DE102011010756A1 - Photostimulable particle systems, processes for their preparation and uses - Google Patents

Abstract

The invention relates to stimulable, especially photostimulable, particle systems and their use as luminescent markers for biological and medical diagnostics, as an optically detectable diffusion probe or as a substrate for the production of security systems, as a marker for recognizing plagiarism and / or originals.

Description

The invention relates to stimulable, in particular photostimulable particle systems and their use as luminescent markers for biological and medical diagnostics, as an optically detectable diffusion probe or as a substrate for the production of security systems, as a marker for the detection of plagiarism and / or originals.

• • Die herkömmliche Materialien weisen materialbedingte Mängel auf: breite Emissionsspektren, geringe Stokes-Verschiebung und/oder eine begrenzte Photostabilität. Dies ist typisch für mit organischen Farbstoffen dotierte NP.
• • Einige Partikelsysteme wie z. B. QDs bestehen auf toxischen Materialien. Im Hinblick auf in vivo Anwendung ist selbst der zeitlich begrenzte Einsatz dieser Marker in lebenden Organismen höchst bedenklich.
• • Nur wenige Materialien besitzen Emission in dem biologischen „optischen Fenster” (650–1200 nm). Darüber hinaus zeigt oft das untersuchte System, wie z. B. in Fall von Untersuchungen an Zellgeweben, eine Autofluoreszenz, die sich mit dem Signal des Markers überlagert.
• • Viele der verwendeten Marker bei verhältnismäßig kurzen Wellenlängen angeregt werden und fluoreszieren, bei denen die Eindringtiefe des Lichts in das Gewebe gering ist.
• • In der Regel sind das anregende Licht und die Fluoreszenz zeitgleich wirksam. Das Signal wird durch Streulicht geschwächt.

Luminescent nanoparticles (NPs) have great potential for application due to their optical properties. They provide a basis for numerous analytical methods in the field of biology and medical diagnostics or are used to produce security systems for the detection of plagiarism and / or originals. There are different materials available such. B. with organic dyes doped particle systems based on polymers or oxidic materials, semiconductor NP (quantum dots, QDs) or NP based on inorganic phosphors doped with rare earth ions F. Caruso: Colloids and Colloid Assemblies. Wiley-VCH, Weinheim (2004) ; Tan, S. Santra, P. Zhang, R. Tapec, J. Dobson: Method for Identifying Cells. F. Hoffmann US 6924116 B2 (2005); V. Desprez, N. Oranth, J. Sprinke, JK Tusa: Nanoparticles for optical sensors, EP 1496126 B1 (2005); A. van Blaaderen, A. Vrij: Synthesis and characterization of colloidal dispersion of fluorescent monodisperse silica spheres. Langmuir 8, (1992) 2921-2931 ; RE Baily, AM Smith, 5. Never: Quantum dots in biology and medicine. Physica E 25, (2004), 1-12 ; R. Lee, Z. Yaniv: Nanoparticle Phosphorus. WO 03/028061 A1 (2003)]. The study methods that can be used often have characteristic limits, which are listed below:

• • Conventional materials have material-related defects: broad emission spectra, low Stokes shift, and / or limited photostability. This is typical of NPs doped with organic dyes.
• • Some particle systems, such as B. QDs insist on toxic materials. With regard to in vivo application, even the temporary use of these markers in living organisms is highly questionable.
• • Few materials have emission in the biological "optical window" (650-1200 nm). In addition, often the examined system, such. For example, in the case of studies on cell tissues, an autofluorescence superimposed on the signal of the marker.
• • Many of the markers used are excited and fluoresce at relatively short wavelengths, where the depth of penetration of the light into the tissue is low.
• • As a rule, the stimulating light and the fluorescence are effective at the same time. The signal is weakened by stray light.

