WO2017034477A1

WO2017034477A1 - Coated upconversion nanoparticles and their methods of preparation

Info

Publication number: WO2017034477A1
Application number: PCT/SG2016/050400
Authority: WO
Inventors: Yong Zhang; Kai Huang
Original assignee: National University Of Singapore
Priority date: 2015-08-21
Filing date: 2016-08-19
Publication date: 2017-03-02

Abstract

There is disclosed a method of tuning the size, shape and fluorescence intensity of upconversion nanoparticles by the steps of (a) forming an upconversion nanoparticle with the chemical formula (I) MA_1-xC_xF₄: Yb_y, B_z; and/or (b) coating the core upconversion nanoparticle with a composition (II): M'A'_1-x'Lu_x'F₄: Yb_y, B'_z, to provide a core-shell nanoparticle, where M, M', A, A', x, x', y, y', B, B', z, z' and C are as defined herein.

Description

COATED UPCONVERSION NANOPARTICLES AND THEIR METHODS OF

PREPARATION

Field of Invention This invention relates to the methods of formation of upconversion nanoparticles (UCNs) and methods of coating the same in a shell material, as well as the products of said processes.

Background

The listing or discussion of a prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or is common general knowledge. Upconversion nanoparticles (UCNs) have been the focus of intense research interest over the last decade. These research efforts have focused on investigating their unique properties, as well as exploring their various applications. This research demonstrates that UCNs are a new class of fluorescent material that surpasses conventional organic dye and quantum dots in terms of nil auto-fluorescence background, deeper penetration of excitation light (e.g. into the tissues of the body), and better photostability. These improved properties in UCNs mean that UCNs show promise as a revolutionary material for bio-imaging, photodynamic therapy, photo-activation and bio-detection. However, the commercialization of UCNs is still hindered by its:

(a) low fluorescent intensity;

(b) lack of tunable color; and

(c) lack of size choices for different application requirements.

The rational doping of lanthanide ions has been reported as an effective way to tune the size of UCNs. With similar ionic radius, lanthanide ions can be doped into a NaYF₄ nanocrystal, which has been proved to be one of the most effective host materials for UCNs, where lanthanide ions take the position of some of the Y³⁺ ions in the crystal lattice. The small difference in radius between the doped ions and the Y³⁺ ion will promote or delay the phase transition of NaYF₄ nanocrystal from the cubic phase to the hexagonal phase during synthesis, thereby affecting the size of the synthesized nanoparticles. One of the goals for UCNs is to be able to select a particular fluorescent property and maintain this property over a range of differing nanoparticle sizes.

The Gd³⁺ ion is most commonly used to decrease the size of UCNs. Due to its larger ionic radius in comparison to Y³⁺, the Gd³⁺ ion promotes the phase transition of the NaYF₄ nanocrystal. Moreover, the difference in radius between the doped ions and Y³⁺ will also affect the electron charge density on the nanoparticle surface, which determines the crystal growth rate. Through density functional theory (DFT) calculation, Liu et a/, demonstrated that the electron charge density of the crystal surface was increased after a larger Gd³⁺ ion replaced the Y³⁺ ion in the NaYF₄ crystal lattice, which is thus repelled by the negatively charged F^" ions and suppresses the growth of the nanoparticle to produce a smaller nanoparticle size, see for example: Liu, X. G. ef a/., Nature, 2010, 463, 1061-1065. Gadolinium (Gd³⁺) also lacks energy levels that interfere with energy transfer in UCNs. Thus, by doping different concentrations of Gd³⁺ into NaYF₄ crystals, UCNs of smaller size can be produced, without much change in the fluorescent properties of the NaYF₄ crystals. Thus, Gd³⁺ can be used to dope UCNs with desirable fluorescent properties to make smaller nanoparticles. However, no way to make said particles larger has been disclosed. When Y³⁺ is replaced by a smaller radius ion, the electron charge density on the surface of growing nanoparticle may be decreased, thus resulting in more attraction of F^" ion(s) to the particle surface to form larger sized UCNs. However, increasing the UCNs size by doping with ianthanides without changing the desired fluorescent properties has met with very little success. For example, it has been reported that one can increase the concentration of Yb³⁺ ions in UCNs, whose ionic radius is smaller than Y³⁺, to make larger UCNs. However, the Yb³⁺ ion is a sensitizer ion and so can be used in the energy transfer process. Given this, changing the concentration of Yb³⁺ in the UCNs causes a significant change in the fluorescent properties of the UCNs because of the back-energy transfer from the activator ions to the sensitizer Yb³⁺ ions. Therefore, the increase of Yb³⁺ concentration not only changes the ratio of peaks in the spectrum, but also decreases the upconversion efficiency and results in UCNs without the desired fluorescent properties. As such, there is still a need to find materials that will enable larger UCNs to be constructed without changing the desired fluorescent properties. NaLuF has been used as a new type of host material for UCNs recently, see for example, Yang, T. et a/., Biomaterials 2012;33:3733-42; Shi, F. et a/., CrystEngComm 2011;13:3782; Zhao, D. et a/., Rsc Adv. 2014;4:13490; Wang, J. et a/., Nanoscale 2013;5:3412-20; Liu, Q. et al., Journal of the American Chemical Society. 2011 ;133:17122-5.

Core-shell structure has been widely reported as a strategy to increase the fluorescence intensity and tune the fluorescence color of UCNs, see for example: Liu, X. et a/., Chem Commun (Camb). 2011;47:11957-9; Lezhnina, M. M. ef a/., Advanced Functional Materials. 2006;16:935-42; Cheng, Q. er a/., Nanoscale. 2012;4:779-84; Dou, Q, et al., Biomaterials. 2013;34:1722-31 ; and Wang, F. ef al., Nat Mater. 2011;10:968-73. However, it is still challenging to coat a shell onto large nanoparticles (e.g. greater than or equal to 40 nm in diameter). During the coating of the shell, there are two processes competing in the reaction of the shell precursors, nucleation and growth. To grow a shell onto core nanoparticles, in the growth process, precursors deposit onto the surface defects of the core nanoparticles, the more defects on the core nanoparticles, and the more chance for the shell precursors to deposit and thus form the shell instead of nucleate. On the bigger core nanoparticles, there are less surface defects, usually when NaYF₄ or NaGdF₄ are used in an attempt to coat bigger core nanoparticles, instead of forming the shell, the shell precursors nucleate and become new small NaYF₄ or NaGdF₄ nanoparticles. Therefore, there is still a need for a shell coating material for UCNs that enables the formation of thick coating shells, leading to an increase in the fluorescence intensity and enabling color tuning over a wider range.

Summary of Invention

Aspects and embodiments of the current disclosure are described with reference to the lettered clauses hereinbelow.

1. A method of tuning the size, shape and fluorescence intensity of upconversion nanoparticles by the steps of:

(a) forming a core upconversion nanoparticle with the chemical formula (I) MA_1-XC_XF₄: Yb_y, B_z; and

(b) coating the core upconversion nanoparticle with a composition (II): M'A'_1-xLu_xF₄: Yb^, Β'_ζ·, to provide a core-shell nanoparticle, wherein:

A, A' and C independently represent Y, Gd, Sc, Nd, La, Lu and Mn (e.g. Y, Gd, Sc, Nd, La and Mn, such as Y, Gd, Sc, and La);

B and B' independently represent one or more of (e.g. one of) Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn (e.g. Mn, or more particularly, Er, Tm, Ho, Ce, Pm, Sm and Eu); M and M' independently represent Na, Li, K, Rb and Cs (e.g. Na, Li, K); in formula (I) and (II):

x and x' independently represent from 0.01 to 1 ;

(1 -x)+x+y+z and (1 -x')+x'+y'+z' represent 100 mol%;

(1-x)+x and (1-χ')+χ' independently represent from 0 mol% to 100 mol% (e.g. 0.001 mol% to 100 mol%);

y and y' independently represent from 0 mol% to 100 mol% (e.g. 0 mol% to 99.999 mol%); and

z and z' independently represent from 0 mol% to 20 mol%.

2. The method of Clause 1 , wherein chemical formula (I) is chemical formula (la):

MAi_-xLu_xF₄: Yb_y, B₂, where M, A, B, x, y and z are as defined in Clause 1. 3. The method of Clause 1 or Clause 2, wherein in formula (I):

x represents from 0.01 to 1 ;

(1-x)+x+y+z represents 100 mol%;

(1-x)+x represents from 0.001 mol% to 100 mol%;

y represents from 0 mol% to 99.999 mol%; and

z represents from 0 mol% to 20 mol%; and in formula (II):

x' represents from 0.01 to 1 ;

(1-x')+x'+y'+z' represents 00 mol%;

(1 -x')+x' represents from 0 mol% to 100 mol%;

y' represents from 0 mol% to 00 mol%; and

z' represents from 0 mol% to 20 mol%.

4. The method of any one of the preceding clauses, wherein in formula (I):

x represents from 0.1 to 1 (e.g. from 0.2 to 0.5); and/or

(1-x)+x represents from 1 mol% to 95 mol% (e.g. from 1 mol% to 90 mol% from 10 mol% to 80 mol%, such as from 20 mol% to 50 mol%, i.e. 48 mol%); and/or

y represents from 2 mol% to 100 mol% (e.g. from 5 mol% to 100 mol%, from 45 mol% to 80 mol%, such as 70 mol%, or from 10 mol% to 30 mol%, such as 20 mol%); and/or

z represents from 0 mol% to 20 mol% (e.g. from 0.1 mol% to 10 mol%, such as from 0.5 mol% to 3 mol%, such as from 1.5 to 2.5 mol%, i.e. 2 mol%), non-limiting embodiments of Clause 4 that may be mentioned herein include compositions of formula (I) wherein:

(a) x represents from 0.2 to 0.5;

(1-x)+x represents from 1 mol% to 95 mol%;

y represents from 2 mol% to 80 mol%; and

z represents from 0 mol% to 20 mol%;

(b) x represents from 0.2 to 0.5;

(1-x)+x represents from 1 mol% to 95 mol%;

y represents from 10 mol% to 30 mol%, such as 20 mol%; and

z represents from from 0.1 mol% to 10 mol%;

(c) x represents from 0.2 to 0.5;

(1-x)+x represents from 10 mol% to 80 mol%;

y represents from 2 mol% to 80 mol%; and

z represents from 1.5 to 2.5 mol%; and

(d) x represents from 0.1 to 1 ;

(1-x)+x represents from 20 mol% to 50 mol%;

y represents 20 mol%; and

z represents from 1.5 to 2.5 mol%.

