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A potential PoCT microfluidic paper-based analytical device (μPAD) with dual-signal generation for C-reactive protein (CRP) screening


   Department of Electrical Engineering and Electronics

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  Dr I Sandall, Prof Ruey-An Doong  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

This project is part of a 4 year Dual PhD degree programme between the National Tsing Hua University (NTHU) in Taiwan and the University of Liverpool in England. As Part of the NTHU-UoL Dual PhD Award students are in the unique position of being able to gain 2 PhD awards at the end of their degree from two internationally recognised world leading Universities. As well as benefiting from a rich cultural experience, Students can draw on large scale national facilities of both countries and create a worldwide network of contacts across 2 continents.

COVID-19 has been spread worldwide, leading to an ongoing pandemic worldwide for more than two years. As cases being infected have already inevitable, we are now entering the new status of the pandemic which is known as the post-COVID conditions. Therefore, a preventive policy is now not so relevant to curb the spread of the disease but rather to drain our research focus into post-mortem management. Generally, there is an increasing number of patients who have been infected with the virus that causes COVID-19 can experience long-term effects from their infection, which is currently adopted as the long COVID symptoms. Furthermore, the dramatic acceleration of reported COVID-19 cases each day has posed a burden on our public health system. Cases like shortage in health practitioners or hospital beds have raised due to the limited health resources. Thus, the patient-centralized biosensor acquired with higher sensitivity is crucial for pandemic management in times to come. In this project, it is aimed to develop a microfluidic biosensor that has the potential to be applied as a PoCT device in detecting CRP level for the purposes of COVID-19 diagnostics and prognosis. This is because CRP serves as a well-established clinical biomarker for inflammation diagnostics and prognosis. Inflammation is an innate response of our body in reaction to viral infections, so chronic inflammation appears as the significant symptom for the long-COVID patient. The new generation of PoCT devices at the ease of access for the public could alleviate the constraint to a certain extent.

The proposed biosensor would be orientated based on biomimetic nanozyme mechanism via sandwich immunoassay. The nanozyme possesses more potential than the natural enzyme simply because it is cheaper, higher resistance under extreme conditions (pH, high temperature etc) and easier to handle. For instance, the graphene quantum dots are proposed as it exhibits peroxidase-like property as similar to horseradish peroxidase (HRP) that is commonly applied in ELISA kit. However, small nanoparticles like GQDs might suffer from inadequate colloidal stability in solution or aggregation during the drying process which would affect the catalytic activity. Thus, the Metal-Organic-Framework (MOF) which possesses a high specific surface area and is relatively more rigid in nature, is suggested to composite with the N-GQDs in order to overcome the shortcomings. On top of that, the proposed IRMOF-3 is also photoluminescent in nature. Therefore, a dual-functionalized sensing probe can be developed with versatile detection based on fluorometry or colorimetry. The biosensor would be designated into a microfluidic paper-based analytical devices (μ-PADs) as it is relatively cheaper among the sensing applications. Apart from that, another novelty of this work is to enable wash-free sandwich immunoassay by incorporating the capacity for buffer collection, which could help in separating the unbounded analyte from the bounded one prior to the colour development. The design for such a capacity could be feasible by optimizing the fluidity morphology and plasmonic techniques. In a nutshell, a novel, robust, versatile and user-friendly PoCT device with acceptable sensitivity could be developed.

For academic enquires please contact Ian Sandall ([Email Address Removed]) or Ruey-An Doong ([Email Address Removed] )

For enquires on the application process or to find out more about the Dual programme please contact [Email Address Removed]

To apply for this opportunity, please visit: https://www.liverpool.ac.uk/study/postgraduate-research/how-to-apply/ and click on the 'Ready to apply? Apply online' button, to start your application. When applying please ensure you Quote the supervisor & project title you wish to apply for and note ‘NTHU-UoL Dual Scholarship’ when asked for details of how plan to finance your studies.


Funding Notes

This project is a part of a 4-year dual PhD programme between National Tsing Hua University (NTHU) in Taiwan and the University of Liverpool in England. It is planned that students will spend 2 years at NTHU, followed by 2 years at the University of Liverpool.
Both the University of Liverpool and NTHU have agreed to waive the tuition fees for the duration of the project and stipend of TWD 11,000/month will be provided as a contribution to living costs (the equivalent of £280 per month when in Liverpool).

References

[1] Geneva: World Health Organization, Available online: https://covid19.who.int/ (last cited: 08 March 2022), 2020.
[2] a) N. R. Smilowitz, D. Kunichoff, M. Garshick, B. Shah, M. Pillinger, J. S. Hochman, J. S. Berger, European heart journal 2021, 42, 2270-2279; b) A. Villoteau, M. Asfar, M. Otekpo, J. Loison, J. Gautier, C. Annweiler, PLOS ONE 2021, 16, e0256931; c) N. Ali, Journal of Medical Virology 2020, 92, 2409-2411.
[3] S. M. Nehring, A. Goyal, B. C. Patel, in Statpearls, StatPearls Publishing Copyright © 2022, StatPearls Publishing LLC., Treasure Island (FL), 2022.
[4] M. B. Pepys, G. M. Hirschfield, Journal of Clinical Investigation 2003, 111, 1805-1812.
[5] J. P. Haran, F. L. Beaudoin, S. Suner, S. Lu, Am J Emerg Med 2013, 31, 137-144.
[6] Q. Li, X. Ding, G. Xia, H.-G. Chen, F. Chen, Z. Geng, L. Xu, S. Lei, A. Pan, L. Wang, Z. Wang, EClinicalMedicine 2020, 23, 100375.
[7] a) N. Chen, M. Zhou, X. Dong, J. Qu, F. Gong, Y. Han, Y. Qiu, J. Wang, Y. Liu, Y. Wei, J. A. Xia, T. Yu, X. Zhang, L. Zhang, The Lancet 2020, 395, 507-513; b) F. Liu, L. Li, M. Xu, J. Wu, D. Luo, Y. Zhu, B. Li, X. Song, X. Zhou, Journal of Clinical Virology 2020, 127, 104370.
[8] M. F. Frances Talaska Fischbach, Kate Stout, Fischbach’s a manual of laboratory and diagnostic tests, 11th ed., Wolters Kluwer, 2022.
[9] W. H. O. Monitoring Nutritional Status & Food Safety Events, 2014, p. 4.
[10] a) C. Hong, X. Meng, J. He, K. Fan, X. Yan, Particuology 2022, 71, 90-107; b) W. Yang, X. Yang, L. Zhu, H. Chu, X. Li, W. Xu, Coordination Chemistry Reviews 2021, 448, 214170; c) A. Payal, S. Krishnamoorthy, A. Elumalai, J. A. Moses, C. Anandharamakrishnan, Food Analytical Methods 2021, 14, 1537-1558.
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