Public Funding for LGC Limited

SRUC provides commercial services to growers of agricultural and horticultural crops through two Crop Clinics via its associate company, SAC Commercial Ltd. This project aims to identify a protocol for the efficient and accurate extraction of the DNA of important crop pathogens and pests from soil samples. By knowing what species of pathogen and/or pest are present in soil, growers can assess the risk of crop damage, and plan more effectively for the deployment of pesticides, choice of resistant varieties for the current crop and in crops to be grown in subsequent years. Currently, protocols for the extraction of DNA from soil is often pathogen/pest specific, so for a grower to know what pathogens or pests may be present relies on multiple soil samples for each pathogen/pest, and different protocols to be used for each one. This is time consuming in terms of the collection of multiple soil samples, the laboratory processing, and ultimately an expensive process for the grower. By streamlining the process through identifying a single reliable protocol that is effective across a range of soil types, and assessing areas of the protocol that may be suitable for automation, the cost of these diagnostic tools to the grower will become more attractive, particularly when multiple pathogens/pests are being identified across a range of different crops. With over 50 soil-borne pathogens and pests of agricultural and horticultural crops in the UK, a means to cost-effectively identify them from soil samples would be a significant benefit to sustainable crop production.

"For many years it has been recognised that there are bacterial infections that persist and are refractory to treatment with antiseptics and antibiotics. Antibiotic resistance is currently recognised as one of the highest threats to human health. The inability, thus far, to discover new antibiotics to offset the speed at which microorganisms acquire resistance implies that novel strategies must be developed to combat infectious disease. Neem Biotech is responding to the this global health crisis through the development of first-in-class synthetic antimicrobial molecules to be used as adjunctive agents in potentiating antibiotic efficacy. This strategy of antibiotic sparing drives lower doses and shorter treatment interventions towards the reduced opportunities for the acquisition of resistance. Neem Biotech has extensive experience in producing garlic-derived compounds, known for their antimicrobial activities. Our leading expertise in sulphur chemistry has allowed us to synthesise a library of synthetic derivatives of ajoene, a garlic-derived molecule with established antimicrobial activities and identify a number of analogues with high antimicrobial activities. Furthermore, these molecules synergise with antibiotics and antiseptics in microbial cell killing. This results in the more rapid and efficacious resolution of infection, reducing its spread and dissemination to other anatomical locations. We are now ready to progress our selected drug candidate into preclinical development, but have encountered an analytical challenge, namely, the inability to detect and quantify our molecule in biological samples such as blood and plasma. This poses extraordinary barriers in taking this promising compound further into the clinic, since we are unable to undertake the required regulatory pharmacological, phamacokinetic and toxicology safety studies. Neem has made several attempts to resolve this analytical problem _in-house_ using LC-MS and has outsourced two CRO's to develop and validate detection methods for our compound, both of which were unsuccessful and costly. LGC is the designated institute for Chemical and Bio-Analytical measurement in the UK, working across several sectors. Led by Chris Hopley, an expert in analytical chemistry and Principal Scientist Mass Spectrometry, the group at LGC has a number of instrument platforms and technologies to develop methods for novel target compounds in biological matrices. Importantly, once developed, this method can be easily transferred to a commercial service towards the successful preclinical studies of our selected and all future organosulphur compound assets developed at Neem Biotech."

Camira Fabrics produces textiles for use in the contract, healthcare and transport upholstery markets. To add functionality to the fabrics a range of finishes are applied to improve the technical performance of the fabrics. This project evaluates the use of the technique of multispectral imaging (MSI) to evaluate the level of chemical residue present following textile finishing. The suitability of the technology for textile inspection will be evaluated taking into account different textile substrates and dyes. The ultimate aim of this project is to build a fit-for-purpose model that can be used by Camira Fabrics to monitor the quality of the textile finishing process.

Sistemic Ltd is a company whose primary business is focused on providing innovative microRNA-based tools for areas of unmet need within cell therapy research, development and manufacturing markets. Cell therapies are seen as the future of treatment and are expected to have great potential, revolutionising medical care capabilities in a range of chronic diseases, such as diabetes and myocardial infarction. A rapidly emerging field of cell therapy is to stimulate pluripotent stem cells (PSCs) to differentiate into the required therapeutic cell types. However, after infusion into a patient, residual contaminating PSCs in the final cell therapy product have the potential to form tumours, which is a safety issue. Regulatory bodies require cell therapy manufacturers to be able to assess the level of contaminating PSCs in derived cell therapy products. In conjunction with the National Measurement Laboratory at LGC (NML), we have a successful safety assay product -- SistemPSCCheck 1.0 - which was developed and validated to address this regulatory requirement for late differentiation stage PSC-derived cell therapies. However, in this developing field of medicine, due to their superior inherent biological properties, early differentiation stage PSC-derived products (progenitor cells - which share both stem cell and differentiated cell attributes) are now the derived cell type of choice to develop cell therapies. We have identified a specificity measurement problem with our assay in its current format that precludes its use with this derived cell type. By leveraging the key expertise and technologies available at the NML, Sistemic will work with the NML to further develop and optimise our current assay to a SistemPSCCheck 2.0 assay which is suitable for detecting residual contaminating PSCs in derived progenitor cell therapies. The outcome of this project will facilitate the safe clinical progress of PSC-derived progenitor cell therapy products to bring them to a clinical product more quickly. This will in turn result in patients getting quicker access to these novel therapies during clinical trial development phases, and ultimately, to a successfully launched clinical product and therefore improvements in quality of life.

Elemental Scientific Instruments, Ltd. is a UK company that supplies sample introduction and automation equipment for elemental analysis (e.g. ICP optical emission spectrometry, ICP-OES or ICP-MS). In recent years the development of state-of-the-art instruments to solve problems for the chemical industry has become the main focus. Most recently, we introduced the prepFAST IC instrument that utilises normal ICP-MS autosampler capabilities with the ability to prepare samples inline (autodilution or autocalibration) and combined it with liquid chromatography (LC). This combined system can take the place of two sample introduction systems within a given laboratory, providing a more efficient and cleaner setup than what is currently available on the market. In addition, this is the first truly metal free LC system available, thus allowing for ultra-trace level analysis of metals (e.g. Cr), and the only LC system that can perform inline sample dilutions. The prepFAST IC can be setup for one single analysis that can do both total metals analysis (e.g. lead, cadmium, mercury and arsenic) and elemental speciation (e.g. arsenic species - arsenobetaine (AsB), arsenite (As III), Dimethylarsinic acid (DMA), Arsenocholine (AsC), Monomethylarsonic acid (MMA), and arsenate (As V)). This is a powerful time saving advantage that will help laboratories in the UK operate more efficiently and with a cleaner sample introduction system thus providing better quality results.

RADWIPES is the brand name of a cleaning product developed by MDCO Ltd. RADWIPES have been developed specifically for radiation decontamination activities associated with the decommissioning cleanup operations of legacy buildings on UK nuclear licensed sites, many of which, fall under the umbrella of the N.D.A. - Nuclear Decommissioning Authority. The initial product was developed in collaboration with Sellafield Sites Limited, in order to assist with their efforts to reduce operator exposure to ionising radiation, reduce the amount of clean up waste for processing, whist also reducing the expense of processing this generated radioactive waste. This of course, is a major cost burden for both the nuclear sites and the British tax payer. The purpose of this project is to analyse and test new innovations of this product in terms of new formulations of the base fluid, new innovative microfibre fabrics and also, new recyclable packaging. This innovative new packaging is being developed to enhance safety on site and have elements of its composition reclaimed under recycling conditions. These products are used in highly sensitive, radioactive conditions and therefore, in order to analyse and test these new materials and formulations correctly, the project will have to simulate the radioactive conditions similar to those found on nuclear sites. These conditions will replicate varying degrees of radioactive contamination on a wide variety of surfaces found on nuclear sites i.e. stainless steel, ferrous metals, plastic, concrete, rubber, wood, brickwork amongst other materials found on site. The data produced will be invaluable in determining new material and product development for the nuclear industry. The second part of the project will focus on the analysis of the composition of these new materials to ensure they contain no elements which would cause any issues with the material waste/effluent routes on site. MDCO Ltd will then have the necessary data to further develop new formulations of the base fluid used in the wipes and also, in line with the company Sustainability and Environmental Policies, look to use raw materials and fabrics which are recyclable/biodegradable. This project will give MDCO the scientific and metrological analysis required to develop their 'Next Generation' of RADWIPES which will enable them to promote and supply these products into all UK licensed nuclear sites. Apart from the savings to the British tax payer, reducing the volume of nuclear waste for processing is a huge benefit to our environment.

