Production of colloidal nanoparticles

Abstract

The invention concerns a hybrid physical-chemical method for producing colloidal nanoparticles. The disclosed processes represent a simple, environmentally friendly method to produce size-controlled colloidal nanoparticles.

Description

[0001] Production of Colloidal Nanoparticles

[0002] Field of the Invention

[0003] The invention concerns a hybrid physical-chemical method for producing colloidal nanoparticles. The disclosed processes represent a simple, environmentally friendly method to produce size-controlled colloidal nanoparticles.

[0004] Background of the Invention

[0005] Nanoparticles, also known as atomic clusters, are assemblies of atoms (or molecules) with a size of up to about 100 nm. The ability to exploit, and in some cases tailor, the unique chemical or physical properties of such nanoparticles has now enabled them to be used in a wide spectrum of applications, such as catalysis, medicine (both diagnostics and therapy) and photonics.

[0006] Metal, in particular gold, nanoparticles, represent one particular subset of nanomaterials that has shown distinctive behaviour on the nanoscale, and this has contributed to progress in nanomedicine and nanotechnology. Specifically, colloidal gold suspensions (in which a gold core is capped by an organic molecular, e.g. polymer, layer) are now commercially available, with the largest application area being biomedicine, with an estimated annual worldwide value of ~ $5 billion in 2022, which is expected to grow to ~$10 billion by 2027 with a compound annual growth rate in excess of 10%.

[0007] The main conventional methods for the synthesis of colloidal gold, which enhances the commercial value of gold by a factor of greater than 100 compared with gold bullion, can be divided into two types. The first type is based on the top-down processing of bulk gold under high-voltage electrical current or powerful irradiation (e.g., laser ablation) in a liquid, wherein the metal atoms are separated and then condense into nanoparticles in the liquid dispersion medium. However, such bulk gold processing methods tend to produce gold nanoparticles with rather non-uniform sizes, making the processes inefficient and / or the colloidal nanoparticles unsuitable for use in key market areas such as biomedicine.

[0008] The second, more popular, type is based on the wet-chemical reduction of gold salts (e.g. halides), with subsequent centrifugation, and has been widely used for colloidal gold synthesis for a number of decades. Such wet-chemical reduction processes do offer a good degree of size control; greater power and concentration of reducing agent generally equates to smaller gold nanoparticles. However, the processes utilise harsh chemical reducing agents such as sodium borohydride and, typically, strong acids such as tetrachloroauric acid (HAuCk) in aqueous solution, which are reduced to produce approximately spherical, or non-spherical, gold nanoparticles. Such wet-chemical reduction processes, therefore, have the potential to result in the formation of impure nanoparticles that include some degree of contaminants (e.g. chlorine and / or boron from the residual salt and reducing agent, respectively), and may render the colloidal nanoparticles unsuitable for use in key market areas such as biomedicine.

[0009] Further, the hybrid process disclosed herein can be used for the production of other metal colloids. These include elemental nanoparticles such as palladium, for use in e.g. catalysis; platinum, for use in e.g. cancer treatment; and silver, for use in e.g. anti-microbial coatings, as well as doped, alloy or compound nanoparticles, for, e.g. multimodal imaging. The hybrid process can also be used for the production of non-metal colloidal nanoparticles. These include doped or undoped semiconductor nanoparticles such as silicon, and insulator nanoparticles such as glass.

[0010] There is, therefore, a hitherto unmet need for an efficient, environmentally friendly, route to producing high purity size-controlled nanoparticle colloids.

[0011] This unmet need is addressed by the unique hybrid physical-chemical process disclosed herein, which provides a simple, cost-effective route to prepare size controlled protected nanoparticles (wherein a vaporizable, e.g. metal, core is capped by a molecular shell-layer) in a contaminant free suspension that reduces solvent and reagent usage and thus environmental and health risks. Statements of Invention

[0012] The present invention is as set out in the accompanying claims.

[0013] The invention provides a method for preparing colloidal nanoparticles, said method comprising:

[0014] (i) providing a solid substrate;

[0015] (ii) depositing a combination of vaporizable atoms and organic or inorganic ligands on the surface of said substrate by physical vapour deposition under vacuum conditions to form a nanocomposite film coated substrate;

[0016] (iii) removing said coated substrate from vacuum conditions; and

[0017] (iv) washing said coated substrate in a liquid solvent under non vacuum conditions to dissolve the nanocomposite coating and form a suspension of colloidal nanoparticles in said solvent.

