A multi-application microarray robot for agri-food research, industrial biotechnology and on-chip manufacturing

Lead Research Organisation: Newcastle University
Department Name: Sch of Natural & Environmental Sciences

Abstract

We are seeking funding to acquire a microarray robot for bioscience research. These machines are in effect printers that instead of ink, print biological samples in the form of spots on a surface such as a slide or membrane. The power of microarrays and their value to life science research is immense because entire libraries of molecules from complex biological systems can be represented in the form of tens of thousands of spots in an area no bigger than a postage stamp. With these arrayed libraries, we can explore interactions between molecules, test for biological activities, screen for new drugs and discover new enzymes. This technology was first applied to nucleic acids (DNA and RNA), but microarrays are now used for research into proteins, carbohydrates, lipids and small molecules. The technology is especially powerful for deciphering interaction networks between genes and proteins and for large scale screening of antibodies, enzymes and other bio-molecules. Furthermore, the latest generation of microarray robots are also advanced manufacturing devices capable of fabricating sensors and assays and can be used for performing multiplexed (many simultaneously) microscale experiments in-situ within the controlled environment of the machine. The equipment that we are requesting will be custom manufactured with bespoke features that greatly enhance its capacity and versatility, by a globally-leading UK company. By embedding this equipment within a new Biosystems Engineering unit at Newcastle University, we will create a truly world-class microarray technology hub that will accelerate research in food security, bioenergy and industrial biotechnology and health bioscience. By working with locally based but globally active industry partners we will use this equipment to drive translational research towards commercialisation. The equipment will also ensure that a new generation of UK students will have access to state-of-the-art technology, bringing a lasting legacy of research benefits.

Technical Summary

We are applying for the latest generation of microarray robot that represents a step-change in the speed, accuracy and quality of bio-printing. Rather than an off-the-shelf machine, our application is for a customised robot developed to our requirements after consultation with academic and industry partners by the world-leading manufacturer of this equipment, Arrayjet, based in Roslin near Edinburgh. Several bespoke features that support the diverse applications of the user group will greatly enhance the robot's versatility and value for money. The machine will have a unique interchangeable tray system (the component that holds the material onto which arrays are printed), which can accommodate not just slides, but membranes and MALDI plates, held in position by a vacuum. We have also specified the Iris (TM) spot monitoring system consisting of twin cameras mounted on either side of the print head that captures images within 300ms of sample deposition. Images are processed in real time, detecting the presence of missing spots, artefacts, merged or misaligned features. No other microarrayer type has this system and it will provide us with an unprecedented level of quality control. The Jetmosphere (TM) environment control system regulates temperature and humidity with the machine, cooling to 5 oC below ambient, with an operating range of 15-25 oC and enabling in-situ multiplexed experiments under desired conditions. The requested equipment will be used for fundamental and applied applications related to nutrition, agri-diagnostics, enzyme discovery, plant and algal biology, industrial biotechnology and protein chemistry. These diverse projects, which are all linked by the need for high throughput capacity that microarrays provide, include: wholegrain analysis; multiplexed lateral flow assay (LFA) agri-diagnostic devices; enzyme discovery; new tools for microarray data integration; label-free drug discovery; understanding carbohydrate processing by soil microbiomes.