Formaldehyde is a significant health risk, and International Agency for Research on Cancer (IARC) classifies formaldehyde as a human carcinogen. There are stringent formaldehyde exposure guidelines that exist for indoor air (80 ppb WHO) that can be even lower at the national level (e.g., France 8 ppb by 2023). People are exposed to formaldehyde from a variety of sources inside their homes. These include many everyday products, such as cosmetics, furniture, and detergents. With the growing health threat that formaldehyde poses, it is becoming more critical to monitor homes and other indoor spaces so that inhabitants can take action to minimise their exposure. Formaldehyde is usually measured by on-site batch sampling and off-site quantification in an external analytical laboratory. These procedures are expensive, time-consuming, require skilled personnel and do not allow on-site monitoring. Formaldehyde measurement in ambient air requires ppb-level detection sensitivity from a monitor. Furthermore, when used in indoor air monitoring, they must be selective to detect ppb-level formaldehyde concentrations in ambient air containing hundreds of compounds. Current products on the market require consumers to sacrifice sensitivity and selectivity for cost; low-cost sensors do not meet the goal of a low detection limit of 20ppb or give false positives to common chemicals such as ethanol. Applied Nanodetectors indoor air quality monitoring system (AND-IAQ01), can detect formaldehyde at ppb levels. It also measures key indoor pollutants, including carbon dioxide, particulate matter (PM2.5), and total volatile organic compounds (TVOC). This device complies with the essential requirements of all relevant harmonised and designated standards required for The UKCA (UK Conformity Assessed) marking. The product is commercially available via key specialist suppliers. The London Government Chemist (LGC) will evaluate our system performance by exposing the device to synthetic air/formaldehyde mixtures (down to 20 ppb) and evaluate the effect of confounding gases.

Circulating tumour DNA (ctDNA) sequencing of plasma samples is becoming commonplace in clinical oncology practice and holds the promise to revolutionise cancer disease diagnosis and management. This promise is impeded by poor standardisation of ctDNA sequencing workflows, particularly in the pre-analytical phase. Limited control materials are currently available and published approaches often apply synthetic oligonucleotides. However, ctDNA does not circulate as free nucleic acid but predominantly as nucleosomes (DNA-histone protein complexes). Volition is the world leader in the production of recombinant-nucleosomes. These are single nucleoprotein complexes designed with the same structure in which mutated ctDNA circulates in the blood of cancer patients. These materials have the potential to fulfil the requirements of the International Liquid Biopsy Standardization Alliance for reference materials to control, monitor and standardise liquid biopsy end-to-end process from pre-analytic cell-free DNA (cfDNA) extraction through technology/assay validation and for QC of clinical sample collection and analysis. The proposed project will involve the characterisation of recombinant-nucleosome materials in terms of quantity, purity, aggregation, integrity and stability as well as their commutability with respect to native patient nucleosomes.

This project will focus on developing a critical quality control (QC) method that will allow manufacturers to test and ensure the quality of an immune therapy (called BioThymus). The BioThymus therapy is designed to treat a life-threatening disease in infants. Children born without a thymus gland (called complete DiGeorge Syndrome or cDGS) have a poorly functioning immune system, and without treatment may die within 3 years. The research that lead to the BioThymus was invented in the UK at University College London and the Francis Crick Institute, and is now being developed by Videregen to treat children with cDGS and in the future it could be used to treat autoimmune diseases. The BioThymus combines mixed cell populations (from stem cells) within a scaffold made from thymus tissue. This provides a copy of a thymus gland structure, which is capable of regenerating the cells of the immune system. Videregen (project lead), will focus on developing the industrial manufacture process compliant with UK and International regulations and standards. The BioThymus's unique cellular aspects are key to its safety and efficacy, but because of the uniqueness of the therapy there are no off-the-shelf methods or kits to measure and quantify the cells used. A standardised, robust and accurate QC test method is required to ensure final product quality, safety and efficacy control. Videregen will collaborate in the project with the cell metrology lab of the National Measurement Laboratory (NML). NML have the necessary expertise and facilities to help address the cell measurement problem, by understanding how the multiple cell properties/attributes in the BioThymus can be harnessed and streamlined into a reproducible QC method that Videregen can incorporate into their manufacture process. BioThymus manufacture for preclinical studies and transition to clinical trials cannot be achieved without reliable QC methods that quantify and identify the cells in the product, which links to product effectiveness. QC methods to define BioThymus's cellular aspects is a critical activity/milestone for therapy development. * Method will be used as a QC measure and final release test. * Method will allow further research to understand relationships between thymic cell phenotype and their function to educate T-cells in-vivo, allowing manufacturing optimisation and therapy effectiveness. * Method will provide regulatory bodies, clinicians and investors a high degree of confidence to adopt or invest in the technology.

Neurodegenerative disorders (NDDs) affect over nine million Europeans and constitute a large economic burden to society. NDD biomarkers have transformed the research landscape by linking diseases to pathological processes and assisting drug development. NDD biomarkers improve the accuracy of diagnosis and prognosis with the use of non invasive tools. However, their implementation in clinical practice is hampered by a lack of standardisation. This project will build on previous EMPIR projects to standardise biomarker measurements, harmonise measurements across assay manufacturers, establish quality assessment programmes, develop and implement new biomarkers.

Cancer is a major burden on European society. Advances in genomics, driven by technologies such as Next Generation Sequencing (NGS), are transforming cancer care, enabling earlier and more accurate diagnosis, guiding therapy selection and driving development of targeted therapies (precision medicine). This improves patient outcomes and health system effectiveness. However, quality and comparability of genomic profiling currently varies significantly and development of standards and metrological means to support the field are in their infancy. This project aims to address this need by applying metrological principles to develop reference measurement systems (RMS) to support cancer genomic diagnostics in compliance with the In-vitro Diagnostic Device Regulation (IVDR EU 2017/746).

Heart failure is when the heart cannot efficiently pump blood around the body due to damage to the heart muscle. As a result, important organs (such as the brain and lungs) do not get enough blood and patients suffer from tiredness and breathlessness and are unable to exercise. As the heart failure progresses, patients experience an ever-decreasing quality of life and an increased dependence on hospital services. The number of heart failure patients continues to increase and, despite new treatments, many remain symptomatic as current treatments do not repair the heart muscle (thereby enabling it to pump blood efficiently again). For these patients, the only way to alleviate these symptoms is a very rare, and highly invasive, heart transplant. The applicants originate from the world-renowned Barts Heart Centre, where this team has developed and tested a cell therapy which uses stem cells taken from the patient's own bone marrow. Once processed, these cells are infused into the heart to help repair the heart muscle (thereby enabling it to pump blood more effectively) and improve the patient's symptoms. A charity, the Heart Cells Foundation, was formed to promote the adoption of cell therapy for heart failure. This charity raises hundreds of thousands of pounds annually, and has created a Compassionate Treatment Unit. The team has treated over 500 heart failure patients, who were told they had no more treatment options, with their own stem cells. The Heart Cells Foundation wishes to commercialise this treatment so it is more widely available nationally and internationally. To lead this commercial step, they formed the Heart Cells Company (HCC). HCC needs approval from regulatory agencies in order to secure the investment needed for a large trial (which could lead to market authorisation - required before the NHS will adopt the treatment). However, regulatory agencies are unwilling to grant HCC approval until it has a more definitive measurement to assess the quality of the cell product. HCC is seeking support from the Analysis for Innovators (A4I) competition to develop this measurement technique (commonly called an assay) to assess the cell product's efficiency and quality. This assay will also enable HCC to improve and research the treatment method to make it more effective in the future. This A4I project will develop this efficiency and quality assay by analysing samples of bone marrow taken from heart failure patients participating in ongoing clinical trials at Barts Heart Centre.

