Occasionally referred to as ‘colloidal gold,’ gold colloid is a suspension comprising sub-micron gold nanoparticles suspended in a solvent - most commonly water. Gold nanoparticles' distinct electronic, optical, and thermal properties have led to their incorporation into a wide range of technologies, such as microscopy, diagnostics, therapeutics, and electronics.
Several important criteria should be considered when using gold colloids in any of these technologies. In every instance, a desirable material must possess the following characteristics.
- The material must be dispersible in the desired solvent.
- The material should be unaggregated and able to monodisperse with narrow size distributions.
- The material must be available at high concentrations.
- The material should feature a well-defined surface or a capping agent.
- The material must exhibit a long shelf life and remain stable under various conditions.
- The material should be highly purified with low concentrations of residual chemicals left over from manufacturing.
Gold nanoparticles can be supplied in either a colloidal nanoparticle formulation or as a dried powder, with the most appropriate format largely depending on the end use of the nanoparticles.
Over the past six years, nanoComposix (a Fortis Life Sciences Company) has developed several proprietary technologies to manufacture high-quality powdered and solution-phase colloidal gold nanoparticles. These materials have been sold to thousands of customers, destined for various applications from medical diagnostics to solar cells.
This article outlines the properties and uses of gold nanoparticles, summarizes nanoComposix’s experiences working with different types of gold nanomaterials, and explores potential challenges users may face when integrating gold nanoparticles into their own experiments and applications.
Gold nanoparticle formulation details
When choosing a gold nanoparticle supplier, several criteria should be considered. These include size distribution, aggregation state, concentration, and stability.
Synthesis of gold colloid
nanoComposix fabricates gold nanoparticles in solution by reducing chloroauric acid (HAuCl4) in the presence of a range of chemical reagents. These reagents can be used to finetune gold nanoparticle characteristics such as size, shape, and surface capping agent.
The first step in this process is the precipitation of gold ions into minute particles referred to as ‘seed’ nanoparticles. These seed nanoparticles function as nucleation sites, and as the remaining gold ions undergo reduction, the nanoparticles grow until either the gold ions or the reducing agent is depleted.
Optimization of gold ions’ and reagents’ reaction kinetics and stoichiometric ratios enables the fabrication of monodispersed gold nanoparticles ranging from 5 nm to 250 nm in size.
Frens and Turkevich wrote two of the most widely cited journal articles on these reactions, which are excellent resources for anyone interested in learning more about them.1,2
Other non-solution-based methods are available for the production of gold nanoparticles, such as exploding wire or laser ablation. However, these methods produce polydisperse material with broad size distributions.
Gold colloid size distribution
It is possible to produce colloidal gold nanoparticles while maintaining a very narrow size distribution. nanoComposix's colloidal gold nanoparticles frequently achieve CVs (a typical measurement of the standard deviation or diameter) of 8-15% for its colloidal formulations within the 5 nm to 100 nm size range.
Because diffusion rates, optical properties, conductivities, and electron densities of gold nanoparticles are all size-dependent, almost every application will benefit from using particles with narrow size distributions.
Gold colloid aggregation state
The aggregation state of gold nanoparticles is widely considered to be the key difference between the material in its colloidal and powdered forms.
Studies have shown that aggregate size dictates the material's properties rather than primary particle size. Therefore, it is preferable that materials be unaggregated.
nanoComposix surveyed a range of commercially available dried nanopowders and determined that they were all aggregated to cluster sizes of 100 nm to 500 nm, irrespective of the nanoparticle’s primary diameter.
A key benefit of colloidal formulations is that gold nanoparticle solutions can be produced in an unaggregated format, maintaining hydrodynamic sizes comparable to the primary size.
nanoComposix recently developed a proprietary technology to process monodisperse colloidal gold nanoparticles into a dried powder.
These particles can easily redisperse without agglomeration, making this gold nanoparticle formulation ideally suited to applications specifically requiring dried powders or ultrahigh concentration gold solutions. This formulation is also a robust choice for applications requiring gold nanoparticles to be mixed with other reagents before use.
Gold colloid concentration
A number of applications benefit from using a high-concentration solution to dilute material in other buffers or solvents. The synthesis method used typically limits the concentration of gold nanoparticles, which range from 0.01 mg to 0.2 mg of gold per mL of solution.
nanoComposix has developed proprietary processing techniques that can increase concentrations of as-produced colloidal material by a factor of 1000 or more without aggregation.
This process also enables users to ‘wash’ the colloid with buffer solutions to remove all residual reactants, resulting in a high-purity solution containing only nanoparticles and surface capping agents.
This washing technique can also generate a new surface state by exposing colloidal material to other molecules that displace existing molecules on the surface. In this instance, additional purification leads to the removal of excess molecules, yielding a new surface with no residuals present in the final formulation.
Gold colloid stability
A range of critical factors can impact the stability of colloidal gold nanoparticles. These include particle sizes, capping agents, concentration, and the local environment. For example, different capping agents provide distinct stability levels to light, heat, pH, salt, and solvents other than water.
Gold colloid batch consistency
Reaction conditions can severely impact colloidal gold synthesis, so these must be prepared in batches where concentrations and mixing rates are highly controlled. nanoComposix monitors batch-to-batch consistency as part of its quality assurance program, thus ensuring product precision and accuracy.