Planned Impact

Our overall impact goal is to create a truly world-leading research hub for microarray-enabled research, globally visible, accessible to a wide range of users and characterised by innovation and creativity using the best equipment in the world. Beneficiaries of this hub in the short, mid and long term include local, national and international academics, industry partners, technicians, and a new generation of young researchers trained in the latest technology. These researchers will benefit from this enabling technology because of the greatly increased analytical capacity it provides: entire libraries of molecules from complex biological can be represented in the form of tens of thousands of spots in high-density arrays. With these arrays, researchers can interrogate interactions between molecules, test for biological activities, and screen for new drugs and discover new enzymes. Also, the machine we are requesting is an advanced manufacturing device capable of fabricating sensors and assays and can be used for performing multiplexed microscale experiments in-situ within controlled environments. In the short term (during the 12 month award period), the equipment will directly benefit an already defined local user group (academics within Newcastle and Northumbria Universities) and industrial partners who have provided detailed descriptions of projects) for projects, which are reliant on microarray technology to make a step change in analytical capacity change or an innovative leap into a new application area (see case for support and letters of support). To ensure that the microarray hub is operational and widely accessible we will train technical staff and be proactive in promoting visibility and the research benefits of the equipment via workshops, seminars, a database and publications. Once the hub is fully operational we will consolidate impact and build legacy of this investment. Training and teaching will be an important impact delivery mechanism and we aim to be the globally leading centre of microarray training excellence. Our two older machines, plus the new one requested will provide us with an unrivalled capacity for providing hands on experience for students and experienced researchers. Exposure to microarrays will be at both undergraduate and post graduate levels and by training a new generation of young scientists, we will secure a lasting legacy in microarray technology. Training at the PhD level will be delivered via our participation in the Liverpool-Durham-Newcastle BBSRC DTP and membership of the Institute for Agri-Food Research and Innovation (an existing cohort of 22 PhD students, growing to 34 by 2021). Longer term impact can only be delivered by extending funding and the new equipment will provide us with a significant new offering to academic and industry led projects via UKRI, EU and private foundation calls. For example, an application based largely on microarray work ('3DGLYCO' - advanced sustainable cleaning solutions) and led by P&G is already under advanced planning for submission as an Innovate UK proposal in 2019. Based on his track record in delivering impact from microarray work, Prof Willats has been invited as a partner on the Horizon 2020 application 'Discovery and characterization of FUcan active eNzymes' (Led by Dr Mirjam Czjzek, Station Biologique de Roscoff, submission 2019) and the Industrial Strategy Challenge Fund proposal ('MinChem', Transforming Food Production, led by Prof. Neil Boonham, Newcastle University, submission 2019). We recently obtained an award of £30,000 from the Northern Accelerator for commercialisation of microarray-based agri-diagnostic sensors via a spin-out ('AgriInnovations'). A development consultancy firm experienced in bridging technologies to global markets has been hired to do this (IVO Associates, Dr Dennis Camilleri).

Publications

10 25 50

publication icon
Mikkelsen MD (2021) Ancient origin of fucosylated xyloglucan in charophycean green algae. in Communications biology

publication icon
Vidal-Melgosa S (2021) Diatom fucan polysaccharide precipitates carbon during algal blooms. in Nature communications

 
Description This award resulted in the acquisition of a state of the art robot that has been used for a number of different bio-science projects with diverse industry and academic partners. The robot allows us to print biological samples at very high spatial densities onto a surface like a membrane or specialized slide. These biological 'microarrays' contain vast amounts of information that can be extracted using molecular probes (for example, antibodies) that bind to specific molecules within each spot of each array. This basic principle can be used in a number of different ways. We have used the equipment for example, to map the degradation of polysaccharides by microbes, screen for new industrial enzymes, discover new molecule probes and gain new insight into the plant root glycobiology.
Exploitation Route These outcomes are already being used to progress the discovery of new enzymes and for diverse glycoprofiling endevours
Sectors Agriculture, Food and Drink,Environment,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description The equipment award has been crucial to a collaboration with an industrial partner, enabling my group to perform research that otherwise would have not been possible. An output leading from this collaborative industrial research was the commercialisation of a new enzyme in cleaning products, now commercialised in several international countries.
First Year Of Impact 2020
Sector Manufacturing, including Industrial Biotechology
Impact Types Economic

 
Description Procter and Gamble
Amount £30,000 (GBP)
Organisation Procter & Gamble 
Sector Private
Country United States
Start 09/2020 
End 10/2023
 
Description Use of microarrays to decipher polysaccharide deconstruction by gut microbiota 
Organisation Norwegian University of Life Sciences (NMBU)
Country Norway 
Sector Academic/University 
PI Contribution We used the microarray robot funded by the 18alert award to undertake glycoprofiling of gut digestate samples
Collaborator Contribution The partners provided the samples used for analysis sand also developed the publication reporting the work
Impact Microbiota-directed fibre activates both targeted and secondary metabolic shifts in the distal gut Leszek Michalak 1, John Christian Gaby 2, Leidy Lagos 3, Sabina Leanti La Rosa 1, Torgeir R Hvidsten 1, Catherine Tétard-Jones 4, William G T Willats 4, Nicolas Terrapon 5 6, Vincent Lombard 5 6, Bernard Henrissat 5 6 7, Johannes Dröge 8, Magnus Øverlie Arntzen 1, Live Heldal Hagen 1, Margareth Øverland 3, Phillip B Pope 9 10, Bjørge Westereng 11 Affiliations expand PMID: 33188211 PMCID: PMC7666174 DOI: 10.1038/s41467-020-19585-0
Start Year 2018