Plasmonic nanoparticles, methods of making plasmonic nanoparticles and sensors made therefrom

Abstract

A method of making free-standing ALD-coated plasmonic nanoparticles. The method comprises providing a plurality of semiconductor quantum dots. One or more conformal layers of dielectric material are deposited over the quantum dots to form dielectric-coated quantum dots. A conformal metallic nanoshell is deposited over the dielectric-coated quantum dots to form plasmonic nanoparticles. At least one layer chosen from i) the conformal layers of dielectric material and ii) the conformal metallic nanoshell is deposited using a vapor phase atomic layer deposition (ALD) process. Plasmonic nanoparticles and systems employing the nanoparticles are also disclosed.

Claims

1. A method of making free-standing ALD-coated plasmonic nanoparticles comprising: providing a plurality of semiconductor quantum dots; depositing one or more conformal layers of dielectric material over the quantum dots to form dielectric-coated quantum dots; and depositing a conformal metallic nanoshell over the dielectric-coated quantum dots to form plasmonic nanoparticles, wherein at least one layer chosen from i) the conformal layers of dielectric material and ii) the conformal metallic nanoshell is deposited using a vapor phase atomic layer deposition (ALD) process, and wherein the plasmonic nanoparticles are free-standing.

2. The method of claim 1, further comprising dispersing the semiconductor quantum dots on a support comprising sacrificial material prior to the depositing the one or more conformal layers of dielectric material; and removing the sacrificial support after the depositing the conformal metallic nanoshell to form the free-standing ALD-coated plasmonic nanoparticles.

3. The method of claim 2, wherein removing the sacrificial support comprises burning out or vaporizing the sacrificial material.

4. The method of claim 1, wherein the ALD process comprises: a) placing the semiconductor quantum dots on a sacrificial support under vacuum at a temperature in the range of 80° C. to 250° C.; b) forming a chemisorbed monolayer of a first reactant on at least a portion of a surface of the semiconductor quantum dots; c) forming an atomic layer of a material over the semiconductor quantum dots by reacting a second reactant with the chemisorbed monolayer of the first reactant; d) repeating steps b) and c) to achieve a desired layer thickness, wherein between each step a), b), c) and d), vacuum is applied to remove an excess of first reactant, second reactant, and reaction byproducts, and any weakly bonded physi-sorption layer on the surface of the quantum dot.

5. The method of claim 4 further comprising adding a third reactant and optionally a fourth reactant to form a coating with ternary or quaternary compositions, respectively.

6. The method of claim 4, wherein the dielectric material is alumina, Al.sub.2O.sub.3; the first reactant is trimethyl aluminum (TMAl) and the second reactant is water.

7. The method of claim 4, wherein the dielectric material is titania, TiO.sub.2; the first reactant is titanium tetrachloride (TCl.sub.4) and the second reactant is water.

8. The method of claim 4, wherein the conformal metallic nanoshell comprises palladium and is formed by the ALD process employing Pd(hfac).sub.2 as the first reactant and hydrogen as the second reactant.

9. The method of claim 1, further comprising, prior to the depositing the one or more conformal layers of dielectric material, coating the semiconductor quantum dots with silica using a liquid phase sol-gel method to form silica-coated quantum dots having a size suitable for vapor phase atomic layer deposition (ALD).

10. The method of claim 1, wherein the plurality of semiconductor quantum dots have diameters of less than 6 nm.

11. The method of claim 10, wherein the semiconductor quantum dot comprises at least one material selected from the compositions of CdSe/ZnS, CdSe/CdS and ZnSe/ZnS.

12. The method of claim 10, wherein the semiconductor quantum dot is a fluorophore, the plasmonic nanoparticle further comprising a second fluorophore selected from the group consisting of semiconductor nanoparticles or organic dyes such as fluorescein and rhodamine.

13. The method of claim 10, wherein the metallic nanoshell comprises one or more metals selected from gold, silver, platinum, palladium, aluminum, copper, and nickel.

14. The method of claim 1, wherein the metallic nanoshell comprises an array of metallic dots, the metallic dots having a diameter of less than 3 nm.

15. The method of claim 1, wherein the metallic nanoshell comprises a non-uniform metallic layer having a thickness in the range of 0.2 nm to 6 nm.

16. The method of claim 1, wherein the metallic nanoshell is a multilayered metallic nanoshell, wherein each layer has a unique composition.

17. The method of claim 1, wherein the one or more conformal layers of dielectric material comprise a material chosen from the compounds of silica, titania and alumina.

18. The method of claim 1, wherein the semiconductor quantum dot comprises at least one material selected from the compositions of CdSe/ZnS, CdSe/CdS and ZnSe/ZnS.

19. The method of claim 18, wherein the semiconductor quantum dot is a fluorophore, the plasmonic nanoparticle further comprising a second fluorophore selected from the group consisting of semiconductor nanoparticles or organic dyes such as fluorescein and rhodamine.

