A brighter future cutting-edge multiphoton imaging at Nottingham

Optical microscopes provide a detailed view into the fundamental processes of life: they let us look at what is happening inside cells, or between different biological networks. Through the development of minimally invasive imaging techniques, we can now do so in intact tissues or even intact whole organisms. The multiphoton microscope is the go-to instrument to be able to achieve such three-dimensional investigations of live tissues. The multiphoton microscope can visualise common fluorescent signals and tissue structures through much longer and less toxic, invisible wavelengths, than would be used on more conventional microscopes. This provides a host of advantages. Firstly, it means that we can observe biological processes with less effect on the system we are studying - this is because molecules present naturally in biological tissues are less likely to be damaged by these longer wavelengths. Secondly, the longer wavelengths used in multiphoton microscopy enable us to look deeper into tissues because longer wavelengths interact less with biological tissues. Thirdly this technique allows us to resolve signals in three-dimensions, including depth, allowing us to differentiate structures that are close to one another, even when one is on top of the other.

These combined abilities, currently not available in Nottingham, open a range of opportunities to investigate important biological processes which are fundamental to the rules of life and health. For example, this multiphoton microscope will enable us to image thick and complex tissues or biological materials that are being developed in Nottingham, in 3D. We will be able to visualise processes occurring in real-time, in the whole animal which is important because many very intricate networks (e.g. nervous system and vascular networks) cannot easily be reproduced in a dish. This platform will also integrate with already existing expertise and workflows in Nottingham, to look at the same samples from many different angles and scales. This enables translational, multimodal research that is not possible anywhere else in the country. With this system, researchers in Nottingham and regional industrial partners, will be able to better understand these complex tissues and systems, and study changes occurring in real-time, with better clarity and minimal effect on the systems being studied.

This multiphoton microscope is an essential tool missing in the research capabilities of academic and industrial networks in Nottingham. It will help attract and retain talented researchers in the Midlands by supporting existing research on the fundamentals of life and health and provide new essential capabilities to the region with yet untapped potential.

The new generation of multiphoton microscopes e.g. by Leica/Olympus/Nikon have excellent sensitivity (via improved detectors), video rate acquisition speeds (8-12kHz resonant scanners) and cost effective multichannel excitation capabilities (through a fixed laser line appended onto a tuneable line) while providing push-button capabilities, like laser alignment and laser power adjustments across tissue depth. This makes these systems powerful and highly user friendly, creating a step-change in the capability of research in Nottingham, both for academic and industrial researchers. Despite significant expertise and need for multiphoton and in vivo microscopy, Nottingham currently has no access to systems that provide deep tissue, video-rate, in vivo enabled microscopy. This Multiphoton Imaging System (MPIS) will therefore fill a large methodological cap in Nottingham, finally enabling investigation in vivo or across thick samples, such as plant tissues or complex three-dimensional tissues and biomaterials.

This system will be located in a multi-use facility in an interdisciplinary research hub (Biodiscovery Institute) which provides access to tissue culture and animal handling infrastructure and expertise, necessary for upstream processing and maintenance of complex, live and in vivo samples. The BDI provides access to many important downstream processes, placing the multiphoton microscope at the centre of complex multiscale correlational workflows, including electron microscopy, spatial RNA sequencing and magnetic resonance techniques.

The user base for this essential tool will be very large and not restricted to the current applicant pool. Its applicability to almost any bioscience research and its user friendliness will broadly enhance many research areas locally and create new capabilities to push the boundaries of current knowledge to understand the rules of life and draw in and retain research talent in Nottingham and the Midlands.