5. The method of any one of the preceding clauses, wherein in formula (II):

x' represents 0.1 to 1 ; and/or

(1-^χ')+^χ' represents from 1 mol% to 99 mol%; and/or

y' represents from 0 mol% to 80 mol% (e.g. from 10 mol% to 70 mol%); and/or z' represents from 0.5 mol% to 10 mol% (e.g. from 1 mol% to 3 mol%, such as 2 mol%), non-limiting embodiments of Clause 5 that may be mentioned herein include compounds of formula (II) wherein:

(a) x' represents 0.1 to 1 ; and

(1-χ')+χ' represents from 1 mol% to 99 mol%;

(b) x' represents 0.1 to 1 ;

y' represents from 0 mol% to 80 mol%; and

z' represents from 0.5 mol% to 10 mol%;

(c) (1-χ')+χ' represents from 1 mol% to 99 mol%;

y' represents from 10 mol% to 70 mol%; and

z' represents from 1 mol% to 3 mol%; and

(d) x' represents 0.1 to 1 ;

(1-χ')+^χ' represents from 1 mol% to 99 mol%;

y' represents from 0 mol% to 80 mol%; and z' represents from from 1 mol% to 3 mol%.

6. The method of Clause 5, wherein the coating of formula (II) is MLuF₄. 7. The method of any one of any one of the preceding clauses, wherein:

A, A' and C independently represent Y or Gd; and/or

B and B' independently represent one or more of Mn, Er or Tm (e.g. Er and Mn, Tm, or more particularly, Er); and/or

M and M' represent Na.

8. The method of any one of the preceding clauses, wherein the core nanoparticle has a diameter of from 10 nm to 1 ,000 nm (e.g. from 35 nm to 150 nm, such as from 40 to 100 nm). 9. The method of any one of the preceding clauses, wherein the core-shell nanoparticle has a diameter of from 15 nm to 5,000 nm (e.g. from 200 nm to 1 ,000 nm, such as from 350 nm to 600 nm). 0. The method of any one of the preceding clauses, wherein the molar ratio of the core to the shell is from 1 :0.1 to 1 :20 (e.g. from 1 :1 to 1 :15, from 1 :2 to 1 :12, such as from 1 :5 to 1 :10).

11. Use of Lu³⁺ to form part of the shell on a core upconversion nanoparticle. 12. The use of Clause 11 , wherein the Lu³⁺ is provided as lutetium(lll) chloride, lutetium(lll) oxide, lutetium(lll) acetate (hydrate), lutetium(lll) fluoride, lutetium(lll) sulfate (hydrate) and lutetium(lll) trifluoroacetate.

13. The use of Clause 11 or Clause 12, wherein the shell on the core upconversion nanoparticle has chemical formula (II) as described in any one of Clauses 1 and 4 to 9.

14. A core-shell upconversion nanoparticle, where:

the core has chemical formula (I): MA_1-XC_XF₄: Yb_y, B_z; and

the shell has chemical formula (II): M'A'_1-xLu_x F₄: Yby, Β'_ζ·, wherein:

A' and C independently represent Y, Gd, Sc, Nd, La, Lu and Mn (e.g. Y, Gd, Sc, Nd, La and Mn, such as Y, Gd, Sc, and La); B and B' independently represent one or more of (e.g. one of) Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn (e.g. Mn, or more particularly, Er, Tm, Ho, Ce, Pm, Sm and Eu);

M and M' independently represent Na, Li, K, Rb and Cs (e.g. Na, Li, K); in formula (I) and (II):

x and x' independently represent from 0.01 to 1 ;

(1-x)+x+y+z and (1-x')+x'+y'+z' represent 100 mol%;

(1-x)+x and (1-χ')+^χ' independently represent from 0 mol% to 100 mol% (e.g. 0.001 mol% to 100 mol%);

z and z' independently represent from 0 mol% to 20 mol%.

The core-shell upconversion nanoparticle of Clause 14, wherein chemical formula chemical formula (la):

MA _-xLu_xF4: Yb_y, B₂, where M, A, B, x, y and z are as defined in Clause 14.

16. The core-shell upconversion nanoparticle of Clause 14 or Clause 15, wherein in formula (I):

x represents from 0.01 to 1 ;

(1-x)+x+y+z represents 100 mol%;

(1-x)+x represents from 0.001 mol% to 100 mol%;

y represents from 0 mol% to 99.999 mol%; and

z and z' independently represent from 0 mol% to 20 mol%; and formula (II):

x' represents from 0.01 to 1 ;

(1-x')+x'+y'+z' represents 100 mol%;

(1-χ')+χ' represents from 0 mol% to 100 mol%;

y' represents from 0 mol% to 100 mol%; and

z' represents from 0 mol% to 20 mol%.

17. The core-shell upconversion nanoparticle of any one of Clauses 14 to 16, wherein in formula (II):

x' represents 0.1 to 1 ; and/or

(1-^χ')+χ' represents from 1 mol% to 99 mol%; and/or y' represents from 0 mol% to 80 mol% (e.g. from 10 mol% to 70 mol%); and/or z' represents from 0.5 mol% to 10 mol% (e.g. from 1 mol% to 3 mol%, such as 2 mol%), non-limiting embodiments of Clause 17 that may be mentioned herein include compounds of formula (II) wherein:

(a) x' represents 0.1 to 1 ; and

(1-χ')+χ' represents from 1 mol% to 99 mol%;

(b) x' represents 0.1 to 1 ;

y' represents from 0 mol% to 80 mol%; and

z' represents from 1 mol% to 10 mol%;

(c) (1-χ')+χ' represents from 1 mol% to 99 mol%;

y' represents from 0 mol% to 70 mol%; and

z' represents from 0.5 mol% to 3 mol%; and

(d) x' represents 0.1 to 1 ;

(1-χ')+χ' represents from 1 mol% to 99 mol%;

Ϋ represents from 0 mol% to 80 mol%; and

z' represents from from 1 mol% to 3 mol%.

18. The core-shell upconversion nanoparticle of Clause 17, wherein the coating of formula (II) is MLuF₄.

19. The core-shell upconversion nanoparticle of any one of Clauses 14 to 18, wherein in formula (I):

x represents from 0.1 to 1 (e.g. from 0.2 to 0.5); and/or

z represents from 0 mol% to 20 mol% (e.g. from 0.1 mol% to 10 mol%, such as from 0.5 mol% to 3 mol%, such as from 1.5 to 2.5 mol%, i.e. 2 mol%), non-limiting embodiments of Clause 19 that may be mentioned herein include compositions of formula (I) wherein:

(a) x represents from 0.2 to 0.5;

(1-x)+x represents from 1 mol% to 95 mol%;

y represents from 2 mol% to 80 mol%; and

z represents from 0 mol% to 20 mol%;

(b) x represents from 0.2 to 0.5; (1-x)+x represents from 1 mol% to 95 mol%;

y represents from 10 mol% to 30 mol%, such as 20 mol%; and

z represents from from 0.1 mol% to 10 mol%;

(c) x represents from 0.2 to 0.5;

(1-x)+x represents from 10 mol% to 80 mol%;

y represents from 2 mol% to 80 mol%; and

z represents from 1.5 to 2.5 mol%; and

(d) x represents from 0.1 to 1 ;

(1-x)+x represents from 20 mol% to 50 mol%;

y represents 20 mol%; and

z represents from 1.5 to 2.5 mol%.

20. The core-shell upconversion nanoparticle of any one of Clauses 14 to 19, wherein:

A, A' and C independently represent Y or Gd; and/or

M and M' represent Na.

21. The core-shell upconversion nanoparticle of any one of Clauses 14 to 20, wherein the core nanoparticle has a diameter of from 10 nm to 1,000 nm (e.g. from 35 nm to 150 nm, such as from 40 to 100 nm).

22. The core-shell upconversion nanoparticle of any one of Clauses 14 to 21 , wherein the core-shell nanoparticle has a diameter of from 15 nm to 5,000 nm (e.g. from 200 nm to 1 ,000 nm, such as from 350 nm to 600 nm).

23. The core-shell upconversion nanoparticle of any one of Clauses 14 to 22, wherein the molar ratio of the core to the shell is from 1 :0.1 to 1 :20 (e.g. from 1 :1 to 1 :15, 1:2 to 1 :12, such as from 1 :5 to 1 :10).

24. An upconversion nanoparticle with the chemical formula (III)

M"D_1-X"Lu_X"F₄: Yby, E_z- wherein:

D represents Y, Gd, Sc, Nd, La and Mn;

E represents Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn;

M" represents Na, Li, K, Rb and Cs;

x" represents from 0.01 to 1 ; (1-x")+x"+y"+z" represents 100 mol%;

(1-x")+x" represents from 0.001 mol% to 100 mol%;

y" represents from 0 mol% to 99.999 mol%; and

z" represents from 0 mol% to 20 mol%.

25. A method of preparing an upconversion nanoparticle according to Clause 24, and tuning the size, shape and fluorescence intensity of said upconversion nanoparticles, by the step of:

forming an upconversion nanoparticle with the chemical formula (III) M"D_1-X "Lu_X"F₄: Yby, Ε_ζ·, wherein:

D represents Y, Gd, Sc, Nd, La and Mn;

E represents Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn;

M" represents Na, Li, K, Rb and Cs;

x" represents from 0.01 to 1 ;

(1 -x")+x"+y"+z" represents 100 mol%;

(1-x")+x" represents from 0.001 mol% to 100 mol%;

y" represents from 0 mol% to 99.999 mol%; and

z" represents from 0 mol% to 20 mol%. Further aspects and embodiments of the current disclosure are described with reference to the lettered clauses hereinbelow.

A. A method of tuning the size, shape and fluorescence intensity of upconversion nanoparticles by the steps of:

(a) forming an upconversion nanoparticle with the chemical formula (IV)

M"A^A _1-aLu_aF₄: Yb_b, B"_c; and/or

(b) coating a core upconversion nanoparticle having the chemical formula (V):

Yb_e, D_f with a composition (VI): M^AAAA^AA|_-aLu_a F₄: Yb_b', B^AA _C, to provide a core-shell nanoparticle, wherein:

A^A, A^AA and C^A independently represent Y, Gd, Sc, Nd, La and Mn (e.g. Y, Gd, La, Sc and La);

B^A, B^AA and D independently represent Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn (e.g. Er, Tm, Ho, Ce, Pm, Sm, Eu);

M^A, M^AA and M^AAA independently represent Na, Li, K, Rb and Cs (e.g. Na, Li, K); in formula (IV) and (VI):

a and a' independently represent from 0.01 to ; (1-a)+a+b+c and (1-a')+a'+b'+c' represent 100 mol%;

(1-a)+a and (1-a')+a' independently represent from 0.001 mol% to 100 mol% b and b' independently represent from 0 mol% to 99.999 mol%; and

c and c' independently represent from 0 mol% to 20 mol%; and in formula (V):

d represents from 0.01 to 1 ;

(1-d)+d+e+f represents 100 mol%;

(1-d)+d represents from 0 mol% to 100mol%

e represents from 0 mol% to 100 mol%; and

f represents from 0 mol% to 20 mol%.

