Periodic Reporting for period 1 - AMBROSIA (A Multiplexed Plasmo-Photonic Biosensing Platform For Rapid And Intelligent Sepsis Diagnosis At The Point-Of-Care)
Reporting period: 2023-01-01 to 2024-06-30
Sepsis is a life-threatening whole-body inflammatory reaction caused by a severe infection (e.g. bacteria, virus). With mortality rates around 35%, sepsis is responsible for 11 million deaths worldwide every year, being the largest killer of children (more than 5 million annually). Furthermore, sepsis survivors commonly suffer long-term health damage with a diminished quality of life and persistent high risk of mortality. The window of opportunity for sepsis management is in hours: the chance of survival drops by 7.6% each hour of disease progression until an appropriate treatment is started. Early and accurate sepsis detection and stratification is essential for enhancing survival rates. This is challenging, due to: i) complex diagnostic criteria requiring multiple screenings for differential diagnosis, (ii) time-consuming methods for identifying the bacterial causes of sepsis. Even worse, these conventional immunoassay techniques are performed in centralized laboratories, causing extra delays due to specimen transfers. Point-of-care (PoC) testing performs the analysis at bedside, enabling earlier diagnosis and facilitating therapy assessment. Currently available PoC platforms, however, do not offer multiplexed capabilities, i.e. they detect a single biomarker and do not identify the bacterial cause of the infection, nor do they offer any decision support system for disease classification.
AMBROSIA aims to transform integrated plasmo-photonic refractive index sensors into a disruptive solution for sepsis diagnosis at the point of care that will offer multiplexed (within a single test) quantification of multiple protein biomarkers and bacteria within a few minutes providing also real-time disease stage classification enabling a rapid and precise decision making for therapy and medical actuation. To realize its ambitious goals, AMBROSIA targets to build upon:
• The adoption of best-in-class integrated plasmo-photonic devices synergizing aluminum (Al) plasmonics and silicon nitride (SiN) photonics. Incorporating Bragg-grating decorated plasmonic stripes envisions to boost sensitivity to unprecedented values of 130000 nm/RIU.
• The co-integration of the plasmo-photonic sensing technology with microelectronics and microfluidics into integrated self-contained disposable sensing chips including on-chip lasers and photodiodes by means of the high-throughput and cost-effective micro-transfer technology (μTP), pioneering the field of manually pluggable disposable sensor chips.
• Optically-enabled artificial intelligence (AI) to provide a real-time identification and classification of disease severity. This will enable rapid knowledge-based critical decision-making and back-checking against misdiagnosis and medical mistakes, allowing for critical time savings and accelerating the pathway towards the optimal medical treatment. AMBROSIA’s disease classification will rely on the adoption of state-of-the-art sepsis medical protocols and their translation into Deep Learning models that will be then deployed on hardware via low-power photonic Deep Neural Networks with electro-optic activations, facilitating in this way rapid and low-energy decisions.
AMBROSIA aims to transform integrated plasmo-photonic refractive index sensors into a disruptive solution for sepsis diagnosis at the point of care that will offer multiplexed (within a single test) quantification of multiple protein biomarkers and bacteria within a few minutes providing also real-time disease stage classification enabling a rapid and precise decision making for therapy and medical actuation. To realize its ambitious goals, AMBROSIA targets to build upon:
• The adoption of best-in-class integrated plasmo-photonic devices synergizing aluminum (Al) plasmonics and silicon nitride (SiN) photonics. Incorporating Bragg-grating decorated plasmonic stripes envisions to boost sensitivity to unprecedented values of 130000 nm/RIU.
• The co-integration of the plasmo-photonic sensing technology with microelectronics and microfluidics into integrated self-contained disposable sensing chips including on-chip lasers and photodiodes by means of the high-throughput and cost-effective micro-transfer technology (μTP), pioneering the field of manually pluggable disposable sensor chips.
• Optically-enabled artificial intelligence (AI) to provide a real-time identification and classification of disease severity. This will enable rapid knowledge-based critical decision-making and back-checking against misdiagnosis and medical mistakes, allowing for critical time savings and accelerating the pathway towards the optimal medical treatment. AMBROSIA’s disease classification will rely on the adoption of state-of-the-art sepsis medical protocols and their translation into Deep Learning models that will be then deployed on hardware via low-power photonic Deep Neural Networks with electro-optic activations, facilitating in this way rapid and low-energy decisions.
The AMBROSIA project had a significant progress over the first 18 months. The main achievements include:
• The most relevant biomarkers for early detection, risk stratification and prognosis evaluation, as well as the assay range requirements for different clinical scenarios have been defined. The most prevalent bacteria have also been identified.
• The architectural designs and specifications of the AMBROSIA sub-modules have been defined.
• The designs of all sub-modules have been completed. Specifically:
o The designs of the plasmo-photonic sensors indicate maximum RI sensitivity of 28000 nm/RIU for the MZI and 13100 nm/RIU for the bimodal configuration without considering the inclusion of Bragg gratings on the plasmonic waveguides.
o The inclusion of Bragg-grating decorated plasmonic sensing waveguides enhances sensitivity at least 2 times compared to a sensor without the Bragg configuration.
o The SiN-to-InP interfaces have been optimized leading to 94.8% (-0.23 dB) coupling efficiency and -50 dB back reflection.
• The mask of the photonic for the 1st fabrication run has been submitted. The chip size is 22 mm x 22 mm and it includes three sections: (i) the sensors area with MZI and bimodal variants (ii) the actives area including the active InP elements, and (iii) the LGT quality control area.
• The first bimodal sensors have been successfully fabricated and characterized. Bimodal operation has been verified and a sensitivity of 9249 nm/RIU has been achieved experimentally.
• SiN-based Bragg gratings have been fabricated on plasmonic stripes and have been characterized. Qualitative agreement between simulations and experiments has been observed.
• The actives coupons fabrication is in progress.
• The μTP process optimization is in progress.
• The most relevant biomarkers for early detection, risk stratification and prognosis evaluation, as well as the assay range requirements for different clinical scenarios have been defined. The most prevalent bacteria have also been identified.
• The architectural designs and specifications of the AMBROSIA sub-modules have been defined.
• The designs of all sub-modules have been completed. Specifically:
o The designs of the plasmo-photonic sensors indicate maximum RI sensitivity of 28000 nm/RIU for the MZI and 13100 nm/RIU for the bimodal configuration without considering the inclusion of Bragg gratings on the plasmonic waveguides.
o The inclusion of Bragg-grating decorated plasmonic sensing waveguides enhances sensitivity at least 2 times compared to a sensor without the Bragg configuration.
o The SiN-to-InP interfaces have been optimized leading to 94.8% (-0.23 dB) coupling efficiency and -50 dB back reflection.
• The mask of the photonic for the 1st fabrication run has been submitted. The chip size is 22 mm x 22 mm and it includes three sections: (i) the sensors area with MZI and bimodal variants (ii) the actives area including the active InP elements, and (iii) the LGT quality control area.
• The first bimodal sensors have been successfully fabricated and characterized. Bimodal operation has been verified and a sensitivity of 9249 nm/RIU has been achieved experimentally.
• SiN-based Bragg gratings have been fabricated on plasmonic stripes and have been characterized. Qualitative agreement between simulations and experiments has been observed.
• The actives coupons fabrication is in progress.
• The μTP process optimization is in progress.
Τhe project has already demonstrated integrated bimodal plasmo-photonic sensors with state-of-the-art sensitivity. Further optimization, successful functionalization and packaging is expected to result in a disruptive PoC device for the diagnosis of sepsis. Towards this direction, patenting of the device will also be needed.