5 Min With...

Dr. Arben Merkoçi

2D Materials + Nanobiosensors + Microfluidics

August 14, 2024

Let’s introduce to our audience Dr. Merkoçi! Who are you? If you had to describe yourself in 1 sentence, what would you say?

My name is Arben Merkoçi and I am ICREA Professor and Group Leader at Catalan Institute of Nanoscience and Nanotechnology, ICN2, in Barcelona.

What are the most

1- Fascinating research

2- Impactful research

3- Fun and whimsical research

You are leading these days?

Fascinating research: We are trying to better understand the electro-optical properties of nanomaterials such as semiconductors (ex. graphene quantum dots), metallic nanoparticles (ex. gold, silver, platinum nanoparticles) and 2D materials (ex.  graphene) and find the way to assemble these together with sustainable platforms (like paper or other biodegradable polymers) to build biosensors. These nanobiosensors can work either as standalone devices (like glucometer used to measure glucose at home by people suffering diabetes)  or as wearables (i.e. patches adhered at the body arm to continuously measure glucose)  and be able to deliver  important info for our health, environment or for many other needs for the citizens.

Impactful research: Most of the research my group in Barcelona is doing is directly related to health. Detecting cancer biomarkers with biosensors is crucial as it enables early diagnosis, which can significantly improve treatment outcomes and survival rates. Biosensors offer rapid, sensitive, and non-invasive detection, making them a valuable tool in personalized medicine and ongoing monitoring of cancer progression. The second example is related to early detection of liver cirrhosis using biosensors. This is vital because it allows for timely intervention, potentially slowing or reversing disease progression. The biosensor we are developing aims to identify a specific biomarker for this disease in blood or other bodily fluids, offering a non-invasive, rapid, and sensitive method for detecting liver damage before symptoms become severe. This early detection connected to a smartphone can improve patient outcomes by enabling earlier treatment, lifestyle changes, and monitoring, ultimately reducing the risk of liver failure or the need for transplantation. The third example biosensor is related to Alzheimer's disease through identifying specific biomarkers in bodily fluids. Early diagnosis is key to managing Alzheimer's, as it allows again as for the previous disease  earlier intervention, potentially slowing disease progression and improving quality of life. Together with other partners and in the framework of a Horizon Europe Project we are putting efforts to build a fully integrated biosensing system that will offer a non-invasive, cost-effective, and rapid way to detect the disease biomarker, enabling regular monitoring and personalized treatment strategies, which are essential in managing this complex neurodegenerative disorder.

Fun and whimsical research: Building of wearable devices with fully integrated electronics is quite fun and whimsical research. We recently developed a sensor network using inkjet-printed nanofunctional inks on a semipermeable substrate for real-time monitoring of critical physiological parameters like temperature, humidity, and muscle contraction. This battery-free, NFC-enabled system can be read via smartphones. We integrated two sensors into a bioinspired adhesive membrane developed by our ICN2 colleagues, which adheres to the skin for continuous data collection. Given the rising heat stroke incidents due to climate change, this system offers crucial monitoring capabilities, particularly for high-risk workers like firefighters (more details at: https://www.sciencedirect.com/science/article/pii/S0956566324004263?via%3Dihub) .

Nano+bio+electronics…What is nanobioelectronics?

Nanobioelectronics is an interdisciplinary field that combines principles from nanotechnology, biology, and electronics to develop devices and systems at the nanoscale that can interact with biological systems. These devices are designed to detect, monitor, and influence biological processes with high precision and sensitivity.

Nanobioelectronics field take advantages of the unique properties of nanomaterials—such as their small size, large surface area, and enhanced electrical, optical, and mechanical properties—to create innovative sensors, actuators, and circuits that can operate at the interface of biology and electronics. These nanodevices can be integrated with biological tissues, cells, or molecules, enabling new ways to diagnose diseases, deliver drugs, and monitor physiological conditions in real-time.

The principle of bioelectronics revolves around the exchange of electrons between biological systems and electronic devices. In this context, bioelectronic devices are designed to interface with biological entities—such as cells, enzymes, or proteins—facilitating the transfer of electrons in a controlled manner. At the core of bioelectronics is the concept of redox (reduction-oxidation) reactions, where electrons are transferred between molecules. In biological systems, many processes, such as respiration and photosynthesis, involve redox reactions where electrons are transferred between biomolecules, like NADH and cytochromes, as part of metabolic pathways. Bioelectronic devices often employ conductive materials, such as electrodes, that can interface with biological molecules or tissues. When these electrodes come into contact with a biological system, they can facilitate electron transfer either by donating electrons (reducing) or accepting electrons (oxidizing) from the biological entity.

