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

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

CMOS Image Sensor for Lateral Flow Immunoassay Readers

Point-of-care systems for the detection of infectious diseases are in great demand especially in developing countries. Lateral flow immunoassays are considered ideal biosensors for point-of-care diagnostics due to their numerous advantages. However, to quantify their results a low power, robust electronic reader is needed. A low power CMOS image sensor is presented that can be used in quantitative lateral flow immunoassay readers. It uses a single low power processing capacitive transimpedance amplifier architecture which includes noise cancellation. A chip containing 4 × 64 pixels was fabricated in CMOS 0.35-μm technology. With uniform illumination at 525 nm and 67 frames per second the chip has 1.9 mVrms total output referred noise and a total power consumption of 21 μW. In tests with lateral flow immunoassays the chip detected concentrations of influenza A nucleoprotein from 0.5 ng/mL to 200 ng/mL.Bio-Electronic