Periodic Reporting for period 2 - ECLIPSE (ECL-based Infectious Pathogen (bio)SEnsor)
Reporting period: 2023-05-01 to 2024-04-30
Infectious diseases are a threat to mankind since their appearance in human history. Despite the advances in science and technology, such threats are still recurrent, as recently shown by the COVID-19 pandemic which has revealed the urgent need for novel tools for pathogen detection that would be at the same time reliable, fast, cheap, portable and simple. Although important progress has been made since the appearance of SARS-CoV-2, we are still far away to have a system with these characteristics at our disposal. For many infectious agents, the most accurate in-vitro diagnostic tests – like the molecular swab for COVID – are still mainly based on the detection of the pathogen nucleic acid by real-time PCR assays. However, PCR-based methods are typically quite complex and relatively slow, requiring DNA/RNA extraction and purification, and sophisticated and expensive devices. These tests need thus to be performed in specialized centres at relatively high costs, limiting their use in massive screenings and in low-income countries. On the hand, rapid tests have shown to be fast, cheap, and relatively simple to use, but they suffer from low reliability, typically yielding a high number of false negative results.
The goal of ECLIPSE is to bridge this gap with a platform that could detect infectious pathogens with a sensitivity and selectivity equal to – or better than – the one afforded by PCR-techniques using a faster process with a portable device, having dimensions comparable to the one of the most common smart-phones.
We will demonstrate the feasibility and validate adaptability of the ECLIPSE platform with three test cases: a virus (SARS-CoV-2), a bacterium (Pseudomonas aeruginosa) and a protozoan parasite (Leishmania infantum). The platform is designed to be applicable to many other infectious agents, making it a “ready for the next pandemic” technology. ECLIPSE is expected to become a game-changer in European countries, a cornerstone for fast testing and reliable tracking of infections, and in developing countries that will benefit from a cheap and simple approach to detect the many infectious diseases that affect millions of people every year.
ECLIPSE platform will use as transduction mechanism, electrochemiluminescence (ECL) that -because it offers high sensitivities – is already the leading signal-transduction technique in many important clinical analyses. In ECL, the light emission is triggered by an electrochemical reaction requiring voltages lower than common batteries, without the need of lamps or lasers; for all these reasons it can allow the construction of portable, low-cost devices.
In particular, our work is structured in the following key points:
• Improve bio- and nano-structures for signal amplification in luminescence-based techniques: with these elements we intend to decrease even more the limits of detection of analytical techniques that are already used in clinical tests;
• Design new biotechnological approaches for the recognition of the desired analytical target endowed with high affinity and selectivity, in this way decreasing the occurrence of false positive and negative results;
• Push the electrochemiluminescence detection technologies to unprecedented sensitivities, through a detailed study of all the mechanisms leading to the generation of light;
• Fabricate suitable prototypes of the analytical platform in order to make the system portable, fast and leading to very cheap tests.
• Pave the way to increased TRL and facilitate adoption by pharma and diagnostic companies with proper IP strategy and possibly the creation of a special purpose vehicle (spin-off).
The goal of ECLIPSE is to bridge this gap with a platform that could detect infectious pathogens with a sensitivity and selectivity equal to – or better than – the one afforded by PCR-techniques using a faster process with a portable device, having dimensions comparable to the one of the most common smart-phones.
We will demonstrate the feasibility and validate adaptability of the ECLIPSE platform with three test cases: a virus (SARS-CoV-2), a bacterium (Pseudomonas aeruginosa) and a protozoan parasite (Leishmania infantum). The platform is designed to be applicable to many other infectious agents, making it a “ready for the next pandemic” technology. ECLIPSE is expected to become a game-changer in European countries, a cornerstone for fast testing and reliable tracking of infections, and in developing countries that will benefit from a cheap and simple approach to detect the many infectious diseases that affect millions of people every year.
ECLIPSE platform will use as transduction mechanism, electrochemiluminescence (ECL) that -because it offers high sensitivities – is already the leading signal-transduction technique in many important clinical analyses. In ECL, the light emission is triggered by an electrochemical reaction requiring voltages lower than common batteries, without the need of lamps or lasers; for all these reasons it can allow the construction of portable, low-cost devices.