20. The method of claim 18, wherein the metallic nanoshell comprises one or more metals selected from gold, silver, platinum, palladium, aluminum, copper, and nickel.

21. The method of claim 18, wherein the metallic nanoshell comprises an array of metallic dots, the metallic dots having a diameter of less than 3 nm.

22. The method of claim 18, wherein the metallic nanoshell comprises a non-uniform metallic layer having a thickness in the range of 0.2 nm to 6 nm.

23. The method of claim 18, wherein the metallic nanoshell is a multilayered metallic nanoshell, wherein each layer has a unique composition.

24. The method of claim 23, wherein the one or more conformal layers of dielectric material comprise a material chosen from the compounds of silica, titania and alumina.

25. The method of claim 24, wherein the plurality of semiconductor quantum dots have diameters of less than 6 nm.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the present teachings and together with the description, serve to explain the principles of the present teachings.

(2) FIG. 1A illustrates semiconductor quantum dots dispersed on a support comprising a sacrificial material, according to an embodiment of the present disclosure.

(3) FIG. 1B illustrates conformal layers deposited over the quantum dots, according to an embodiment of the present disclosure.

(4) FIG. 1C illustrates dissolving the sacrificial material of the support, according to an embodiment of the present disclosure.

(5) FIG. 1D illustrates that the resulting coated QDs of FIG. 1B can be separated from the sacrificial support, according to an embodiment of the present disclosure.

(6) FIG. 2 illustrates a semiconductor quantum dot coated with a dielectric material and a metallic shell, according to an embodiment of the present disclosure.

(7) FIG. 3 illustrates a metallic nanoshell covering a quantum dot, as described herein, the metallic nanoshell comprising an array of metallic dots, according to an embodiment of the present disclosure.

(8) FIG. 4A illustrates a quantum dot encapsulated with a non-uniform metallic layer according to an embodiment of the present disclosure.

(9) FIG. 4B depicts the spatial distribution of the EFE for a plasmonic nanoparticle, similar to that shown in FIG. 4A, with a mean silica radius of 23 nm and an excitation wavelength of 800 nm, according to an example of the present disclosure.

(10) FIG. 5 illustrates a multi-shelled plasmonic nanoparticle (MSPN), according to an embodiment of the present disclosure.

(11) FIG. 6 illustrates a schematic diagram of a pH sensor with pH-sensitive ligands that may be functionalized on the outer surface of the proposed PQD nanoparticles to facilitate pH sensing via SERS measurements, according to an embodiment of the present disclosure.

(12) FIG. 7 is a block diagram of a nanosensor system, according to an embodiment of the present disclosure.

(13) FIG. 8 illustrates a 2-dimensional “false color” plot of the magnitude of the computed EFE at the center of the PQD as a function of the Ag layer thickness and the relative permittivity of the dielectric spacer for an incoming plane wave at a wavelength of 800 nm, according to an example of the present disclosure.

(14) FIG. 9 is a plot depicting the EFE as a function of relative dielectric permittivity for Au and Ag films of 2.6 nm, according to an example of the present disclosure.

(15) FIG. 10A is a plot depicting EFE for a 2-metal-shell plasmonic particle as a function of innermost layer thicknesses, according to an example of the present disclosure.

(16) FIG. 10B is a plot depicting EFE for a 2-shell plasmonic particle as a function of outermost layer thicknesses, according to an example of the present disclosure.

(17) FIG. 10C is a plot showing spatial distribution of EFE for a 2-shell plasmonic particle, according to an example of the present disclosure.

(18) FIG. 10D is a plot showing magnified spatial EFE plot for 2-shell plasmonic particle, according to an example of the present disclosure.

(19) FIG. 11 shows 35 nm silica shells uniformly coating QDs prepared using a microemulsion route involving TEOS as a silica source. The 6 nm QDs can be seen as dark spots, and the scale corresponds to 50 nm.

(20) It should be noted that some details of the figure have been simplified and are drawn to facilitate understanding of the embodiments rather than to maintain strict structural accuracy, detail, and scale.

DESCRIPTION OF THE EMBODIMENTS

(21) Reference will now be made in detail to embodiments of the present teachings, examples of which are illustrated in the accompanying drawings. In the drawings, like reference numerals have been used throughout to designate identical elements. In the following description, reference is made to the accompanying drawing that forms a part thereof, and in which is shown by way of illustration a specific exemplary embodiment in which the present teachings may be practiced. The following description is, therefore, merely exemplary.

(22) An embodiment of the present disclosure is directed to a method of making free-standing ALD-coated plasmonic nanoparticles. Referring to FIG. 1A, the method comprises providing a plurality of semiconductor quantum dots (QDs) 10 and other optionally embedded fluorophores such as organic dyes. One or more conformal layers of dielectric material 12 are deposited over the quantum dots 10 to form dielectric-coated quantum dots, as illustrated in FIG. 1B. A conformal metallic nanoshell 14 is deposited over the dielectric-coated quantum dots to form plasmonic nanoparticles 16. At least one layer chosen from i) the conformal layers of dielectric material and ii) the conformal metallic nanoshell is deposited using a vapor phase atomic layer deposition (ALD) process.