B. The method of Clause A wherein in formula (IV):

a represents from 0.1 to 1 (e.g. from 0.2 to 0.5); and/or

(1-a)+a represents from 1 mol% to 95 mol% (e.g. from 10 mol% to 80 mol%, such as from 20 mol% to 50 mol%); and/or

b represents from 2 mol% to 80 mol% (e.g. from 10 mol% to 30 mol%, such as 20 mol%); and/or

c represents from 0 mol% to 20 mol% (e.g. from 0.1 mol% to 10 mol%, such as from 1.5 to 2.5 mol%), non-limiting embodiments of Clause B that may be mentioned herein include compositions of formula (IV) wherein:

(a) a represents from 0.2 to 0.5;

(1-a)+a represents from 1 mol% to 95 mol%;

b represents from 2 mol% to 80 mol%; and

c represents from 0 mol% to 20 mol%;

(b) a represents from 0.2 to 0.5;

(1-a)+a represents from 1 mol% to 95 mol%;

b represents from 10 mol% to 30 mol%, such as 20 mol%; and c represents from from 0.1 mol% to 10 mol%;

(c) a represents from 0.2 to 0.5;

(1-a)+a represents from 10 mol% to 80 mol%;

b represents from 2 mol% to 80 mol%; and

c represents from 1.5 to 2.5 mol%; and

(d) a represents from 0.1 to 1 ;

(1-a)+a represents from 20 mol% to 50 mol%;

b represents 20 mol%; and

c represents from 1.5 to 2.5 mol%. C. The method of Clause B, wherein the nanoparticles of formula (IV) are selected from the group consisting of

Yb₀.₂o, Er₀.₀₂; Y₀-7₄Lu₀.26F₄: Yb₀.₂o, Er₀.₀₂; M^AYo-62l-Uo.38F₄: Yb₀.2o. Er₀.o2; and M^AY₀-36l-Uo.6₄F₄: Yb₀.2o, Er₀.02-

D. The method of Clause A wherein in formula (VI):

a' represents 0.1 to 1 ; and/or

(1-a')+a' represents from 1 mol% to 99 mol%; and/or

b' represents from 0 mol% to 80 mol% (e.g. from 10 mol% to 70 mol%); and/or c' represents from 0.5 mol% to 10 mol% (e.g. from 1 mol% to 3 mol%, such as 2 mol%), non-limiting embodiments of Clause D that may be mentioned herein include compounds of formula (VI) wherein:

(a) a' represents 0.1 to 1 ; and

(1-a')+a' represents from 1 mol% to 99 mol%;

(b) a' represents 0.1 to 1 ;

b' represents from 0 mol% to 80 mol%; and

c' represents from 0.5 mol% to 10 mol%;

(c) (1-a')+a' represents from 1 mol% to 99 mol%;

b' represents from 10 mol% to 70 mol%; and

c' represents from 1 mol% to 3 mol%; and

(d) a' represents 0.1 to 1 ;

(1-a')+a' represents from 1 mol% to 99 mol%;

b' represents from 0 mol% to 80 mol%; and

c' represents from from 1 mol% to 3 mol%.

E. The method of Clause D, wherein the coating of formula (VI) is MLuF₄.

F. The method of Clause A wherein in formula (V):

d represents from 0.1 to 1 ; and/or

(1-d)+d represents from 1 mol% to 90 mol% (e.g. from 20 mol% to 50 mol%, such as 48 mol%); and/or

e represents from 5 mol% to 100 mol% (e.g. from 45 mol% to 80 mol%, such as 70 mol%); and/or

f represents from 0 mol% to 20 mol% (e.g. from 0.5 mol% to 3 mol%, such as 2 mol%), non-limiting embodiments of Clause F that may be mentioned herein include compounds of formula (V) wherein:

(a) (1-d)+d represents from 1 mol% to 90 mol%; and f represents from 0 mol% to 20 mol%;

d represents from 0.1 to 1 ;

(1-d)+d represents from 1 mol% to 90 mol%; and

e represents from 5 mol% to 100 mol%;

d represents from 0.1 to 1 ;

(1-d)+d represents from 20 mol% to 50 mol%;

e represents from 45 mol% to 80 mol%; and

f represents from 0.5 mol% to 3 mol%; and

d represents from 0.1 to 1 ;

(1-d)+d represents from 1 mol% to 90 mol%;

e represents from 45 mol% to 80 mol%; and

f represents from 0 mol% to 20 mol%.

The method of any one of Clauses A to F, wherein:

Α^Λ, A" and C^A independently represent Y or Gd; and/or

B^A, B^AA and D independently represent Er or Tm (e.g. Er); and/or

M^A, M^AA and M" independently represent Na.

H. The method of Clause A(a), Clauses B to C, and Clause G, as dependent upon said clauses, wherein the formed nanoparticle has a diameter of from 10 nm to 1 ,000 nm (e.g. from 25 nm to 500 nm, such as from 35 nm to 150 nm).

I. The method of Clause A(b) or Clauses D to F, and Clause G, as dependent upon said clauses, wherein the core nanoparticle has a diameter of from 10 nm to 1 ,000 nm.

J. The method of Clause I, wherein the core nanoparticle has a diameter of from 35 nm to 250 nm (e.g. from 40 to 150 nm).

K. The method of Clause A(b) or Clauses D to F, Clause G, as dependent upon said clauses, and Clauses I to J, wherein the core-shell nanoparticle has a diameter of from 15 nm to 5,000 nm (e.g. from 200 nm to 1,000 nm, such as from 350 nm to 600 nm).

L. The method of Clause A(b) or Clauses D to F, Clause G, as dependent upon said clauses, and Clauses I to J, wherein the molar ratio of the core to the shell is from 1 :0.1 to 1 :20 (e.g. from 1:1 to 1 :15, from 1 :2 to 1 :12, such as from 1 :5 to 1 :10).

M. Use of Lu³⁺ to: (a) dope an upconversion nanoparticle; and/or

(b) form part of the shell on a core upconversion nanoparticle.

N. The use of Clause M, wherein the Lu is provided as lutetium(lll) chloride, lutetium(lll) oxide, lutetium(lll) acetate (hydrate), lutetium(lll) fluoride, lutetium(lll) sulfate (hydrate) and lutetium(lll) trifluoroacetate.

O. The use of Clause M(a) or Clause N, wherein the doped upconversion nanoparticle has chemical formula (IV) as described in any one of Clauses A to C, G and H.

P. The use of Clause M(b), wherein the shell on the core upconversion nanoparticle has chemical formula (VI) as described in any one of Clauses A, D to G and I to L. Q. An upconversion nanoparticle with the chemical formula (IV) M^AAY_aLu_aF₄: Yb_b, B^* _c wherein:

Α^Λ represents Y, Gd, Sc, Nd, La and Mn;

B" represents Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn;

Μ^Λ represents Na, Li, K, Rb and Cs;

a represents from 0.01 to 1 ;

(1-a)+a+b+c represents 100 mol%;

(1-a)+a represents from 0.001 mol% to 100 mol%;

b represents from 0 mol% to 99.999 mol%; and

c represents from 0 mol% to 20 mol%.

R. The upconversion nanoparticle of Clause Q wherein in formula (IV):

a represents from 0.1 to 1 (e.g. from 0.2 to 0.5);

(1-a)+a represents from 1 mol% to 95 mol% (e.g. from 10 mol% to 80 mol%, such as from 20 mol% to 50 mol%);

b represents from 2 mol% to 80 mol% (e.g. from 10 mol% to 30 mol%, such as 20 mol%); and

c represents from 0 mol% to 20 mol% (e.g. from 0.1 mol% to 10 mol%, such as from 1.5 to 2.5 mol%), non-limiting embodiments of Clause R that may be mentioned herein include compositions of formula (IV) wherein:

(a) a represents from 0.1 to 1 ; and

(1-a)+a represents from 1 mol% to 95 mol%;

(b) a represents from from 0.2 to 0.5; (1-a)+a represents from 10 mol% to 80 mol%;

b represents from 2 mol% to 80 mol%;

(c) a represents from 0.1 to 1 ;

(1-a)+a represents from 20 mol% to 50 mol%;

b represents from 10 mol% to 30 mol%; and

c represents from 0 mol% to 20 mol%; and

(d) a represents from from 0.2 to 0.5;

(1-a)+a represents from 10 mol% to 80 mol%;

b represents from 10 mol% to 30 mol%; and

c represents from 1.5 to 2.5 mol%.

S. The upconversion nanoparticle of Clause R, wherein the nanoparticles of formula (IV) are selected from the group consisiting of

Yb₀.2o. Er₀.₀2, M^AYo-74Luo.26F₄: Yb₀.2₀, Er₀.₀2, MYO-62LU₀.38F₄: Yb₀.₂o, Er₀.o₂, and M^/V₀-36Lu₀.64F₄: Yb_{0 2}o,

T. The upconversion nanoparticle of Clause Q or Clause R, wherein the formed nanoparticle has a diameter of from 10 nm to 1 ,000 nm (e.g. from 35 nm to 150 nm).

U. A core-shell upconversion nanoparticle, where:

the core has chemical formula (V): M^AACY_dLu_dF₄: Yb_e, D_f; and the shell has chemical formula (VI): M^AA"A^AY_aLu_A'F₄: Yb_b', ΒΎ-, wherein:

A" and C" independently represent Y, Gd, Sc, Nd, La and Mn;

Β^ΛΛ and D independently represent Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn; Μ^ΛΛ and Μ^ΛΛΛ independently represent Na, Li, K, Rb and Cs; in formula (V):

d represents from 0.01 to 1 ;

(1-d)+d+e+f represents 100 mol%;

(1-d)+d represents from 0 mol% to 100mol%;

e represents from 0 mol% to 100 mol%; and

f represents from 0 mol% to 20 mol%; and in formula (VI):

a' represents from 0.01 to 1 ;

(1-a')+a'+b'+c' represents 100 mol%;

(1-a')+a' represents from 0.001 mol% to 100 mol%; b' represents from 0 mol% to 99.999 mol%; and

c' represents from 0 mol% to 20 mol%.