Europe is facing significant healthcare challenges driven by an ageing population coupled with an increase in chronic diseases like cancer, diabetes, heart disease, and brain conditions. These conditions require diverse and complex treatments, which increase healthcare costs. Nanomedicine and nano-enabled medical devices therapeutics (defined here as nanotherapeutics) are vital for tackling health and societal challenges, providing versatile technical solutions. This project responds to the immediate metrological needs expressed by industry, regulatory agencies and policymakers to develop and validate traceable measurement methods and candidate reference materials (CRMs) for the assessment of the critical quality attributes (CQAs) of nanotherapeutics. The project will focus on clinical formulations, including synthetic lipid-based nanotherapeutics, including lipid nanoparticles (LNPs) for the RNA delivery and liposomes, and metal oxide nanoparticles (MONPs) used for localised cancer treatment, gene therapy, vaccines (COVID-19) or as contrast agents. By providing fit for purpose methodologies, standardised methods and CRMs to regulators and industrial stakeholders, the project will support their clinical translation, providing more efficacious nanotherapeutics with fewer side effects to improve the patient’s quality of life and enhancing the competitiveness of the European health technology industry.

Resistance to antibiotics is one of the most concerning challenges society currently faces. It is on a par with climate change and accumulation of plastic in the ocean. It is a reflection on the importance of this challenge that many new technologies are being developed to help doctors select the correct antibiotic for a given infection. The misdirected use of antibiotics is one of the drivers of antibiotic resistance, inappropriate prescriptions increase the number of drug resistant infections and accelerate the process of reaching the point where current medicines no longer work. Microplate Dx is a company attempting to address this issue through an innovative technological solution which effectively shrinks traditional microbial culture on large agar plates down on to a microchip style technology and allows the resistance pattern of bacteria causing the infection to be determined. This allows clinicians to make informed decisions about which drug to prescribe in under one hour. Technologies like this will have a big role to play in improving 'antibiotic stewardship' and preserving the stocks of medicine we currently have. To take the Microplate Dx prototype from concept to reality it is necessary to address several measurement issues around the product itself so that its manufacturability and scalability can be properly demonstrated. Showing that the gel deposits, which go onto the chip can be deposited with high consistency is crucial to demonstrating manufacturability and also, being able to show that the various chemicals added to the gel which make the test work are evenly distributed throughout is a key performance factor which needs to be verified. In this project, Microplate Dx will work with the National Measurement Laboratory who through access to their biological printer and surface characterisation instrumentation will assist with these two challenges. Achieving these goals will help the company with moving its technological development forward and sourcing future investments and revenue.

Quantum Science Ltd (QS) is an award-winning British materials innovation company that focuses on developing, manufacturing, and supplying quantum dots (QDs), nanomaterials and technologies for infrared imaging and sensing markets. QS has developed a proprietary INFIQ(R) technology to manufacture colloidal quantum dot (CQD) materials as greatest potential platforms for next-generation defence, surveillance, machine vision, medical, automotive, consumer electronics, spectroscopy, and infrared imaging applications. QS INFIQ(R) CQD materials have advantages of tuneable optoelectronic properties across a broad spectral bandwidth, solution processability, substrate compatibility and high scalability at low cost. QS is supplying its INFIQ(R) CQD materials to customers who use them for short-wave infrared (SWIR) photodetectors. To provide our customers with the best materials offering the greatest device performance, it is necessary to have a detailed understanding of the effect of organic ligands utilised in the CQD synthesis and residual impurities from ligand exchange process on downstream processes such as ink formulation and device fabrication. Such insights can be obtained via development of direct measurement and characterisation techniques for the CQDs and ink formulations. QS does not have in-house expertise and facilities to solve these measurement problems and propose to collaborate with the scientists from the National Measurement Laboratory (NML) at LGC group who have cutting-edge facilities and specialised expertise. This project aims to develop reliable techniques and direct measurement systems to quantify ligand composition, impurities, and their interaction with of INFIQ(R) CQD. These will provide feedback on the efficiency of ligand exchange processes and ink formulations, and establish tools for material quality control. Overcoming such measurement challenges will improve QS' product competitiveness, advance customers' device performance, increase sales, gain more market share, and open new markets.

Advanced Biophysical Characterisation (ABCs) of LNPs is a collaborative project between Nanovation UK, STFC and NML to characterise lipid nanomedicines to create a cost-effective and accessible treatment for liver disease. Currently, the only curative treatment for liver disease is transplantation. Reducing the number of patients progressing to end-stage liver cirrhosis and liver cancer will have a significant impact for patients. The use of lipid nanoparticles (LNPs) as delivery vehicle of the mRNA vaccines against Covid-19, has emphatically shown these systems a) are safe and effective in humans, b) can be developed at unprecedented speed, c) can be manufactured at scale and d) can be produced at low cost (approx. £15 a dose). LNP-mRNA based therapies have been proven to reverse liver fibrosis but, due to inefficient LNP-mRNA delivery to the liver, required repeated, high dosing which resulting in significant and adverse toxicity. Therefore improved LNP delivery systems are required. A major outstanding challenge in advancing LNP technologies is a lack of understanding of how LNP structure impacts their performance as nanomedicines. This means most discovery programs rely on primarily empirical screening of large libraries of LNPs. At Nanovation, we have a library of novel lipids and LNP compositions and a basic design, make and test cycle for LNP optimisation. Subsets of our LNPs fulfil our assessment quality criteria but do not perform as expected. We suspect this is due to the influence of particle structure but have a limited ability to quantify this. Generating scientific understanding of the structural similarities / differences between the structure of our highest performing LNPs and low performing LNPs is key to developing ways to maximise the performance of our LNP products. This project will address these challenges.

no public description

no public description

no public description

Advanced Furnace Technology has been providing high quality graphite purification to the semiconductor industry for many years. Our service removes trace metals and dopants from graphite parts for use in high purity processes. Through the capabilities of the National Measurement Laboratory, this project will provide analytical data for our purification service to demonstrate the high levels of purity that we achieve for our clients. The ability to evidence our high quality purification process will be of great value to our business. The data achieved through this project will allow us to attract new business and enable us to build scale up equipment and expand in the market.

With the development of new DNA-based therapies and technologies the demand for nucleic acid products continues to increase. The requirement for large quantities of high-quality DNA and the need to produce more difficult sequences for advanced therapeutics have brought the production of DNA to its limits. Current methods of DNA manufacture rely on bacterial fermentation which suffers from both manufacturing capacity issues and low sequence stability during bacterial growth. Touchlight's synthetic biology DNA production process overcomes the current limitation of bacterial fermentation using enzymatic means of production. This _in vitro_ DNA technology is able to produce large-scale, high-quality constructs using a DNA polymerase to amplify DNA templates and a protelomerase to cleave and ligate amplified DNA into minimal cassettes for use in therapeutics and synthetic biology applications. Continuous developments in the process have resulted in both increased capacity and reduced footprint for DNA manufacture alleviating some of the current bottlenecks associated with nucleic acid production Although large advances in this process have been made in DNA manufacturing a greater understanding of how DNA behaves in a cellular context will allow the production of improved DNA products and platform. Touchlight has developed new DNA constructs with improved cellular and nuclear targeting abilities resulting in increased protein expression however the limited knowledge and ability to monitor DNA within a cell makes further optimisation challenging. A more detailed understanding of the DNA subcellular localisation is therefore essential for the continuing improvement of Touchlight's core constructs. The knowledge generated from this project will increase Touchlight's ability to satisfy DNA demand and will contribute directly to improving human health. Translated improvements in nuclear entry efficiency for Touchlight's leading _in vitro_ DNA manufacturing process will help meet the increasing demand of DNA constructs from Industrial partners and decrease the costs of DNA therapeutics.