(23) In an embodiment, the semiconductor quantum dots are optionally dispersed on a support 18 comprising a sacrificial material 20, as illustrated in FIG. 1A. Examples of the sacrificial material include carbon or organic materials that can be etched by oxygen plasma, UV irradiation, or highly oxidization solvent; metals or metal oxides or other inorganic materials that can be easily removed by acids or bases, e.g. electroplated copper, which can be dissolved by an acid, such as HNO.sub.3; polymers or salts or other materials that can be dissolved by using solvent, e.g. PMMA that can be rinsed off using acetone, NaCl salt that can be rinsed off by water; or any suitable volatile material that will be burned out or vaporized at elevated temperatures. Depending on the chemistry of the sacrificial material surface, the ALD may or may not deposit a film on the sacrificial material. In an embodiment, layer 20 has a hydrophobic surface (e.g., carbon) so that ALD will not occur on the sacrificial material.

(24) ALD can be employed to provide highly conformal dielectric and metal coatings of the QDs. The ALD technique is particularly beneficial for forming the plasmonic particles of the present disclosure because it allows the thickness of the coating to be precisely controlled by varying the number of ALD cycles. In addition, the ALD can allow for a variety of materials to be used as coatings that may not otherwise be easily coated onto the QDs. For example, titania has a higher refractive index than silica, which is desirable for plasmonic nanoparticles of the present disclosure. However sol-gel synthesis of titania is more difficult due to the higher reactivity of the alkoxide precursor. According to an embodiment of this disclosure, ALD is used to provide the desired conformal dielectric coatings, such as titania, over the QDs.

(25) The ALD process comprises: a) optionally placing the semiconductor quantum dots on a sacrificial support under vacuum at a temperature in the range of 80° C. to 250° C.; b) forming a chemisorbed monolayer of a first reactant on at least a portion of a surface of the semiconductor quantum dots; c) forming an atomic layer of a material over the semiconductor quantum dots by reacting a second reactant with the chemisorbed monolayer of the first reactant; and d) repeating steps b) and c) to achieve a desired layer thickness. Between each step a), b), c) and d), a vacuum may be applied and optionally an inert gas can be pumped through the ALD vacuum chamber to remove an excess of first reactant, second reactant, and reaction byproducts, and any weakly bonded physi-sorption layer on the surface of the quantum dot.

(26) Any suitable number or type of reactant gases can be employed depending on the desired composition of the layer to be deposited by the ALD process. For example, the process can include adding a third reactant and optionally a fourth reactant to form a coating with ternary or quaternary compositions, respectively. If the dielectric material to be deposited is alumina, (Al.sub.2O.sub.3), the first reactant in the ALD process can be trimethyl aluminum (TMAl) and the second reactant can be water. In another example where the dielectric material is titania (TiO.sub.2) the first reactant is titanium tetrachloride (TCl.sub.4) and the second reactant is water. In and example where the layer(s) to be deposited by ALD include the conformal metallic nanoshell, the nanoshell can comprise palladium, the first reactant is Pd(hfac).sub.2 and the second reactant is hydrogen. Various other films and known ALD precursors for making the films are shown in Table 1 below. The vapor phase (ALD) techniques will not only allow a larger choice of high quality ultrathin (<10 nm thickness) dielectric (such as titania) and metal films, but also enable the possibility of getting unprecedented film uniformity and thickness control for both the dielectric and metal film layers.

(27) TABLE-US-00001 TABLE 1 ALD product ALD precursors References Al.sub.2O.sub.3 TMAl + H.sub.2O [George, 2010.sup.1; Bent, 2014.sup.2] TiO.sub.2 TiCl.sub.4 + H.sub.2O [George, 2010.sup.1; Bent, 2014.sup.2] SiO.sub.2 TMOS + H.sub.2O [George, 2010.sup.1; Bent, 2014.sup.2] ZnO DMZ + H.sub.2O [George, 2010.sup.1; Bent, 2014.sup.2] Pt MeCpPtMe.sub.3 + O.sub.2 or H.sub.2 at [Aaltonen, 2005].sup.3 200-350° C. Pd Pd(hfac).sub.2 + H.sub.2 at [Aaltonen, 2005].sup.3 80-130° C. Ru RuCp.sub.2 + O.sub.2 at 225-275° C. [Aaltonen, 2005].sup.3 Ir Ir(acac).sub.3 + O.sub.2 225-400° C. [Aaltonen, 2005].sup.3 Au Au Iminopyrrolidinates, [Coyle, 2014].sup.4 plasma ALD Ag Ag Iminopyrrolidinates, [Coyle, 2014.sup.4; Hämäläinen, 2014].sup.5 plasma ALD .sup.1George, Steven M., Chem. Rev. 2010, 110, 111-131, the disclosure of which is incorporated herein by reference in its entirety. .sup.2Bent, Stacey F. et al., Materials Today Volume 17, Number 5 June 2014, the disclosure of which is incorporated herein by reference in its entirety. .sup.3Aaltonen, Titta, “Atomic Layer Deposition of Noble Metal Thin Films,” Academic Dissertation, Dept. of Chemistry, University of Helsinki, 2005, the disclosure of which is incorporated herein by reference in its entirety. .sup.4Coyle, Jason P. et al., Chem. Mater. 2013, 25, 1132-1138, the disclosure of which is incorporated herein by reference in its entirety. .sup.5Hämäläinen, J. et al., Chem. Mater. 2014, 26, 786-801, the disclosure of which is incorporated herein by reference in its entirety.