[0018] It has been surprisingly found that such a hybrid physical-chemical method represents a cost-effective route to prepare highly pure size-controlled nanoparticles which minimises I reduces, and preferably eliminates, usage of expensive and / or toxic solvents and reagents compared with conventional nanoparticle synthetic processes, thereby reducing environmental and health risks.

[0019] As used herein, the term ‘nanoparticles’ refers to particles that are between about 1 to about 100 nm in diameter, and comprise clusters or assemblies of vaporizable atoms or molecules. In preferred embodiments, such nanoparticles comprise or consist of clusters or assemblies of one or more metal atoms or metal containing molecules. In alternative embodiments, such nanoparticles may comprise or consist of a clusters or assemblies of one or more non-metallic semiconductor (e.g. silicon) or insulator (e.g. glass) particles.

[0020] Similarly, the term ‘colloidal nanoparticles’ refers, in the context of the present specification, to a stabilized solution of core-shell nanoparticles, i.e. a vaporizable, preferably metallic, particle core disposed within a capping layer formed from an organic or inorganic ligand, structure.

[0021] As used herein, the term ‘vaporizable atoms’ refers to any atom or particle that can be vaporized and deposited onto a surface by physical vapor deposition under vacuum conditions. In preferred embodiments, said vaporizable atoms comprise or consist of metal atoms.

[0022] As would be readily appreciated by the skilled reader, the term ‘vacuum conditions’ refer in the context of the present specification to a closed environment having gas pressure of about 10’1Pa or below, preferably about 10’3Pa or below, and more preferably aboutIO’4Pa or below. Conversely, in the context of the present specification, ‘non-vacuum conditions’ refers to an open or closed environment having a gas pressure of greater than about 102Pa, preferably greater than about 103Pa, and more preferably greater than about than about 104Pa. In preferred embodiments, ‘non-vacuum conditions’ refer to a standard atmospheric pressure environment (at sea level, this equates to a pressure of about 101 kPa).

[0023] In its broadest aspect, the method of the invention is not limited to the deposition of any particular vaporizable atom(s), and is suitable for forming colloidal nanoparticles comprising any metallic core. The method is equally suitable for forming colloidal nanoparticles comprising a non-metallic semiconductor or insulator core. However, in preferred embodiments, colloidal metal nanoparticles are formed, and still more preferably the deposition process of step (ii) comprises depositing metal atoms selected from: gold (Au), silver (Ag), copper (Cu), palladium (Pd), platinum (Pt), iron (Fe), titanium (Ti) or an alloy comprising one or more of said metals, and, optionally, one or more dopant elements. Most preferably, step (ii) comprises depositing gold atoms, thereby resulting in the formation of colloidal gold nanoparticles.

[0024] As the skilled person will readily appreciate, capping agents or ligands, which may be organic or inorganic, are utilised in colloidal nanoparticle syntheses to stabilize the interface where nanoparticles interact with the preparation medium and control aggregation I prevent coagulation during colloidal synthesis and subsequent storage / use. Further, these stabilizing agents can play a key role in altering the physico-chemical and biological characteristics of the formed nanoparticles, with the steric and chemical bonding (e.g. charge exchange) effects of such capping ligands being responsible for modifying said characteristics.

[0025] Therefore, in its broadest aspect, the method of the invention is not limited to the deposition of any particular organic or inorganic capping ligand, and may be selected by the skilled reader based on need and / or availability without difficulty. However, in preferred embodiments, the deposition process of step (ii) comprises depositing one or more organic, and / or biodegradable and / or biosoluble and / or non-toxic, ligands. In more preferred embodiments, step (ii) comprises depositing one or more organic ligands selected from: surfactants, small molecule ligands, alkanethiols, oligonucleotides, polypeptides, polymers, amino acids, dendrimers, cyclodextrins and polysaccharides. In particularly preferred embodiments, the ligand is an organic ligand selected from: polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), bovine serum albumin (BSA), ethylene diamine tetra acetic acid (EDTA), Chitosan, a quaternary ammonium surfactant such as cetrimonium bromide (CTAB), an amino acid, citrate or any combination thereof. In particularly preferred embodiments, the capping ligand is an organic water- soluble polymer, and is most preferably PVP. In alternative, preferred, embodiments, the ligand is an organic ligand selected from: oligonucleotides, polypeptides, proteins, amino acids, or any combination thereof. The use of such ligands in the process of the invention would result in the direct formation of biospecific, size controlled, nanoparticles that are free from contamination.