In particular, our work is structured in the following key points:
• Improve bio- and nano-structures for signal amplification in luminescence-based techniques: with these elements we intend to decrease even more the limits of detection of analytical techniques that are already used in clinical tests;
• Design new biotechnological approaches for the recognition of the desired analytical target endowed with high affinity and selectivity, in this way decreasing the occurrence of false positive and negative results;
• Push the electrochemiluminescence detection technologies to unprecedented sensitivities, through a detailed study of all the mechanisms leading to the generation of light;
• Fabricate suitable prototypes of the analytical platform in order to make the system portable, fast and leading to very cheap tests.
• Pave the way to increased TRL and facilitate adoption by pharma and diagnostic companies with proper IP strategy and possibly the creation of a special purpose vehicle (spin-off).
We have obtained large signal amplifications for several of the structures designed, synthesised and characterised, and in particular in the case of silica nanostructures and engineered biostrctures, results that have an impact in many sectors of clinical analyses, well beyond the aim of the project. This is also true and the large signal enhancements obtained with new nanostructured electrodes, that represents a clear advancement with respect to the state of the art. In addition, efficient recognition systems have bee developed, with very interesting results.
ECLIPSE is expected to become a game-changer in developed countries – where the ability to perform a cheap, fast and reliable tracking of infections represents an indispensable tool to limit the effects of epidemics. An even more diffuse impact can be envisaged for developing countries, that will benefit from a cheap and simple approach to detect the many infectious diseases that affect millions of people every year, causing a too large number of casualties.
ECLIPSE’s results can have a direct impact also toward another of the most important challenges that medicine has to face in the next future, i.e. antimicrobial resistance (AMR), that has been declared one of the top 10 global public health threats facing humanity by WHO (https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance(opens in new window)) having tremendous social and economic effects in both developed and developing countries.
To exploit all the ECLIPSE’s key results further actions are necessary, inside and outside the specific aims of the project, with the possibility to access finance and markets. A new spin-off company has been established, and we are planning to apply for a Transition scheme by the EIC, to scale up TRL.
ECLIPSE is expected to become a game-changer in developed countries – where the ability to perform a cheap, fast and reliable tracking of infections represents an indispensable tool to limit the effects of epidemics. An even more diffuse impact can be envisaged for developing countries, that will benefit from a cheap and simple approach to detect the many infectious diseases that affect millions of people every year, causing a too large number of casualties.
ECLIPSE’s results can have a direct impact also toward another of the most important challenges that medicine has to face in the next future, i.e. antimicrobial resistance (AMR), that has been declared one of the top 10 global public health threats facing humanity by WHO (https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance(opens in new window)) having tremendous social and economic effects in both developed and developing countries.
To exploit all the ECLIPSE’s key results further actions are necessary, inside and outside the specific aims of the project, with the possibility to access finance and markets. A new spin-off company has been established, and we are planning to apply for a Transition scheme by the EIC, to scale up TRL.
We can summarise some of the main advancement with respect to the state of the art as it follows:
1. we have prepared new families of electrochemiluminescence luminophores addressing the problem of self-quenching in ECL measurements, obtaining in this way large signal amplifications.
2. Engineered biostructures developed in this project are surpassing the signal obtained using antibody-based assay by two order of magnitude.
3. We have developed a novel dual emission-and-electrochemical sensing assay principle that is complementary to ECL measurements.
4. We have developed a biostructure able to recognize antibiotic-resistant mutants of P. aeruginosa clinical strains, and to produce a system able to capture them with high efficiency indicating the possible successful use, both for a diagnosis and therapy, of this biostructure to fight Antimicrobial Resistance (AMR).
5. A new, more efficient, electrode material has been obtained for which an increase of more than one order of magnitude in the integrated signal has been obtained.
1. we have prepared new families of electrochemiluminescence luminophores addressing the problem of self-quenching in ECL measurements, obtaining in this way large signal amplifications.
2. Engineered biostructures developed in this project are surpassing the signal obtained using antibody-based assay by two order of magnitude.
3. We have developed a novel dual emission-and-electrochemical sensing assay principle that is complementary to ECL measurements.
4. We have developed a biostructure able to recognize antibiotic-resistant mutants of P. aeruginosa clinical strains, and to produce a system able to capture them with high efficiency indicating the possible successful use, both for a diagnosis and therapy, of this biostructure to fight Antimicrobial Resistance (AMR).
5. A new, more efficient, electrode material has been obtained for which an increase of more than one order of magnitude in the integrated signal has been obtained.