(28) The ALD technique is very flexible, but a major challenge involves the handling of QD nanoparticles, which are generally less than 6 nm in diameter, such as less than 3 nm in diameter, during the ALD coating process. According to an embodiment of the present disclosure, a two-step approach can be employed to allow ALD coating of QDs. In step one, the method includes coating the semiconductor dots prior to depositing the one or more conformal layers of dielectric material. For example, the semiconductor quantum dots can be coated with silica using a liquid phase sol-gel method to form silica-coated quantum dots having a size suitable for vapor phase atomic layer deposition (ALD). Such liquid phase techniques are generally well known for depositing silica and can preserve the fluorescence of the QDs after the silica coating. The liquid phase coated QD structures are of a size that allows handling via ALD. For example, the liquid phase coated particles can have a diameter ranging from about 10 nm to about 200 nm, such as about 15 nm to about 150 nm, such as about 20 nm to about 100 nm. In step two, the ALD dielectric and/or metal nanoshell layers can be deposited over free flowing silica-coated quantum dots using the above described vapor phase ALD process.

(29) Following the deposition of the dielectric and/or the metallic nanoshell, the resulting coated QDs can be separated from the sacrificial support, such as by etching or dissolving the sacrificial material 20 of the support, as shown in FIGS. 1C and 1D. Then the coated QDs can be further processes in any desired manner, such as to purify or otherwise clean the coated QDs. The semiconductor quantum dot 10 of the resulting plasmonic nanoparticles 16 may be partially encapsulated, as shown in FIG. 1D. Alternatively, the semiconductor quantum dot 10 may be fully encapsulated. For instance, the deposition of the dielectric and/or the metallic nanoshell can be repeated after removing the sacrificial layer 20 in order to fully encapsulate the semiconductor quantum dot 10. In one embodiment, the sacrificial material 20 can be removed after ALD of the dielectric material 12, followed by a second ALD of dielectric to fully encapsulate the quantum dot 10 in the dielectric material 12. A similar, two-step ALD process can then be carried out to deposit metallic nanoshell 14 using ALD so as to fully encapsulate the dielectric material 12 in the metallic nanoshell 14. Any other suitable process can also be employed for fully or partially encapsulating the semiconductor quantum dot 10 using ALD.

(30) An embodiment of the present disclosure is also directed to plasmonic nanoparticles. The nanoparticles comprise a semiconductor quantum dot 10, as shown in FIG. 2. At least one conformal layer of dielectric material 12 is disposed over the semiconductor quantum dot. A conformal metallic nanoshell is disposed over the at least one conformal layer of dielectric material 12, such that one or more of the conformal layers of dielectric insulating material are between the semiconductor quantum dot 10 and the metallic nanoshell 14. At least one layer chosen from i) the conformal layers of dielectric material and ii) the conformal metallic nanoshell is deposited using vapor phase atomic layer deposition (ALD).

(31) Any suitable semiconductor quantum dots can be employed in the plasmonic nanoparticles of the present disclosure. For example, the semiconductor quantum dots can comprise at least one material selected from the compositions of CdSe/ZnS, CdSe/CdS and ZnSe/ZnS.

(32) In an embodiment, the semiconductor quantum dot is a fluorophore and the plasmonic nanoparticle further comprising a second fluorophore. For instance, the second fluorophore can be selected from the group consisting of semiconductor nanoparticles, such as any of the quantum dots described herein, or organic dyes such as fluorescein or rhodamine.

(33) The layer of dielectric material 12 (sometimes referred to herein as the “dielectric layer”) can comprise any suitable material that has the desired permittivity and that can be formed in a suitably conformal layer that does not inhibit the function of the plasmonic nanoparticle. In an embodiment, the at least one dielectric insulating layer comprises at least one material chosen from the compounds of silica, titania and alumina. The dielectric layer 12 can be deposited to be sufficiently thick so as to minimize nonradiative decay and improve the plasmonic resonant enhancement of the plasmonic nanoparticle. The total thickness of the dielectric layer 12 (including the combined thickness of the ALD deposited dielectric and any optional dielectric deposited by liquid phase techniques) can range, for example, from about 3 nm to about 100 nm, such as about 5 nm to about 50 nm, such as about 10 nm to about 20 nm.