Batches must meet strict specifications before processing and sale, including the size distribution, hydrodynamic diameter, zeta potential, optical properties, and solution pH of the nanoparticles. Each material is provided with comprehensive specification sheets detailing its characterization.
Gold colloid purification and functionalization
Purifying gold nanoparticles from soluble impurities by extensively washing them with clean buffer solutions is possible. The nanoparticles’ surface can be functionalized by adding further tightly binding capping reagents to the solution.
Once a strong ligand or capping agent has been adsorbed onto the particle’s surface, displacing this with a weaker capping agent is challenging. For example, gold nanoparticles synthesized with tannic acid will feature tannic acid that cannot be displaced from the surface by citrate, which binds more weakly. The tannic acid will, therefore, remain bound to the surface.
Should the tannic acid-coated nanoparticles described in this example be exposed to a more tightly binding ligand, such as PVP, the tannic acid will be displaced, and the nanoparticles will become stabilized with the more tightly binding ligand.
Applications
Gold nanoparticles are already incorporated into a diverse array of technologies and applications.
Diagnostics
The affinity of sulfhydryl (-SH) groups for the gold surface readily conjugates gold nanoparticles to peptides, antibodies, synthetic oligonucleotides, and other proteins.3,4,5 These qualities have led to gold-biomolecule conjugates being incorporated into various diagnostic applications, where their bright red color is a crucial characteristic of home and point-of-care tests, such as home pregnancy tests.
A recent study has highlighted the beneficial application of nanoComposix’s gold nanoparticles in agglutination assays.6 In this study, NanoXact Citrate Gold Nanospheres were coated with Red Blood Cell Membranes (RBCM) to capture and crosslink with fibrinogen molecules in plasma.
This process caused hemagglutination of the gold nanospheres, allowing the detection of fibrinogen via spectrophotometry. Fibrinogen is a widely regarded biomarker that has exhibited links to sepsis and cardiovascular diseases (CVD). The technique employed in this study illustrated a wide dynamic range of detection of fibrinogen from 0.01 to 10 mg/mL.
[Figure 3]
Therapeutics
The potential use of gold nanoparticles as agents for photothermal—and microwave-based therapeutics is currently being investigated.7 This involves functionalizing the nanoparticle surface with an antibody or antibody fragment that specifically targets tumor cells.
Once they reach the tumor, nanoparticles can be illuminated with infrared or microwave radiation to heat them. Because both radiation types pass through skin and tissue, this process allows the heated nanoparticles to destroy the targeted tumor cells.
Electron microscopy
Gold nanoparticles labeled with specifically targeted antibodies can stain cells and tissues for subsequent imaging using a transmission electron microscope (TEM). Gold is an exceptional contrast agent for TEM imaging, as it exhibits a much larger electron density than biomolecules. It is also possible to perform multiparameter experiments using multiple sizes of gold nanoparticles, each labeled with a different antibody.
Conclusions
Whether the final product is in powdered or colloidal form, producing nanomaterial poses many challenges. This is especially the case when designing a material destined for many applications.
nanoComposix provides a comprehensive range of gold colloids with precisely engineered shapes, sizes, and surfaces, allowing it to accommodate diverse application requirements.
References and further reading
- Frens, G. "Controlled nucleation for the regulation of the particle size in monodisperse gold suspensions" Nature (London), Phys. Sci. 1973, 241, 20-22.
- Turkevich, J.; Stevenson, P. C.; Hillier, J. "A study of the nucleation and growth processes in the synthesis of colloidal gold" Discuss. Faraday. Soc. 1951, 11, 55-75.
- Mirkin, C.; Letsinger, R. L.; Mucic, R. C.; Storhoff, J. J. "A DNA-based method for rationally assembling nanoparticles into macroscopic materials" Nature 1996, 382, 607-609.
- Wang, Z.; Levy, R.; Fernig, D.G.; Brust, M. "The Peptide Route to Multifunctional Gold Nanoparticles" Bioconjugate Chemistry 2005, 16, 497-500.
- Johne, B.; Hansen, K.; Mork, E.; Holtlund, J. "Colloidal gold conjugated monoclonal antibodies, studied in the BIAcore biosensor and in the Nycocard immunoassay format" Journal of Immunological Methods 1995, 1, 167-174.
- Kim, I.; Lee, D.; Lee, S. W.; Lee, J. H.; Lee, G.; Yoon, D. S. "Coagulation-Inspired Direct Fibrinogen Assay Using Plasmonic Nanoparticles Functionalized with Red Blood Cell Membranes" ACS Nano 2021, Just Accepted.
- Huang, X.; Jain, P. K.; El-Sayed, I. H.; El-Sayed, M. A. "Plasmonic photothermal therapy (PPTT) using gold nanoparticles" Lasers in Medical Science 2008, 23, 217-228.
About nanoComposix
Since 2004, nanoComposix has provided monodisperse and unagglomerated metal and metal-oxide nanomaterials to thousands of customers. Hundreds of different variants of material, size, shape, and surface are available as stock products and we have produced over 2000 custom core/shell, biofunctionalized, fluorescent, and magnetic nanocomposites to meet client specifications. nanoComposix produced the NIST nanosilver reference material and our particles have been utilized in over 2000 peer-reviewed publications. All of our materials are supplied with certificates of analysis that include electron microscopy, hydrodynamic diameter, and optical data for each batch to guarantee products meet specifications.
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