One solution could be a time delay of the light emission compared to the excitation. This phenomenon can be observed with phosphorescent materials. For phosphorescent materials, fluorescence decays slowly after stimulation, sometimes for hours or even days. First up to one hour of phosphorescent markers have already been developed and successfully tested on living mice [D. Scherman, M. Bessodes, C. Chaneac, DL Gourier, JP. Jolivet, Q. le Masne, S. Maitrejean, F. Pelle: Persistent luminescent nanoparticles used in the form of a diagnostic agent for in vivo optical imaging. US 2009/0155173 (2009); Q. le Masne, C. Chanéac, J. Seguin, F. Pellé, S. Maîtrejean, JP. Jolivet, D. Gourier, M. Bessodes: Nanoprobes with near-infrared persistent luminescent for in vivo imaging. PNAS 104, (2007) 9266-9271 ].

Based on the known from the prior art materials, it was an object of the present invention to provide nanoparticle systems, which allows the highest possible persistence of stored energy after charging such particles. In addition, the particle systems should be stimulated by stimulating with a targeted light pulse, which may preferably also be in the infrared light range for stimulated emission, so that the originally stored energy of such particles can be selectively retrieved when needed.

This object is related to the nanoparticle with the features of claim 1, with respect to a nanoparticle system containing a plurality of particles according to the invention, with the features of claim 11, with respect to a method for producing a corresponding nanoparticle system with the features of claim 12 and with respect to possible uses of such Nanoparticle systems with the features of claim 14 solved. The respective dependent claims are advantageous developments.

According to the invention, a nanoparticle is provided which can be converted into an electronically charged state by supplying energy and can be induced to emit electromagnetic radiation by means of stimulation by electromagnetic radiation.

The nanoparticles according to the invention, in particular those of the core-shell type discussed below, are characterized in that, after being charged with light of a wavelength between 100 and 800 nm, with X-rays and / or electron beams by stimulated emission by a light pulse with a light pulse Wavelength between 500 and 1600 nm emit photons with a wavelength between 400 and 1300 nm.

Surprisingly, it has been found in the nanoparticles according to the invention, in particular those of the core-shell type, that the duration of the light pulse, which can be used for stimulated emission and retrieval of the light energy stored in the charged particle, can be very short, e.g. B. about 1 microseconds or less ( A. Winnacker, "X-ray Imaging with Photostimulable Storage Phosphors and Future Trends". Physica Medica, Vol. IX (1993), 95-101 ). The stimulated emission can be used, for example, by using a laser pulse, wherein the energy density of the stimulation laser can be about 100 μJ / cm ² or less ( R. Schätzing, R. Fasbender, P. Kersten, New High Speed Scanning Technique for Computed Radiography, Proc. SPIE 4682 (2002) 511-520 ). As a result, enormous advantages in terms of signal / noise ratio allows, whereby the particles according to the invention significantly advantageous from those of the prior art, for. B. from the US 2009/0155173 take off known microparticles.

The particle is characterized by energy storage and thus enabling a time shift between excitation (charge) and detection necessary for background-free detection. For this purpose, the sample to be examined can be marked with particulate markers which have been charged by irradiation with UV or blue light, or an X-ray pulse before the examination. Subsequent minutes or even hours following stimulation of the sample with red or infrared (IR) light will result in emission in the visible or near-infrared region, i.e., in the background. H. at shorter wavelengths than the wavelengths of the excitation light. This allows observations of development and transport processes in biological objects over a longer period of time. A specific area can be irradiated with the focused UV or blue light or electron beam, and the charged markers can be detected. The photostimulable phosphors have convincing advantages here: the entire stored energy (or, if necessary, only part of it) can be retrieved with an infrared pulse at the desired later point in time.

As a result, applications are made possible in which the detection of marked objects takes place offset in time from the optical excitation, with the aim of enabling background-free or stray-light-free detection.

