Tunable resistive pulse sensing explained

Tunable resistive pulse sensing (TRPS) is a single-particle technique used to measure the size, concentration and zeta potential of particles as they pass through a size-tunable nanopore.^{[1] [2]}

The technique adapts the principle of resistive pulse sensing, which monitors current flow through an aperture, combined with the use of tunable nanopore technology, allowing the passage of ionic current and particles to be regulated by adjusting the pore size.^{[3] [4]} The addition of the tunable nanopore allows for the measurement of a wider range of particle sizes and improves accuracy.

Technique

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.^[5]

Nanopore-based detection allows particle-by-particle assessment of complex mixtures.^{[6] [7]} By selecting an appropriately sized nanopore and adjusting its stretch, the nanopore size can be optimized for particle size and improve measurement accuracy.  

Adjustments to nanopore stretch, in combination with a fine-control of pressure and voltage allow TRPS to determine sample concentration^[8] and to accurately derive individual particle zeta potential^[9] in addition to particle size information.

Applications

TRPS was developed by Izon Science Limited, producer of commercially available nanopore-based particle characterization systems.^[10] Izon Science Limited currently sell one TRPS device, known as the "Exoid". Previous devices include the "qNano", the "qNano Gold" and the "qViron". These systems have been applied to measure a wide range of biological and synthetic particle types including viruses and nanoparticles. TRPS has been applied in both academic and industrial research fields, including:

• Drug delivery research (e.g. lipid nanoparticles and liposomes)
• Extracellular vesicles such as exosomes
• Virology and vaccine production
• Biomedical diagnostics
• Microfluidics

Notes and References

1. Sowerby SJ, Broom MF, Petersen GB . Dynamically resizable nanometre-scale apertures for molecular sensing. . Sensors and Actuators B: Chemical. . April 2007 . 123 . 1 . 325–330 . 10.1016/j.snb.2006.08.031 .
2. Vogel R, Willmott G, Kozak D, Roberts GS, Anderson W, Groenewegen L, Glossop B, Barnett A, Turner A, Trau M . Quantitative sizing of nano/microparticles with a tunable elastomeric pore sensor . Analytical Chemistry . 83 . 9 . 3499–506 . May 2011 . 21434639 . 10.1021/ac200195n .
3. Roberts GS, Kozak D, Anderson W, Broom MF, Vogel R, Trau M . Tunable nano/micropores for particle detection and discrimination: scanning ion occlusion spectroscopy . Small . Weinheim an Der Bergstrasse, Germany . 6 . 23 . 2653–8 . December 2010 . 20979105 . 10.1002/smll.201001129 .
4. Willmott GR, Vogel R, Yu SS, Groenewegen LG, Roberts GS, Kozak D, Anderson W, Trau M . Use of tunable nanopore blockade rates to investigate colloidal dispersions . Journal of Physics: Condensed Matter. 22 . 45 . 454116 . November 2010 . 21339603 . 10.1088/0953-8984/22/45/454116 . 1005.4255 . 2010JPCM...22S4116W . 11162451 .
5. Vogel R, Pal AK, Jambhrunkar S, Patel P, Thakur SS, Reátegui E, Parekh HS, Saá P, Stassinopoulos A, Broom MF . 6 . High-Resolution Single Particle Zeta Potential Characterisation of Biological Nanoparticles using Tunable Resistive Pulse Sensing . Scientific Reports . 7 . 1 . 17479 . December 2017 . 29234015 . 10.1038/s41598-017-14981-x . 5727177 . 2017NatSR...717479V .
6. 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 . 6 . Measuring particle concentration of multimodal synthetic reference materials and extracellular vesicles with orthogonal techniques: Who is up to the challenge? . Journal of Extracellular Vesicles . 10 . 3 . e12052 . January 2021 . 33473263 . 7804049 . 10.1002/jev2.12052 .
7. 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 . 6 . A standardized method to determine the concentration of extracellular vesicles using tunable resistive pulse sensing . Journal of Extracellular Vesicles . 5 . 1 . 31242 . January 2016 . 27680301 . 5040823 . 10.3402/jev.v5.31242 .
8. Willmott GR, Samuel SC, Vogel R . Pressure dependence of particle transport through resizable nanopores. . 2010 International Conference on Nanoscience and Nanotechnology . February 2010 . 128–131 . IEEE . 10.1109/ICONN.2010.6045207 .
9. Vogel R, Anderson W, Eldridge J, Glossop B, Willmott G . A variable pressure method for characterizing nanoparticle surface charge using pore sensors . Analytical Chemistry . 84 . 7 . 3125–31 . April 2012 . 22369672 . 10.1021/ac2030915 .
10. News: IZON launch world's first commercial nanopore platform . PRLog . June 23, 2009.