IEEE BioCAS 2021

Filterless TRF Reader with CMOS Sensor ASIC for Lateral Flow Immunoassays. Alexander Hofmann¹, Peggy Reich¹, Martin Grabmann¹, Georg Gläser¹, Max Trübenbach², Alexander Rolapp¹, Marco Reinhard¹, Friedrich Scholz², and Eric Schäfer¹

¹IMMS, ²Senova Gesellschaft für Biowissenschaft und Technik mbH

Abstract — In this paper, we present a filterless time-resolved fluorescence (TRF) measurement system with an optoelectronic CMOS sensor for highly sensitive readout of lateral flow assay (LFA) test strips. An application-specific integrated circuit (ASIC) was designed in a standard 0.35-μm CMOS technology and includes a 5 × 5 CMOS sensor array. Each sensor pixel contains a 100 μm × 100 μm photodiode acting as signal transducer. For the precise control of the measurement sequence and its timing regime, a microcode engine (MCE) has been realized in a field-programmable gate array (FPGA). An active LED discharge concept was implemented to prevent long afterglow of the light source after it is turned off. To characterize the TRF reader with respect to uniform and reproducible signal intensities, suitable europium (III) [Eu 3+] chelate particles were used as fluorescence standards. Different concentrations of europium-based nanoparticles (NP) on test strips were quantified with the TRF reader. Furthermore, we compared the developed TRF reader to a commercial colorimetric LFA reader system using human C-reactive protein (hCRP) as model analyte. The CMOS sensor ASIC based filterless TRF reader showed a detection dynamic range (DDR) of 4 orders of magnitude with a LoD of 0.2 ng/ml for the quantification of CRP, which was 3.5 times better than the LoD of the commercial LFA reader.