High-Throughput Single-Molecule Sensors: How Can the Signals Be Analyzed in Real Time for Achieving Real-Time Continuous Biosensing?

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Samenvatting

Single-molecule sensors collect statistics of single-molecule interactions, and the resulting data can be used to determine concentrations of analyte molecules. The assays are generally end-point assays and are not designed for continuous biosensing. For continuous biosensing, a single-molecule sensor needs to be reversible, and the signals should be analyzed in real time in order to continuously report output signals, with a well-controlled time delay and measurement precision. Here, we describe a signal processing architecture for real-time continuous biosensing based on high-throughput single-molecule sensors. The key aspect of the architecture is the parallel computation of multiple measurement blocks that enables continuous measurements over an endless time span. Continuous biosensing is demonstrated for a single-molecule sensor with 10,000 individual particles that are tracked as a function of time. The continuous analysis includes particle identification, particle tracking, drift correction, and detection of the discrete timepoints where individual particles switch between bound and unbound states, yielding state transition statistics that relate to the analyte concentration in solution. The continuous real-time sensing and computation were studied for a reversible cortisol competitive immunosensor, showing how the precision and time delay of cortisol monitoring are controlled by the number of analyzed particles and the size of the measurement blocks. Finally, we discuss how the presented signal processing architecture can be applied to various single-molecule measurement methods, allowing these to be developed into continuous biosensors.

Originele taal-2Engels
Pagina's (van-tot)2271-2281
Aantal pagina's11
TijdschriftACS Sensors
Volume8
Nummer van het tijdschrift6
DOI's
StatusGepubliceerd - 23 jun. 2023

Bibliografische nota

Funding Information:
We thank Stijn Haenen for developing the automated fluidic control system used in the experiments. Part of this work was funded by the Dutch Research Council (NWO), Section Applied and Engineering Sciences, under grant number 16255. Part of this work was funded by the Safe-N-Medtech H2020 project under grant agreement no. 814607. Part of this work was funded by the Consense H2020 project under Marie Skłodowska-Curie grant agreement number 955623.

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