[0026] As used herein, the term ‘oligonucleotide’ refers to a single or double stranded DNA or RNA sequence comprising from 5 to 100, and preferably from 10 to 50, nucleotides.

[0027] As used herein, the term ‘polypeptide’ refers to a continuous, unbranched, chain of no more than 50 amino acids joined together via peptide bonds, and so includes dipeptides, tripeptides and oligopeptides, i.e. chains comprising fewer than 20 amino acids. As used herein, the term ‘protein’ refers to a biomolecule comprising one or more chains of at least 50 amino acids that are joined together via peptide bonds. Said one or more chains may be folded or unfolded and / or branched or unbranched.

[0028] The solid substrate on which the nanocomposite is formed is also not particularly limited and includes, but is not limited to, silicon or carbon-based materials (such as graphene, carbon nanotubes, fullerenes and amorphous- Carbon), an oxide, a nitride, a glass, or a MXene. However, in some embodiment, the substrate is a silicon material, which may optionally be doped with one or more heteroatoms (e.g., boron or phosphorus) which regulate the electrical and thermal properties. The presence of dopants or defects at the surface of the substrate may be advantageous in controlling surface diffusion (and so, by extension, nanoparticle size) of the deposited atoms on the substrate.

[0029] The extent of film thickness of the deposited nanocomposite on the surface of the substrate can be measured or calculated by a variety of methods. For example, film thickness is typically calculated by layer deposition rate and deposition time, and measured with spectroscopic ellipsometry.

[0030] Preferably, said nanocomposite film thickness varies from a single monolayer to about 100 pm, more preferably from about 5 nm to about 50 pm, and most preferably from about 50 nm to 10 pm, on the substrate.

[0031] Additionally or alternatively, the weight ratio of deposited vaporizable atoms to capping ligand within the nanocomposite layer, which can be controlled and calculated by the values from quartz crystal microbalance (QCM) measurements, preferably ranges from about 10:90 to about 95:5.

[0032] As already noted, the method of the invention comprises depositing a combination of vaporizable atoms and capping ligands on the surface of the substrate by process such as by evaporation, sputtering or pulsed laser deposition physical vapour deposition (PVD) under vacuum conditions. As would be readily apparent to a person of ordinary skill in the art, the vaporizable atoms and ligands may be deposited via any conventional physical PVD. However, such processes exclude cluster deposition processes, wherein atom clusters are formed (e.g., via condensation in the gas phase) prior to deposition onto the surface of the substrate. Instead, said PVD techniques comprise an atom deposition process, wherein individual atoms or molecules are deposited, and then diffuse and aggregate into nanoparticles, on the substrate surface or within the nanoparticle hybrid film.

[0033] In preferred embodiments, the atoms and / or organic or inorganic ligands are deposited on the surface of the substrate by evaporation deposition.

[0034] The PVD deposition of vaporizable atoms and capping ligands in step (ii) of the method of the invention can be carried out in separate independent deposition steps, or both vaporizable atoms and capping ligands may be codeposited in a single deposition step. In either of said processes, the substrate is coated with one or more layers, wherein each of said layers preferably comprises or consists of said vaporizable atoms and / or said organic or inorganic ligands. Therefore, in said embodiments, the substrate does not comprise any solvent (e.g. water) soluble layer(s) such as an intermediate salt layer, and preferably does not contain any other layers in addition to the PVD deposited vaporizable atom and / or capping ligand layer(s).

[0035] Therefore, in some embodiments, deposition step (ii) comprises or consists of the simultaneous co-deposition of vaporizable atoms and ligands on the surface of the substrate by physical vapour deposition under vacuum conditions to form a nanocomposite film of nanoparticles embedded in a continuous phase of ligand material. This co-deposition step may be repeated one or more times to build film thickness as required.

[0036] In alternative embodiments, the deposition step (ii) comprises or consists of the sequential deposition of a ligand layer followed by a vaporizable atom layer onto the surface of the substrate by physical vapour deposition under vacuum conditions to form a nanocomposite laminate film comprising a layer of nanoparticles captured on a layer, or between two layers, of ligand material. However, said vaporizable atoms may also penetrate into the ligand layer(s) and form nanoparticles therein. As will be readily appreciated, these sequential deposition steps may be repeated one or more times to form two or more layers of ligand material and, optionally, two or more layers of nanoparticles. Further in such sequential deposition embodiments, the nanocomposite laminate film preferably forms a sandwich structure in which n layers of nanoparticles are deposited between n+1 layers of ligand material.

