Particle-by-Particle Charge Analysis of DNA-Modified Nanoparticles Using Tunable Resistive Pulse Sensing

Abstract

Resistive pulse sensors, RPS, are allowing the transport mechanism of molecules, proteins and even nanoparticles to be characterised as they traverse pores. Previous work using RPS has shown that the size, concentration and zeta potential of the analyte can be measured. Here we use tunable resistive pulse sensing (TRPS) which utilises a tunable pore to monitor the translocation times of nanoparticles with DNA modified surfaces. We start by demonstrating that the translocation times of particles can be used to infer the zeta potential of known standards and then apply the method to measure the change in zeta potential of DNA modified particles. By measuring the translocation times of DNA modified nanoparticles as a function of packing density, length, structure, and hybridisation time, we observe a clear difference in zeta potential using both mean values, and population distributions as a function of the DNA structure. We demonstrate the ability to resolve the signals for ssDNA, dsDNA, small changes in base length for nucleotides between 15-40 bases long and even the discrimination between partial and fully complementary target sequences. Such a method has potential and applications in sensors for the monitoring of nanoparticles in both medical and environmental samples.

A tunable nanopore sensor for the detection of metal ions using translocation velocity and biphasic pulses

“…55 The relative velocity of the particle can then be calculated from the pulse width, Figure S1 24 . Multiple time points are recorded along the peak and are donated T 0.90 , T 0.80 , T 0.70 etc., and the reciprocal of the average time from each point can be used to calculate the relative particle velocity 24 .…”

“…Secondly, in each ionic strength and pH experiment the zeta potential of the pore wall would need to be known to calculate the zeta potential of the particle. 24,56 To keep the method simple and applicable in further applications the actual zeta potential of the particle is not calculated and for further simplicity in the subsequent figures we use only one measurement to represent the particle speed which is 1/T 0.50 .…”

“…31 As with all RPS sensors the only consumable is the tunable pore, eliminating the need for a carrier gas, fluidics, or optics. TRPS has been validated to accurately determine the concentration, size and surface charge of dispersed inorganic particles 24,[32][33][34][35][36][37] as well as the concentration of a range of biological analytes, which have been reviewed previously. 38,39 Conical nanopores, as used within TRPS, exhibit ionic rectification properties.…”

Tunable Resistive Pulse Sensing: Potential Applications in Nanomedicine

“…More recently, Blundell et al [37] studied the changes in zeta potential of DNA modified particles using TRPS. The high sensitivity of TRPS enabled them to resolve the signals for single stranded and double stranded DNA fragments and detect small changes in base length for oligonucleotides between 15 and 40 bases long and discriminate between partial and fully complementary target sequences.…”

Determination of Zeta Potential via Nanoparticle Translocation Velocities through a Tunable Nanopore: Using DNA-modified Particles as an Example

“…Analyzing individual particles as they pass through a nanopore is advantageous for multimodal samples as TRPS can successfully and effectively distinguish a range of particle sizes amongst a single sample. Tunable resistive pulse sensing completes size 10 , zeta potential 12,18 and concentration 15 measurements simultaneously in a single run and can therefore still differentiate samples of similar, if not the same, size by their surface charge 19 ; an advantage over alternative sizing techniques.…”