Reinvigorating Process Analytical Technology Using Virus Lasers

Innovation in biomedical research has outpaced innovation in biological manufacturing meaning that cutting-edge biological therapies are often very expensive. For instance, Kymriah costs nearly $500K per patient.
The overarching goal of the fellowship is to develop highly advanced detection and monitoring systems for biological manufacturing using virus lasers. I invented the virus laser in which dye-labelled virus particles are used as the critical component of laser systems to quantify biomolecules. They have the potential to operate in complex biological environments, bind the full range of biomolecules of interest in industrial bioprocesses and generate a laser signal.
The aim is to directly monitor the critical quality attributes that affect the safety and efficacy of the product at all stages of the bioprocess. Virus lasers represent a disruptive breakthrough in biological sensing with the potential to resolve the pressing monitoring and control challenges holding back the transition towards smarter, more productive manufacturing facilities better prepared to deliver innovative, new therapies to patients at commercially-viable but affordable prices.
I will build on existing intellectual property, technical expertise and experimental work to develop a lab-based instrument and set of probes that can monitor the concentration of product and one toxic protein at the earliest stages of the bioprocess before purification. I will then translate the instrument and probes into the Quality Control lab of the industrial partner and compare its performance to competing technologies. Finally, I will integrate the instrument and probes directly into one of the industrial partner's bioprocess and then quantify its performance.
The immediate impact would be the creation of a new business that sells the instrument and probes as a solution to the long-standing analytical problems currently facing the industry. Greater process control would substantially reduce the technical risk of developing and validating a bioprocess providing UK manufacturing a major strategic advantage. This would reduce drug shortages due to manufacturing issues, reduce the cost and risk of manufacturing biologics and impact the regulatory landscape. Ultimately, these advances will increase the number of effective therapies available for use in hospital trusts and strengthen the business case for smaller companies developing biological therapies for uncommon diseases, improving the quality of life for thousands, possibly millions, of patients.
Manufacturing bioprocesses are just one example of a system that can be controlled through biological detection and monitoring. Beyond this fellowship, I want to implement virus lasers as the key sensing element in feedback-control loops in a variety of contexts, from manufacturing facilities to the healthcare frontline in resource-limited settings. I will undertake pioneering, multidisciplinary research into virus lasers at the interface of synthetic biology and laser physics which would pave the way for future innovation activities in these areas.
I plan to achieve lasing at ultra-low concentrations to investigate how energy is transferred in virus lasers and to determine the sensitivity limit of this technique. I will establish a biological structure - laser function link using cutting-edge optical detection and the world's leading free-electron laser facility for photobiology. I will then use these techniques to investigate in-depth the mechanisms behind a novel detection paradigm unique to virus lasers. The knowledge created will lead to more advanced laser probes and inspire synthetic biologists to design nano-engineered laser systems with novel characteristics. The long term impact of the first lasers was profound, and likewise virus lasers will lead to the creation of new industries and fields of discovery.

Innovation in biomedical research has outpaced innovation in biological manufacturing meaning that cutting-edge biologics including complex engineered proteins, vaccines, and viral vectors for gene delivery are often very expensive. For instance, Kymriah costs nearly $500K per patient. The primary impact of this fellowship would be progression towards smarter, more productive manufacturing facilities better prepared to deliver innovative, new therapies to patients at commercially-viable but affordable prices.
The overarching goal is to reinvigorate process analytical technology for biological manufacturing by using virus lasers to directly monitor critical quality attributes of the product at all stages of the bioprocess. This goal has strong overlap with the strategic objectives of EPSRC's Manufacturing the Future theme and with the BBSRC long-standing prioritisation of industrial biotechnology.
The immediate impact would be the creation of a new business that would adopt a defendable niche in the supply chain for biological manufacturing companies selling the instrument and probes as a solution to the long-standing analytical problems currently facing the industry.
In the short term, the innovation would lead to the full adoption of Quality by Design principles and reduce the technical and commercial risk of developing and validating a bioprocess, reducing drug shortages and providing UK manufacturing a major strategic advantage. In the medium term, this progression would increase the chance of effective therapies being approved by NiCE for use in hospital trusts and strengthen the business case for smaller companies developing biologics for uncommon diseases, improving the quality of life for thousands, possibly millions, of patients.
The spiralling cost of healthcare is a major political and economic problem around the world and this is being exacerbated by the high cost of many of the most promising drug candidates. In the long term, the successful realisation of the potential societal benefits of major biotechnological advances will hinge on the development of innovative process analysis and control tools such as virus lasers.
Manufacturing bioprocesses are just one example of a system that can be controlled through biological detection and monitoring. A long-term impact goal is to provide a sensitive, precise and reliable biological sensing element that can be incorporated into feedback-control loops in a range of contexts at different scales. For instance, at the scale of an individual patient, virus lasers would be used to detect biomarkers to first diagnose and then monitor the response of the patient to therapy. At a larger scale, virus lasers could be incorporated into connected point-of-care diagnostics to detect pathogens in resource-limited settings as part of a wider disease outbreak response system. The research proposed would pave the way for future innovation activities in these areas and further patent applications may be required to protect the intellectual property (IP) created. In the short term, the aim is to reach a TRL of 4+ ready for commercial exploitation.
The regulator plays a pivotal role in ensuring that the biological products and safe and efficacious. A medium term goal would be to steer the regulatory focus onto critical quality attributes instead of parameters that merely correlate with those attributes, which I would advocate for at conferences and dissemination events.
I would employ an open innovation approach to IP and data sharing to facilitate the adoption of virus laser technology beyond biosensing to achieve technological goals orthogonal to my own long term vision, and to inspire new concepts in nanotechnology and synthetic biology. The long term economic impact of the first lasers was profound, and likewise virus lasers might lead to the creation of new industries.