V. The core-shell upconversion nanoparticle of Clause U, wherein in formula (VI): a' represents 0.1 to 1 ; and/or

(1-a')+a' represents from 1 mol% to 99 mol%; and/or

b' represents from 0 mol% to 80 mol% (e.g. from 10 mol% to 70 mol%); and/or c' represents from 0.5 mol% to 10 mol% (e.g. from 1 mol% to 3 mol%, such as 2 mol%), non-limiting embodiments of Clause V that may be mentioned herein include compounds of formula (VI) wherein:

(a) a' represents 0.1 to 1 ; and

(1-a')+a' represents from 1 mol% to 99 mol%;

(b) a' represents 0.1 to 1 ;

b' represents from 0 mol% to 80 mol%; and

c' represents from 1 mol% to 10 mol%;

(c) (1-a')+a' represents from 1 mol% to 99 mol%;

b' represents from 0 mol% to 70 mol%; and

c' represents from 0.5 mol% to 3 mol%; and

(d) a' represents 0.1 to 1 ;

(1-a')+a' represents from 1 mol% to 99 mol%;

b' represents from 0 mol% to 80 mol%; and

c' represents from from 1 mol% to 3 mol%.

W. The method of Clause U wherein in formula (V):

d represents from 0.1 to 1 ; and/or

f represents from 0 mol% to 20 mol% (e.g. from 0.5 mol% to 3 mol%, such as 2 mol%), non-limiting embodiments of Clause W that may be mentioned herein include compounds of formula (V) wherein:

(a) (1-d)+d represents from 1 mol% to 90 mol%; and

f represents from 0 mol% to 20 mol%;

(b) d represents from 0.1 to 1 ;

(1-d)+d represents from 1 mol% to 90 mol%; and

e represents from 5 mol% to 100 mol%; (c) d represents from 0.1 to 1 ;

(1-d)+d represents from 20 mol% to 50 mol%;

e represents from 45 mol% to 80 mol%; and

f represents from 0.5 mol% to 3 mol%; and

(d) d represents from 0.1 to 1 ;

(1-d)+d represents from 1 mol% to 90 mol%;

e represents from 45 mol% to 80 mol%; and

f represents from 0 mol% to 20 mol%. X. The core-shell upconversion nanoparticle of any one of Clauses U to W, wherein the core nanoparticle has a diameter of from 10 nm to 1 ,000 nm (e.g. from 35 nm to 150 nm, such as from 40 to 100 nm).

Y. The core-shell upconversion nanoparticle of any one of Clauses U to X, wherein the core-shell nanoparticle has a diameter of from 15 nm to 5,000 nm (e.g. from 200 nm to 1 ,000 nm, such as from 350 nm to 600 nm).

Z. The core-shell upconversion nanoparticle of any one of Clauses U to Y, wherein the molar ratio of the core to the shell is from 1 :0.1 to 1 :20 (e.g. from 1 :1 to 1 :15, 1 :2 to 1 :12, such as from 1 :5 to 1 :10).

Drawings

The invention will be described with reference to the drawings below.

Fig. 1: Schematic representation comparing the formation of NaYF₄ and NaLuF₄ nanoparticles, and shells on a core nanoparticle, using the LaMer nucleation model. Fig. 2: X-ray diffraction (XRD) patterns of NaY/LuF₄: Yb, Er UCNs doped with different concentrations of Lu³⁺ and core-shell UCNs of NaYF₄: Yb, Er@5X(NaLuF₄: Yb, Tm). Standard XRD patterns of p-NaYF₄ and p-NaLuF₄ are plotted as references.

Fig. 3: TEM images of NaYF₄:Yb,Er UCNs doping with Lu³⁺ at different concentration, 0%, 10%, 20%, 30%, and 50%, from (a) to (e), respectively; scale bar is 50 nm. (f) Average size of the above samples measured by dynamic light scattering (DLS); (g) Diagram of energy transfer in NaYF₄:Yb,Er UCNs comparing tuning the UCNs size through increasing Yb³⁺ concentration (left) and by doping Lu³⁺ ions (right); (h) Luminescence spectra of NaYF₄:Yb,Er UCNs with different concentrations of Lu³⁺ doping; and (i) luminescence intensity ratio of blue/green and red/green in NaYF₄:Yb,Er UCNs with different concentrations of Lu³⁺ doping.

Fig. 4: Comparing of NaYF4 and NaLuF4 shell coating onto core UCNs under different incubation time. TEM image of core UCNs (a), core-shell UCNs with NaYF4 shell incubated for 1 hour (b) and 4 hours (c), core-shell UCNs with Nal_uF4 shell incubated for 1 hour (d); scale bar is 50 nm. Different activator ions, Er and Tm, are doped separately into core and shell, respectively (e); and (f) Luminescence spectra of core- shell UCNs with NaYF4 or NaLuF4 shell incubated for 1 hour and 4 hours. The core/shell ratio of the above samples are 1 :1.

Fig. 5: Comparison of NaYF₄ and NaLuF₄ shell coating onto core UCNs with different core/shell ratio: TEM image of core-shell UCNs with NaYF₄ shell at 1 :5 (a) and 1 :10 (b) core/shell ratio, scale bar is 100 nm; core-shell UCNs with Nal_uF shell at 1 :5 (c) and 1 :10 (d) core/shell ratio, scale bar is 100 nm; (e) Luminescence spectra of core-shell UCNs with NaYF₄ or NaLuF₄ shell with different core/shell ratio; Er and Tm are doped in core and shell, respectively; and (f) Optical images of the core-shell UCNs with NaLuF₄ shell at different core/shell ratios.

Fig. 6: Coating NaLuF₄ shell onto bigger core UCNs: TEM image of core UCNs (a), core- shell UCNs with NaLuF₄ shell with 1 :5 (b) and 1 :10 (c) core/shell ratio, scale bar is 200 nm; (d) Average size of the above samples measured by DLS; and (e) Luminescence spectra of the above samples; Er and Tm are doped in core and shell, respectively.

Fig. 7: Fluorescence microscope differentiable UCNPs with multiple colors. Fluorescent micrograph of (a) NaLuF₄:Yb,Er; (b) NaLuF₄:Yb,Er@2x(NaLuF₄:Yb,Tm); (c) NaLuF₄:Yb,Er@4x(NaLuF₄:Yb,Tm); (d) NaLuF₄:Yb,Tm; (e) NaLuF₄:Yb,Er,Mn; (f) NaLuF₄:Yb,Er,Mn@3x(NaLuF₄:Yb,Er); (g) NaLuF₄:Yb,Er,Mn@3x(NaLuF₄:Yb,Tm); and their mixture (h). Insertions are their corresponding luminescent photographs. Scale bar is 5 μιτι for (a) to (g), and 20 pm for (h). (i) and (j) are TEM images of core-shell UCNs.

DESCRIPTION In a first aspect of the invention, there is provided a method of tuning the size, shape and fluorescence intensity of upconversion nanoparticles by the steps of:

(a) forming a core upconversion nanoparticle with the chemical formula (I) MA_1-XC_XF₄: Yb_y, B₂; and

(b) coating the core upconversion nanoparticle with a composition (II): M'A'i-_x LUx F₄: Yb^, Β'_ζ·, to provide a core-shell nanoparticle, wherein:

A, A' and C independently represent Y, Gd, Sc, Nd, La, Lu and Mn (e.g. Y, Gd, Sc, Nd, La and Mn, such as Y, Gd, Sc, and La); B and B' independently represent Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn (e.g. Er, Tm, Ho, Ce, Pm, Sm and Eu);

x and x' independently represent from 0.01 to 1 ;

(1 -x)+x+y+z and (1 -x')+x'+y'+z' represent 100 mol%;

(1 -x)+x and (1 -χ')+χ' independently represent from 0 mol% to 100 mol% (e.g. 0.001 mol% to 100 mol%);

y and y' independently represent from 0 mol% to 100 mol% (e.g. 0 mol% to

99.999 mol%); and

z and z' independently represent from 0 mol% to 20 mol%.

In a second aspect of the invention, there is provided a core-shell upconversion nanoparticle, where:

the core has chemical formula (I): MAi_-xC_xF₄: Yb_y, B_z; and

the shell has chemical formula (II): M'A'_1-X'Lu_X'F₄: Yby, Β'_ζ·, wherein:

A' and C independently represent Y, Gd, Sc, Nd, La, Lu and Mn (e.g. Y, Gd, Sc, Nd, La and Mn, such as Y, Gd, Sc, and La);

B and B' independently represent Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn (e.g. Er, Tm, Ho, Ce, Pm, Sm and Eu);

M and M' independently represent Na, Li, K, Rb and Cs (e.g. Na, Li, K);

in formula (I) and (II):

x and x' independently represent from 0.01 to 1 ;

(1 -x)+x+y+z and (1-x')+x'+y'+z' represent 100 mol%;

(1 -x)+x and (1-χ')+χ' independently represent from 0 mol% to 100 mol% (e.g. 0.001 mol% to 00 mol%);

z and z' independently represent from 0 mol% to 20 mol%.

In embodiments of the first and second aspects of the invention, it will be noted that in formula (I) A and C may be identical, resulting in core nanoparticles having a formula (lb): MXF₄: Yb_y, B₂, where X represents Y, Gd, Sc, Nd, La, Lu and Mn (e.g. Y, Gd, Sc, Nd, La and Mn, such as Y, Gd, Sc, and La) and M, y and z are as defined hereinbefore. It will also be appreciated that B may represent one or more (e.g. one) metals. Examples of such core nanoparticles include, but are not limited to, NaLuF₄: Yb,Er, Nal_uF : Yb.Tm, and NaLuF : Yb.Er.Mn.