One of the key applications of nanobioelectronics is in the development of biosensors that can detect specific biomolecules, such as proteins, DNA, or metabolites, at very low concentrations. These sensors have the potential to revolutionize medical diagnostics by providing rapid, accurate, and non-invasive detection of diseases, including cancer, diabetes, and neurological disorders.

Another important aspect of nanobioelectronics is the creation of bioelectronic interfaces that can communicate with the nervous system. These interfaces can be used to develop advanced prosthetics, brain-computer interfaces, and therapies for neurological conditions by directly interfacing with neurons and other cells.

Nanobioelectronics is a rapidly advancing field with the potential to transform healthcare, biotechnology, and environmental monitoring by enabling the development of highly sensitive, miniaturized, and multifunctional devices that can interact seamlessly with biological systems.

Printer + paper =…sensors? How is it even possible?

Printed sensors and biosensors on paper (known also as paper-based sensors and biosensors) platforms represent an innovative approach to creating low-cost, flexible, and environmentally friendly devices for detecting and monitoring various chemical, biological, and physical parameters. These devices are produced by printing functional inks, containing conductive materials or bio-recognition elements, directly onto paper substrates using techniques such as inkjet printing, screen printing, or flexography.

For the fabrication of printed sensors and biosensors conductive inks, such as carbon or other metallic nanoparticles (ex. silver, gold nanoparticle-based inks), to form circuits or sensing elements on paper are used. Biological recognition elements, such as enzymes, antibodies, or DNA, also may be incorporated into the ink. When these devices are used their sensing elements interact with specific target molecules (e.g., glucose, toxins, or pathogens), triggering a measurable electrical, optical, or colorimetric response.

Paper-based sensors and biosensors are significantly cheaper to produce than traditional electronic sensors. The use of inexpensive paper substrates and scalable printing techniques makes them accessible for widespread use, especially in resource-limited settings. Paper is lightweight, flexible, and foldable, making these sensors highly portable and easy to integrate into various applications, from wearable devices to point-of-care diagnostics. Paper is biodegradable and recyclable, making these devices environmentally friendly. This contrasts with traditional sensors made from non-biodegradable materials like plastics and metals. Printed sensors on paper can be mass-produced quickly and efficiently, enabling rapid deployment in large quantities. This is especially valuable in situations requiring immediate response, such as pandemics or environmental disasters.

These devices can be tailored for various applications, including healthcare (e.g., glucose monitoring, rapid disease diagnostics), environmental monitoring (e.g., detecting pollutants in water or air), food safety (e.g., detecting pathogens in food products), and wearable technology.

Printed sensors and biosensors on paper platforms offer a revolutionary approach to sensing technology, combining low cost, portability, environmental sustainability, and rapid production. They are essential for expanding access to diagnostic tools, especially in remote or resource-constrained areas, and for advancing the development of smart, disposable, and eco-friendly devices across multiple industries.

AI…AI…AI…is AI doing anything useful in your field as a nanoscientist?

Artificial intelligence (AI) is playing a transformative role in nanoscience, particularly for researchers working on nanobiosensors. By leveraging AI, nanoscientists can accelerate research, optimize designs, and uncover new insights that would be difficult or time-consuming to achieve through traditional methods.

Nanoscience experiments often generate big amounts of data, including imaging, spectroscopy, and simulation results. AI, especially machine learning algorithms, can process and analyze this data more efficiently than human researchers. AI can identify patterns, correlations, and anomalies that might be overlooked, leading to new discoveries and deeper understanding. AI algorithms can predict the properties of new nanomaterials by analyzing existing data and simulating different configurations at the atomic level. This approach helps researchers to identify promising materials for specific applications more quickly, reducing the trial-and-error process in experimental research. AI-driven automation enables the design and execution of complex experiments with minimal human intervention. This is particularly useful in nanofabrication, where precision and reproducibility are critical. AI can optimize experimental parameters, ensuring consistency and improving the quality of results.

