Ultrasensitive Bead-Based Immunoassay for Real-Time Continuous Sample Flow Analysis

The performance of heterophase immunoassays is often limited by the kinetics of analyte binding. This problem is partially solved by bead-based assays, which are characterized by rapid diffusion in the particle suspension. However, at low analyte concentrations, the binding rate is still low. Here,...

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Main Authors: Yuri M. Shlyapnikov, Elena A. Shlyapnikova
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Biosensors
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Online Access:https://www.mdpi.com/2079-6374/15/5/316
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author Yuri M. Shlyapnikov
Elena A. Shlyapnikova
author_facet Yuri M. Shlyapnikov
Elena A. Shlyapnikova
author_sort Yuri M. Shlyapnikov
collection DOAJ
description The performance of heterophase immunoassays is often limited by the kinetics of analyte binding. This problem is partially solved by bead-based assays, which are characterized by rapid diffusion in the particle suspension. However, at low analyte concentrations, the binding rate is still low. Here, we demonstrate a further improvement of analyte binding kinetics in bead-based immunoassays by simultaneously concentrating both an analyte and magnetic beads in a compact spatial region where binding occurs. The analyte is electrophoretically concentrated in a flow cell where beads are magnetically retained and dragged along the channel by viscous force. The flow cell is integrated with a microarray-based signal detection module, where beads with bound analyte scan the microarray surface and are retained on it by single specific interactions, assuring ultra-high sensitivity of the method. Thus, a continuous flow assay system is formed. Its performance is demonstrated by simultaneous detection of model pathogen biomarkers, cholera toxin (CT) and staphylococcal enterotoxin B (SEB), with a detection limit of 0.1 fM and response time of under 10 min. The assay is capable of real-time online sample monitoring, as shown by a 12 h long continuous flow analysis of tap water for SEB and CT.
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spelling doaj-art-7adcc77a99ed4d4b970fbf7a67e735982025-08-20T01:56:17ZengMDPI AGBiosensors2079-63742025-05-0115531610.3390/bios15050316Ultrasensitive Bead-Based Immunoassay for Real-Time Continuous Sample Flow AnalysisYuri M. Shlyapnikov0Elena A. Shlyapnikova1Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, RussiaInstitute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, RussiaThe performance of heterophase immunoassays is often limited by the kinetics of analyte binding. This problem is partially solved by bead-based assays, which are characterized by rapid diffusion in the particle suspension. However, at low analyte concentrations, the binding rate is still low. Here, we demonstrate a further improvement of analyte binding kinetics in bead-based immunoassays by simultaneously concentrating both an analyte and magnetic beads in a compact spatial region where binding occurs. The analyte is electrophoretically concentrated in a flow cell where beads are magnetically retained and dragged along the channel by viscous force. The flow cell is integrated with a microarray-based signal detection module, where beads with bound analyte scan the microarray surface and are retained on it by single specific interactions, assuring ultra-high sensitivity of the method. Thus, a continuous flow assay system is formed. Its performance is demonstrated by simultaneous detection of model pathogen biomarkers, cholera toxin (CT) and staphylococcal enterotoxin B (SEB), with a detection limit of 0.1 fM and response time of under 10 min. The assay is capable of real-time online sample monitoring, as shown by a 12 h long continuous flow analysis of tap water for SEB and CT.https://www.mdpi.com/2079-6374/15/5/316bead-based ultrasensitive immunoassaymagnetic beadscholera toxinstaphylococcal enterotoxin B
spellingShingle Yuri M. Shlyapnikov
Elena A. Shlyapnikova
Ultrasensitive Bead-Based Immunoassay for Real-Time Continuous Sample Flow Analysis
Biosensors
bead-based ultrasensitive immunoassay
magnetic beads
cholera toxin
staphylococcal enterotoxin B
title Ultrasensitive Bead-Based Immunoassay for Real-Time Continuous Sample Flow Analysis
title_full Ultrasensitive Bead-Based Immunoassay for Real-Time Continuous Sample Flow Analysis
title_fullStr Ultrasensitive Bead-Based Immunoassay for Real-Time Continuous Sample Flow Analysis
title_full_unstemmed Ultrasensitive Bead-Based Immunoassay for Real-Time Continuous Sample Flow Analysis
title_short Ultrasensitive Bead-Based Immunoassay for Real-Time Continuous Sample Flow Analysis
title_sort ultrasensitive bead based immunoassay for real time continuous sample flow analysis
topic bead-based ultrasensitive immunoassay
magnetic beads
cholera toxin
staphylococcal enterotoxin B
url https://www.mdpi.com/2079-6374/15/5/316
work_keys_str_mv AT yurimshlyapnikov ultrasensitivebeadbasedimmunoassayforrealtimecontinuoussampleflowanalysis
AT elenaashlyapnikova ultrasensitivebeadbasedimmunoassayforrealtimecontinuoussampleflowanalysis