In alternative embodiments of the first and second aspects of the invention, A and C may be different and B may be one or more metals. For example, chemical formula (I) may be chemical formula (la): MAi_-xLu_xF₄: Yb_y, B_z, where M, A, B, x, y and z are as defined hereinbefore. Examples of such core nanoparticles include, but are not limited to, MYo.87Luo.13F4: Ybo.20. E10.02, MY0.74Luo.2eF4: Ybo.20, Er₀.o2, MY₀.₆₂Luo.3₈F₄: Yb₀.₂o, Er₀.₀2, and MYo.36Luo.64F4: Ybo.20, Er₀.o₂. As noted above, the total of all metals in the nanoparticle (with the exclusion of M) should together represent a total of 100 mol% of the metal within the nanoparticles. In the above examples, Y and Lu make up a total of 78 mol% of the total metals in the nanoparticle (excluding M), whereas Yb and Er represent 20 mol% and 2 mol%, respectively. The values provided for Y and Lu in the above formulae represent the proportion of the respective metal in the 78 mol% (analagous to 100 parts by weight). In certain embodiments, M may be Na.

In embodiments of the first and second aspects of the invention, in formula (I):

x may represent from 0.01 to 1 ;

(1-x)+x+y+z may represent 100 mol%;

(1-x)+x may represent from 0.001 mol% to 100 mol%;

y may represent from 0 mol% to 99.999 mol%; and

z may independently represent from 0 mol% to 20 mol%; and in formula (II):

x' may represent from 0.01 to 1 ;

(1-x')+x'+y'+z' may represent 100 mol%;

(1-χ')+χ' may represent from 0 mol% to 100 mol%;

y' may represent from 0 mol% to 100 mol%; and

z' may represent from 0 mol% to 20 mol%.

In still further embodiments of the first and second aspects of the invention, in formula (I): x may represent from 0.1 to 1 (e.g. from 0.2 to 0.5); and/or

(1-x)+x may represent from 1 mol% to 95 mol% (e.g. from 1 mol% to 90 mol% from 10 mol% to 80 mol%, such as from 20 mol% to 50 mol%, i.e. 48 mol%); and/or

y may represent from 2 mol% to 100 mol% (e.g. from 5 mol% to 100 mol%, from

45 mol% to 80 mol%, such as 70 mol%, or from 10 mol% to 30 mol%, such as 20 mol%); and/or z may represent from 0 mol% to 20 mol% (e.g. from 0.1 mol% to 10 mol%, such as from 0.5 mol% to 3 mol%, such as from 1.5 to 2.5 mol%, i.e. 2 mol%). For example, compositions of formula (I) that may be mentioned herein include compositions of formula (I) wherein:

(a) x represents from 0.2 to 0.5;

(1-x)+x represents from 1 mol% to 95 mol%;

y represents from 2 mol% to 80 mol%; and

z represents from 0 mol% to 20 mol%;

(b) x represents from 0.2 to 0.5;

(1-x)+x represents from 1 mol% to 95 mol%;

y represents from 10 mol% to 30 mol%, such as 20 mol%; and

z represents from from 0.1 mol% to 10 mol%;

(c) x represents from 0.2 to 0.5;

(1-x)+x represents from 10 mol% to 80 mol%;

y represents from 2 mol% to 80 mol%; and

z represents from 1.5 to 2.5 mol%; and

(d) x represents from 0.1 to 1 ;

(1-x)+x represents from 20 mol% to 50 mol%;

y represents 20 mol%; and

z represents from 1.5 to 2.5 mol%.

In still further embodiments of the first and second aspects of the invention, in formula (II):

x' may represent 0.1 to 1 ; and/or

(1-χ')+χ' may represent from 1 mol% to 99 mol%; and/or

y' may represent from 0 mol% to 80 mol% (e.g. from 10 mol% to 70 mol%); and/or

z' may represent from 0.5 mol% to 10 mol% (e.g. from 1 mol% to 3 mol%, such as 2 mol%). For example, compositions of formula (II) that may be mentioned herein include compositions of formula (II) wherein:

(a) x' represents 0.1 to 1 ; and

(1-χ')+χ' represents from 1 mol% to 99 mol%;

(b) x' represents 0.1 to 1 ;

y' represents from 0 mol% to 80 mol%; and

z' represents from 0.5 mol% to 10 mol%;

(c) (1-χ')+χ' represents from 1 mol% to 99 mol%;

y' represents from 10 mol% to 70 mol%; and z' represents from 1 mol% to 3 mol%;

x' represents 0.1 to 1 ;

(1-χ')+χ' represents from 1 mol% to 99 mol%;

y' represents from 0 mol% to 80 mol%; and

z' represents from from 1 mol% to 3 mol%;

x' represents 0.1 to 1 ;

y' represents from 0 mol% to 80 mol%; and

z' represents from 1 mol% to 10 mol%;

(1-χ')+χ' represents from 1 mol% to 99 mol%;

y' represents from 0 mol% to 70 mol%; and

z' represents from 0.5 mol% to 3 mol%; and

x' represents 0.1 to 1 ;

(1-χ')+χ' represents from 1 mol% to 99 mol%;

y' represents from 0 mol% to 80 mol%; and

z' represents from from 1 mol% to 3 mol%.

In further embodiments of the first and second aspects of the invention, the coating provided by formula (II) may MLuF . In further embodiments of the first and second aspects of the invention, in formula (I) and (II):

A, A' and C independently represent Y or Gd; and/or

M and M' represent Na.

In further embodiments of the first and second aspects of the invention, the core nanoparticle may have a diameter of from 10 nm to 1 ,000 nm (e.g. from 35 nm to 150 nm, such as from 40 to 100 nm). In yet further embodiments of the first and second aspects of the invention, the core-shell nanoparticle may have a diameter of from 15 nm to 5,000 nm (e.g. from 200 nm to 1 ,000 nm, such as from 350 nm to 600 nm). It will be appreciated that even if the core nanoparticle deviates from the above-mentioned range, that the core-shell nanoparticle may still fall within the range given for its diameter above (and vice versa). In further embodiments of the first and second aspects of the invention, the molar ratio of the core to the shell may be from 1 :0.1 to 1 :20 (e.g. from 1 :1 to 1:15, from 1 :2 to 1 :12, such as from 1 :5 to 1 :10). In embodiments of the invention, the core nanoparticle of formula (I) does not contain a polymer.

In a third aspect of the invention, there is provided a use of Lu³⁺ to form part of the shell on a core upconversion nanoparticle. For example, the Lu³⁺ is provided as lutetium(lll) chloride, lutetium(lll) oxide, lutetium(lll) acetate (hydrate), lutetium(lll) fluoride, lutetium(lll) sulfate (hydrate) and lutetium(lll) trifluoroacetate. It will be appreciated that the shell on the core upconversion nanoparticle has chemical formula (II) as described in the first and second aspects of the invention. In a fourth aspect of the invention, there is provided an upconversion nanoparticle with the chemical formula (III) M"Di_-X"Lu_X"F₄: Yby-, E₂- wherein:

D represents Y, Gd, Sc, Nd, La and Mn;

E represents Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn;

M" represents Na, Li, K, Rb and Cs;

x" represents from 0.01 to 1 ;

(1-x")+x"+y"+z" represents 100 mol%;

(1-x")+x" represents from 0.001 mol% to 100 mol%;

y" represents from 0 mol% to 99.999 mol%; and

z" represents from 0 mol% to 20 mol%.

In a fifth aspect of the invention, there is provided a method of preparing an upconversion nanoparticle according to the fourth aspect of the invention, and tuning the size, shape and fluorescence intensity of said upconversion nanoparticles, by the step of:

forming an upconversion nanoparticle with the chemical formula (III) M"Di_-X"Lu_X"F₄: Yby, E_z-, wherein:

D represents Y, Gd, Sc, Nd, La and Mn;

E represents Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn;

M" represents Na, Li, K, Rb and Cs;

x" represents from 0.01 to 1 ;

(1-x")+x"+y"+z" represents 100 mol%;

(1-x")+x" represents from 0.001 mol% to 100 mol%;

y" represents from 0 mol% to 99.999 mol%; and z" represents from 0 mol% to 20 mol%.

The fourth and fifth aspects of the invention may be interchangeable with the relevant part of the sixth aspect of the invention and the eighth aspect of the invention discussed hereinbelow.

In a sixth aspect of the invention, there is provided a method of tuning the size, shape and fluorescence intensity of upconversion nanoparticles by the steps of:

(a) forming an upconversion nanoparticle with the chemical formula (IV) M^AA^ft _1-aLuaF₄: Yb_b, B^A _C; and/or

(b) coating a core upconversion nanoparticle having the chemical formula (V): M"CYciLu_dF4: Yb_e, D_f with a composition (VI): M^MAA^A ._a u_a F₄: Yb_b; B'Y, to provide a core-shell nanoparticle, wherein:

A", Α^λλ and C" independently represent Y, Gd, Sc, Nd, La and Mn (e.g. Y, Gd, La, Sc and La);

Β^Λ, Β^ΛΛ and D independently represent Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn (e.g. Er, Tm, Ho, Ce, Pm, Sm, Eu);

M", M^a" and IVT" independently represent Na, Li, K, Rb and Cs (e.g. Na, Li, K); in formula (IV) and (VI):

a and a' independently represent 0.01 to 1 ;

(1-a)+a+b+c and (1-a')+a'+b'+c' represent 100 mol%;

c and c' independently represent from 0 mol% to 20 mol%; and in formula (V):

d represents 0.01 to 1 ;

(1 -d)+d+e+f represents 100 mol%;

(1 -d)+d represents from 0 mol% to 100mol%

e represents from 0 mol% to 100 mol%; and

f represents from 0 mol% to 20 mol%

As noted above, the method of preparation of the upconversion nanoparticles may make use of both methods (a) and (b). That is, in certain embodiments of the invention, the core nanoparticle of method (b) may be the upconversion nanoparticle prepared in method (a), such that formula (IV) and formula (V) are identical. In other embodiments, the core nanoparticle of formula (V) may be different to the nanoparticle of formula (IV). For example, the nanoparticle of formula (V) may be NaYbF₄.

In a seventh aspect of the invention, there is provided an upconversion nanoparticle with the chemical formula (IV) M^AA^A _1-aLu_aF₄: Yb_b, B"_c wherein:

A" represents Y, Gd, Sc, Nd, La and Mn (e.g. Y, Gd, La, Sc and La);

B^A represents Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn (e.g. Er, Tm, Ho, Ce,

Pm, Sm, Eu);

Μ^Λ represents Na, Li, K, Rb and Cs (e.g. Na, Li, K);

a represents 0.01 to 1 ;

(1-a)+a+b+c represents 100 mol%;

(1-a)+a represents from 0.001 mol% to 100 mol%;

b represents from 0 mol% to 99.999 mol%; and

c represents from 0 mol% to 20 mol%.

