyses requiring special equipment and trained staff. While accurate, they can be less accessible and slower, making real-time monitoring and quick decisions difficult.

In contrast, the introduction of affordable ion-selective electrodes is a significant improvement. They are budget-friendly and easy to use, making monitoring more available to a broader audience, not just specialized labs Table 1. This is especially important in places with limited resources, where traditional methods might not work. Additionally, these electrodes allow for real-time monitoring, enabling faster reactions to changes in ion levels. This is crucial in areas like agriculture, healthcare, and the food industry to control the level of ions to prevent illnesses.

While these electrodes are cost-effective and user-friendly, it’s essential to evaluate their accuracy and reliability against traditional methods. Ongoing improvements in electrode technology are focused on closing any gaps in precision. The goal is for these tools to be practical, affordable, and accurate in ion-level monitoring. Therefore, these electrodes are a promising advancement in ion solution analysis, offering efficiency, affordability, and the potential for broad application.

Table 1. Comparison of ion-selective electrodes with traditional approaches
MethodAdvantagesDisadvantages
Spectrophotometry– Relatively inexpensive equipment.
– Good for quantitative analysis of specific compounds.
– Broad application in organic and inorganic chemistry.
– Reagents and maintenance add to costs.
– Limited by the specificity of the reagents.
– Generally not portable.
Atomic Absorption Spectroscopy (AAS)– High sensitivity for metals and some non-metals.
– Cost-effective for specific ion measurements.
– Durable, long-lasting equipment.
– High initial equipment cost.
– Limited to elements that can be atomized.
– Requires specific expertise and training.
Inductively Coupled Plasma Mass Spectrometry (ICP-MS)– Very high initial equipment cost.
– Large, complex systems, not portable.
– Intensive maintenance and calibration are needed.
– Very high initial equipment cost.
– Large, complex systems, not portable.
– Intensive maintenance and calibration needed.
Titrations– Simple and straightforward method.
– No need for expensive equipment.
– High accuracy for concentration determination.
– Time-consuming, especially for multiple samples.
– Requires skilled technique for accurate results.
– Limited to the titrant’s reactive properties.
Ion-Selective Electrodes (ISEs)– Initial development can be expensive.
– Some analyses may require longer processing times.
– Regular calibration and maintenance are needed.
– Initial development can be expensive.
– Some analyses may require longer processing times.
– Regular calibration and maintenance needed.

3. Nanoparticles in Wearable Health Devices

In the world of electrochemical sensors, particularly for health tracking, nanomaterials have sparked a surge of innovation. Right now, the focus is mainly on carbon-based nanomaterials that are crucial for boosting the performance of wearable electrodes.

3.1. Carbon-Based Nanomaterials for Electrodes

In developing electrochemical sensors for health monitoring, carbon-based nanomaterials emerged as key elements, offering distinct advantages in electrode design. These materials, particularly graphene and carbon nanotubes, are highly valued for their unique electrical and mechanical properties.

Graphene, characterized by its two-dimensional structure of a single layer of carbon atoms, provides exceptional electrical conductivity and a large surface area. These attributes are critical in enhancing the sensitivity and responsiveness of ion-selective electrodes, making them more efficient for wearable health monitoring devices. The ability of graphene to detect subtle changes in ion concentrations swiftly makes it a valuable component in advanced health monitoring technologies.

Carbon nanotubes, an essential type of carbon-based nanomaterial, add strength and chemical steadiness to electrodes. Their tube-like nanostructure provides a sizeable reactive surface, which is crucial for accurate and selective ion detection. The sturdiness of carbon nanotubes helps wearable sensors last longer, which is vital for regular health tracking. Using these carbon-based materials in wearable electrodes is a big step forward in sensor technology, improving both how well health monitors work and how easy they are to use.

3.2. Innovations in Nanoparticle Integration

 In the rapidly advancing field of wearable electrochemical sensors, adding nanoparticles is a significant breakthrough. This advancement is not just in the materials themselves but also in the innovative ways they are incorporated into sensor designs.