Humanity faces three enormous challenges: feeding 9.8 billion people by 2050, mitigating climate change and eliminating the existential threat of diseases including zoonotic pandemics. BiologIC is developing the world's first biocomputer. BiologIC's ambition is to build a world leading UK biocomputing industry to unleash the full potential of synthetic biology. BiologIC's technology aims to revolutionise bioprocessing in the way the integrated circuit revolutionised information processing. The outcome would be a paradigm shift in the detection and mitigation of diseases, the production of foods, the development of new biofuels and biomaterials and DNA data processing. BiologIC's breakthrough digital hardware architectures use multi-material 3D-printing to fabricate fluidics, electronics, thermals, optics and pneumatic circuits into integrated bioprocessors. These bioprocessors are assembled within biocomputing devices that increase the processing power of synthetic biology. The devices also incorporate a dense network of biosensors, such as pH and dissolved oxygen, generating rich data to drive adaptive workflows. Products are being developed to advance applications in research, diagnostics, therapies such as new vaccines, cultured meat and biofuels and are designed to power the next generation of synthetic biology at scale. The scope of work is to couple the performance of the bioprocesses with appropriate analytes and metrics to help monitor the quality of the biologic produced or detected under defined operating conditions. Establishing relations between the process and product would require bespoke, non-trivial analysis, possibly using different and complementary measurements. The analysis will investigate and validate the feasibility of BiologIC's architectures and support development of high-throughput bioprocessing systems. In the longer term, this work is expected to underpin a scheme for continuous monitoring of product quality, leading to next generations of our 3D-printed devices.

Lipid nanoparticles and liposomes offer a revolutionary method of delivering previously infeasible therapeutics in a controlled manner for more effective treatment. These nanomaterials allow for increased penetration into target tissues, altered bioavailability, and have potential for improved targeting within the body. Exploiting these characteristics offers huge promise in terms of improved patient outcomes while minimising harsh side-effects. Currently it is difficult to rapidly measure drug-load distribution and drug-release profiles of nanomedicines without using proxies and extrapolations. As a consequence, the nanomedicine field suffers from poor reproducibility and reliability at the drug-screening level. Understanding of these parameters is required by researchers, manufacturers and regulators to optimise the dosing and performance of these highly-targeted nanotherapeutics. We have recently launched an instrument that can accurately measure real-time drug-load distribution and release profiles of drug-loaded nanoparticles, including liposomes and lipid-nanoparticles (LNPs). Our multiparameter sensors provide a novel and high-precision method for rapid characterisation of nanotherapeutics based on their unique optical signatures, measuring both size and refractive index simultaneously and independently on a particle-by-particle basis. Oxford HighQ's instrument is capable of measuring multiple critical attributes of nanoformulations, including: * Drug mass per nanoparticle (as a function of size) * Real-time drug-release profiles * Shell/coating thickness and density * Refractive index * Size and polydispersity This project will provide reference datasets for lipid-based nanoparticle formulations used in healthcare. The key objectives of this project are to provide orthogonal measurements of the physicochemical properties of therapeutic nanoparticles in order to demonstrate the performance parameters of Oxford HighQ's instruments, such as its resolution and limit of detection, and to provide a range of reference points for nanoparticle characterisation supporting the use of the instruments in the QA/QC testing of advanced therapies.

One of the most widely taken medications are Proton Pump Inhibitors(PPI) for the reduction of stomach acid. At present only solid forms or very limited stability suspensions are available. These suspensions often block feeding tubes in hospitalised patients with these tubes having to be replaced at considerable cost and discomfort for the patient. The development of a liquid alternative is therefore a major step forward and would have considered benefit to both health care providers and ultimately to the patient. The major issue with PPI's is that they are notoriously unstable and will rapidly degrade when exposed to a wide range of external influences such as heat, oxygen, light and acid environments. As it is an orally ingested medication the problem of acid degradation in the stomach has previously been overcome by placing them in a 'gastro-protective' coating that allows the PPI to pass through the stomach and be absorbed in the less acidic lower gut. This causes other issues such as speed of absorption. The aim of this project is to improve on the stability work already carried out by the company using their unique solubilisation platform. It is important to look at the products to define the presence of precipitates or crystal formation and what size they may be to determine their effect on stability and to understand the possibility of using filtering techniques to remove them. Once this has been completed we will be able to look at other factors effecting overall stability and improve the shelf-life of the products while being assured that we have a 'pure liquid' that will not stick to or block tubes and so improve the life of patients and healthcare workers.

The project combines Sixfold's Programmable Oligonucleotide Delivery System (PODS) with the unique and deep expertise of LGC in quantitative bio-measurement of proteins, and NPL in analysis and measurement of physicochemical and biofunctional properties of nanomaterials, including advanced imaging. PODS have demonstrated a highly promising safety profile for delivery of Cell&Gene therapeutics such as short-interfering RNA (siRNA) for gene-silencing. The aim now is to optimise siRNA-PODS's efficacy by incorporating a protein corona (PC) manipulation module. To that end, the project employs an iterative technical approach, takes advantage of the interdisciplinary expertise of the consortium and leverages LGC's/NPL's unique facilities, equipment and know-how. This allows for optimisation of PODS that can be seamlessly integrated into the development of Advanced Therapy Medicinal Products (ATMPs), enabling PODS to quickly progress through preclinical development, and expediting commercialisation.Given their high specificity/selectivity for gene-silencing, siRNAs have the potential to provide effective treatment options for a variety of genetically-driven diseases including cancer. The first ever regulatory approval of Alnylam's siRNA therapy in 2018 \[1\] has validated the clinical and commercial opportunity for such therapies. The major limiting factor for their further clinical and commercial success is the lack of safe and effective systems for systemic delivery of siRNAs to specific diseased cells. This is recognised by academia and industry \[2\]. Current approaches (primarily viral- and lipid-based) are sub-optimal given their limited specificity, toxicity, and complex/expensive manufacturing \[2\], limiting the type and number of addressable disease indications.PODS can address the drug delivery challenge given their unique, biocompatible design based on a central nanoscaffold, which can be functionalised with multiple therapeutics and highly-specific targeting molecules that recognise biomarkers on cancer-but not healthy-cells.Preclinical data indicates a highly competitive safety profile of siRNA-PODS cancer therapy. However, the gene-silencing efficacy remains to be optimised. siRNA-PODS' efficacy is limited by recruitment of PC onto PODS upon intravenous administration. The PC can dramatically influence the physical properties, pharmacokinetics and pharmacodynamics of nanoparticles \[3\].By utilising LGC's/NPL's expertise, the project enables the necessary advanced (i) proteomic, (ii) morphological and (iii) functional profiling of PC-bound-PODS, allowing for incorporation of optimised PC manipulation module(s) for enhanced therapeutic efficacy. This would accelerate the completion of preclinical development, unlocking Sixfold's ability to generate first revenue from licensing agreements and expediting clinical development not only for our primary indication but also for other diseases, contributing to the competitiveness of the UK's ATMP sector.\[1\]Alnylam\_Press Release\_30.08.18.\[2\]Karim\_ME\_et\_al.\_Pharmaceutic\_2018.\[3\]Nguyen\_VH\_&\_Lee\_BJ\_Int\_J\_Nanomedicine\_2017\.

"Puraffinity is a technology company developing novel materials for water treatment. Our leading product is made by attaching ""molecular receptors"" to solid granules. Molecular receptors are molecules that bind specifically to other target molecules. These granules that have the receptors attached can then be packed into tanks and used to capture the target molecules from a water stream by flowing the water through the tank, like a big Brita (tm) filter. Our leading product captures of compounds called ""PFAS"" which are difficult to remove with current filters and are toxic to humans and the environment. One of the compounds used to make the molecular receptor is complex and variable. It has been hugely challenging to accurately characterize or quantify. To solve this challenge, we have partnered with The National Measurement Laboratory (NML) at LGC, leaders in chemical measurement science. This project will focus on developing two analysis methods for this compound. A highly accurate and detailed method utilizing state of the art equipment at LGC and a second, a rapid detection method to quickly test for the reagent in any lab. These new measurement methods will allow the production process and product quality of the final water treatment material to be improved. This will make the final water treatment product more cost effective and help achieve the necessary certifications it requires to be deployed in a range of water applications."

