Reinvigorating Process Analytical Technology Using Virus Lasers

使用病毒激光器重振过程分析技术

• 批准号: MR/T02156X/1
• 负责人: John Hales
• 金额: $ 127.68万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT02156X%2F1
• 关键词: Reinvigorating; Process; Analytical; Technology; Using

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.

生物医学研究的创新超过了生物制造的创新，这意味着尖端的生物疗法往往非常昂贵。例如，Kymriah每名患者的费用接近50万美元。该奖学金的首要目标是开发用于使用病毒激光的生物制造的高度先进的检测和监测系统。我发明了病毒激光器，其中染料标记的病毒颗粒被用作激光系统的关键组件，以定量生物分子。它们有可能在复杂的生物环境中工作，结合工业生物过程中感兴趣的所有生物分子，并产生激光信号。目的是在生物过程的所有阶段直接监测影响产品安全性和有效性的关键质量属性。病毒激光代表着生物传感领域的一项颠覆性突破，有可能解决阻碍向更智能、更具生产力的制造设施过渡的紧迫监测和控制挑战，以便更好地准备以商业上可行但负担得起的价格向患者提供创新的新疗法。我将以现有的知识产权、技术专长和实验工作为基础，开发一种基于实验室的仪器和一套探测器，可以在纯化前的生物过程的最早阶段监测产品和一种有毒蛋白质的浓度。然后，我将翻译仪器并调查工业合作伙伴的质量控制实验室，并将其性能与竞争技术进行比较。最后，我将把仪器和探头直接集成到一个工业合作伙伴的生物过程中，然后量化它的表现。直接的影响将是创建一个新的业务，销售仪器和探头，作为该行业目前面临的长期分析问题的解决方案。更好的工艺控制将大大降低开发和验证生物工艺的技术风险，为英国制造业提供重大战略优势。这将减少由于制造问题造成的药品短缺，降低生产生物制品的成本和风险，并影响监管格局。最终，这些进展将增加可用于医院信托基金的有效疗法的数量，并加强小公司为罕见疾病开发生物疗法的商业案例，改善数千甚至数百万患者的生活质量。制造生物过程只是可以通过生物检测和监测来控制系统的一个例子。除了这项研究之外，我还希望在各种环境中，从制造设施到资源有限的医疗保健第一线，将病毒激光作为反馈控制循环中的关键传感元素。我将在合成生物学和激光物理学的交界处对病毒激光进行开创性的多学科研究，这将为未来这些领域的创新活动铺平道路。我计划在超低浓度下实现激光，以研究能量在病毒激光中的传递方式，并确定这项技术的灵敏度极限。我将建立一个生物结构-激光功能链接，使用尖端的光学探测和世界领先的光生物学自由电子激光设备。然后，我将使用这些技术深入研究病毒激光独有的新检测范例背后的机制。所创造的知识将导致更先进的激光探测器，并激励合成生物学家设计具有新特性的纳米工程激光系统。第一批激光的长期影响是深远的，同样，病毒激光将导致新的行业和发现领域的创造。