Separation of charge carriers and their localization ("trapping") are necessary for phosphorescence and photostimulated luminescence (PSL). In nanocrystals (NK), however, the desired stability of trapped electrons / holes can be a problem, because, because of the small distances between the traps, the recombination is possible by a "tunneling". The so-called "blinking" of NKs provides an indication of the possibility of charge separation and trapping: with a constant excitation, the luminescence of some NKs is lost, and after some time, it is formed again. It is known that the charging of NKs is responsible for the interruptions of the luminescence. During optical excitation, NKs form electron-hole pairs whose recombination leads to light emission. However, it is possible that one of the two charge carriers leaves the NK. The other charge carrier inside the NK prevents the radiative recombination of the next e-h pairs by Auger relaxation. Measurements with electrostatic force microscopy showed that in CdSe the electron leaves the particle and the hole remains. The particle is again emissive as soon as the electron returns. The "on" and "off" states of NK can take from a few microseconds to minutes. The nature of the traps is unclear. The localization on the particle surface or on the interface between the core and the shell, in the coupled ligands or in the surrounding matrix is suspected. The appearance of the blinking thus confirms the possibility of storing electrons and holes on the nanoscale.

The spatial separation of charge carriers can be improved by the use of two-component semiconductor systems. Such coupled NKs or core / shell particles have been designed for a variety of purposes including solar cells and photocatalysts. The generated electrons are accumulated in the semiconductor where the conduction band is deeper, the holes are trapped in the valence band of the other semiconductor. Examples of such systems are TiO2-CdS, ZnO-CdS and SnO2-CdSe, CdS-AgI, Cd3P2-TiO2, Cd3P2-ZnO, AgI-Ag2S, ZnO-ZnS and ZnSe (core) / CdSe (shell). This design principle can also be used for the shift of the emission spectrum to lower energies, which reduces the unwanted scattering of luminescence in biological samples.

Overall, the separate storage of electrons / holes on the nanoscale seems feasible. The targeted nanomarkers will be concerned with bringing these stored charge carriers to radiative recombination thermally or optically (PSL).

The nanoparticles Zn ₂ SiO ₄ : Mn ²⁺ , considered as an example here, obviously have intrinsic traps, which can store charge carriers at room temperature. The traps can be charged with UV light and emptied with red light. This produces the green emission of Mn ²⁺ . The charge spectrum showed a maximum around 260 nm, which corresponds to an electronic transition from the ground state of the Mn ²⁺ ion to the conduction band (photoionization).

In particular, it is preferred if the half-life t _{1/2 of} the spontaneous decay of the charged state is at least 1 second, preferably at least 1 minute, particularly preferably at least 30 minutes.

Preferred embodiments provide that the conversion into the electronically charged state takes place by means of electromagnetic radiation, preferably by electromagnetic radiation having a wavelength of between 100 and 800 nm, in particular UV radiation, and / or by X-radiation and / or by electron beams.

The radiation used to stimulate the emission may have a wavelength between 200 to 2000 nm, preferably between 400 to 1600 nm.

The wavelength of the emission is preferably between 200 to 4000 nm, preferably 400 to 1600 nm.

Preferred particle sizes are between 2 to 1000 nm. It is further preferred if the nanoparticle is present as a core-shell nanoparticle. Likewise, however, there is the possibility that the nanoparticle is designed as a "full particle".

Thus, a stimulable nanoparticle is preferably provided which can be converted into an electronically charged state by light having a wavelength between 100 and 800 nm and / or with X-rays or electron beams, and by a light pulse having a wavelength of photons between 500 and 1600 nm for emission of light of a wavelength between 400 and 1300 nm can be excited.

• a) das einen amorphen Kern aus Silica oder aus einer Verbindung ausgewählt aus der Gruppe bestehend aus Silica, Silicaten, Vanadaten, Wolframaten, Phosphaten, Oxiden, Sulfiden, Sulfaten, Aluminaten und/oder Halogeniden, wie z. B. Fluorobromiden, eines ersten Hauptgruppen-, Übergangs- oder Lanthanidmetalls,
• b) eine auf dem amorphen Kern aufgebrachte stimulierbare Schale, enthaltend mindestens eine Verbindung ausgewählt aus der Gruppe bestehend aus Silica, Silicaten, Vanadaten, Wolframaten, Phosphaten, Oxiden, Sulfiden, Sulfaten, Aluminaten und/oder Halogeniden, wie z. B. Fluorobromiden, eines ersten Hauptgruppen-, Übergangs- oder Lanthanidmetalls, die mit Übergangsmetall- oder Lanthanidmetall-Ionen mindestens einer zweiten, vom ersten Hauptgruppenmetall, Übergangsmetall oder Lanthanidmetall verschiedenen Sorte eines Übergangsmetalls oder Lanthanidmetalls dotiert sind, umfasst, wobei

der Durchmesser des Silicakerns zwischen 10 und 290 nm, bevorzugt zwischen 10 und 260 nm, besonders bevorzugt zwischen 10 und 50 nm oder 75 und 260 nm beträgt.According to the invention, a stimulable nanoparticle is further provided,

