Rapid Optimization of Metal Nanoparticle Surface Modification with High-Throughput Gel Electrophoresis

Abstract

The ability to effectively control and optimize surface modification of metal nanoparticles is paramount to the ability to employ metal nanoparticles as diagnostic and therapeutic agents in biology and medicine. Here we present a high-throughput two-dimensional-grid gel electrophoresis cell (2D-GEC)-based method, capable of optimizing the surface modification of as many as 96 samples of metal nanoparticles in approximately 1 h. The 2D-GEC method determines not only the average zeta-potential of the modified particles but also the homogeneity of the surface modification by measuring the distance between the front of the sample track and the area where the maximum optical density is achieved. The method was tested for optimizing pH and concentration of the modifiers (pM) for functionalizing gold nanorod thiol-containing acidic agents.

Non‐Invasive Probing of Nanoparticle Electrostatics

“…Consequently, probing the electron transfer between a surface and a NP moving in solution phase during a socalled NP impact experiment, allows the assessment of electrostatic interactions for very small distances of both-a concept that is presented here. 2 The methodology of NP impact experiments utilizes the Brownian motion-driven collisions of suspended NPs with a potentiostated inert conductive surface to study the electron transfer at an individual NP. [27] Once a NP approaches the electrode closely enough for charge transfer to occur, the charge associated with this electron transfer can be detected quantitatively as a spike in a current-time curve.…”

“…For instance electrophoresis [1,2] and electrostatic sieving [3] employ the different mobility of charged species in an external electric field for their separation or for surface modification. Numerous reports, illustrated in Table 1, exist in which electrostatics are invoked as an explanation for the interaction between charged solution-phase nanoparticles (NPs) or molecular species and conducting surfaces.…”

Gel electrophoretic analysis of differently shaped interacting and non-interacting bioconjugated nanoparticles

“…Gel electrophoresis is a ubiquitous tool for biomolecular analysis and, more recently, for nanoparticle characterization and there are future opportunities for integration into lab-on-a-chip devices and higher-throughput 2D gel analysis. 30 Furthermore, improving both the modeling of nanoparticle transport 44 along with exploring different combinations of NP shapes and sizes will further increase the utility of this platform for the analysis of even more complex mixtures of interacting NP-protein bioconjugates featuring different particle shapes and protein functionalizations. …”

“…19 Recently, a 2D GE platform (0.8% agarose) has been demonstrated for even higher throughput analysis of PEG-modied gold nanorod samples. 30 Most gel-based studies have focused on individual nanoparticles. However, there have been a few studies involving the aggregation of relatively small nanoparticles to conrm the controlled assembly of DNAfunctionalised nanoparticles into different aggregate sizes, 24,[31][32][33] and no studies that we are aware of for systems involving protein bioaffinity interactions.…”

Detection, characterization and quantification of inorganic engineered nanomaterials: A review of techniques and methodological approaches for the analysis of complex samples

“…The capability of AGE for separating nanoparticles of different sizes and shapes was demonstrated by Hanauer et al [172], by using silver and gold nanoparticles derivatized by functionalization with polylethylene glycols, in order to control their charge and electrophoretic mobility. In this regard, AGE has been used almost exclusively for the separation and characterization of on purpose functionalized nanoparticles, like DNA and RNA bioconjugated Au NPs [173], or after derivatization, by using different thiol-containing ligands [174]. Detection of the nanoparticles in the cases cited above were based on visual analysis of the gels [173,174], optical extinction spectroscopy [172], hyperspectral imaging [174] or TEM [172].…”