"AQR has identified a clear market opportunity for a viable, sustainable and reliable drinking water treatment process at small community and single household scale. Currently, the UK water industry heavily subsidises treatment in rural, smaller communities since the cost of providing effective treatment makes it unaffordable for these customers. The AQR Safe Water(r) process provides effective disinfection in raw surface waters that can be particularly challenging due to a high organic, coloured content. Additional pre-treatment is necessary for current disinfection processes to operate effectively. UV disinfection can only operate in clear water, has significant power requirements and requires regular replacement of bulbs. Chlorine disinfection has been trialled at small-scale but failed due to the dosage requirements causing ineffective disinfection by over- or under-dosing. This project is concerned with understanding the interaction between the AQR Safe Water(r) disinfection process and organic content in raw surface water, to confirm the treated water is safe for human consumption. Current regulation is based on UV and chlorine disinfection that requires UV Transmittance (UVT) to reach 100 % and organic content to be reduced to zero, so that UV disinfection can operate effectively and chlorine does not produce potentially carcinogenic byproducts. However, water is visibly clear above 60 % UVT and if not using chlorine, there is no risk of producing harmful byproducts. The outputs from this project will help inform regulation and expedite AQR's market entry and retain AQR's significant competitive advantage. Supply of safe drinking water is taken for granted by developed nations, but is becoming under threat from ageing infrastructure, an increasing global population and climate change. Water security is a global challenge, alongside strict global sustainability and resource-efficiency targets to be achieved by 2030 \[source: UN Sustainable Development Goal 6\]. Globally, 8 out of 10 people in rural areas still have no access to safe drinking water \[source: UN Millennium Development Goal 7\]. The demand for water is rising, set to exceed supply in the UK as early as 2025 in highly populated areas \[source: BBC\], while the rising cost of water creates incentives for water companies to explore water conservation and re-use. The AQR Safe Water(r) system is a low-power process that uses no added chemicals and has a flexible, modular unit assembly. It can be easily operated using mains, solar or wind power and is ideal for single households and small communities, i.e. in rural and dispersed environments, globally."

Advanced dressing products providing antimicrobial properties can improve healing rates, alleviating suffering, and ongoing healthcare costs. Some wounds represent more clinically severe (acute) situations such as large area burns/scalds or significant wounds on patients less able to fight off infections. In such situations, high risk of wound infection represents risk to life, necessitating the use of premium dressing products with powerful antimicrobial properties. Such products carry higher expense (both manufacture and end-user costs), but their use is justifiable to reduce mortality rates in high-risk situations. There is market demand for a more moderate-cost antimicrobial wound dressing product, intended for use in sub-acute, but hard to heal wounds, where the risk of chronic infection leading to longer term wound care is significant. Specifically, there is market-pull for a polyurethane foam product employing a silver-based antimicrobial action. The improved wound dressing product that this work relates to, is designed to directly address this market need by providing a line-development of our existing polyurethane foam-based product family. The innovative nature of the antimicrobial product must be well understood in terms of its compatibility with living tissue and its overall safety. Full understanding of these characteristics requires analysis of the physical and chemical nature of the product as may be expected from intended use. The scientific analytical methods required to obtain this information are not available off-the-shelf and A4I funding will allow us to identify and access the most appropriate cutting-edge analytical expertise and methods provided within the UK national measurement system.

"Pireta Ltd is an e-textile start-up business that has been spun out of the National Physical Laboratory (NPL). Pireta's technology uses an innovative chemical process to add electrical conductivity to areas of fabric. Conductive patterns can be prepared onto textiles with high resolution. Our technology is similar to, and competes with, conventional inks but differs in important respects. Pireta technology allows electronic systems to be assembled directly on fabrics, enabling a new generation of truly wearable smart garments and e-textiles. The fabric is first printed with a silver nanoparticle (AgNP) catalyst pattern. The fabric is then passed into an electroless copper (e-Cu) plating bath, in which the process attaches a thin, highly-durable copper layer at the fibre level, resulting in excellent conductivity but with no impact on the performance of the textile. This means that electronics can be integrated into stretchable, breathable, washable smart garments that can be worn close to the body with ease and comfort, making them truly wearable. The vision of this project is to create high quality ink system at volume. Today we have a laboratory scale process and need to create new process interventions to achieve our aim. In detail we need to achieve high retention of silver nanoparticles on the fabric substrate from a printing process. Leeching of nanoparticles (NP), creates waste, poisons our e-Cu, reduces conductivity in a final product. Innovation by NML working on developing metrology methods that will provide critical feedback to Pireta, to allow it innovate and create deposition techniques for AgNP. Furthermore, in our e-Cu process with very high deposition rates, because we plate on fabrics, the dynamic between consumption and replenishment will be studied. NML's compositional measurement of the e-Cu will be invaluable in creating the replenishment strategy. NML will develop a single particle analysis technique, and Pireta will innovate new AgNP deposition techniques. The reduction in silver nanoparticle leach out will include washing procedures of printed fabric samples and analysis of the silver nanoparticle concentration. Hence, new procedures for the deposition will lead to reduced amounts of silver nanoparticle leach-out from printed fabric, significantly improving e-Cu bath quality. The project will validate techniques for a range of fabrics."

"The project combines Sixfold's Programmable Oligonucleotide Delivery System (PODS) with deep expertise of NML in quantitative bio-measurement and NPL in qualitative and quantitative advanced imaging to determine and optimise PODS in vivo profile. PODS have demonstrated a highly promising safety profile for delivery of Cell&Gene therapeutics such as short-interfering RNA (siRNA) for gene-silencing. The aim now is to complete preclinical studies and meet the requirements of the regulatory agencies by collecting more robust data on PODS' pharmacokinetics/dynamics profile. To that end, the project employs an iterative technical approach, takes advantage of the interdisciplinary expertise of the consortium and leverages NML's/NPL's unique facilities, equipment and know-how. This allows for optimisation, enabling PODS to quickly progress through preclinical development, and expediting commercialisation. Given their high specificity/selectivity for gene-silencing, siRNAs have the potential to provide effective treatment options for a variety of genetically-driven diseases including cancer. The first ever regulatory approval of Alnylam's siRNA therapy in 2018\[1\] has validated the clinical and commercial opportunity for such therapies. The major limiting factor for their further clinical and commercial success is the lack of safe and effective systems for systemic delivery of siRNAs to specific diseased cells. This is recognised by academia and industry\[2\]. Current approaches (viral-based/lipid-based) are sub-optimal given their limited specificity, toxicity, and complex/expensive manufacturing\[2\], limiting the type and number of addressable disease indications. PODS can address the drug delivery challenge given their unique, biocompatible design based on a central ""naked"" RNA nanoscaffold, which can be functionalised with multiple therapeutics and highly-specific targeting molecules that recognise biomarkers on cancer -but not healthy- cells. Preclinical data indicates a highly competitive safety profile of siRNA-PODS cancer therapy. However, to complete the preclinical studies and meet the requirements of the regulatory agencies, Sixfold must collect more robust data on PODS' pharmacokinetics/dynamics profile. Although Sixfold has performed biodistribution studies in rodents, the results of these experiments have not allowed for quantitative analysis on the composition of PODS, their by-products and their exact distribution in tissues. By utilising NML's and NPL's expertise, the project will enable the necessary advanced in vivo analysis/measurement of:(i)intact PODS versus by-products, (ii)spatial distribution and subcellular localisation in tissue. This would accelerate the completion of preclinical development, unlocking Sixfold's ability to generate first revenue from licensing agreements and expediting clinical development not only for our primary indication but also other diseases, contributing to the competitiveness of the UK's _Advanced Therapies_. \[1\]Alnylam\_Press Release\_30.08.18.\[2\]Karim\_ME\_et\_al.\_Pharmaceutic 2018"