[0037] As already noted, following deposition of the vaporizable atoms and ligands onto the solid substrate, individual atoms diffuse and aggregate into nanoparticles, thereby forming the nanocomposite coated substrate on the substrate surface. The nanocomposite coated substrate is then removed from vacuum conditions and, in step (iv), washed in a liquid solvent under nonvacuum conditions to dissolve the nanocomposite coating, thereby forming a suspension of colloidal nanoparticles in said solvent.

[0038] As will be readily appreciated, the choice of solvent used in wash I dissolution step (iv) is not particularly limited, provided the chosen solvent is compatible with the ligand component of the nanocomposite coating. For example, in preferred embodiments the solvent is water (for environmental and biocompatibility reasons), and the ligand component is an organic water- soluble ligand such as PVP.

[0039] Wash step (iv) may immediately follow (i.e. within 1 day) the removal of the nanocomposite from vacuum conditions. However, it will also be readily appreciated that said wash step may be delayed for a period of time (e.g. from 2 days to 6 months or more), thereby permitting storage and / or transport of the nanocomposite coated substrate in a preferred solid form, before forming the colloidal nanoparticles at a later time point and / or location as desired.

[0040] The specific method by which the coated substrate is washed in dissolution step (iv) is not limited, provided that the substrate is brought into contact with the solvent to dissolve the nanocomposite coating, thereby forming a suspension of colloidal nanoparticles in said solvent. Therefore, in some embodiments, the coated substrate is washed by exposure to a flow of solvent, e.g., by spraying. However, in preferred embodiments, the coated substrate is washed by immersion of the coated substrate in a fixed volume of solvent, thereby forming a high concentration of colloidal nanoparticles in said solvent.

[0041] The skilled reader will also appreciate that the method of the invention may advantageously comprise one or more additional process steps. However, in preferred embodiments, if any additional processing step(s) are included, said steps do not include the deposition of one or more additional solvent (e.g. water) soluble layer(s), and more preferably does not include the deposition of any other layer(s) to the nanocomposite film coated substrate formed in step (ii).

[0042] In one such preferred example, the nanocomposite coated substrate is subjected to a processing step (ii-a), after step (ii) but prior to step (iii), to modify particle size and density on the substrate surface. Suitable processing methods include, but are not limited to, heating, ion-beam irradiation, laser irradiation, and electron beam irradiation. Where ion-beam or electron beam irradiation is employed, the substrate upon which the nanocomposite is formed is preferably doped with one or more dopant materials to provide a charge conducting substrate.

[0043] Alternatively or additionally, the method may further comprise, after step (iv), a ligand exchange step (v) wherein the organic or inorganic ligand used to form the colloidal nanoparticle is exchanged for one or more alternative organic or inorganic ligands, thereby altering the physico-chemical and biological characteristics of the final nanoparticles. Such ligand exchange steps are conventional chemistry processes that the skilled person could routinely complete using standard chemical techniques based on need and / or availability without difficulty.

[0044] Throughout the description and claims of this specification, the words “comprise” and “contain” and variations of the words, for example “comprising” and “comprises” mean “including but not limited to” and do not exclude other moieties, additives, components, integers or steps. Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.

[0045] Any references, including any patent or patent application, cited in this specification are hereby incorporated by reference. No admission is made that any reference constitutes prior art. Further, no admission is made that any of the prior art constitutes part of the common general knowledge in the art.

[0046] Other features of the present invention will become apparent from the following examples. Generally speaking, the invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including the accompanying claims and drawings). Thus, features, integers, characteristics, compounds or chemical moieties described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein, unless incompatible therewith.

[0047] Moreover, unless stated otherwise, any feature disclosed herein may be replaced by an alternative feature serving the same or a similar purpose.

[0048] The Invention will now be described by way of example only with reference to the Examples below and to the following Figures wherein:

[0049] Figure 1. Schematic illustration of the apparatus and method for preparing colloidal metal nanoparticles;

[0050] Figure 2. STEM images and size distribution of gold nanoparticles formed by direct deposition in vacuum onto amorphous-carbon TEM film supports (‘grids’);

[0051] Figure 3. STEM images and size distribution of gold nanoparticles embedded within or supported upon a PVP polymer film;

[0052] Figure 4. STEM images and size distribution of dissolution-generated colloidal gold nanoparticles from a Sequentially deposited Gold-PVP nanocomposite matrix.