Recent developments seen a surge in creative techniques for embedding nanoparticles into wearable electrodes. One approach involves creating composite materials that blend nanoparticles with flexible, biocompatible substrates. This method ensures that the sensors are highly sensitive due to the nanoparticles and are comfortable and practical for everyday wear. The development of more user-friendly yet still-effective wearable health monitoring is revolutionized by using these composites.

Additionally, advancements in nanofabrication techniques allow for more precise placement and orientation of nanoparticles within the sensors. This precision is crucial in enhancing the selectivity and sensitivity of the electrodes, ensuring that they can accurately detect specific ion concentrations in real time. Combining nanoparticles with these sophisticated methods is crucial in expanding the capabilities of wearable health monitoring devices, leading to more precise, dependable, and user-friendly health tracking options.

3.3. Challenges in Nanomaterial Application

In the field of wearable electrochemical sensors, the application of nanomaterials, while pioneering, presents its own challenges. These obstacles must be navigated to fully harness the potential of these advanced materials in health monitoring devices.

One significant challenge in the application of nanomaterials is the manufacturing process. Creating electrodes incorporating nanomaterials like graphene and carbon nanotubes requires precision and consistency. The process must be scalable and cost-effective for widespread adoption, which is a complex endeavor. Ensuring the uniformity and quality of nanomaterials across large batches is crucial for the reliability of wearable sensors. This aspect of manufacturing remains a focus area for ongoing research and development.

Another critical issue is the stability and durability of nanomaterials in varying environmental conditions. Wearable sensors expose the variation of temperatures, humidity, and physical stresses, which can impact the performance of nanomaterials. It’s important to ensure these materials keep their sensitivity and effectiveness over time, particularly in the bendable forms needed for wearable technology. Recently, researchers explore ways to enhance the stability of nanomaterials, aiming to extend the lifespan and effectiveness of wearable ion-selective electrodes in everyday use.

4. Patient Monitoring and Disease Prevention

In the changing world of healthcare, “Patient Monitoring and Disease Prevention” emerge as a crucial area. Wearable ion-selective electrodes are making a significant impact here. Using advanced nanomaterials, these devices allow for real-time health monitoring and offer ongoing tracking of vital health signs.

4.1. Real-Time Health Monitoring

Introducing wearable electrodes revolutionizes health monitoring by moving from occasional checks to continuous tracking. These devices, equipped with advanced ion-selective electrodes, provide real-time health monitoring, a key development for proactive healthcare management.

Wearable electrodes constantly monitor crucial health indicators, offering a continuous flow of data that is extremely useful for overseeing and managing chronic illnesses. This instant data gathering lets us quickly notice changes in the body, leading to fast medical responses. For people with conditions like diabetes or heart disease, this ongoing monitoring can be lifesaving. It provides insights into their health that were not possible with sporadic testing approaches.

Furthermore, the convenience and non-invasiveness of these wearable devices encourage consistent usage, ensuring continuous health data collection. This aspect is crucial in building comprehensive health profiles, aiding in early disease detection and preventive healthcare. Wearable electrodes provide continuous health monitoring in an easy-to-use format, establish new benchmarks in patient care, and integrate health tracking smoothly into everyday life.

5. Application of Ion-selective electrodes in the Healthcare system

Maintaining balanced ion levels in the body is essential for preventing various diseases [2]. Ions such as potassium, sodium, calcium, magnesium, etc., play crucial roles in vital bodily functions, including regulating nerve impulses, muscle contractions, and hydration levels. Imbalances can lead to conditions like hypertension due to excess sodium or hypokalemia from low potassium levels, which can affect heart and muscle function. Calcium and magnesium are vital for bone health, and their deficiency can lead to osteoporosis. Regular monitoring and managing ion intake through diet or medication can help maintain these levels, ensuring health and preventing disease onset .

At Metrohm Company, the researchers designed a method for measuring potassium levels using an ion-selective electrode (ISE). This method involves a specific electrode sensitive to potassium ions, allowing for the accurate and selective measurement of potassium concentrations in various samples. The article’s focus on ion-selective electrode technology underscores its importance in analytical chemistry and diagnostics, as well as potential applications of this technique in fields like healthcare, environmental monitoring, or research [3].

BIOS Lab-on-a-Chip Group focuses on developing and using solid contact potassium selective electrodes in various biomedical contexts. They explore ion-selective electrodes and their applications in the medical and biological sciences and biomedical applications [4].

