Nanoscale Characterisation of Biological and Bioinspired Materials using Integrated Fluidic Force - High-Resolution Confocal Microscopy

Lead Research Organisation: University of Nottingham
Department Name: Sch of Biosciences


We propose a new imaging platform that combines ultra-fast confocal imaging with the the nano-fluidic functionality delivered by an integrated Fluidic Force microscope (FluidFM-UFCLSM). The proposed capability opens a new phase of exploration of biological systems by enabling characterisation of localised biochemical and physiological processes. The proposed capability provides new avenues for specific applications such as new antimicrobial agents, functional genetics and the development of sustainable crops. The unique design of FluidFM-UFCLSM enables accommodating an array of complex biological samples to perform quantitative and predictive characterisation of biofilms, tissues, whole plants, small animals, insects, mucosal membranes, food systems and tissue scaffold hydrogels. The unique feature of FluidFM-UFCLSM is it will enable study of the smallest units of biological organisation such as proteins as well as larger objects such as cells, tissues and organs. The use of FluidFM-UFCLSM cuts across many disciplines and delivers benefits to a broad range of research topics in the areas of biofilm formation, plant science, tissue engineering, food science and cell physiology. Some examples of FluidFM-UFCLSM applications are:
1) Elucidate anti-microbial resistance and the localised mechanisms underpinning quorum sensing
1) Probe interaction between immune cells with lung epithelium as one of the key pathways of Covid-19 pathogenies
2) Uncover the secrets of plant development and mechanical signalling to develop new resistant crops
3) Probe the effect of nutrition on gut microbiome and associated health outcomes
4) Explore new plant-mimetic materials for designing new food-compatible films for environmentally sustainable food production
The broader areas of impact will be achieved by supporting emerging areas research that targets the major problems and challenges of food security, improved nutrition, animal and human health, combatting antimicrobial resistance, microbiome research, industrial biotechnology, waste valorisation, sustainable agricultural and synthetic biology.

Technical Summary

The proposed capability is enabled by integrating an open architecture Fluidic Force Microscope (FluidFM) with a Confocal Laser Scanning Microscope (CLSM), equipped with an ultra-fast (UF) scanning unit and automated multi-scale (from nano to sub-millimetre) positioning system with a large Z-range. Thus, the proposed capability enables exploration of biological systems using an optically guided fluidic component to enable: a) delivering target chemicals, such as drugs, gene editing enzymes and antibodies to the cell surfaces and tissues; b) utilising FluidFM cantilever as a micropipette to manipulate cells and other particulate objects, such as viral capsids; and c) using FluidFM to perform nanoscale patterning and 3D printing.
Due to a large XYZ range (>100 um for FluidFM and 500 um for CLSM) and 10 mm sample space, the FluidFM-UFCLSM uniquely enables accommodating complex biological systems and challenging samples such as biofilms, whole plants and small animals. These characteristics make the proposed equipment stand out on the global arena.
In addition to ultra-fast scanning, the FluidFM-UFCLSM will also have high-resolution capabilities, and will enable correlative imaging down to < 120 nm resolution, on a single platform.
The proposed equipment will have a motorised micro-positioning stage and automated cross-talking of assimilated software in order to enable high-speed analysis at multiple areas of interest and accelerated testing capabilities. Image analysis of large arrays of image data requires new approaches to data analysis, which will include recently developed techniques in machine learning for the analysis of complex multi-dimensional data. This will allow the routine analysis of high-dimensional data at a speed that can match the data capture, with a minimum requirement on researcher time.
The equipment will be housed in the Containment Level 2 environment to enable accommodating biological samples and Hazard group 2 biological agents.


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Description The new FluidFM-UFCLSM (aka "BioFluidic Microscope") has been fully installed and commissioned. Upon installation, the equipment underwent numerous runs in the test regime and underwent a thorough safety assessment. The laser safety certificate was completed in February 2024, and the Standard Operating Procedures were developed and recorded on file on March 7, 2024. The first training sessions for new users began on March 1, 2024. These sessions attracted more than 15 users across disciplines, with around 55% of users representing areas associated with biomedical research, 25% in the areas of plant, food, and environmental sciences, and 20% representing physical sciences and engineering.

Currently, the use of equipment is planned and budgeted for in the successful grants BB/X014843/1 and BB/T008369/1 (project ref 2886711), as well as two submitted applications for consideration by UKRI councils. The soft launch started at the University of Nottingham and will be followed by regional (East Midlands) and national launches to ensure that the UK community of researchers has the ability to access this equipment. The very first announcement to the public disclosing the capabilities of the Biofluidic Microscope was made at the Food Physics Conference 2024 (January 31 - February 1), which took place at the Institute of Physics Headquarters.
Exploitation Route Academic beneficiaries include areas of biological, biomedical and biomaterial science research. The new instrument will be offering new opportunities for nano-scale characterisation of biological and bioinspired materials, with the level of control that has not been possible to attain before. Industrial partners are attracted by this opportunity. Several projects are currently under consideration by several industry partners, representing major food, pharmaceutical and biotechnology companies.
Sectors Agriculture

Food and Drink


Creative Economy


Pharmaceuticals and Medical Biotechnology

Description Diving Deeper: Unravelling How Plants Regulate Root Growth Angle (New Investigator Award)
Amount £690,039 (GBP)
Funding ID BB/X014843/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 11/2023 
End 05/2027
Title 3D printing platform for developing custom-designed microscopy stages and platforms for Biofluidic Microscopy 
Description Biofluidic Microscopy (BFM) is a highly adaptable technique. However almost all novel applications requires a custom stage to be designed. Whether this stage is needed to contain and trap the sample of offer certain ability for solvent or gas exchange, the success of experiment rests on the ability to develop new and adapt existing platforms for the needs of specific application or experiment. In my lab, we have developed a platform for high resolution 3D resin printing, that enables designing and prototyping new design for the use with BFM. The facility will be open to all users of BFM and will have mechanisms of equitable access to all users. 
Type Of Material Improvements to research infrastructure 
Year Produced 2024 
Provided To Others? Yes  
Impact Development of micro-array platform for microgel entrapment 
Description EPNOE Research Roadmap 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Within the European Polysaccharide Network of excellence, we have developed a Research Roadmap 2040 for the future of polysaccharide research. This targets policymaker and research groups as well as general public. The main objective of this document is to illustrate that polysaccharides are at the central point of the world of tomorrow as a transition to sustainable technologies is crucial for the future of humanity. Proper utilisation of polysaccharide resources has the potential to increase biodiversity, enhance food safety and sustainability, and decrease CO2 emissions and pollution. Three main drivers strongly push the use of polysaccharides: 1) The emergence of a bio economy that increases the contribution of bio-based products; 2) They are polymers with exceptional properties, opening routes for novel applications in all sectors of human activities like materials science, nutrition, health, personal care, and energy; 3) The renewable character of polysaccharides, making them the primary CO2 neutral candidates for the global transformation to a more sustainable world.
The launch event for the EPNOE Research Roadmap 2040 took place on the 31 January 2023 at the Thermotechnisch Instituut, KU Leuven, Belgium and attracted more that 100 participants attending in person and online. Two members of the European Commission attended the event, alongside representatives from the industry. The action points to be taken by the Commission is to implement the RRM2040 into their next stratigic document. The working group for this is currenlty being established.
Year(s) Of Engagement Activity 2022,2023