Fleet Bioprocessing Ltd. are experts in the development of immunoassays, widely-used tests for the diagnosis of diseases which rely on the well-known specificity of antibodies to detect specific molecules. Examples in common use include tests for detecting HIV and hepatitis, for diagnosing thyroid hormone abnormalities, or for differentiating heart attacks from other conditions such as angina which may display similar symptoms. New immunoassays are under development all the time, e.g. to improve the detection of cancer tumours or to monitor factors associated with the development of Alzheimer's disease. Immunoassays rely on the successful chemical "labelling" of antibodies and related proteins, so for example that they can be detected efficiently via the presence of a fluorescent dye - and Fleet are expert in the bioconjugation techniques required for this purpose. Fleet routinely use simple analytical techniques to characterise these labelled antibody conjugates, allowing us to determine basic information such as the antibody concentration and the mean number of dye molecules per antibody molecule. However these techniques tell us nothing about whether the labelled antibody conjugate has retained its ability to detect the molecule of interest, or has been damaged in the labelling process. For example it is possible to attach too many dye molecules to an antibody, with the result that its ability to bind the target molecule is compromised. It would be very useful to have access to a rapid, inexpensive analytical method allowing us to confirm that the conjugate has successfully retained its structure during the labelling procedure. Fleet have evaluated several techniques for this purpose, but to date all have failed to meet our requirements; simple techniques based on spectroscopy which would meet our needs of being rapid and inexpensive have not shown adequate sensitivity to differentiate between "good" and "bad" conjugates, while techniques capable of achieving the required sensitivity have proved prohibitively expensive and/or time-consuming. An initial project with LGC and NPL (completed in March 2019) identified techniques with exciting potential to fill this knowledge gap, and to better understand the mechanism of conjugate inactivation. This follow-up project aims to confirm the potential of these techniques. Fleet will prepare a range of antibody conjugates for evaluation and assess them in a model immunoassay, while LGC and NPL will characterise them using a range of candidate analytical techniques. This will hopefully allow us to confirm the capability of these techniques for routine use by Fleet Bioprocessing Ltd.

"SilverRay Ltd. is a start-up company whose primary goal is to exploit the technology developed in a large area, high sensitivity broad-band X-ray detectors. This proprietary technology has demonstrated its sensitivity to be 2-3 orders of magnitude higher than the conventional organic detectors; while operating at low voltage and offer excellent conformability to non-planar surfaces. One of its key selling points is the potential for low cost manufacurability of the technology over large areas. The detector active material consists of an 'X-ray sensitive ink' containing an interpenetrating network of organic material and inorganic nanoparticles. The 'X-ray sensitive ink' can be used to coat films over any substrate, especially without constraints for flexible detectors. Thus far, small area detectors (area < 1 cm2) have been developed with the scale-up currently being carried out by SilverRay Ltd. Challenges lie within the production of uniform thick film coatings, where the company seeks for the application of uniform nanoparticle distributions through-out the film depth and spatially across pixel-to-pixel. A well-uniformed distribution of inorganic nanoparticles is crucial to the imager, as the high atomic number nanoparticles are the key component which makes the ink sensitive to X-rays and as a result generate charge carriers. Therefore, it is expected to have a uniform distribution of nanoparticles on each pixel of the backplane, so that the charge generation from each pixel due to X-rays is uniform and identical to each other. In this project, we will focus on the fabrication of large area thick film coating and these films will be characterised by the A4I partners; NPL and LGC. They will be working on how to optimise their instrumentation further to analyse the uniformity of nanoparticles with higher precision towards its nanoscale morphology, and present a solution that can be implemented in an in-situ printing manufacturing environment. The outcome of this project will facilitate the company to have a better understanding on routes to optimise the active layer of the detector which would lead to higher performances and faster responses."

CCm and LGC are collaborating to establish continuous measurement methods for water treatment; leading to improved industry efficiency, reduced water bills and improved environmental benefits.

"Muc-Off strive to take the 'myth and anecdote' out of bicycle chain lubrication by the application of good science and results-based data. The tribology (wear and friction) of chain links is extremely complex with many components in the chain undergoing different friction regimes, and for this reason much testing is on application-based Dynamometers. For the development of the next generation of lubricants we will rely more heavily on chemical analysis and fast repeatable tribology testing. This will allow: \* A better, more transparent, understanding of the performance and environmental impact for the consumer \* Faster product development \* More targeted performance gains \* Less development iterations. The research will create a novel measurement and analysis process to determine and score lubricant component's performance and environmental impact. The research also includes a fast, highly repeatable, novel process to measure and analyse the performance and durability. This will be validated on our application specific Dynamometers"

"Purely Pickled Eggs Ltd specialise in the development and production of a range of different flavours of pickled eggs. The aim of the project is to introduce a new measurement technique to monitor vinegar stability, improve control management and reduce inconsistencies in quality. Successful completion of the project would mean that the business is able to: * introduce improved measurement at key stages of the pickling process to efficiently and effectively manage quality controls * analyse the propensity for long term consistency of the pickled product This will result in improved operational processes and longer batch production runs therefore enabling the business to enter larger markets aswell as guiding new flavour development. Vinegar is the result of a complex inter-relationship between a raw material, sugar, alcohol, yeast, bacteria and oxygen to produce acetic acid. This is a chemically volatile product that is controlled through the measurement and analysis of its level of pH and level of acidity. However with the addition of the flavourings and infusing, processing and storage phases involved in production the properties of vinegar can become altered. This has implications for the cosmetic and structural quality of the final product with evidence of cloudiness, deposits and egg disintegration. The project will focus on improving measurement tools that will efficiently and effectively analyse the impact of re-introduction of raw material, sugar, alcohol, yeast, bacteria and oxygen during the production process upon the stability of the vinegar solution. Measurement of common elements used in all processes will be facilitated alongside fingerprint analysis of elements that are specific to each flavour. The project will include cross validation of the effects of the processing of the vinegar on the pH of the final product (such as addition of flavourings and heating) and analyse whether the pH measurements correlate effectively with acidity levels. The data generated will enable us to improve the stability of the pickling solution and reduce inconsistencies to arrive at refined operational guidelines. The project will also determine how the improved measurement tool can be employed as standard within the production process going forward in order to achieve accuracy and precision in an efficient manner. This is an innovative project in that it aims to refine measurement tools for managing previously uncontrolled inconsistencies common to the wider pickling community, providing real competitive advantage."

For many years it has been recognised that there are bacterial infections that persist and are refractory to treatment with antiseptics and antibiotics. Antibiotic resistance is currently one of the highest threats to human health, given the increasing number of pathogens that develop resistance to known antibiotics as well as the inability, thus far, to discover new ones to offset acquired resistance. Neem Biotech is thus responding to the this world health crisis through the development of first-in-class synthetic anti-microbial molecules to be used as adjunctive agents in potentiating antibiotic efficacy. Neem Biotech has extensive experience in producing garlic-derived compounds known for their antimicrobial activities. Our leading expertise in organosulphur chemistry has allowed us to identify a number of synthetic compounds with high antimicrobial activities and that synergise with antibiotics and antiseptics in microbial cells killing. This results in the more rapid and efficacious resolution of infection, reducing its spread and dissemination to other anatomical locations. Having now progressed our selected drug candidate into preclinical development, we have encountered an analytical challenge, namely, the inability to detect and quantify our molecule in biological samples such as blood and plasma. This poses extraordinary barriers in taking this promising compound further into the clinic since we are unable to undertake the required regulatory pharmacological, phamacokinetic and toxicology safety studies. Neem has made several attempts to resolve this analytical problem in-house using LC-MS and has outsourced two CRO's to develop and validate detection methods for our compound, both of which were unsuccessful and costly. LGC is the designated institute for Chemical and Bio-Analytical measurement in the UK, working across several sectors. Led by Chris Hopley, an expert in analytical chemistry and Principal Scientist Mass Spectrometry, the group at LGC has a number of instrument platforms and technologies to develop methods for novel target compounds in biological matrices. Importantly, once developed, this method can be easily transferred to a commercial service towards the successful preclinical studies of our selected and all future organosulphur compound assets developed at Neem Biotech.

