Developing low-drift pH monitoring technologies for high-value bioprocessing and pharmaceutical production

研究问题包括设计一种适合GMP（仿制药）制造的在线非侵入性，稳定，可控的传感器，能够在全pH范围（1-14）的全水介质中工作，盐和API（活性药物成分）浓度极端，保质期长（使用2-4周），并且与工艺中使用的材料具有生物相容性。此外，该传感器具有通用特性，能够识别过程中存在的不同缓冲，以确保质量控制。总体目标是开发一种pH值和缓冲液识别传感器，用于药品的下游加工。第一年的目标是设计一个pH传感器。为了实现这一目标，必须实现以下目标：-通过进行批判性文献综述来选择材料和方法，比较目前商业上可用的材料和学术界正在开发的材料，以及这种新传感器与现有传感器的不同之处，以及它如何改进传感技术；-选择合适的转导机制，以便最容易和最快地读取结果；-测试传感器原型并提高其质量，以确保最佳结果和最敏感/准确/选择性的传感器。该项目首先对现有技术和新型传感方法进行文献调查，使用现有的固定技术和转导方法来实现所需的目标。然后，学生将在实验室进行实验工作，从不同传感机制的概念验证开始，并分析收到的数据以改进性能。之后，学生将进行工业实验，以记录所设计的装置与系统的兼容性。这个项目的新颖之处在于用于制造这些传感器的技术，因为目前市场上没有高精度和灵敏度传感的可能性，没有漂移，因此可以长时间使用。

The research questions include the design of an on-line non-invasive, stable, controllable sensor suitable for GMP (generic medicinal product) manufacturing, able to operate in fully aqueous media of the full pH range (1-14), extremes of salt and API (active pharmaceutical ingredient) concentrations, long shelf-life (2-4 weeks in service) and biocompatible with the materials used in the process. Furthermore, this sensor with universal properties is able to identify different buffers present in the process to assure quality control.The overall aim is to develop a pH and buffer identification sensor to be used in downstream processing of pharmaceuticals. The first year's goal is to design a pH sensor. To attain this, the following objectives must be fulfilled:- Materials and methods selection by conducting critical literature review, comparing what is currently available commercially and what is being developed in the academia and how this new sensor differs from the current ones and how it improves the sensing technologies,- Suitable transduction mechanism selection for easiest and fastest readouts of the results, suitable for rapid and remote sensing,- Testing the prototypes of sensors and improving their qualities to ensure the best result and the most sensitive/accurate/selective sensor possible.This project begins with a literature survey on available technologies and the novel sensing approach, using already existing immobilisation techniques and transduction approaches to achieve the required goal. The student will then conduct experimental work in the lab, starting on proof of concept of different sensing mechanisms and analysing the data received to improve the performance. After this, the student will conduct experiments in industry to record the compatibility of the designed device with the system.The novelty of this project is in the technology used to manufacture these sensors, as currently there is nothing in the market with high precision and sensitivity sensing possibilities, that have no drift and thus can be used for long time.