• a) the one amorphous core of silica or a compound selected from the group consisting of silica, silicates, vanadates, tungstates, phosphates, oxides, sulfides, sulfates, aluminates and / or halides, such as. Fluorobromides, a first main group, transition or lanthanide metal,
• b) an applied on the amorphous core stimulable shell containing at least one compound selected from the group consisting of silica, silicates, vanadates, tungstates, phosphates, oxides, sulfides, sulfates, aluminates and / or halides, such as. Fluorobromides, a first main group, transition or lanthanide metal doped with transition metal or lanthanide metal ions of at least one second grade of a transition metal or lanthanide metal other than the first main group metal, transition metal or lanthanide metal

the diameter of the silica core is between 10 and 290 nm, preferably between 10 and 260 nm, particularly preferably between 10 and 50 nm or 75 and 260 nm.

The above-mentioned compound may include main group, transition or lanthanide metals of all the groups of the Periodic Table of the Elements. The compounds of a first main group metal are thus u. a. also to count Ca and Sr compounds.

A preferred embodiment provides that the second grade of transition metal or lanthanide metal ions used for the doping is selected from the group consisting of Pb ²⁺ , Mn ²⁺ , Cu ⁺ , Dy ³⁺ , Sm ³⁺ , Eu ²⁺ , Eu ³⁺ , Tb ³⁺ , La ³⁺ , Ce ³⁺ , Pr ³⁺ , Nd ³⁺ , Gd ³⁺ , Ho ³⁺ , Er ³⁺ , Tm ³⁺ , Yb ³⁺ , Lu ³⁺ and / or Combinations of this.

It is also preferred if the compound forming the core and / or the shell-forming or shell-forming compound is independently selected from the group consisting of MgSiO ₃ , Zn ₂ SiO ₄ , ZnMgSi ₂ O ₆ , CaMgSi ₂ O ₆ , Sr ₂ MgSiO ₇ , SrAl ₂ O ₄ , CaAl ₂ O ₄ , YVO ₄ , GdVO ₄ , NaGd (WO ₄ ) ₂ , CaWO ₄ , Y ₂ O ₃ , LaPO ₄ , ZnS, CaS, BaFBr and / or combinations thereof.

In particular, the following doped materials are suitable as a constituent of the core and / or the shell or as the total material of the core and / or the shell:
Zn ₂ SiO ₄ : Mn ²⁺ , YVO ₄ : Dy ³⁺ / Sm ³⁺ , NaGd (WO ₄ ) ₂ : Eu ³⁺ , NaGd (WO ₄ ) ₂ : Eu ³⁺ , CaWO ₄ : Eu ³⁺ / Tb ³⁺ , YVO ₄ : Eu ³⁺ , Y ₂ O ₃ : Eu ³⁺ , GdVO ₄ : Eu ³⁺ , CaPO ₄ : Ce ³⁺ / Tb ³⁺ , ZnS: Cu ¹⁺ / Pb ²⁺ , CaS: Eu ²⁺ / Sm ³⁺ , BaFBr: Eu ²⁺ , ZnMgSi ₂ O ₆ , CaMgSi ₂ O ₆ and MgSiO ₃ , wherein the last three mentioned silicates are doped with manganese, europium or dysprosium ions and Sr ₂ MgSi ₂ O ₇ , which is doped with Europium and / or dysprosium ions, as well as the silicate Ca _0.2 Zn _0.9 Mg _0.9 Si ₂ O ₆ , which is doped with Eu ²⁺ , Dy ³⁺ and / or Mn ²⁺ .