Odijk et al. designed a novel ion-selective to measure the level of potassium in the brain, which is crucial in understanding brain disorders[5].

At Heinrich Heine University Düsseldorf, Rose et al. designed microelectrodes to measure extracellular ion concentrations, particularly in brain tissues, and they are essential for understanding the ionic dynamics during various neural activities. The double-barreled and concentric designs of these microelectrodes allow for precise and simultaneous measurement of different ions or the combination of ionic measurement with other physiological parameters. This research is vital for advancing our knowledge of brain function and the ionic mechanisms that underlie neural activity and disorders [6].

Miras et al. developed cost-effective ion-selective electrodes for monitoring potassium and nitrate levels in nutrient solutions. These electrodes are particularly valuable in agriculture and hydroponics, where nutrient management is crucial for optimal plant growth. The study probably explores the design and fabrication of these electrodes, emphasizing their affordability and efficiency in simultaneously measuring multiple ions. This approach could significantly improve nutrient management by providing real-time, accurate data on crucial nutrient levels, enabling more precise control over the nutrient environment. The article would be particularly relevant for researchers and practitioners in plant science, agriculture, and environmental monitoring, offering insights into advancing technology in nutrient analysis while maintaining cost-effectiveness [7].

At Åbo Akademi University, researchers developed the new potassium ion-selective electrodes (ISEs) using lipophilic multi-walled carbon nanotubes (MWCNTs) as the solid contact. These electrodes indicated high sensitivity and selectivity towards potassium ions, which are essential in various scientific and environmental applications. The focus is on leveraging the unique properties of these electrodes for precise and efficient analysis in the field of analytical chemistry [8].

Isildak et al. designed a novel membrane electrode to determine nitrate ions in water samples and fruNANit juices. It focuses on using membrane electrodes infused with silver bis diethyldithiocarbamate for their high selectivity and sensitivity to nitrate ions. This potentiometric approach, known for its simplicity and cost-effectiveness, offers precise measurements with minimal interference from other substances. However, challenges might include the membrane’s potential instability and the method’s specificity to nitrate ions, which could limit broader application. Overall, the study contributes significantly to advancements in ion-selective electrode technology, enhancing nitrate ion detection in various environments [9].

designed the novel ion-selective electrodes based on multiwall carbon nanotubes to measure the level of salicylate ions in the Aspirin table, which could prevent some diseases [10].

6. Risks, Challenges, and Ethical Considerations

6.1. Risk Assessment in Wearable Sensing

This section delves into the potential risks associated with using wearable tech devices, emphasizing the need for thorough evaluation and management of these risks. Wearable technologies, rapidly becoming integral in healthcare for monitoring and diagnostic purposes, bring unique challenges in terms of privacy, security, and health-related risks. The primary concern revolves around the security and privacy of the data collected by these devices. Sensitive health information, if not adequately protected, can be vulnerable to breaches, posing significant privacy threats. Furthermore, the accuracy and reliability of these devices in health monitoring are crucial. Any inaccuracies in data could lead to misdiagnosis or inappropriate health interventions, potentially endangering users’ health.

Additionally, the long-term health impacts of continuously wearing these devices, including potential skin irritations, allergies, or other side effects, require thorough investigation. As wearable technologies become more prevalent, it’s essential to balance their benefits with a comprehensive understanding and mitigation of these risks. This involves rigorous testing and standards compliance and clear communication with users about potential risks and safe usage guidelines. While wearable technologies hold immense potential in healthcare, a careful and informed approach is necessary to maximize their benefits while safeguarding against the associated risks.

6.2. Overcoming Technical Challenges

This section discussed the challenges faced in developing and applying advanced technologies. A key obstacle is integrating new systems into existing setups. This requires careful planning and design to ensure compatibility and smooth functioning. As technologies evolve, they often necessitate new protocols and standards for effective and safe operation. This adaptation isn’t just technical; it also involves educating and training users to use these technologies effectively.