(34) The metallic nanoshell can comprise any suitable metals. In an embodiment, the metallic nanoshell comprises one or more metals selected from gold, silver, platinum, palladium, aluminum, copper, and nickel. In general, the thickness of the metal nanoshell 14 can range, for example, from about 0.1 nm to about 15 nm, such as about 0.2 to about 8 nm, such as about 0.2 to about 6 nm or about 1 nm to about 5 nm.

(35) In an embodiment, the metallic nanoshell is a multilayered metallic nanoshell, wherein each layer has a unique composition. For example, the metallic nanoshell can include two or more layers chosen from gold, silver, platinum, palladium, aluminum, copper, and nickel.

(36) The metallic nanoshell can be a highly conformal, continuous layer so as to uniformly encapsulate all or a portion of the particle. Alternatively, the metallic nanoshell can be non-conformal and/or discontinuous. For example, the metallic nanoshell can comprises a dense array of metallic dots 30, as illustrated in FIG. 3. The metallic dots 30 can have a diameter of, for example, less than 3 nm. In another embodiment, the metallic nanoshell comprises a non-uniform metallic layer 14, as illustrated by FIG. 4A. The non-uniform metallic layer 14 can having a thickness that varies within, for example, the range of 0.2 nm to 6 nm. The thickness and uniformity of the metallic nanoshell can be optimized to provide an increased electric field enhancement, as desired.

(37) Referring to FIG. 2, the radius, r1, of the dielectric coated Qd can range, for example, from about 5 nm to about 100 nm, such as about 10 nm to about 50 nm, such as about 15 nm to about 25 nm. In an embodiment, the radius, r2, of the plasmonic nanoparticle can range, for example, from about 6 nm to about 130 nm, such as about 15 nm to about 60 nm, such as about 20 nm to about 40 nm.

(38) FIG. 5 shows an example embodiment of a multi-shelled plasmonic nanoparticle (MSPN). The MSPN includes a semiconductor quantum dot 10, an optional dielectric layer 12-1 that is formed by liquid phase deposition and a dielectric layer 12-2 that is formed by ALD, by methods as described herein. Optional dielectric layer 12-1 and ALD dielectric layer 12-2 fully or partially encapsulate the quantum dot 10. A metal nanoshell 14-1 fully or partially encapsulates dielectric layers 12-1,12-2 and quantum dot 10. A further dielectric layer 12-3 fully or partially encapsulates conductive nanoshell 14-1. A further conductive nanoshell 14-2 fully or partially encapsulates dielectric layer 12-3. Still further dielectric layers 12-N and metal nanoshell layers 14-N can be employed, as shown in FIG. 5, where “N” represents the number of dielectric layers or metal nanoshell layers. Such structures are described in further detail in U.S. Pat. No. 9,267,889, the disclosure of which is incorporated herein by reference in its entirety, Each of the concentric dielectric layers 12-2 to 12-N and metal nanoshell layers 14-1 to 14-N can comprise any of the dielectric or metal layers described herein and can be formed by ALD techniques, as also described herein. The number of nanoshells, “N” can be any number. As an example; N for the metal nanoshell layers can range from 1 to 10, such as 2 to 4, while the associated number of dielectric layers would be whatever number will provide the desired dielectric separation between each of the metal nanoshells.

(39) In appropriately-designed PQD structures, as elaborated further herein, the proposed dielectric and multi-layered metallic nanoshell layers will not only help enhance the electric fields in the center of the nanostructure, thus increasing the brightness of the nanoparticles, but will also chemically isolate the QDs from human tissue and significantly reduce the toxicity of such TPAF nanoparticles if used in biological applications.

(40) In an embodiment, the plasmonic nanoparticles of the present disclosure can exhibit significant fluorescence intensity changes due to relatively sharp resonance peaks. Further, the absorption and emission properties can optionally be chosen to be optimal for wavelengths and intensities that are readily achievable from, for example, relatively standard commercial Ti-sapphire laser systems. It has been found that at a “nominal” intensity of, for example, 8 GW/cm.sup.2, the TPAF signals from “bare” ultrasmall CdSe QDs at excitation wavelengths near 780 nm were observed to be ˜8 times larger than those at 850 nm and ˜68 times larger than those at 900 nm (See Wang, L. et al., “Maximization of nonlinear fluorescence from ultrasmall (≤2 nm) semiconductor quantum dots to be used for deep tissue imaging,” Journal of the Optical Society of America B 26, 2161 (2009)), indicating that such a choice of QDs should be highly relevant for use in the optimization of the proposed PQDs.

