MEMS-enabled miniaturised multimodal microscopy through pulsed structured illumination

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The build-up of antimicrobial resistance is developing to become one of the biggest modern health challenges, one that has emerged over the last decade and places a significant threat on modern day medical treatments. While fantastic research in deciphering build-up and interaction mechanisms between cells and micro-organisms that lead to drug resistance are ongoing, tool-kits to evaluate, image and visualise these interactions in real-time 3D environments and with subcellular resolution are limited to very well-funded research labs and central facilities. While access to these is enabled in the UK through time requests in grant applications, the possibility to have systems in situ and in an environment that fosters biological development would present a significant potential to leverage further research momentum and invention to tackle this wide ranging significant health challenge.In this proposal, miniaturised 3D imaging systems with super-resolution capability will be developed, allowing to resolve samples beyond the physical diffraction limit based on active optical microsystems and 3D-printing. This will allow the creation of small scale and portable systems which could drastically alter the access gap and costs currently present in state-of-the art subcellular biomedical imaging systems, both in research as well as in pre-clinical settings. We seek to address this by combining fluorescence and acoustic based imaging modalities, enabling high-throughput investigations through multi-modal parallel systems which can show new insights in the behaviour of microbial-cell interactions and antimicrobial resistance development.By creating fluorescence and acoustic super-resolution imaging systems in a combined small-scale form factor, the complimentary information content from both imaging techniques will be characterised and evaluated. From initial system designs an iterative improvement process with feedback from biomedical researchers will be followed to have multiple cycles of development, design, fabrication and test to create a targeted miniaturised super-resolution system that can significantly help solving problems of antimicrobial resistance build-up.The primary objective is a centimetre scale 3D super-resolution system with active micro-optics for full digital control of the imaging content, with the research also looking at novel resolution and information fusion potentials of the complementary imaging modalities, generating real-time process information for end-users. The outcome of this research project will advance significantly the availability of state-of-the-art biomedical imaging systems in environments on national and international level, specifically for large scale parallel investigations and lower funded labs, as present in many developing countries.