[0053] Figure 5. STEM images and size distribution of colloidal gold nanoparticles from Co-deposited Gold-Sodium Citrate Nanocomposite Matrices.

[0054] Figure 6. STEM images and size distribution of colloidal gold nanoparticles from a Sequentially deposited Gold-Sodium Citrate Nanocomposite Matrix. Figure 7. STEM images and size distribution of colloidal gold nanoparticles from Co-deposited Gold-Potassium Citrate Nanocomposite Matrices.

[0055] MATERIALS AND METHODS

[0056] The production of colloidal gold, i.e. a suspension of gold nanoparticles capped with an organic stabilising ligand such as polyethylene glycol (‘PEG’), polyvinylpyridone (‘PVP’), cetyltrimethylammonium bromide (CTAB) or citrate in a solvent, was explored by a two-step process as illustrated in Figure 1.

[0057] In particular, in a first (deposition) step, a solid matrix of colloidal gold has been produced via the creation of a solid nanocomposite matrix by physical vapour deposition of both gold atoms and organic molecules onto a solid support substrate under vacuum conditions. A specific example of this approach is the layer-by-layer method, wherein a thin silicon wafer (4-inch diameter) was attached to the surface of the mounting block, made of copper. A layer of organic material (PVP), which will subsequently provide the ligands of the capped nanoparticles, was deposited onto the wafer via vacuum sublimation of a solid polymer using a polymer evaporator. The polymer evaporator was operated under 160-220°C, and a layer of PVP with a thickness of 50 nm was deposited onto the silicon wafer. Following polymer deposition, a layer of gold atoms (6 angstrom thick) was deposited under vacuum onto the polymer film. This was achieved by performing metal evaporation at 1300°C with a deposition rate of 0.1 angstrom per second. Without wishing to be bound to any particular theory, it is believed that in such a process individual gold atoms form nanoparticles by diffusion and aggregation upon and / or within the polymer film in this step.

[0058] If necessary, this process can be repeated multiple times until a desired thickness and amount of both gold and polymer molecules is obtained. For a layer by layer structure, a PVP layer of ~ 5 nm thick can be used in the subsequent layers. In these proof-of-concept experiments, the nanoparticle matrix architecture consisted of “one layer of PVP + one layer of gold + one layer of PVP.” Upon completion of the deposition step, the coated silicon wafer was then removed from the vacuum chamber block via a valve and load-lock system, which enables the vacuum in the main chamber to be preserved. Once removed from vacuum conditions, in a second (dissolution) step, the wafer bearing the nanocomposite film was transferred into deionised water (15 mL), wherein the nanocomposite film was dissolved and the gold nanoparticles and the ligand material were released, forming the desired suspension of colloidal gold nanoparticles in water.

[0059] As a proof of concept, the materials produced at the end of the first (deposition) and second (dissolution) phases have been examined by scanning transmission electron microscopy (STEM), and compared with a reference example in which gold nanoparticles were produced under vacuum by direct evaporation of gold atoms from a thermal evaporator onto amorphous-carbon TEM film supports (‘grids’).

[0060] Example 1 (Reference): In vacuo Formation of Gold Nanoparticles on TEM Grids

[0061] TEM grids were directly mounted onto several different locations of the block before gold deposition by vacuum evaporation. Gold atoms were deposited onto these TEM grids by direction thermal evaporation for ~ 1 min, at which point the atoms were expected to diffuse and aggregate into nanoparticles on the surface of the grids. The production of gold nanoparticles was then characterised by STEM, following removal of the samples from the vacuum through the load lock.

[0062] STEM images following gold deposition, and size distribution analysis, are shown in Figure 2. Notably, this figure demonstrates that following vacuum evaporation deposition of gold atoms, the TEM gird surface was uniformly covered with gold nanoparticles, having an average diameter of ~2.9 nm. This confirms that direct deposition of atoms can be used for the assembly of supported nanoparticles with a high rate of raw material usage. Example 2 (Step 1): In vacuo Formation of Gold-Polymer Nanocomposite Matrix

[0063] In one embodiment of the claimed method, production of colloidal gold nanoparticles comprises, as a first step, the deposition under vacuum of a layer of organic material, which subsequently forms the organic ligands of the nanocomposite matrix, upon the surface of the solid support removably mounted on the mounting block in a vacuum chamber equipped with a thermal evaporator.