(41) In an embodiment, the particles of the present disclosure can be tuned to maximize the output signals for their effective use in biological imaging and luminescent marker applications. This can be done by: (a) using semiconductor materials with relatively high intrinsic quantum efficiencies, (b) optimizing the size of such quantum dots to obtain emission wavelengths that coincide with the availability of efficient photomultiplier or photodetector systems, (c) enhancing the TPAF signals via use of the best designs for plasmonic electric field enhancement (EFE) in the PQD structures, and (d) optimizing the choice of the excitation wavelengths for QDs chosen in accordance with the first two factors.

(42) In an embodiment, the plasmonic nanoparticles of the present disclosure can be configured for two-photon absorption-induced fluorescence (TPAF) imaging. This can be accomplished by the addition of one or more Surface Enhanced Raman Specroscopy (SERS) active molecules adsorbed on an outer surface of the metallic nanoshell. As shown in FIG. 6, the SERS active molecules may include, for example, 4-mercaptopyridine (4MPy) or 4-mercaptobenzoic acid (pMBA). Techniques for attaching such SERS molecules to the outer surface of the plasmonic nanoparticles are well known in the art.

(43) In particular, the illustration of FIG. 6 shows a schematic diagram of a pH nanosensor. This nanosensor comprises a semiconductor quantum dot core 10, surrounded by an dielectric layer 12, which in turn is surrounded by an ultra-thin metal nanoshell 14. Any of the dielectric and/or metal layers described herein can be employed. In one example, the metal nanoshell is a gold or silver nanoshell. The outer layer of the nanoshell 14 is surrounded by an adsorbate of a SERS active molecule (also referred to herein as a ligand), such as pMBA or 4MPy. A feature of the nanoparticle of FIG. 6 is that it enables the simultaneous obtainment of a SERS “signature” signal along with an ultra-bright luminescence from the semiconductor quantum dot to facilitate ultra-precise spatial location of the source of the SERS emission. More specifically, the pH-sensitive SERS shifts in the chosen ligands, such as 4MPy, to provide pH information via the enhanced SERS in the plasmonic particle, while the TPA-induced fluorescence from the PQD core provides clear information on the location of the nanoparticle with micron or sub-micron spatial precision.

(44) As stated above, a modality with which we will use this nanoparticle is by using 2-photon absorption enabled luminescence that occurs simultaneously in the PQD while using the same near-infrared excitation for near-infrared SERS spectroscopy on the surface of the PQD to measure analyte concentrations. One advantage of the PQD nanoparticle over conventional fluorescent quantum dots is the fact that enclosing the quantum dot inside the metallic nanoshell both provides a high enhancement of the local field within the shell, enabling high luminescence efficiency, as well as complete isolation of the quantum dot from the external environment, alleviating problems related to quantum dot toxicity and fluorescence blinking. The outer surface plasmonic enhancement in the proposed PQD will also cause significant enhancements of the SERS signals while enabling spatial information of the location of the measured analyte via the ultrabright TPAF luminescence.

(45) In general, organic acids and bases serve effectively as pH sensitive ligands. The organic acids and bases are chosen based on their relative dissociation constants (Kds), stabilities, and measurable change in SERS signature on protonation/deprotonation. As implied in FIG. 6, pyridine, benzoic acid, and phenol-based compounds can be used as the base structures of the pH-ligands because their conjugated symmetric ring systems are highly Raman active and changes in the protonation state will dramatically affect the SERS spectrum. In particular, 4MPy is an excellent example of a pH-sensitive SERS reporter. This compound has been used frequently as a ligand since it is commercially available and well studied. Any other suitable pH sensitive ligand can be used in addition to or in place of 4MPy. It is noted that such molecules can be functionalized with substituents of varying bulk and electronic properties. These substituents will, in turn, shift the Kd and thus tune the pH sensitive region of the reporter. It is known that the molecules adsorbed on the surface of SERS particles are sensitive to locally changing chemical environments, and manifest themselves as changes in the SERS spectra. See, for example, Hu, J. et al., “Surface-enhanced Raman spectroscopy study on the structure changes of 4-mercaptopyridine adsorbed on silver substrates and silver colloids,” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 58, 2827-2834, doi:10.1016/S1386-1425(02)00074-4, 2002, the disclosure of which is incorporated herein by reference in its entirety.

(46) The sensors of the present disclosure can be employed in a variety of applications. For example, as mentioned above, the sensors can be used in methods for bio-sensing applications, pH sensing or Calcium ion sensing. The plasmonic particles can also be employed in methods for treating cancer. One such method comprises employing the plasmonic nanoparticle for enhancing light intensity for generation of reactive oxygen species (ROS) in light-induced destruction of malignant cancer cells. Such a method can comprise introducing a plurality of the plasmonic nanoparticles of the present disclosure into a patient to be treated for cancer and exciting the plasmonic particles with an illumination source so as to generate reactive ion species in the presence of cancer cells in the patient.