Entering more in my field, designing nanobiosensors involves selecting appropriate nanomaterials, optimizing their functionalization, and ensuring sensitivity and specificity. AI can simulate various designs and predict their performance, helping researchers identify the most effective configurations before physical prototyping. This accelerates the development process and reduces costs. Nanobiosensors often produce complex data that require sophisticated analysis to detect the presence of target biomolecules. AI algorithms, particularly deep learning models, can be very useful to recognize patterns in this data, even in noisy environments of real measuring scenarios. AI can enhance the sensitivity and accuracy of nanobiosensors by improving signal-to-noise ratios and distinguishing between specific and non-specific binding events.

AI can integrate data from nanobiosensors with other patient data (e.g., genetic, clinical, lifestyle information) to provide personalized diagnostic insights. By analyzing data from multiple sources, AI can help tailor treatments to individual patients, improving outcomes in fields like cancer therapy, infectious disease management, and chronic disease monitoring. In applications like continuous health monitoring, AI enables real-time analysis of data from nanobiosensors, allowing for immediate decision-making. For instance, AI can detect early signs of disease or health deterioration and prompt timely interventions, which is critical in managing conditions like diabetes or cardiovascular diseases.

I think that AI is revolutionizing nanoscience by enhancing data analysis, speeding up material discovery, automating experiments, and improving the design and performance of nanobiosensors. For researchers in the field of nanobiosensors, AI will offer powerful tools to create more sensitive, accurate, and personalized diagnostic devices, ultimately advancing healthcare and enabling innovative solutions to complex biological challenges.

If you could design an experiment without any limitations of time or money… what would it be?

In a hypothetical experiment with no constraints on time or budget, I would design an advanced biosensor system to achieve unprecedented levels of sensitivity, specificity, and functionality. This universal biosensor would be capable of detecting a wide range of biomarkers with ultra-high sensitivity and specificity, integrating real-time data processing, and providing actionable insights for personalized medicine. The use of state-of-the-art nanomaterials such as 2D materials and advanced quantum dots for the biosensor’s sensing elements would definitively be quite effective. Engineering a diverse array of bio-recognition elements, including antibodies, aptamers, peptides, and DNA probes, to target a wide spectrum of biomarkers would be crucial. Integrate these elements onto the sensor surface using printing or stamping techniques would open the way to advancing of low cost and efficient paper/plastic-based bisoensors with multiple sensing modalities into a single device (electrochemical or optical). Use of advanced signal amplification techniques taking advantages of new plasmonic or electrocatalytic nanostructures and nanocapsules to enhance the sensor’s sensitivity and enable the detection of extremely low concentrations of biomarkers will be quite beneficious. Another important aspect to consider will be sampling. Integration of the biosensor with microfluidics for automated sample handling and pre-processing also is a must. In collaboration with experts in the field the development of a microprocessor with embedded AI algorithms for real-time data analysis and interpretation directly on the chip would be quite revolutionary in addition to the design of a wireless communication system using advanced technologies such as 5G or future wireless standards to transmit data in real-time to cloud-based platforms for further analysis.

Future nanobiosensing systems would also be connected to a comprehensive database that includes patient-specific genetic, clinical, and lifestyle data. By developing AI models to analyze data from the biosensor in the context of this database, would provide personalized insights and recommendations with interest for the people healthcare.

An interesting advance will be the implementation of a closed-loop system where the nanobiosensor can interact with therapeutic devices, such as drug delivery systems, based on the real-time data analysis. This advanced device would adjust medication dosages or release therapeutic agents in response to detected biomarker levels. The efficiency of such nanobiosensors must be validated during In Vitro and In Vivo testing. En extensive in vitro validation using a variety of biological samples (e.g., blood, saliva, urine) and in vivo testing in animal models would be necessary followed by human clinical trials to ensure the device’s safety, efficacy, and accuracy. The full development and applicability of such devices would request environmental testing that is related to the assessment of the nanobiosensor’s performance under diverse environmental conditions to ensure robustness and reliability in various settings. Ethical review engaging with bioethicists and regulatory bodies throughout the development process to address any ethical concerns and ensure compliance with regulatory standards is extremely important as well. Finally the global health impact should be considered. This will be done through collaboration with global health organizations to explore the potential impact of the biosensor on public health, particularly in underserved regions where advanced diagnostics are needed most.