[0064] In this example, the water-soluble polymer polyvinylpyridone (PVP) was chosen for deposition as an example of a common organic ligand material, and a silicon wafer was used as a removable support. A sandwich structure consisting of one (50 nm) layer of PVP + one layer of gold (1 min deposition) + one (5nm) layer of PVP nm)” was deposited on the surface of the silicon wafer by sequential direct evaporation.

[0065] In an optimised geometry it should be possible to capture essentially all the evaporated materials on the removable support using this method, to ensure efficient use of the materials and minimal need for the recovery of waste materials. Further, it is expected that the metal and organic ligand materials may be evaporated simultaneously to produce a similar nanocomposite film of metal nanoparticles in which the metal nanoparticles are embedded in the ligand material.

[0066] STEM images, and size distribution analysis, following formation of the abovementioned sandwich structure are shown in Figure 3. Solely for the purpose of measurement, said structure was deposited onto a TEM grid. Notably, this figure clearly demonstrates that the surface is covered with gold nanoparticles, which are understood to be embedded within or supported upon the deposited PVP film.

[0067] Some bubbles of PVP were also found on the surface, which was due to the aggregation or uneven distribution of PVP molecules during polymer evaporation in this instance. Further, the average diameter of the gold nanoparticles was ~ 1.9 nm, which is smaller than the size of the gold nanoparticles directly deposited on the TEM grid. Without wishing to be bound to any particular theory, a possible explanation for this finding is that the addition of PVP layers presents more defect sites on the deposition surface that can act as nucleation centres for the growth of gold nanoparticles by the diffusion of landed gold atoms.

[0068] Example 3 (Step 2): Ex vacuo Dissolution Formation of Colloidal Gold Nanoparticles

[0069] After deposition of the gold-PVP nanocomposite matrix according to Example 2, the coated silicon wafer was removed from the vacuum chamber by allowing the chamber pressure to rise to atmosphere and removal of a flange, but optimally the support should be removed through a valve and load lock arrangement which leaves the main chamber under vacuum. The 4-inch silicon wafer was washed after removal from the vacuum chamber with 15 mL of deionised water. Then some of the suspension created by the dissolution of the nanocomposite matrix was drop-cast onto a fresh amorphous-carbon TEM grid for STEM study.

[0070] STEM images, and size distribution analysis, of colloidal gold nanoparticles, generated by dissolution and then deposited on the grid, are shown in Figure 4. Notably, this figure clearly shows that gold nanoparticles are present on the TEM grid, which implies the successful generation of gold nanoparticles by dissolution following washing the covered silicon wafer.

[0071] Further, the average diameter of the colloidal gold was found to be ~ 2.8 nm. No change in particle size is expected when the nanoparticles are drop-cast, which is not to say that, e.g., some aggregation, is impossible. This size is somewhat larger than the size of nanoparticles found in the solid matrix grown on the TEM grid (Example 2, Figure 3), which could indicate that there is a measure of further aggregation of gold atoms or clusters during the dissolution process. Alternatively it could be that the size of clusters grown on / in a PVP film on a silicon wafer is larger than grown on / in a PVP film on an amorphous carbon TEM grid film. Example 4 In vacuo Formation and Ex vacuo Dissolution, of Gold- Sodium Citrate Nanocomposite Matrix

[0072] To further demonstrate the utility of the method of the present invention, the methods of Examples 2 and 3 were replicated, with minor revision, to form colloidal gold nanoparticles from gold - citrate nanocomposite matrix.

[0073] In these proof of principle experiments, sodium citrate was chosen for deposition as a further example of a common organic ligand material, and a silicon wafer was again used as a removable support. A two-layer structure was deposited on the surface of the silicon wafer by sequential direct evaporation consisting of one layer of sodium citrate (350°C ; 120 min) + one layer of co-deposited gold (1080 °C ; 10 min, deposition rate 0.0045 A / s) and sodium citrate (350 °C ; 10 min).