(47) The plasmonic nanoparticles of the present disclosure can be employed as nanosensors for use in nanosensor systems. Referring to FIG. 7, an embodiment of such as nanosensor system 100 comprises an illumination source 102, an optical signal detector 104 and a plasmonic nanoparticle 106. The plasmonic nanoparticle 106 used as the nanosensor can be any of the plasmonic particles described herein. The plasmonic nanoparticle 106 can be contained in any desirable entity, such as a biological entity (e.g., a human or animal). Illumination source 102 can include, among other sources, a light source such as a laser. As would be understood by one of ordinary skill in the art, illumination source 102 can be implemented using a light source with associated optical elements to focus, steer, or wavelength shift output from the light source. The illumination source 102 can be selected based on the characteristics of the plasmonic nanoparticle 106. Alternatively, the plasmonic nanoparticle can be selected based on the characteristics of the illumination source. The selection of illumination source 102 and the plasmonic nanoparticle can be made considering characteristics of both the illumination source and the plasmonic nanoparticle in view of the application for which they are to be applied.

(48) Detection device 104 can include imaging components and/or any other components suitable for detecting light generated by the plasmonic nanoparticles. Such components can include filters to separate light generated by the plasmonic nanoparticle in response to excitation light from an appropriate illumination source 102 from any light from the illumination source 102 that is reflected from entity 108 and the plasmonic nanoparticle. In addition, filters can be used to separate a number of signals that are generated by the plasmonic nanoparticle or the plasmonic nanoparticle in combination with other elements for measuring characteristics of entity 108. Detection device 104 can include data collection equipment such as imaging camera or various types of spectrographic equipment.

EXAMPLES

Example 1

(49) The following examples are based on calculations performed using the Mie scattering theory with a vector spherical harmonic (VSH) model, as reported in Ru, E. L. et al., “Principles of Surface-Enhanced Raman Spectroscopy: and related plasmonic effects,” (Elsevier Science: 2008). The calculations were made based on bulk dielectric constants for Ag and Au at several wavelengths corresponding to optimal TPAF excitation of a PQD containing a 6 nm CdSe QD as a function of the noble metal film thicknesses and the dielectric permittivity of the spacer dielectrics (with silica and titania—with relative permittivities of 2.3 and 6.2—as the most promising candidates as practical dielectrics).

(50) FIG. 8 shows a representative plot of such computations, more specifically depicting a 2-dimensional “false color” plot of the magnitude of the computed EFE at the center of the PQD as a function of the Ag layer thickness and the relative permittivity of the dielectric spacer for an incoming plane wave at a wavelength of 800 nm. Similar computations were performed for Au films over a broad range of wavelengths. FIG. 9 summarizes some of these results by depicting the EFE as a function of relative dielectric permittivity for Au and Ag films of 2.6 nm, indicating very clearly that EFEs of over 12 (and enhancements of TPAF signals by 20,000) may potentially be obtained using relatively simple Au/Ag-titania-encapsulated quantum dots of practical dimensions.

Example 2

(51) Because nanoshells of thicknesses <3 nm may be difficult to fabricate reliably, alternate multilayered and multishelled nanostructures were explored with larger metal film thicknesses and relatively high EFEs. As shown in the preliminary calculations of FIG. 10, which depicts the case of a multilayered nanostructure with 2 silver shells and titania dielectric spacers, much larger enhancements in the EFE may be achieved at the luminescence source (the QD core) and at the outer SERS (surface-enhanced Raman scattering) active surface even with just a first level of optimization of the device dimensions. For this example, based on an excitation wavelength of 800 nm, with an 8 nm thick Ag outer shell and an 80 nm outer diameter titania (relative permittivity of 6.2), the maximum EFE increases with small layer thicknesses; however, even for an inner gold layer as large as 6 nm the maximum EFE observed was over 23, corresponding to an anticipated maximum TPAF signal enhancement of over 280,000, and an anticipated TPAF signal enhancement of over 200,000 over a broad range of relatively practical nanoparticle dimensions. A spatial field enhancement plot of this optimal structure is shown in FIG. 10C and a “zoomed-in” plot for the inner layers shown in FIG. 10D. The anticipated EFEs on the surface of the outer shell were larger than 35, corresponding to anticipated SERS signal enhancements of over 1.5 million. This “first-level optimized” structure corresponds to a 12 nm radius inner titania layer, 6 nm thick inner Ag shell, 80 nm thick outer titania layer, and an outer Ag shell of 8 nm thickness. Even though this structure is larger and a little more complex, it should be much easier to fabricate because of the larger metal film thicknesses needed, and should be very usable for several of the intended applications, such as TPAF-based nonlinear in vivo imaging of vascular tissue. See Larson, Daniel R., et al., “Water-Soluble Quantum Dots for Multiphoton Fluorescence Imaging in Vivo,” Science 300 (5624) (May 30): 1434-1436.