"Silicon Fuel is nano-material which is manufactured and pressed into pellets by Silicon Fuel Ltd. These pellets react with water to generate hydrogen, which can be used to supply a fuel cell to generate electricity. This new material has the potential to facilitate the developing hydrogen economy, by allowing the use of cheaper hydrogen generation equipment, making hydrogen gas cheaper and easier to access. For example, it could allow the installation of cheaper hydrogen refuelling stations for delivering hydrogen to fuel cell electric vehicles. If the hydrogen generated from Silicon Fuel can be certified to international standards, then it has a demonstrably high purity which allows it to be used in a range of applications (such as refuelling fuel cell electric vehicles). The current method of manufacturing Silicon Fuel results in low levels of impurities in the pellets, which can be transferred to the hydrogen gas when it is generated. Although the impurities do not prevent the running of fuel cells, they can prevent certification of the hydrogen gas to international standards, likely limiting the market acceptance of Silicon Fuel technology. This project aims to accurately measure the levels of key impurities in the raw Silicon Fuel material, and in the hydrogen it generates, and to develop an improved method for manufacturing Silicon Fuel so that the amount of impurities present are reduced to the minimum possible levels. We hope this will facilitate the certification of Silicon Fuel, leading to market acceptance and uptake."

"Nanomaterial particle sizing has been available for many years initially via ensemble methods (such as DLS) and then through particle by particle techniques (such as NTA, TRPS) and there is now an ISO standard for this. More recently these latter techniques have added the capability to count particles and therefore infer a concentration. However, the metrology associated with this has lagged. NTA is leading technology and has published reproducibility's of +/- 15%. However, without controllable standards and advanced metrology practices the improvement in reproducibility has recently stalled. NPL and LGC have recently worked together in this arena and we find an information asymmetry where each organisation has specific expertise in reference concentration samples (LGC), metrology approaches to assigning uncertainties (NPL), which allows the targeting for further optimisation and instrument development (Malvern Panalytical). Whilst each aspect individually may not be considered innovative, the bringing together of these three skills promises to improve the technology further enhancing the state-of-the-art in nanoparticle concentration measurement. Therefore we aim to bring together the knowledge of the best practice for handling a new traceable concentration standard from LGC, and the expertise in developing uncertainty measurements (in addition to some work already done on this by LGC), with the concentration calibration and instrument expertise of Malvern Panalytical to advance the process of handling samples and identifying key contributors to variation to reduce variation concentration measurements between Malvern Panalytical's thousands of customers in this field."

"**Fleet Bioprocessing Ltd.** are expert in the development of **immunoassays,** highly sensitive and specific antibody-based _in vitro_ diagnostic procedures widely used in the diagnosis of disease states. Immunoassay performance is critically dependent on **labelled antibody and antigen conjugates** which enable **immobilisation** or **detection** of these proteins: typical examples include **biotin-labelled antigens** which facilitate binding to a streptavidin-coated surface, and **fluorescent-labelled antibodies** which enable exquisitely sensitive detection _via_ **fluorometric** quantification. The performance of any given immunoassay is largely defined by the behaviour of these conjugates, which ideally display 100% retention of antibody/antigen binding activity, whilst incorporating an optimally high level of label to facilitate immobilisation or detection. A trade-off between these competing aims is required for optimal performance. The chemistry required to _create_ such conjugates is well-established; with Fleet's expertise, existing **bioconjugation** techniques are routinely exploited to yield conjugates with world-class immunoassay performance. By contrast, **the availability of** **rapid and inexpensive procedures for effective analysis and characterisation of these conjugates is extremely limited.** Simple cheap techniques can be used to determine basic conjugate characteristics such as antibody concentration or mean biotin or enzyme incorporation, but these provide no information on whether the antibody or antigen has retained immunological functionality; **without this information it is impossible to know whether the conjugate will perform effectively in the immunoassay**. This means that the only available additional approach is to ""try it in the assay"", which (see _Need or Challenge_ section) has serious weaknesses. The knowledge gap that this application aims to address, therefore, is t**o identify inexpensive and relatively fast techniques capable of confirming that antibody or antigen has retained adequate functionality during the conjugation process**. A technique capable of showing quickly and cheaply that the tertiary structure of the antigen or antibody remained intact after conjugation would be a massive step forward of great significance to our company and to the industry in general. Initial discussions with LGC and NPL have indicated that both parties have access to analytical techniques which may directly or indirectly help to address this knowledge gap, including (from LGC) **hydrogen/deuterium exchange mass spectrometry (HDX-MS)** and **ion mobility spectrometry mass spectrometry (IMS-MS)** and (from NPL) **circular dichroism spectroscopy (CD), Fourier transform infrared spectroscopy (FT-IR)** and **isothermal titration calorimetry (ITC).** This project comprises the preparation of suitable conjugate panels and determination of their immunoassay performance (Fleet), coupled with comparative evaluation of these conjugates using the techniques outlined above (LGC, NPL)."

Non-communicable diseases (NCDs) including cancer and cardiovascular disease (CVD) are major causes of death globally. The South African Medical Research Council (SAMRC) has responded to the dire need for translatable research by supporting the development of a novel genetic testing platform focused on disease pathways that are shared by many NCDs. To link to the United Nations' Sustainable Development Goal of ensuring health and promoting well-being, LGC (UK) in collaboration with the SAMRC's spinout company, Gknowmix, and Stellenbosch University has developed a novel point of care (PoC) diagnostic testing system and screening tool to improve the clinical management of patients with breast cancer and its associated co-morbidities. This testing platform is made possible by using the LGC ParaDNA technology that enables detection of genetic changes that are important in the development of breast cancer. Genetic testing may be done by non-expert users and within 1 hour, compared to standard laboratory methods that takes 1 week from sample collection to result reporting. For the first time, PoC technology will be used to detect changes in the two main breast cancer susceptibility genes (BRCA1 and BRCA2), as well as changes in other genes shared by various NCDs. The patient reports generated using this technology helps to determine whether further testing is necessary in patients with treatment failure, medication side-effects or co-morbidities that are not explained by the initial assessment. Combining the unique ParaDNA PoC technology with the proprietary algorithms of Gknowmix, enables this system to be scaled in South Africa and globally, with significant benefit to patients with breast cancer and those at risk of developing CVD and other associated NCDs. The availability of genetic testing at the PoC enables better access to genetic testing and overall care, reduced costs and faster reporting for timely implementation of effective intervention strategies.

The project is to develop an on-line method for screening and detecting the rancidity and quality of coconut cream. The objective is to be able to detect traces of rancid coconut cream ahead of its use in the production of coconut Yogurt, with production yield and quality control benefits. The outcome of the project is likely to have wider applicability in the UK since coconut cream is a growing alternative to dairy ingredients in an increasing number of foods. The project is lead by The Coconut Collaborative, an innovative manufacturer of Coconut Yogurts and supported by LGC and STFC who will respectively investigate the suitability and sensitivity of Multispectral Imaging and Raman spectroscopy as an on line measurement method for screening for coconut cream rancidity.

The wearable chemical sensor-cortisol project is an industrial research project that will allow SouthWestSensor (SWS) Ltd to offer a novel chemical sensor device for the measurement of cortisol, to be used in hospitals, community care and sport science. SWS Ltd has already established sensor devices for the measurement of chemical concentrations for a variety of biomarkers from body fluids such as glucose, lactate and thiols. This project will set up a new collaboration between SWS and LGC group, to develop a novel device for continuous measurement of cortisol – an important hormone indicator to many diseases. Because cortisol changes in circadian cycles, with the magnitude varying from person to person, the single point measurements currently performed in hospital do not give a representative picture of cortisol in the subject. This new device will provide a step forward for the thorough and accurate measurement and better diagnostics of related diseases. Since cortisol is linked to stress wearable devices can also provide a real time and continuous measurement of training effect and the body condition of elite athletes.

Air Quality Research Ltd (AQR) has developed a novel energy-saving non-chemical process for disinfection of fluids. This is achieved by generating a suite of charged radical species, including Hydroxyls, which are recognised as Nature’s most effective disinfection agents. To date, AQR lacks a detailed understanding of the suite of charged radicals generated by the novel AQR disinfection process, preventing further product enhancements and restricting AQR to markets with batch disinfection process needs. The proposed project aims to quantitatively measure the proportion of Hydroxyl radicals as a function of the system performance. This will help AQR optimise the disinfection process and improve this capability so that the current batch treatment process can be speeded up and scaled up. The project will also explore how to selectively generate Hydroxyls to maximise the disinfection potential for a single-pass treatment process, to deliver a higher value proposition. The project will enable AQR to offer an enhanced product in existing and new markets, targeting industrial wastewater treatment at the point of production, prior to discharge to sewer drainage or environmental waters. This will offer cost-savings for wastewater re-use and reduced wastewater treatment and environmental benefits in terms of compliance with strict environmental regulations and control of emerging chemical contaminants.

