Continuous Biomarker Monitoring with Single-Molecule Resolution
Menno Prins, Professor, Eindhoven University of Technology & Helia BioMonitoring
Single-molecule techniques have become impactful in bioanalytical sciences because of their high detection sensitivity and digital quantitation. However, in the upcoming field of sensors for continuous biomolecular monitoring, the advantages of single-molecule methodologies are yet to be discovered. Here, I will describe a biosensing technology for the continuous monitoring of biomolecular targets, based on measuring the Brownian motion of tethered particles [1-5]. The sensor consists of particles tethered to a surface, where the particles as well as the surface are provided with specific binder molecules. Motion time traces are recorded of hundreds of particles, each revealing digital binding and unbinding events. The events are statistically analyzed and related to the biomarker concentration in solution. Large molecules (proteins, nucleic acids) and small molecules (metabolites, hormones, oligonucleotides) have been measured, across a wide range of concentrations (picomolar to millimolar). In this talk I will describe the BPM sensing principle (Biosensing based on Particle Motion), show experimental results, and discuss applications in industry and healthcare, for early warning and closed-loop control based on real-time biochemical data. Lin et al, ‘Click-coupling to anti-fouling polymers greatly improves the stability of a continuous monitoring sensor with single-molecule resolution’, submitted Lubken et al, ‘How reactivity variability of biofunctionalized particles is determined by superpositional heterogeneities’, ACS Nano (2021) https://pubs.acs.org/doi/10.1021/acsnano.0c08578 Yan et al, ‘Continuous small-molecule monitoring with a digital single particle switch’, ACS Sensors (2020) https://pubs.acs.org/doi/pdf/10.1021/acssensors.0c00220 Lubken et al, ‘Multiplexed continuous biosensing by single-molecule encoded nanoswitches’, Nano Letters (2020) https://pubs.acs.org/doi/10.1021/acs.nanolett.9b04561 Visser, Yan, et al, ‘Continuous biomarker monitoring by particle mobility sensing with single molecule resolution’, Nature Communications (2018) https://www.nature.com/articles/s41467-018-04802-8
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