Example 3

(52) Another representative example of a composite nanoparticle, as illustrated in FIG. 4A, is for the case of a QD core/silica shell/gold shell (QDSG) in which the outer gold shell is nonuniform, (the model employed a metal layer thickness that varied from 3 nm to 6 nm). The radius, r.sub.1, was 23 nm; r.sub.2 was 26 nm and r.sub.3 was 29 nm. The physical importance of modeling such a structure lies in the fact that for small metal film thicknesses, thin film deposition techniques often likely lead to non-uniform (and sometimes discontinuous) metal shells. In order to obtain high-accuracy and rapid simulations of such nonuniform shells, a novel multi-trace boundary integral equation (BIE) method was employed. Compared to existing numerical methods, such as differential equation based methods, the BIE method provides several significant advantages, including: (a) very high accuracy for high density composite materials, and a need for much fewer unknowns for precise solutions, (b) much more robust preconditioning and rapid convergence for composites involving multi-scale geometry features, (c) rapid and accurate virtual prototyping of the PQD structures. FIG. 4B depicts the spatial distribution of the EFE for a QDSG nanoparticle with a mean silica radius of 23 nm and an excitation wavelength of 800 nm. It was observed that the EFEs on the surface of the outer shell were larger than 40, the field enhancement outside the quantum dot in the QDSG structure reached a value of 35, and the field enhancement was approximately a factor of 8 near the center of the quantum dot, strongly indicating the promise of such nanostructures for TPAF applications. The use of titania leads to much higher field enhancements, as indicated in Table 1 below.

Example 4

(53) Modelling as described in Example 1 was employed to estimate EFEs for plasmonic nanoparticles having various material combinations and the results are shown in Table 1. It is useful to point out that EFE's of over 5 were also obtained with several other metal-insulator combinations, including Pt, Pd, Ni, and Cu with appropriately chosen metal film and insulator thicknesses, permitting several choices of materials combinations for the proposed plasmonic quantum dots, although Au and titania are the preferred metal and insulator choices.

(54) TABLE-US-00002 TABLE 1 EFE's estimated for the highly uniform PQD structures corresponding to the simple near-ideal PQDs of FIG. 4A High Uniformity EFE @ Dielectric Metal Required λ = 800 nm EFE @ λ = 950 nm SiO.sub.2 Ag yes 8 5.5 SiO.sub.2 Au yes 7 4.5 TiO.sub.2 Ag yes 23 18

Example 5

(55) CdSe/ZnS QDs having a size variation of better than 5% were obtained commercially from Ocean Nanotech. These quantum dots were coated with silica using a coating technique described generally in the literature. The approach including using a reverse microemulsion where the QD, tetraethylorthosilicate (TEOS) and ammonia were localized within reverse micelles resulting in the growth of a silica layer on the QD. A TEM image of the silica-coated QDs from the inventors preliminary work is shown in FIG. 11, in which silica spheres with a diameter <35 nm and a dark QD “core” are evident, as described in Klopfer, M. et al., Plasmonic quantum dots for nonlinear optical applications” Opt. Mater. Express 1, 1353-1366 (2011). The method of synthesis is flexible in that the thickness of the silica layer can be controlled and it allows us to generate uniform coatings of silica on the QDs without affecting their optical properties.

(56) All of the published documents recited in this disclosure are incorporated herein by reference in their entireties. If there is a conflict between any definition of a term recited in any of the incorporated documents and a term recited in this disclosure, the meaning of the term as determined by the text of this disclosure absent the incorporations by reference is controlling.

(57) Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the disclosure are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Moreover, all ranges disclosed herein are to be understood to encompass any and all sub-ranges subsumed therein.

(58) While the present teachings have been illustrated with respect to one or more implementations, alterations and/or modifications can be made to the illustrated examples without departing from the spirit and scope of the appended claims. In addition, while a particular feature of the present teachings may have been disclosed with respect to only one of several implementations, such feature may be combined with one or more other features of the other implementations as may be desired and advantageous for any given or particular function. Furthermore, to the extent that the terms “including,” “includes,” “having,” “has,” “with,” or variants thereof are used in either the detailed description and the claims, such terms are intended to be inclusive in a manner similar to the term “comprising.” Further, in the discussion and claims herein, the term “about” indicates that the value listed may be somewhat altered, as long as the alteration does not result in nonconformance of the process or structure to the illustrated embodiment. Finally, “exemplary” indicates the description is used as an example, rather than implying that it is an ideal.

(59) It will be appreciated that variants of the above-disclosed and other features and functions, or alternatives thereof, may be combined into many other different systems or applications. Various presently unforeseen or unanticipated alternatives, modifications, variations, or improvements therein may be subsequently made by those skilled in the art which are also intended to be encompasses by the following claims.