Further examples are:
CaS: Ln (with Ln, Ce, Sm, Eu),
Silicates Zn ₂ SiO ₄ doped with Mn ²⁺ or Ln 1, Ln 2 (with Ln (1,2): Ce ³⁺ , Eu ³⁺ , Tb ³⁺ , Sm ³⁺ , as alternative Y ₂ SiO ₅ : Eu ³⁺ , Ce ³⁺ Tb ³⁺
Aluminates (Sr, Ca) Al ₂ O ₄ : Ln (with Ln: Ce ³⁺ , Pr ³⁺ , Nd ³⁺ , Eu ²⁺ / Eu ³⁺ , Tb ³⁺ , Dy ³⁺ , Er ³⁺ )
ZnS: Cu, Pb and different calcium phosphates.

Specific examples of luminescent materials that are suitable for core and / or shell are, for. B .: (very hygroscopic); CsI: Tl; CsI: Na; LiF: Mg; LiF: Mg, Ti; LiF: Mg, Na; KMgF ₃ : Mn; BaFCl: Eu; BaFCl: Sm; BaFBr: Eu; BaFCl _0.5 Br _0.5 : Sm; BaY ₂ F ₈ : A (A = Pr, Tm, Er, Ce); BaSi ₂ O ₅ : Pb; BaMg ₂ Al ₁₆ 0 ₂₇ : Eu; BaMgAl ₁₄ O ₂₃ : Eu; BaMgAl ₁₀ O ₁₇ : Eu; BaMgAl ₂ O ₃ : Eu; Ba ₂ P ₂ O ₇ : Ti; (Ba, Zn, Mg) ₃ Si ₂ O _7: Pb; Ce (Mg, Ba) Al ₁₁ O ₁₉ ; Ce _0.65 Tb _0.35 MgAl ₁₁ O ₁₉ : Ce, Tb; MgAl ₁₁ O ₁₉ : Ce, Tb; MgF ₂ : Mn; MgS: Eu; MgS: Ce; MgS: Sm; MgS: (Sm, Ce); (Mg, Ca) S: Eu; MgSiO ₃ : Mn; 3.5MgO x 0.5MgF ₂ x GeO ₂ : Mn; MgWO ₄ : Sm; MgWO ₄ : Pb; 6MgO × As ₂ O ₅ : Mn; (Zn, Mg) F ₂ : Mn; (Zn ₄ Be) SO ₄ : Mn; Zn ₂ SiO ₄ : Mn; Zn ₂ SiO ₄ : Mn, As; Zn ₃ (PO ₄ ) ₂ : Mn; CdBO ₄ : Mn; CaF ₂ : Mn; CaF ₂ : Dy; CaS: A (A = lanthanide, Bi); (Ca, Sr) S Bi; CaWO ₄ : Pb; CaWO ₄ : Sm; CaSO ₄ : A (A = Mn, lanthanide); 3Ca ₃ (PO ₄ ) ₂ x Ca (F, Cl) ₂ : Sb, Mn; CaSiO ₃ : Mn, Pb; Ca ₂ Al ₂ Si ₂ O ₇ : Ce; (Ca, Mg) SiO ₃ : Ce; (Ca, Mg) SiO ₃ : Ti; 2SrO