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Particles crossing a nanopore are detected one at a time as a transient change in the ionic current flow, which is denoted as a blockade event with its amplitude denoted as the blockade magnitude. As blockade magnitude is proportional to particle size, accurate particle sizing can be achieved after calibration with a known standard. This standard is composed of particles of a known size and concentration. For TRPS, carboxylated polystyrene particles are often used.<ref name=":2">{{cite journal | vauthors = Vogel R, Pal AK, Jambhrunkar S, Patel P, Thakur SS, Reátegui E, Parekh HS, Saá P, Stassinopoulos A, Broom MF | display-authors = 6 | title = High-Resolution Single Particle Zeta Potential Characterisation of Biological Nanoparticles using Tunable Resistive Pulse Sensing | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 17479 | date = December 2017 | pmid = 29234015 | doi = 10.1038/s41598-017-14981-x | pmc = 5727177 | bibcode = 2017NatSR...717479V }}</ref>
Nanopore-based detection allows particle-by-particle assessment of complex mixtures.<ref name=":2" /><ref>{{cite journal | vauthors = Vogel R, Savage J, Muzard J, Camera GD, Vella G, Law A, Marchioni M, Mehn D, Geiss O, Peacock B, Aubert D, Calzolai L, Caputo F, Prina-Mello A | display-authors = 6 | title = Measuring particle concentration of multimodal synthetic reference materials and extracellular vesicles with orthogonal techniques: Who is up to the challenge? | journal = Journal of Extracellular Vesicles | volume = 10 | issue = 3 | pages = e12052 | date = January 2021 | pmid = 33473263 | pmc = 7804049 | doi = 10.1002/jev2.12052 }}</ref><ref name=":3">{{cite journal | vauthors = Vogel R, Coumans FA, Maltesen RG, Böing AN, Bonnington KE, Broekman ML, Broom MF, Buzás EI, Christiansen G, Hajji N, Kristensen SR, Kuehn MJ, Lund SM, Maas SL, Nieuwland R, Osteikoetxea X, Schnoor R, Scicluna BJ, Shambrook M, de Vrij J, Mann SI, Hill AF, Pedersen S | display-authors = 6 | title = A standardized method to determine the concentration of extracellular vesicles using tunable resistive pulse sensing | journal = Journal of Extracellular Vesicles | volume = 5 | issue = 1 | pages = 31242 | date = January 2016 | pmid = 27680301 | pmc = 5040823 | doi = 10.3402/jev.v5.31242 }}</ref
Adjustments to nanopore stretch, in combination with a fine-control of pressure and voltage allow TRPS to determine sample concentration <ref>{{cite conference | vauthors = Willmott GR, Samuel SC, Vogel R | title = Pressure dependence of particle transport through resizable nanopores. | conference = 2010 International Conference on Nanoscience and Nanotechnology | date = February 2010 | pages = 128–131 | publisher = IEEE | doi = 10.1109/ICONN.2010.6045207 }}</ref> and to accurately derive individual particle zeta potential<ref name="Vogel_2012">{{cite journal | vauthors = Vogel R, Anderson W, Eldridge J, Glossop B, Willmott G | title = A variable pressure method for characterizing nanoparticle surface charge using pore sensors | journal = Analytical Chemistry | volume = 84 | issue = 7 | pages = 3125–31 | date = April 2012 | pmid = 22369672 | doi = 10.1021/ac2030915 }}</ref> in addition to particle size information.
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