In embodiments of the sixth and seventh aspects of the invention, in formula (IV):

a may represent 0.1 to 1 (e.g. from 0.2 to 0.5);

(1-a)+a may represent from 1 mol% to 95 mol% (e.g. from 10 mol% to 80 mol%, such as from 20 mol% to 50 mol%);

b may represent from 2 mol% to 80 mol% (e.g. from 10 mol% to 30 mol%, such as 20 mol%);

c may represent from 0 mol% to 20 mol% (e.g. from 0.1 mol% to 10 mol%, such as from 1.5 to 2.5 mol%). It will be appreciated that the ranges listed herein in the first and second aspects of the invention may be used individually or in any technically feasible combination. For example, compositions of formula (IV) that may be mentioned herein may include compositions where:

(a) a represents from 0.1 to 1 ; and

(1-a)+a represents from 1 mol% to 95 mol%;

(b) a represents from from 0.2 to 0.5;

(1-a)+a represents from 10 mol% to 80 mol%;

b represents from 2 mol% to 80 mol%;

(c) a represents from 0.1 to 1 ;

(1-a)+a represents from 20 mol% to 50 mol%;

b represents from 10 mol% to 30 mol%; and

c represents from 0 mol% to 20 mol%; and

(d) a represents from from 0.2 to 0.5;

(1-a)+a represents from 10 mol% to 80 mol%; b represents from 10 mol% to 30 mol%; and

c represents from 1.5 to 2.5 mol%.

(e) a represents from 0.2 to 0.5;

(1-a)+a represents from 1 mol% to 95 mol%;

b represents from 2 mol% to 80 mol%; and

c represents from 0 mol% to 20 mol%;

(f) a represents from 0.2 to 0.5;

(1-a)+a represents from 1 mol% to 95 mol%;

b represents from 10 mol% to 30 mol%, such as 20 mol%; and

c represents from from 0.1 mol% to 10 mol%;

(g) a represents from 0.2 to 0.5;

(1-a)+a represents from 10 mol% to 80 mol%;

b represents from 2 mol% to 80 mol%; and

c represents from 1.5 to 2.5 mol%;

(h) a represents from 0.1 to 1 ;

(1-a)+a represents from 20 mol% to 50 mol%;

b represents 20 mol%; and

c represents from 1.5 to 2.5 mol%.

In embodiments of the invention, the nanoparticle of formula (V) does not contain a polymer.

In yet further embodiments of the sixth and seventh aspects of the invention, formula (IV) may relate to a nanoparticle having the following formula: MYo.87Luo.13F4: Yb₀.2o, Er_{0 0}2. M o.74Luo.26F4: Ybo.20, Er₀.₀₂, MYo-6₂Luo.38F₄: Yb₀.₂o, Er₀.₀₂, and M o.36Luo.64F4: Yb₀.₂₀, Er₀.o2. As noted above, the total of all metals in the nanoparticle (with the exclusion of M) should together represent a total of 100 mol% of the metal within the nanoparticles. In the above examples, Y and Lu make up a total of 78 mol% of the total metals in the nanoparticle (excluding M), whereas Yb and Er represent 20 mol% and 2 mol%, respectively. The values provided for Y and Lu in the above formulae represent the proportion of the respective metal in the 78 mol% (analogous to 100 parts by weight). In certain embodiments, M may be Na.

In certain embodiments of the sixth and seventh aspects of the invention that may be mentioned herein, the formed nanoparticle of method (a) or formula (IV) may have a diameter of from 10 nm to 1 ,000 nm (e.g. from 25 nm to 500 nm, such as from 35 nm to 150 nm). In an eighth aspect of the invention, there is provided a core-shell upconversion nanoparticle, where:

the core has chemical formula (V): M^MCY_dLu_dF₄: Yb_e, D_f; and the shell has chemical formula (VI): M^AnAA^A\_aLu_a F₄: Yb_b', Β^Λ ₀·, wherein:

Α^ΛΛ and C" independently represent Y, Gd, Sc, Nd, La and Mn (e.g. Y, Gd, La, Sc and La);

Β^Λ and D independently represent Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn (e.g. Er, Tm, Ho, Ce, Pm, Sm, Eu); and

Μ^ΛΛ and M^™ independently represent Na, Li, K, Rb and Cs (e.g. Na, Li, K); in formula (V):

d represents 0.01 to 1 ;

(1-d)+d+e+f represents 100 mol%;

(1-d)+d represents from 0 mol% to 100mol%;

e represents from 0 mol% to 100 mol%; and

f represents from 0 mol% to 20 mol%; and in formula (VI):

a' represents 0.01 to 1 ;

(1-a')+a'+b'+c' represents 100 mol%;

(1-a')+a' represents from 0.001 mol% to 100 mol%;

b' represents from 0 mol% to 99.999 mol%; and

c' represents from 0 mol% to 20 mol%.

In embodiments of the sixth and eighth aspects of the invention, in formula (VI):

a' may represent 0.1 to 1 ;

(1-a')+a' may represent from 1 mol% to 99 mol%;

b' may represent from 0 mol% to 80 mol% (e.g. from 10 mol% to 70 mol%); c' may represent from 0.5 mol% to 10 mol% (e.g. from 1 mol% to 3 mol%, such as 2 mol%). It will be appreciated that the ranges listed herein may be used individually or in any technically feasible combination. For example, compositions of formula (VI) that may be mentioned herein may include compositions where:

(a) a' represents 0.1 to 1 ; and

(1-a')+a' represents from 1 mol% to 99 mol%;

(b) a' represents 0.1 to 1 ;

b' represents from 0 mol% to 80 mol%; and c' represents from 0.5 mol% to 10 mol%;

(c) (1-a')+a' represents from 1 mol% to 99 mol%;

b' represents from 10 mol% to 70 mol%; and

c' represents from 1 mol% to 3 mol%; and

(d) a' represents 0.1 to 1 ;

(1-a')+a' represents from 1 mol% to 99 mol%;

b' represents from 0 mol% to 80 mol%; and

c' represents from from 1 moI% to 3 mol%;

(e) a' represents 0.1 to 1 ;

b' represents from 0 mol% to 80 mol%; and

c' represents from 1 mol% to 10 mol%;

(f) (1-a')+a' represents from 1 mol% to 99 mol%;

b' represents from 0 mol% to 70 mol%; and

c' represents from 0.5 mol% to 3 mol%;

(g) a' represents 0.1 to 1 ;

(1-a')+a' represents from 1 mol% to 99 mol%;

b' represents from 0 mol% to 80 mol%; and

c' represents from from 1 mol% to 3 mol%.

In certain embodiments of the sixth and eighth aspects of the invention, formula (VI) may represent M" uF₄. For example, IVT^* may represent Na.

In embodiments of the sixth and eighth aspects of the invention, in the core nanoparticle of formula (V):

d may represent 0.1 to 1 ;

(1-d)+d may represent from 1 mol% to 90 mol% (e.g. from 20 mol% to 50 mol%, such as 48 mol%);

e may represent from 5 mol% to 100 mol% (e.g. from 45 mol% to 80 mol%, such as 70 mol%);

f may represent from 0 mol% to 20 mol% (e.g. from 0.5 mol% to 3 mol%, such as 2 mol%). It will be appreciated that the ranges listed herein may be used individually or in any technically feasible combination. For example, compositions of formula (II) that may be mentioned herein may include compositions where:

(a) (1-d)+d represents from 1 mol% to 90 mol%; and

f represents from 0 mol% to 20 mol%;

(b) d represents from 0.1 to 1 ;

(1-d)+d represents from 1 mol% to 90 mol%; and e represents from 5 mol% to 100 mol%;

d represents from 0.1 to 1 ;

(1-d)+d represents from 20 mol% to 50 mol%;

e represents from 45 mol% to 80 mol%; and

f represents from 0.5 mol% to 3 mol%;

d represents from 0.1 to 1 ;

(1-d)+d represents from 1 mol% to 90 mol%;

e represents from 45 mol% to 80 mol%; and

f represents from 0 mol% to 20 mol%;

(1-d)+d represents from 20 mol% mol% to 48 mol%; and

f represents from 0 mol% to 20 mol%;

d represents from 0.1 to 1 ;

(1-d)+d represents from 1 mol% to 50 mol%; and

e represents from 45 mol% to 80 mol%;

d represents from 0.1 to 1 ;

(1-d)+d represents from 20 mol% to 90 mol%;

e represents from 45 mol% to 70 mol%; and

f represents from 0.5 mol% to 20 mol%;

d represents from 0.1 to 1 ;

(1-d)+d represents from 20 mol% to 50 mol%;

e represents from 45 mol% to 80 mol%; and

f represents from 0.5 mol% to 3 mol%.

In further embodiments of the invention, the core nanoparticle may have a diameter of from 10 nm to 1,000 nm. For example, the core nanoparticle may have a diameter of from 35 nm to 250 nm, such as from 40 to 150 nm.

In still further embodiments of the invention, the core-shell nanoparticle may have a diameter of from 15 nm to 5,000 nm (e.g. from 200 nm to 1 ,000 nm, such as from 350 nm to 600 nm).

In still further embodiments, the core-shell upconversion nanoparticle described hereinbefore may be one where the molar ratio of the core to the shell is from 1 :0.1 to 1 :20 (e.g. from 1 :1 to 1 :15, such as from 1 :5 to 1 :10). Specific molar ratios of the core to the shell that may be mentioned include 1 :1 , 1 :2, 1 :5 and 1 :10. As will be appreciated, it is possible to coat the core nanoparticle with a thin shell (hence core to shell molar ratios as low as 1 :0.1) or with a thick shell, such as using a molar ratio of core to shell of 1 :1 , 1 :2, 1 :5 and 1 :10.

In yet further embodiments of the invention:

Α^Λ, A" and C^* may independently represent Y or Gd; and/or

Β^Λ, Β^ΛΛ and D may independently represent Er or Tm (e.g. Er); and/or

Μ^Λ, IVT and Μ^ΛΛΛ may independently represent Na.

It will be appreciated that part (b) of the sixth aspect of the invention and the eighth aspect of the invention, and their embodiments, may be interchangeable with the first and second aspects of the invention wherever possible to do so.

In a ninth aspect of the invention, there is provided a use of Lu³⁺ to:

(a) dope an upconversion nanoparticle; and/or

(b) form part of the shell on a core upconversion nanoparticle.

In embodiments of the invention, the Lu³⁺ may be provided as lutetium(lll) chloride, lutetium(lll) oxide, lutetium(lll) acetate (hydrate), lutetium(lll) fluoride, lutetium(lll) sulfate (hydrate) and lutetium(lll) trifluoroacetate.

