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Circuits and Systems for Lateral Flow Immunoassay Biosensors at the Point-of-Care

Pilavaki, Evdokia; (2018) Circuits and Systems for Lateral Flow Immunoassay Biosensors at the Point-of-Care. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Lateral Flow Immunoassays (LFIAs) are biosensors, which among others are used for the detection of infectious diseases. Due to their numerous advantages, they are particularly suitable for point of care testing, especially in developing countries where there is lack of medical healthcare centers and trained personnel. When the testing sample is positive, the LFIAs generate a color test line to indicate the presence of analyte. The intensity of the test line relates to the concentration of analyte. Even though the color test line can be visually observed for the accurate quantification of the results in LFIAs an external electronic reader is required. Existing readers are not fully optimized for point-of-care (POC) testing and therefore have significant limitations. This thesis presents the development of three readout systems that quantify the results of LFIAs. The first system was implemented as a proof of concept of the proposed method, which is based on the scanning approach without using any moving components or any extra optical accessories. Instead, the test line and the area around it, are scanned using an array of photodiodes (1 × 128). The small size of the pixels gives the system sufficient spatial resolution, to avoid errors due to positioning displacement of the strip. The system was tested with influenza A nucleoprotein and the results demonstrate its quantification capabilities. The second generation system is an optimized version of the proof of concept system. Optimization was performed in terms of matching the photodetectors wavelength with the maximum absorption wavelength of the gold nanoparticles presented in the tested LFIA. Ray trace simulations defined the optimum position of all the components in order to achieve uniform light distribution across the LFIA with the minimum number of light sources. An experimental model of the optical profile of the surface of LFIA was also generated for accurate simulations. Tests of the developed system with LFIAs showed its ability to quantify the results while having reduced power consumption and better limit of detection compared to the first system. Finally, a third generation system was realized which demonstrated the capability of having a miniaturized reader. The photodetector of the previous systems was replaced with a CMOS Image Sensor (CIS), specifically designed for this application. The pixel design was optimized for very low power consumption via biasing the transistors in subthreshold and by reusing the same amplifier for both photocurrent to voltage conversion and noise cancellation. With uniform light distribution at 525 nm and 76 frames/s the chip has 1.9 mVrms total output referred noise and a total power consumption of 21 μW. In tests with lateral flow immunoassay, this system detected concentrations of influenza A nucleoprotein from 0.5 ng/mL to 200 ng/mL.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Circuits and Systems for Lateral Flow Immunoassay Biosensors at the Point-of-Care
Event: UCL
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2018. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) Licence (https://creativecommons.org/licenses/by-nc-nd/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Electronic and Electrical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10062444
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