Moreover, the dependability and longevity of new technologies are critical, especially in essential applications. Maintaining consistent performance in various conditions and over long periods is challenging. This demands thorough testing and ongoing enhancements based on feedback and performance data. In tackling these technical hurdles, the focus should not only be on the technological side but also the user experience. It’s vital to ensure the technology is advanced, easy to use, and accessible. Directly addressing these challenges is essential for successfully implementing and broadly adopting new technologies.

7. Future Perspective and Interdisciplinary Collaboration

Emerging trends in sensor technology are shaping the future of wearable health devices, making them more sophisticated and effective. These advancements are especially notable in integrating advanced wearable sensors, revolutionizing personal health monitoring and management. Ion-selective electrodes, particularly those utilizing nanomaterials, are at the forefront of these developments. However, they face challenges in maintaining reliability over time and in various environments, which is crucial for accurate health tracking. Another challenge is designing these high-tech devices to be user-friendly and comfortable for everyday wear. As the technology evolves, there is a growing need for electrodes capable of monitoring a broader range of ions and health indicators, enhancing their utility in healthcare.

Progress in creating more effective wearable ion-selective electrodes with nanomaterials demands collaboration across multiple disciplines, including materials science, biomedical engineering, data analysis, and healthcare. The focus is shifting towards improving these devices’ functionality and user experience to meet diverse health monitoring needs. Additionally, addressing ethical concerns such as data privacy and security is paramount. Collaborative efforts across these fields are essential in overcoming these challenges and fully realizing the potential of this technology to transform health monitoring and disease prevention.

8. References

[1] Heikenfeld, J., Jajack, A., Rogers, J., Gutruf, P., Tian, L., Pan, T., Li, R., Khine, M., Kim, J. and Wang, J., 2018. Wearable sensors: modalities, challenges, and prospects. Lab on a Chip18(2), pp.217-248. DOI: 10.1039/c7lc00914c

[2] Dimeski, G., Badrick, T. and St John, A., 2010. Ion-selective electrodes (ISEs) and interferences- a review. Clinica Chimica Acta411(5-6), pp.309-317. DOI: 10.1016/j.cca.2009.12.005

[3] https://www.metrohm.com/

[4] https://www.utwente.nl/en/eemcs/bios/

[5] Odijk, M., Van Der Wouden, E.J., Olthuis, W., Ferrari, M.D., Tolner, E.A., Van Den Maagdenberg, A.M.J.M. and van den Berg, A., 2015. Microfabricated solid-state ion-selective electrode probe for measuring potassium in the living rodent brain: Compatibility with DC-EEG recordings to study spreading depression. Sensors and Actuators B: Chemical207, pp.945-953. DOI:10.1016/j.snb.2014.06.138

[6] Haack, N., Durry, S., Kafitz, K.W., Chesler, M. and Rose, C.R., 2015. Double-barreled and concentric microelectrodes for measurement of extracellular ion signals in brain tissue. JoVE (Journal of Visualized Experiments), (103), p.e53058. DOI: 10.3791/53058

[7] Miras, M., García, M.S., Martínez, V. and Ortuño, J.Á., 2021. Inexpensive ion-selective electrodes for the simultaneous monitoring of potassium and nitrate concentrations in nutrient solutions. Analytical Methods13(31), pp.3511-3520. DOI: 10.1039/D1AY00956G

[8] Papp, S., Kozma, J., Lindfors, T. and Gyurcsányi, R.E., 2020. Lipophilic Multi‐walled Carbon Nanotube‐based Solid Contact Potassium Ion‐selective Electrodes with Reproducible Standard Potentials. A Comparative Study. Electroanalysis32(4), pp.867-873. DOI: 10.1002/elan.202000045

[9] Isildak, O. and Yildiz, I., 2023. Highly selective potentiometric determination of nitrate ions using silver bisdiethyldithiocarbamate based membrane electrodes. Electrochimica Acta459, p.142587.
DOI: 10.1016/j.electacta.2023.142587

[10] Jahromi, Z.A.Y., Mazloum-Ardakani, M. and Reza, H., 2017. Using Potentiometry and Electrochemical Impedance Spectroscopy Techniques for Studying Effect of Nanomaterials on Salicylate Ion-selective Electrode. ANALYTICAL & BIOANALYTICAL ELECTROCHEMISTRY9(5), pp.562-573.