In embodiments of the invention, the doped upconversion nanoparticle may have the chemical formula (IV) as described hereinabove.

In yet further embodiments of the invention, the shell on the core upconversion nanoparticle may have the chemical formula (VI) as described hereinabove.

Examples

General Procedure 1: NaYi._xLu_xF₄: Yb, Er/Tm UCNs synthesis

All chemicals were purchased from Sigma-Aldrich and used without further purification. NaYF₄: 20%Yb, 2%Er nanoparticles were synthesized following protocols reported previously with modification (Li, Z. Q. and Zhang, Y. Nanotechnology. 2008; 19). 0.78 mmol YCI₃, 0.20 mmol YbCI₃ and 0.02 mmol ErCI₃ were mixed with 6 mL oleic acid and 15 mL 1-octadecene in a 100 mL flask. The solution was heated to 150 °C to form a homogenous solution, and then cooled down to room temperature. A solution of 4 mmol NH₄F and 2.5 mmol NaOH in 10 mL of methanol was added into the flask and stirred for 30 min. Subsequently, the solution was heated to 100 °C to remove the methanol. After methanol was evaporated, the solution was heated to 300 °C and incubated at that temperature for 1 hour under an argon atmosphere and then cooled to room temperature. The UCNs were precipitated with 10 mL of acetone, collected after centrifugation, then washed thrice with ethanol/water (1 :1 v/v) and finally dispersed in cyclohexane for subsequent use.

NaYF₄: Yb, Er UCNs with different doping concentrations can be synthesized similarly by changing the amount of the lanthanide chlorides used stoichiometrically. UCNs doped with a certain concentration of Lu³⁺or Gd³⁺, can also be synthesized similarly, where LuCI₃ or GdCI₃ stoichiometrically replaces part of the YCI₃. Finally, this process may be adapted by analogy to provide nanoparticles according to formula (I): MA_1-xLu_xF₄: Yb_y, B_z and formula (II): 'C₁._aLu_aF₄: Yb_b, D_c, said formulae being as described herein. General Procedure 2: NaYF₄: Yb, Er@ Nal_uF : Yb, Tm core-shell UCNs synthesis

0.745 mmol LuCI₃, 0.25 mmol YbCI₃ and 0.05 mmol ErCI₃ were mixed with 6 mL oleic acid and 5 mL 1-octadecene in a 100 mL flask. The solution was heated to 150 °C to form a homogenous solution, and then cooled down to room temperature. A solution of the NaYF₄: Yb, Er core nanocrystals dispersed in cyclohexane that can be obtained using the protocol of General Procedure 1 was added to the flask. The solution was maintained at 70 °C to remove the cyclohexane solvent and then subsequently cooled down to room temperature. A solution of 4 mmol NH F and 2.5 mmol NaOH in 10 mL of methanol was added into the flask and stirred for 30 min. Subsequently, the solution was heated to 100 °C to remove the methanol. After methanol was evaporated, the solution was heated to 300 °C and incubated at that temperature for 1 hour under an argon atmosphere and then cooled to room temperature. The nanocrystals were precipitated with 10 mL of acetone, collected after centrifugation, then washed thrice with ethanol/water (1 :1 v/v) and finally dispersed in cyclohexane for subsequent use.

UCNs having a different core/shell mole ratio are synthesized similarly by changing the stoichiometric amount of the shell precursor and prolonging the incubation time as necessary. A similar process is also used when seeking to use Y³⁺ as the coating material, wherein LuCI₃ is replaced by YCI₃. It will be appreciated that the process above may be used to formulate any coating formulation that falls within the scope of formula (III): M"A'_1-X'Lu_X'F₄: Yb^, Β'_ζ·, said formula being as described herein. General Procedure 3: NaLuF₄: Yb, Er Tm/Mn@ NaLuF₄: Yb, Er/Tm/Mn core-shell UCNs synthesis

0.68 mmol LuCI₃, 0.20 mmol YbCI_3> 0.02 mmol ErCI₃ and 0.10 mmol MnCI₂ were mixed with 6 ml. oleic acid and 15 mL 1-octadecene in a 100 mL flask. The solution was heated to 150 °C to form a homogenous solution, and then cooled down to room temperature. A solution of the Nal_uF₄: Yb, Tm core nanocrystals dispersed in cyclohexane that can be obtained using the protocol of General Procedure 1 was added to the flask. The solution was maintained at 70 °C to remove the cyclohexane solvent and then subsequently cooled down to room temperature. A solution of 4 mmol NH₄F and 2.5 mmol NaOH in 10 mL of methanol was added into the flask and stirred for 30 min. Subsequently, the solution was heated to 100 °C to remove the methanol. After methanol was evaporated, the solution was heated to 300 °C and incubated at that temperature for 1 hour under an argon atmosphere and then cooled to room temperature. The as prepared NaLuF₄: Yb, Tm@ NaLuF₄: Yb, Er, Mn core-shell nanocrystals were precipitated with 10 mL of acetone, collected after centrifugation, then washed thrice with ethanol/water (1:1 v/v) and finally dispersed in cyclohexane for subsequent use.

UCNs having a different core/shell mole ratio are synthesized similarly by changing the stoichiometric amount of the shell precursor and prolonging the incubation time as necessary. It will be appreciated that the process above may be used to formulate any coating formulation that falls within the scope of formula (II): M"A'_1-xLu_x F₄: Yb^, CV, said formula being as described herein. Characterization

Transmission electron microscopy (TEM) images were recorded on a JEOL 201 OF transmission electron microscope (Jeol Ltd., Tokyo, Japan) operating at an acceleration voltage of 200 kV. Fluorescence spectra of were recorded on a Hitachi F-500 fluorescence spectrophotometer (Hitachi High-Technologies Corporation, Tokyo, Japan) equipped with an NIR continuous wave laser with emission at 980 nm (Photonitech (Asia) Pte. Ltd., Singapore). The size distribution statistics were measured with a Malvern zetasizer nano series (Malvern Instruments Ltd., Worcestershire, UK). Luminescent photograph of UCNPs under excitation of 980 nm continuous wave laser were taken with a commercial Canon 550D camera (Canon Inc., Tokyo, Japan) without any filter. Luminescence micrograph were taken under a cytoviva microscope (Nikon Inc., Tokyo, Japan) specially fitted with a continuous wave 980 nm laser excitation source (Opto-Link Corp., Hong Kong) under 100 times magnification.

Example 1: Tuning UCNs size by Lu doping

Monodispersed NaYF₄: Yb, Er UCNs were synthesized using the process described in General Procedure . NaY_1-xLu_xF₄: Yb, Er UCNs doped with different concentrations of Lu³⁺ were synthesized under the same experimental conditions, except for varying the doping concentration of Lu³⁺ (a total of from 10 mol% to 50 mol%, where the molar amounts of Y, Lu, Yb and Er are taken together to be 100 mol%; Yb being 20 mol% and Er being 2 mol% of the total for all compositions).

X-ray diffraction (XRD) characteraziation of the UCNs demonstrate that a pure hexagonal phase was obtained in the NaY/LuF₄: Yb, Er nanoparticles having different concentrations of Lu³⁺ doping (see fig. 2). The XRD peaks sequentially shift towards a high-angle as the Lu³⁺ concentration increases. This peak shifting confirms that the crystal lattice shrinks due to the increasing replacement of Y³⁺ by the smaller radius Lu³⁺.

The size of the UCNs were characterized by TEM. As shown in Figure 3a-e, the size of the UCNs obtained were from 20 nm to 100 nm as the doping concentration of Lu³⁺ was increased from 0 mol% to 50 mol% (of the total metal molar ratio, as calculated based upon Lu, Y, Yb and Er). As discussed hereinebfore, with the increase in Lu³⁺ concentration, the nucleation process is suppressed, which benefits the growth process, thereby making the nanoparticles grow in size. The size of the above samples were also determined by dynamic light scattering (DLS) and these results are summarised in Figure 3f. As shown in Figure 3f, the trend of growing size agrees well with the size increment by Lu³⁺ doping observed in the TEM images. The absolute size values measured by DLS can be larger than that observed from a TEM image because the former technique measures the hydrodynamic radius, while the later technique captures the actual radius of the nanoparticles.

The luminescence spectra (fig. 3h) shows that the luminescence intensity increases as the concentration of Lu³⁺ increases. Without wishing to be bound by theory, it is suggested that this is because, as the size of UCNs increases, more sensitizer and activator ions are isolated from the surface defects. Nevertheless, the red to green and blue to green ratios of the emission peaks still remain the same across the samples (fig. 3i). This confirms that Lu³⁺ does not interfere with the energy transfer from Yb³⁺ to Er³⁺ or with the back energy transfer from Er to Yb (fig. 3g). Thus, UCNs with tunable size but similar fluorescent properties can be obtained effectively by l_u³⁺ doping.

Example 2: Coating Nal_uF₄ onto a large core UCNs

The smaller radius of Lu³⁺ compared to Y³⁺ also makes the Lu³⁺ ion useful for shell coating, especially onto UCNs having a size greater than or equal to 40 nm.

NaYo.48Ybo.5F₄:Er₀.o2 (or Trrio.02) core UCNs were synthesized using General Procedure 1 to provide UCNs nanoparticles with a diameter of around 40 nm (fig. 4a). The use of 50 mol% Yb³⁺ doping resulted in a significantly larger nanoparticle than is normally obtained with the conventional NaYF₄:Yb, Er with 20 mol% Yb doping and 2 mol% Er doping, which has a diameter of around 20 nm. Using General Procedure 2, the coating of NaYF₄ and NaLuF₄ shell onto the large-core UCNs prepared above was compared. With an incubation time of one hour, the Nal_uF shell was successfully coated onto the core (fig. 4d), while NaYF₄ formed new small nuclei and did not fully coat onto the core (fig. 4b). Without wishing to be bound by theory, it is suggested that this effect can also be attributed to the diameter difference between Y³⁺ and Lu³⁺. As described above, this is due to the relative low stability of NaLuF₄ nucleus, which suppresses the nucleation of the shell precusor, and the decreased electron charge density on the surface of the NaLuF₄ coated nanoparticles, which is benificial for shell growth (see also fig. 1). When the incubation time was prolonged from 1 hour to 4 hours, both NaLuF₄ and NaYF shells were formed on the core UCNs (fig. 4c). However, the fluorescence spectra (fig. 4f) shows that NaLuF₄ is more preferable to use as the shell host than NaYF₄. This is because it gives a stronger fluorescence intensity from samples incubated for both 1 hour and 4 hours.