x 6 (B ₂ O ₃ ) x SrF ₂ : Eu; 3Sr ₃ (PO ₄ ) ₂ x CaCl ₂ : Eu; A ₃ (PO ₄ ) ₂ × ACl ₂ : Eu (A = Sr, Ca, Ba); (Sr, Mg) ₂ P ₂ O ₇ : Eu; (Sr, Mg) ₃ (PO ₄ ) ₂ Sn; SrS: Ce; SrS: Sm, Ce; SrS: Sm; SrS: Eu; SrS: Eu, Sm; SrS: Cu, Ag; Sr ₂ P ₂ O ₇ : Sn; Sr ₂ P ₂ O ₇ : Eu; Sr ₄ Al ₁₄ O ₂₅ : Eu; SrGa ₂ S ₄ : A (A = lanthanide, Pb); SrGa ₂ S ₄ : Pb; Sr ₃ Gd ₂ Si ₆ O ₁₈ : Pb, Mn; YF ₃ : Yb, He; YF ₃ : Ln (Ln = lanthanide); YLiF ₄ : Ln (Ln = lanthanide); Y ₃ Al ₅ O ₁₂ : Ln (Ln = lanthanide); YAI ₃ (BO ₄ ) ₃ Nd, Yb; (Y, Ga) BO _3: Eu; (Y, Gd) BO ₃ : Eu; Y ₂ Al ₃ Ga ₂ O ₁₂ : Tb; Y ₂ SiO ₅ : Ln (Ln = lanthanide); Y ₂ O ₂ S: Ln (Ln = lanthanide); YVO ₄ A (A = lanthanide, In); Y (P, V) O ₄ : Eu; YTaO ₄ : Nb; YAlO _3: A (A = Pr, Tm, Er, Ce); YOCl: Yb, Er; LnPO ₄ : Ce, Tb (Ln = lanthanide or mixture of lanthanides); LuVO ₄ : Eu; GdVO ₄ : Eu; Gd ₂ O ₂ S: Tb; GdMgB ₅ O ₁₀ : Ce, Tb; LaOBr: Tb; La ₂ O ₂ S: Tb; LaF ₃ : Nd, Ce; BaYb ₂ F ₈ : Eu; NaYF ₄ : Yb, He; NaGdF ₄ : Yb, He; NaLaF ₄ : Yb, Er; LaF ₃ : Yb, Er, Tm; BaYF ₅ : Yb, He; GaN: A (A = Pr, Eu, Er, Tm); Bi ₄ Ge ₃ O ₁₂ ; LiNbO _3: Nd, Yb; LiNbO ₃ : He; LiCaAlF ₆ : Ce; LiSrAlF ₆ : Ce; LiLuF ₄ : A (A = Pr, Tm, Er, Ce); Li ₂ B ₄ O ₇ : Mn; Y ₂ O ₂ Eu; Y ₂ SiO ₅ : Eu; CaSiO ₃ : Ln, where Ln = 1, 2 or more lanthanides.
M ^I X: xBi with M ¹ = Rb and X = Cl, Br and / or I
RbX: xTl with X = Br and / or Cl and / or I
YOX: zA with X = Cl and / or Br, and A = Ce or Tb