This next-generation nanobiosensor that combines multiple sensing modalities, advanced data processing, and personalized medicine capabilities can be developed by pushing the boundaries of current technology and integrating cutting-edge materials and techniques. Such nanobiosensor could revolutionize diagnostics and personalized healthcare, offering unprecedented insights and precision in detecting and managing a wide range of diseases.

If you could have a superhero power. What would it be?

If I could choose a superhero power helpful to my filed, it might be the ability to instantly understand and solve complex problems across various fields, from science and technology to social issues and personal challenges. This power would let me employ  knowledge to make a profound impact on the world, drive innovation, and help others in meaningful ways. It would be a power that would align with curiosity and a drive to create positive change, echoing my interest in advancing technologies and solving real-world problems. Indeed If I could have any superhero power, my first mission would be to bring peace across the world 😊.

Mystery dinner party…Dead or Alive, who would be 3 guests you would invite to your dinner party?

For a mystery dinner party themed around my field of expertise, which involves nanoscience, biosensors, and innovative technology, I would hypothetically invite these three notable guests (although the first two are not alive):

Richard Feynman - A brilliant physicist known for his work in quantum mechanics and nanotechnology. Feynman’s visionary ideas about manipulating matter at the atomic scale laid the groundwork for modern nanoscience. His curiosity and unique perspective would bring a lively and insightful dimension to my discussions.

Marie Curie - A pioneering scientist in radioactivity, Marie Curie’s groundbreaking research in physics and chemistry earned her two Nobel Prizes. Overall her dedication to scientific discovery would offer valuable historical context and inspiration for advancements in materials science and biosensors.

Dr. Frances Arnold - A Nobel Prize-winning chemist renowned for her work in directed evolution and enzyme engineering. Dr. Arnold’s expertise in creating biological systems with tailored functions aligns well with the development of biosensors and advanced materials, offering valuable perspectives on engineering and design. Beyond her scientific achievements, Frances’ extraordinary personal journey includes diverse experiences, such as working as a taxi driver (to support herself while pursuing her education), adding a unique dimension to her remarkable career. 

These three figures would provide a rich mix of historical insight and foundational knowledge relevant to my field.

If you could leave a question for the next guest, what would that be?

Given the innovative and interdisciplinary nature of my interests, I may leave a question that bridges past advancements with future possibilities. Here’s a thoughtful question I could leave for the next guest:

"What emerging technology or breakthrough in your field do you believe will have the most profound impact on the future of biosensors and nanotechnology, and how do you envision it transforming both scientific research and everyday applications?"

This question would encourage the next guest to reflect on the future of the field, considering both theoretical advancements and practical applications, and helps maintain a forward-looking dialogue at my mystery dinner party.

Question from our previous guest - David Breber: What is some recent research in another field which really surprised you?

In recent years, several groundbreaking developments in fields adjacent to nanoscience and biosensors have captured significantly my attention and could be quite surprising.

First, Quantum Biology for which scientists have explored how quantum mechanics might influence biological processes, such as photosynthesis and enzyme reactions. The idea that quantum effects, typically associated with the behavior of particles at the atomic level, could directly impact biological systems challenges traditional views and opens new avenues for understanding and manipulating biological processes.

Second, CRISPR-Based Diagnostics, that is leading to the development of highly sensitive diagnostic tools. Researchers have engineered CRISPR systems to detect specific DNA or RNA sequences associated with various diseases, including COVID-19, with remarkable accuracy. The application of CRISPR, originally known for gene editing, to rapid and precise diagnostics showcases an unexpected and transformative use of the technology, potentially revolutionizing how we detect and respond to infections and genetic disorders.

Third, Synthetic Biology and Xenobiology with the ability to engineer entirely new forms of life with synthetic genetic materials challenges the boundaries of biology that could lead to innovative applications in medicine, industry and other fields.

Fourth, Neurotechnology and Brain-Computer Interfaces that have enabled more sophisticated interactions between the human brain and external devices such as the possibility to allow individuals to control robotic limbs or communicate directly with computers using only their thoughts. The ability to translate neural activity into actionable commands brings us closer to integrating human cognition with technology in ways once thought to be science fiction.

These recent developments highlight the accelerating speed of innovation across various fields and offer exciting possibilities that intersect with my interests in nanotechnology and biosensors.

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