A thicker shell was also obtained by adding in more NaLuF₄ shell precursor. By using NaLuF as the shell precursor, coated shells with tremendous shell thicknesses were obtained at 1 :5 and 1 :10 core shell ratio (molar ratio), which resulted in the size of the nanoparticle growing from 40 nm for the original core to 200 nm and 300 nm for the core- shell nanoparticles (fig. 5c and 5d). The fluorescence intensity of the nanoparticle also increased as the thickness of the shell grows (fig. 5e).

As the core and shell are both fluorescent, they can both emit fluorescent light at different wavelengths (i.e. different emission colors). For example, the core may emit green light, whereas the shell may emit blue light. Thus, by coating the shell with different thickness (e.g. 1 :1 core/shell ratio and 1:2 core/shell ratio), different optical codes can be obtained (e.g. code 1 may have a 1 :1 green/blue intensity ratio, and code 2 may have a 1 :2 green/blue intensity ratio). Thus, in addition to enhancing the fluorescence intensity of the nanoparticles, by coating a luminescent core with different thicknesses and using the fluorescence of the core as a constant reference, ratiometric differentiable optical codes can be produced in a large number, owing to the feasibility of shell coating with tremendous thickness. The coating of NaLuF₄ and NaYF₄ onto an even larger core were compared using a UCNs with a diameter of around 100nm (fig. 6a). This nanoparticle was prepared using 70 mol% of Yb, while retaining the same proportion of Er or Tm. A NaLuF₄ shell at 1 :5 and 1:10 core shell ratio can still be successfully coated onto the 100 nm core and provides core-shell nanoparticles at the size of 200 nm and 400 nm (fig. 6b and c). In contrast, the NaYF₄ shell only grows slightly even at the core shell ratio of 1 :10 and with prolonged incubation time. The fluorescence spectra also indicates that the NaLuF₄ shells grow more effectively on a 100 nm nanoparticle by giving stronger fluorescence (fig. 6e). Example 3: Micro-sized multicolor UCNs distinguishable under fluorescence microscope

Taking advantage of the lutetium's ability of coating thick shell onto big core UCNs, multicolor shell with different thickness were successfully coated onto the core UCNs (Nal_uF₄:Yb,Er (green in color); Nal_uF₄:Yb,Tm (blue in color); and NaLuF₄:Yb,Er,Mn (saddlebrown in color)) and multi-color micro-sized core-shell UCNs were obtained (Fig. 7). These core nanoparticles were prepared using General Procedure 3.

By combining the different groups of doped ions in the core-shell structure with different core/shell ratios, for example, Yb and Er; Yb and Tm; Yb, Er and Mn, micro-sized core- shell UCNs were obtained with several intermediate colors, for example, cyan, sky blue, orange and purple. The size of the core-shell UCNs were grown up to 1 pm (FIG. 7). Due to the Abbe diffraction limit, the maximum resolution of a normal optical microscope is roughly half of the wavelength of light involved, which means >200 nm for visible light. Thus, adjacent fluorescent nanoparticles with a size smaller than 200 nm cannot be distinguished under a normal fluorescent microscope. The micro-sized UCNs developed here allow the Abbe diffraction limit of an optical microscope to be overcome, and so they can be identified/distinguished using a normal fluorescent microscope. In other words, as their emission colors differ from each other, the core-shell UCNs and can be easily identified/distinguished in a mixture using a normal fluorescence microscope.

Claims

(b) coating the core upconversion nanoparticle with a composition (II): M'AV_X'Lu_X'F₄: Yb , B'_z>, to provide a core-shell nanoparticle, wherein:

A, A' and C independently represent Y, Gd, Sc, Nd, La, Lu and Mn;

B and B' independently represent one or more of Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu,

Tb, Dy and Mn;

M and M' independently represent Na, Li, K, Rb and Cs; in formula (I) and (II):

x and x' independently represent from 0.01 to 1 ;

(1-x)+x+y+z and (1-x')+x'+y'+z' represent 100 mol%;

(1-x)+x and (1-χ')+χ' independently represent from 0 mol% to 100 mol%;

y and y' independently represent from 0 mol% to 100 mol%; and

z and z' independently represent from 0 mol% to 20 mol%.

2. The method of Claim 1 , wherein chemical formula (I) is chemical formula (la):

MAi_-xLu_xF₄: Yb_y, B_z, where M, A, B, x, y and z are as defined in Claim 1.

3. The method of Claim 1 , wherein in formula (I):

x represents from 0.01 to 1;

(1-x)+x+y+z represents 100 mol%;

(1-x)+x represents from 0.001 mol% to 100 mol%;

y represents from 0 mol% to 99.999 mol%; and

z represents from 0 mol% to 20 mol%; and in formula (II):

x' represents from 0.01 to 1 ;

(1-x')+x'+y'+z' represents 100 mol%;

(1-χ')+χ' represents from 0 mol% to 100 mol%;

y' represents from 0 mol% to 100 mol%; and

z' represents from 0 mol% to 20 mol%.

4. The method of Claim 1 , wherein in formula (I):

x represents from 0.1 to 1 ; and/or

(1-x)+x represents from 1 mol% to 95 mol%; and/or

y represents from 2 mol% to 100 mol%; and/or

z represents from 0 mol% to 20 mol%.

5. The method of Claim 1 , wherein in formula (II):

x' represents 0.1 to 1 ; and/or

(1-χ')+χ' represents from 1 mol% to 99 mol%; and/or

y' represents from 0 mol% to 80 mol%; and/or

z' represents from 0.5 mol% to 10 mol%.

6. The method of Claim 5, wherein the coating of formula (II) is MLuF₄.

7. The method of Claim 1 , wherein:

A, A' and C independently represent Y or Gd; and/or

B and B' independently represent one or more of Mn, Er or Tm; and/or

M and M' represent Na.

8. The method of Claim 1 , wherein the core nanoparticle has a diameter of from 10 nm to 1,000 nm and/or the core-shell nanoparticle has a diameter of from 15 nm to 5,000 nm.

9. The method of Claim 1 , wherein the molar ratio of the core to the shell is from 1 :0.1 to 1 :20.

10. A core-shell upconversion nanoparticle, where:

the core has chemical formula (I): MA_1-XC_XF₄: Yb_y, B_z; and

the shell has chemical formula (II): M'A'_1-xLu_xF₄: Yb , Β'_ζ·, wherein:

A' and C independently represent Y, Gd, Sc, Nd, La, Lu and Mn;

B and B' independently represent on or more of Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn;

M and M' independently represent Na, Li, K, Rb and Cs; in formula (I) and (II):

x and x' independently represent from 0.01 to 1;

(1-x)+x+y+z and (1-x')+x'+y'+z' represent 100 mol%; (1-x)+x and (1-χ')+χ' independently represent from 0 mol% to 100 mol%;

y and y' independently represent from 0 mol% to 100 mol%; and

z and z' independently represent from 0 mol% to 20 mol%.

11. The core-shell upconversion nanoparticle of Claim 10, wherein chemical formula (I) is chemical formula (la):

MA_1-xl_u_xF₄: Yb_y, B₂, where M, A, B, x, y and z are as defined in Claim 10.

12. The core-shell upconversion nanoparticle of Claim 10, wherein in formula (I): x represents from 0.01 to 1 ;

(1-x)+x+y+z represents 100 mol%;

(1-x)+x represents from 0.001 mol% to 100 mol%;

y represents from 0 mol% to 99.999 mol%; and

z and z' independently represent from 0 mol% to 20 mol%; and in formula (II):

x' represents from 0.01 to 1 ;

(1-x')+x'+y'+z' represents 100 mol%;

(1-χ')+χ' represents from 0 mol% to 100 mol%;

y' represents from 0 mol% to 100 mol%; and

z' represents from 0 mol% to 20 mol%.

13. The core-shell upconversion nanoparticle of Claim 10, wherein in formula (II): x' represents 0.1 to 1 ; and/or

(1-χ')+χ' represents from 1 mol% to 99 mol%; and/or

y' represents from 0 mol% to 80 mol%; and/or

z' represents from 0.5 mol% to 10 mol%.

14. The core-shell upconversion nanoparticle of Claim 10, wherein the coating of formula (II) is MLuF₄.

15. The core-shell upconversion nanoparticle of Claim 10, wherein in formula (I): x represents from 0.1 to 1 ; and/or

(1-x)+x represents from 1 mol% to 95 mol%; and/or

y represents from 2 mol% to 100 mol%; and/or

z represents from 0 mol% to 20 mol%.

16. The core-shell upconversion nanoparticle of Claim 10, wherein:

A, A' and C independently represent Y or Gd; and/or

B and B' independently represent one or more of Mn, Er or Tm; and/or

M and M' represent Na.

17. The core-shell upconversion nanoparticle of Claim 10, wherein the core nanoparticle has a diameter of from 10 nm to 1 ,000 nm and/or the core-shell nanoparticle has a diameter of from 15 nm to 5,000 nm.

18. The core-shell upconversion nanoparticle of Claim 10, wherein the molar ratio of the core to the shell is from 1:0.1 to 1 :20.

19. An upconversion nanoparticle with the chemical formula (III)

M"D_1-x»Lu_X"F₄: Yby, E_z- wherein:

D represents Y, Gd, Sc, Nd, La and Mn;

E represents Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn;

M" represents Na, Li, K, Rb and Cs;

x" represents from 0.01 to 1 ;

(1-x")+x"+y"+z" represents 100 mol%;

(1-x")+x" represents from 0.001 mol% to 100 mol%;

y" represents from 0 mol% to 99.999 mol%; and

z" represents from 0 mol% to 20 mol%.

20. A method of preparing an upconversion nanoparticle according to Claim 19, and tuning the size, shape and fluorescence intensity of said upconversion nanoparticles, by the step of:

forming an upconversion nanoparticle with the chemical formula (III) M"D_1-x»Lu_X"F₄: Yby-, E_z-, wherein:

D represents Y, Gd, Sc, Nd, La and Mn;

E represents Er, Tm, Ho, Ce, Pr, Nd, Pm, Sm, Eu, Tb, Dy and Mn;

M" represents Na, Li, K, Rb and Cs;

x" represents from 0.01 to 1 ;

(1-x")+x"+y"+z" represents 100 mol%;

(1-x")+x" represents from 0.001 mol% to 100 mol%;

y" represents from 0 mol% to 99.999 mol%; and

z" represents from 0 mol% to 20 mol%.