[0074] After deposition of the gold-sodium citrate nanocomposite matrix, the coated silicon wafer was removed from the main chamber through a valve and load lock arrangement where the load lock was allowed to rise to atmospheric pressure, leaving the main chamber under vacuum. The silicon wafer was washed after removal from the vacuum chamber with 5 mL of deionised water, and a portion of the suspension created by the dissolution of the nanocomposite matrix was drop-cast onto a fresh amorphous-carbon TEM grid for STEM study.

[0075] STEM images, and size distribution analysis, of colloidal gold nanoparticles, which were generated by dissolution and then deposited onto the grid, are shown in Figure 5a. Notably, this figure clearly shows that gold nanoparticles are present on the TEM grid, which implies that gold nanoparticles were successfully generated by the simultaneous evaporation of metal and organic ligand followed by washing of the coated silicon wafer. Further, the colloidal gold nanoparticles were circular in shape, and had an average diameter of 3.19 ± 1.00 nm.

[0076] As an additional experiment, a further two-layer structure was deposited on the surface of a fresh silicon wafer by sequential direct evaporation consisting of one layer of sodium citrate (350°C ; 180 min) + one layer of co-deposited gold (1100 °C ; 10 min, deposition rate 0.01 A / s) and sodium citrate (350 °C ; 10 min). Again, the silicon wafer was washed using deionised water, and STEM images, and size distribution analysis, of the resultant colloidal gold nanoparticles, are shown in Figure 5b. Again, this figure clearly shows that gold nanoparticles are present on the TEM grid, with discrete circular particles having an average diameter of 2.31 ± 0.86 nm are visible.

[0077] As a yet further example, a two-layer structure was deposited onto a silicon wafer by sequential direct evaporation consisting of one layer of sodium citrate (350°C ; 120 min) + one layer of gold (1100 °C ; 10 min, deposition rate 0.01 A / s). Once again, the silicon wafer was washed using deionised water, and STEM images, and size distribution analysis, of the resultant colloidal gold nanoparticles, are shown in Figure 6. Again, this figure clearly shows that gold nanoparticles are present on the TEM grid, with unform and small discrete particles having an average diameter of 1 .45 ± 0.70 nm visible.

[0078] Example 5 In vacuo Formation and Ex vacuo Dissolution, of Gold- Potassium Citrate Nanocomposite Matrix

[0079] The methods of Example 4 have also been replicated, with minor revision, to form colloidal gold nanoparticles from a gold - potassium citrate nanocomposite matrix.

[0080] In these experiments, a two-layer structure was deposited on the surface of a silicon wafer by sequential direct evaporation consisting of one layer of potassium citrate (230°C ; 60 min) + one layer of co-deposited gold (1100 °C ; 60 min, deposition rate 0.01 A / s) and potassium citrate (230 °C ; 60 min).

[0081] After deposition of the gold-potassium citrate nanocomposite matrix and removal from the vacuum chamber, the coated silicon wafer was washed with 5 mL of deionised water, and STEM images, and size distribution analysis, of the resultant colloidal gold nanoparticles are shown in Figure 7a. This figure clearly shows that gold nanoparticles are present on the TEM grid, albeit in reduced number, with particles (including some worm structures, having an average diameter of 10.99 ± 3.69 nm visible. As a further example, a two-layer structure was deposited onto a silicon wafer by sequential direct evaporation consisting of one layer of potassium citrate (230°C ; 180 min) + one layer of co-deposited gold (1100 °C ; 60 min, deposition rate 0.01 A / s) and potassium citrate (230 °C ; 60 min). Once again, the silicon wafer was washed using deionised water, and STEM images, and size distribution analysis, of the resultant colloidal gold nanoparticles, are shown in Figure 7b. Again, this figure clearly shows that gold nanoparticles are present on the TEM grid, with predominantly round or circular particles having an average diameter of 6.51 ± 2.67 nm visible.

[0082] SUMMARY

[0083] Proof-of-principle experiments have successfully demonstrated for the first time a novel, simple and cost-effective route to produce colloidal nanoparticles. The method employs direct deposition (in particular evaporation deposition, but other physical vapour deposition methods, e.g. sputtering could equally be used) of vaporizable atoms and capping ligand molecules on a support under vacuum. The deposition of vaporizable atoms and capping ligand molecules can be sequential or simultaneous, as shown in the proof of principle experimentation disclosed herein.

[0084] The resulting solid matrix of nanoparticles embedded in or on the ligand film can be transformed into a colloidal nanoparticle solution Ex vacuo by transferring the deposited matrix out of the vacuum chamber and washing with a solvent e.g. water.

