Samenvatting
Continuous biosensors measure concentration-time profiles of biomolecular substances in order to allow for comparisons of measurement data over long periods of time. To make meaningful comparisons of time-dependent data, it is essential to understand how measurement imprecision depends on the time interval between two evaluation points, as the applicable imprecision determines the significance of measured concentration differences. Here, we define a set of measurement imprecisions that relate to different sources of variation and different time scales, ranging from minutes to weeks, and study these using statistical analyses of measurement data. The methodology is exemplified for Biosensing by Particle Motion (BPM), a continuous, affinity-based sensing technology with single-particle and single-molecule resolution. The studied BPM sensor measures specific small molecules (glycoalkaloids) in an industrial food matrix (potato fruit juice). Measurements were performed over several months at two different locations, on nearly 50 sensor cartridges with in total more than 1000 fluid injections. Statistical analyses of the measured signals and concentrations show that the relative residuals are normally distributed, allowing extraction and comparisons of the proposed imprecision parameters. The results indicate that sensor noise is the most important source of variation followed by sample pretreatment. Variations caused by fluidic transport, changes of the sensor during use (drift), and variations due to different sensor cartridges and cartridge replacements appear to be small. The imprecision due to sensor noise is recorded over few-minute time scales and is attributed to stochastic fluctuations of the single-molecule measurement principle, false-positive signals in the signal processing, and nonspecific interactions. The developed methodology elucidates both time-dependent and time-independent factors in the measurement imprecision, providing essential knowledge for interpreting concentration-time profiles as well as for further development of continuous biosensing technologies.
Originele taal-2 | Engels |
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Pagina's (van-tot) | 4924-4933 |
Aantal pagina's | 10 |
Tijdschrift | ACS Sensors |
Volume | 9 |
Nummer van het tijdschrift | 9 |
Vroegere onlinedatum | 21 aug. 2024 |
DOI's | |
Status | Gepubliceerd - 27 sep. 2024 |
Bibliografische nota
Publisher Copyright:© 2024 The Authors. Published by American Chemical Society.
Financiering
We thank Robin Spelbrink and Christel Seegers for discussions on sensor improvements and for critically reading the manuscript. We thank Erwin Dijkstra for performing measurements at Avebe. We thank Avebe for providing the PFJ samples. Part of this work was funded by The Netherlands Topsectors Agri&Food, HTSM, and Chemistry under contract number LWV20.117. Part of this work was funded by The Netherlands National Growth Fund Programme NXTGEN HighTech. Part of this work was funded by the HIGHFIVE project which received funding under the EU Interregional Innovation Investments Instrument under grant agreement 101083989.
Financiers | Financiernummer |
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Netherlands National Growth Fund Programme | |
Netherlands Topsectors Agri & Food | LWV20.117 |
European Commission | 101083989 |