Sistemic Ltd is a company whose primary business is focused on providing innovative microRNA-based tools for areas of unmet need within cell therapy research, development and manufacturing markets. Cell therapies are seen as the future of treatment and are expected to have great potential, revolutionising medical care capabilities in a range of chronic diseases, such as diabetes and myocardial infarction. Cell therapies are increasingly using pluripotent stem cells (PSCs) to generate derived cell therapy products. However, PSCs can form tumours, which is a safety issue requiring the need to demonstrate the level of contaminating PSCs. Currently there is no simple established way to assess contamination. We have developed a prototype product based around using biomarkers to detect contaminating PSCs in a derived cell therapy product. Innovate UK will support Sistemic through access to innovative and advanced measurement and analytical technologies offered by a partnership with LGC. The outcome of this project will facilitate the safe clinical progress of PSC-derived cell therapy products to bring them to a clinical product more quickly. This will in turn result in patients getting quicker access to these novel therapies during clinical trial development phases, and ultimately, to a successfully launched clinical product and therefore improvements in quality of life.

We urgently need earlier detection of cancer and other diseases. Earlier detection leads to lower costs, better survival and higher quality of patient life by allowing earlier and more effective treatment options. Astrimmune responded to this challenge with an advanced filter product that allows the isolation of circulating tumour cells and other rare cells, from liquid biopsies, like blood and urine. A cost effective, non-invasive general population screening for cancer or other diseases is a very worthy goal that will save money and extend lives. We started out monitoring people that already had cancer before attempting general screening. We encountered a problem with autofluorescence of the filter while conducting fluorescent microscopy of cells retrieved on the filter. Autofluorescence is the natural emission of light by structures when they have absorbed light. Autofluorescence from U.S. paper money is used to identify counterfeit money. This Innovate UK grant is to develop alternative dyes for the purpose of identifying cancer cells and other rare cells of interest that are captured on our filter. Our current state-of-the-art disposable filter is superior to competitor filter designs and is more cost-effective than expensive processes currently being used. Our goal is to eventually have an inexpensive way to screen the whole population, on a regular basis, to identify health problems sooner. The earlier the problems are identified, the better the chances of a long and healthy life. Solving the autofluorescence problem will be a big achievement, immediately helping researchers, patients and providers of care.

Current safety methods for product release such as the compendial sterility test are inadequate for a large number of autologous cell and gene therapy products due to their short shelf life. This problem is exacerbated by the long complex manufacturing processes during which microbial contamination can occur. As a result sterility testing has to be performed during manufacture and the products released with an element of risk. This project, led by GSK and supported by the Cell Therapy Catapult and LGC, will address this issue by developing a rapid sterility test (<1hr) based on a novel technology to allow real time product release. The project will also develop a high sensitivity approaches which will quantify live and dead microbial contaminants for in-process testing and be used to validate the readout of the rapid sterility test. These technologies will be a major innovation for the field and will provide a much needed technical solution to allow cell and gene therapies to be tested for safety prior to their use.

This project will deliver innovative products that drive the development of enhanced analytical systems to meet the changing needs of diagnosis and stratification of cancer patients. This will allow patients to benefit from recent advances in molecular pathology by delivering more reliable and earlier diagnosis, personalized therapies and disease monitoring to achieve improved outcomes. The project will develop, test and validate materials derived from cell lines that will be engineered to reflect the genetic modifications seen in different cancers. This approach will enable the project partners to produce new and highly innovative reference standards (including formalin fixed paraffin embedded cell blocks and genomic DNA) as well as methods and protocols that can be used in all laboratories to increase efficiency and sensitivity of diagnostic testing and enable standardized, controllable proficiency testing across all geographical locations.

To develop quantitative elemental imaging of tissue sections for the study of common age-related diseases such as Alzheimer's and Age Related Macular Degeneration.

Awaiting Public Summary

The manufacture of cells in a controlled and reproducible manner is a critical challenge in regenerative medicine. We will develop an integrated platform technology for the rapid identification of novel, efficient stem cell expansion and differentiation protocols that are optimised for translation to clinical grade manufacturing. Several innovative technologies will be combined to perform high throughput GMP compatible screens to discover novel cell production protocols. These protocols will be transferred to a scaled-up bioprocess where a novel cell imaging technology will be utilised to monitor cell performance. Successful protocols will be translated to a GMP manufacturing process for final validation. In this way, safe, robust, cost-effective GMP validated protocols will be rapidly discovered, greatly reducing the cost and time for development of regenerative cell therapeutics.

The CLIENT project sets out to achieve a platform for rapid in-clinic STI analysis so as to enable a 'test and treat' service within the clinic whilst the patient briefly waits. The project, led by LGC, is assembled through 7 parallel Work Packages shared amongst the 4 partnering teams to the project. On the technical front the key challenge is to build on the rapid and sensitve sequence-specific detection achieved by HyBeacon probe technology with either isothermal or PCR methodology for simple end-user operation. This will then be partnered with approriate amplification instrumentation and sample preparation. Evaluation of amplification methods is being led by LGC with the University of Southampton School of Chemistry focussing on improvements to existing probe technology. The point-of-care instrumentation is being developed by OptiGene to partner the probe technology and the Chlamydia Research group the University of Southampton are providing expertise in STI handling and sample prep as well as insight into end-user requirments.

The British Regen Industry Tool Set (BRITS) is an industry driven project aimed at establishing reliable market data and creating both detailed bioprocess economics models and higher level business models for integration into a highly valuable and timely set of decisional tools. The individual components will themselves be highly novel, and the final integrated tool set will be a major step change for the cell therapy industry. BRITS will encompass the entire supply chain. This will including direct links through the main innovation routes available within the NHS. Via its wider business benefit activities BRITS will interact with all the UK stakeholders to facilitate the uptake of the outputs of the project and build and maintain the vital linkages between the diverse stakeholders in order to promote the joined-up approach that will be required if the UK is to be at the international forefront of cell therapy, not just scientifically but also commercially.

Awaiting Public Summary

This project set out to address the need for a more efficient ‘discovery’ of suitably robust routes to manufacture of cell lines for use in whole cell vaccines and whole cell therapies. The goal was to develop a suite of tools to identify impacts of bioprocessing; this included the development of ultra scale-down (USD) platform technology and a panel of biological tests to predict and characterize the cellular response to processing. The project has established the ultra scale-down platform and analytical strategy to allow new cell lines to be addressed and new processes optimised. The project has examined a number of cell lines and has demonstrated the generality of the approach. A panel of biological tests ranging from rapid and requiring low cell numbers (membrane integrity, cell size, surface marker analysis) to longer more complex analyses (cell death, cytokine release, biopotency) have been developed and are largely generic meaning that they can be applied to many different cell therapeutics. A novel method for identifying novel biomarkers resulting from cellular stress has been developed for mass spectrometry. An Artificial Neural Network has been employed using data from USD bioprocessing experiments to aid the prediction of cell quality outcomes following bioprocessing, the aim here was to create a predictive tool that identify limits of processing. ANN is shown to be a powerful tool in identifying subtle changes in the data that may be due to parameters not previously considered. Our findings enable early stage bioprocess development of therapeutics. The data generated from this project has indicated that each cell line studied has a different response to shear stress. This will impact upon new whole cell therapies currently emerging. We have developed the tool set to identify the robustness of cells during bioprocessing and a broad set of parameters. However, ‘fine tuning’ should be carried out on individual cell types before designing the whole bioprocess. In addition, it has become clear that it is not only the engineering parameters that require careful control, cell culture parameters prior bioprocessing are highly important and should be kept in mind by researchers bringing new therapies to clinic.

Awaiting Public Summary

Awaiting Public Summary

Awaiting Public Summary

Awaiting Public Summary