Claims

CLAIMS1 ) A method for preparing colloidal nanoparticles, said method comprising: i. providing a solid substrate; ii. depositing a combination of vaporizable atoms and organic or inorganic ligands on the surface of said substrate by physical vapour deposition under vacuum conditions to form a nanocomposite film coated substrate; iii. removing said coated substrate from vacuum conditions; and iv. washing said coated substrate in a liquid solvent under non vacuum conditions to dissolve the nanocomposite coating and form a suspension of colloidal nanoparticles in said solvent.2) The method according to claim 1 , wherein said vaporizable atoms are metal atoms.3) The method according to claim 2, wherein step (ii) comprises depositing metal atoms selected from: gold, silver, copper, palladium, platinum, iron, titanium or an alloy comprising one or more of said metals, and, optionally, one or more dopant elements.4) The method according to claim 3, wherein step (ii) comprises depositing gold atoms.5) The method according to any of the preceding claims, wherein step (ii) comprises depositing one or more organic and / or biodegradable and / or biosoluble ligands.6) The method according to claim 5, wherein step (ii) comprises depositing one or more organic ligand selected from: surfactants, small molecule ligands, alkanethiols, oligonucleotides, polypeptides, polymers, amino acids, dendrimers, cyclodextrins and polysaccharides.7) The method according to claim 6, wherein said ligand is an organic ligand selected from: polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), bovine serum albumin (BSA), ethylene diamine tetra acetic acid (EDTA), Chitosan, a quaternary ammonium surfactant, an amino acid, citrate or any combination thereof.8) The method according to claim 6, wherein said ligand is an organic ligand selected from: oligonucleotides, polypeptides, proteins, amino acids, or any combination thereof.9) The method according to any one of the preceding claims, wherein said substrate is selected from silicon; a carbon-based material such as graphene, carbon nanotubes, fullerenes or amorphous-carbon; an oxide, a nitride, a glass, or a MXene.10)The method according to claim 9, wherein said substrate is a silicon material, optionally doped with one or more heteroatoms (e.g. boron or phosphorus).11 )The method according to any one of the preceding claims, wherein said nanocomposite film has a thickness of from about 5 nm to about 50 pm.12)The method according to any one of the preceding claims, wherein the weight ratio of said vaporizable atoms to organic or inorganic ligand within the nanocomposite layer ranges from about 10:90 to about 95:5.)The method according to any one of the preceding claims, wherein said vaporizable atoms and / or said organic or inorganic ligands are deposited on the surface of the substrate by evaporation deposition. )The method according to any of the preceding claims, wherein said substrate is coated with one or more layers, wherein each of said layers comprises or consists of said vaporizable atoms and / or said organic or inorganic ligands. )The method according to any one of the preceding claims, wherein step (ii) comprises or consists of the simultaneous co-deposition of said vaporizable atoms and said organic or inorganic ligands on the surface of the substrate by physical vapour deposition under vacuum conditions to form a nanocomposite film of nanoparticles embedded in a continuous phase of ligand material. )The method according to any one of claims 1 to 14, wherein step (ii) comprises or consists of the sequential deposition of an organic or inorganic ligand layer followed by a vaporizable atom layer onto the surface of the substrate by physical vapour deposition under vacuum conditions to form a nanocomposite laminate film comprising a layer of nanoparticles captured on a layer, or between two layers, of ligand material. )The method according to claim 16, wherein said nanocomposite laminate film forms a sandwich structure in which n layers of nanoparticles are deposited between n+1 layers of ligand material.18)The method according any one of the preceding claims, wherein said liquid solvent is water.19)The method according to any one of the preceding claims, wherein step (iv) comprises immersion of the coated substrate in a fixed volume of said liquid solvent.20)The method according to any one of the preceding claims, wherein said nanocomposite coated substrate is subjected to a processing step (ii- a), after step (ii) but prior to step (iii).21 )The method according to claim 20, wherein said processing step does not include the deposition of one or more additional solvent soluble layer(s), to the nanocomposite film formed in step (ii).22)The method according to claim 20 or claim 21 , wherein step (ii-a) comprises heating, ion-beam irradiation, laser irradiation, and / or electron beam irradiation.23)The method according to any one of the preceding claims, further comprising, after step (iv), a ligand exchange step (v) wherein the organic or inorganic ligand used to form said colloidal nanoparticle is exchanged for one or more alternative organic or inorganic ligands.

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