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NANO2021-Nanoteknologi, nanovitenskap, mikroteknologi og avanserte materialer

High-throughput Synthesis of Non-spherical Plasmonic Nanoparticles (NPs) for Applications in Endotoxin Sensing (Nano-Syn-Sens)

Alternative title: Syntetese av høy gjennomstrømning av ikke-sfæriske plasmoniske nanopartikler (NP) for applikasjoner i endotoksinsensering (Nano-Syn-Sens)

Awarded: NOK 4.9 mill.

Lipopolysaccharides (LPS), found in the outer membrane of the Gram-negative bacteria such as E.coli, Salmonella and Pseudomonas, can cause endotoxemia, septic shock and multi-organ failure in humans, even at sub nano-molar levels. Currently, there is no reliable sensor for detection of LPS in blood and biopharmaceuticals, despite a need for such. Nano Syn Sens has investigated the potential of gold nanoparticles (Au NPs) in biosensing, by exploiting their optical properties. Such optical properties are dependent on NP size, shape, morphology, functionalization and the surrounding environment – the latter forming the basis of biosensing. Within the scope of the project, we have developed fundamental understanding of how reaction conditions can influence the growth of non-spherical Au NPs by using a complementary approach that combines experimental and multi-scale modelling. Our results have shed light on how the cationic surfactant used in this process to direct anisotropy, binds to the growing seed particles. This finding will guide researchers to exert finer control on the synthetic method to control Au NP morphology. By focusing on tannic acid as a reducing agent, the project has demonstrated that a plethora of shapes can be produced by fine-tuning the choice of chemicals. Some of the shapes reported show the tunability of the chosen synthesis method. A highlighted achievement of the project is the first demonstration of a droplet-based milli fluidic process development for transferring the batch into a continuous process. The built platform has been shown to produce anisotropic particles coupled with on-line measurement of optical properties. This is the first step towards achieving a controlled synthesis of Au NPs in milli fluidic setup through feedback control guided by online measurement of optical properties. Selected Au NPs have been functionalized to immobilize them to the optical fibre-based biosensors. An important outcome is the development and validation of robust functionalization procedures to replace the surfactant from the surface of the Au NPs, which will enable advanced surface chemistry for biosensing. As a proof-of-concept, the fibre-based biosensor has been shown to capture effective binding of endotoxins, although further optimization is required to enhance sensitivity. Overall, Nano-Syn-Sens has enabled scientific collaboration among the Norwegian and Indian partners through co-ordinated research activities as outlined in the aims and objectives of the bilateral project. Besides educating 3 PhD students directly and 3 PhD students indirectly (partly connected to the project), several master students, research assistants and engineers in both institutes, the project has helped in establishing research ties for long-term co-operation. Through mutual visits of the PIs, structured discussions and project meetings and several scientific dissemination activities, the project has ensured cross-disciplinary collaboration.

The project has educated 3 PhDs and 10 MScs directly and 3 PhDs and more than 5 MScs indirectly (partly connected to the project) and trained several research assistants and engineers in both institutes. The project has enhanced understanding of fundamental pathways leading to formation of anisotropic Au NPs, which will impact further knowledge development in the field of size and shape control of nanomaterials. Robust procedures developed for functionalization of the Au NPs will find large scale utilization in biomedical applications, beyond its demonstrated use in the field of biosensing. Developed two-phase milli fluidic route for the synthesis of such Au NPs is the first step towards developing self-controlling reactors for high-throughput synthesis of nanomaterials in flow processes. The demonstration of chemisorption of anisotropic Au NPs on optic-fiber probes will enable their utilization in the field of biosensing. The scientific results have been actively published in relevant, international peer-reviewed journals of high quality along with oral and poster presentations in international conferences. The knowledge gained has also been shared via joint workshops, seminars and project meetings. Popular communication has been at the forefront of researcher training. The project consortium has already used the developed knowledge as teaching materials in respective courses at the two institutes. Besides, the research results have laid the foundation for the application of more than 5 research proposals over the last two years, some of which are under evaluation.

This project aims to understand and control growth of anisotropic Au NPs in seeded-growth strategies using a complementary approach that combines experimental and multi-scale modelling techniques for both batch and continuous processes. The obtained Au NPs will then be functionalized for biosensing of endotoxins based on optical fibre technology. The project aims to improve health and promote new medical technology and also provide greater insight into the impacts of nanomaterials on human health and ecosystems. The project team comprises experts in experimental as well as theoretical methods with special competences in NP fabrication, characterization, scale-up and mathematical modelling. State-of-the art nano research infrastructure at NTNU Nanolab will be used for fabrication and characterization while multi-scale modelling knowledge, approaches and facilities at IIT-M will be used for developing process models that capture the growth. The proposal aims to solve a pressing societal need of providing cheap, in-house and improved healthcare and medical facilities in biosensing which will be realized in the Biosensors Labortory at IIT-M. Although several reports exist documenting seeded growth, to our knowledge, there exists no comprehensive mathematical modelling in case of binary surfactant mixtures. Further, using microfluidic routes, high throughput of anisotropic Au NPs will be achieved. Functionalization of the Au NPs to chemisorb them on fibreoptic sensors will help realize ultrasensitive plasmonic sensors for endotoxin detection. The project would therefore provide fundamental understanding of nucleation and growth of anisotropic Au NPs with an aim to fabricate in-house sensors, the technology behind which can be patented. It also aims to educate 3 PhDs within the research area over the project period, foster ongoing collaborative research between the partners and establish research ties for long-term co-operation.

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NANO2021-Nanoteknologi, nanovitenskap, mikroteknologi og avanserte materialer