• 1. Halogenide: z. B. XY₂ (X = Mg, Ca, Sr, Ba; Y = F, Cl, J); CaF₂:Eu(II); BaF₂:Eu; BaMgF₄:Eu; LiBaF₃Eu; SrF₂Eu; SrBaF₂Eu; CaBr₂Eu-SiO₂; CaCJ₂:Eu; CaCJ₂:Eu-SiO₂; CaCJ₂:Eu,Mn-SiO₂; CaJ₂:Eu; CaJ₂:Eu,Mn; KMgF₃:Eu; SrF₂:Eu(II); BaF₂:Eu(II); YF₃; NaYF₄; MgF₂:Mn; MgF₂:Ln (Ln = Lanthanid(en)). KBr: In⁺ RbBr:Ga, CsBr:Ga, RbBr:Eu²⁺, CsBr:Eu²⁺, Cs₂NaYF₆:Ce³⁺, CsNaYF₆:Pr³⁺ CaF₂:Eu³⁺ (oder Eu²⁺), Sm³⁺,
• 2. Erdalkalisulfate: z. B. XSO₄ (X = Mg, Ca, Sr, Ba); SrSO₄:Eu; SrSO₄:Eu,Mn; BaSO₄:Eu; BaSO₄:Eu,Mn; CaSO₄; CaSO₄:Eu; CaSO₄:Eu,Mn; sowie gemischte Erdalkalisulfate, auch in Kombination mit Magnesium, z. B. Ca,MgSO₄:Eu,Mn.
• 3. Phosphate und Halophosphate: z. B. CaPO₄:Ce,Mn; Ca₅(PO₄)₃Cl:Ce,Mn; Ca₅(PO₄)₃F:Ce,Mn; SrPO₄:Ce,Mn; Sr₅(PO₄)₃Cl:Ce,Mn; Sr₅(PO₄)₃F:Ce,Mn; die letzteren auch codotiert mit Eu(II) oder codotiert mit Eu,Mn; α-Ca₃(PO₄)₂:Eu; β-Ca₃(PO₄)₂:Eu,Mn; Ca₅(PO₄)₃Cl:Eu; Sr₅(PO₄)₃Cl:Eu; Ba₁₀(PO₄)₆Cl:Eu; Ba₁₀(PO₄)₆Cl:Eu,Mn; Ca₂Ba₃(PO₄)₃Cl:Eu; Ca₅(PO₄)₃F:Eu²⁺X³⁺; Sr₅(PO₄)₃F:Eu²⁺X³⁺ (X = Nd, Er, Ho, Tb); Ba₅(PO₄)₃Cl:Eu; β-Ca₃(PO₄)₂:Eu; CaB₂P₂O₉:Eu; CaB₂P₂O₉:Eu; Ca₂P₂O₇:Eu; Ca₂P₂O₇:Eu,Mn; Sr₁₀(PO₄)₆Cl₂:Eu; (Sr,Ca,Ba,Mg)₁₀(PO₄)₆Cl₂:Eu; LaPO₄:Ce; CePO₄; LaPO₄:Eu; LaPO₄:Ce; LaPO₄:Ce,Tb; CePO₄:Tb; Zn₃(PO₄)₂:Mn²⁺ (Zn₃(PO₄)₂:Mn²⁺,Al³⁺Zn₃(PO₄)₂:Mn²⁺,Ga³⁺ Sr₃(PO₄)₂:Eu²⁺, Sr₅(PO₄)₃:Eu²⁺, Sr₂PO₄:Eu²⁺
• 4. Borate: z. B. LaBO₃; LaBO₃:Ce; ScBO₃:Ce; YAIBO₃:Ce; YBO₃:Ce; Ca₂B₅O₉Cl:Eu; xEuO × yNa₂O × zB₂O₃. Sr₂BO₃X:Eu²⁺ mit X = Cl, Br und/oder I Sr_2-x(B₅O₉)_5-y/2X_y:D_x mit X = Halogenide und D = Eu²⁺, Ce³⁺
• 5. Vanadate: z. B. YVO₄; YVO₄:Eu; YVO₄:Dy; YVO₄:Sm; YVO₄:Bi; YVO₄:Bi,Eu; YVO₄:Bi,Dy; YVO₄:Bi,Sm; YVO₄:Tm; YVO₄Bi,Tm; GdVO₄; GdVO₄:Eu; GdVO₄:Dy; GdVO₄:Sm; GdVO₄:Bi; GdVO₄:Bi,Eu; GdVO₄:Bi,Dy; GdVO₄:Bi,Sm; YVO₄:Eu; YVO₄:Sm; YVO₄:Dy.
• 6. Aluminate: z. B. MgAl₂O₄:Eu; CaAl₂O₄:Eu; SrAl₂O₄Eu; BaAl₂O₄:Eu; LaMgAl₁₁O₁₉:Eu; BaMgAl₁₀O17:Eu; BaMgAl₁₀O₁₇:Eu,Mn; CaAl₁₂O₁₉:Eu; SrAl₁₂O₁₉:Eu; SrMgAl₁₀O₁₇:Eu; Ba(Al₂O₃)₆:Eu; (Ba,Sr)MgAl₁₀O₁₇:Eu,Mn; CaAl₂O₄:Eu,Nd; SrAl₂O₄Eu,Dy; Sr₄Al₁₄O25:Eu,Dy. MAl₂O₄ (M = Ca, Sr, Mg, Ba), insbesondere BaAl₂O₄; Sr₅Al₈O₇ (dotiert mit Eu und Dy). Alumosilikate CaSrAlSiO₇ und Ca₂Al₂SiO₇ (ebenfalls mit Eu,Dy-Dotierung).
• 7. Silikate: z. B. BaSrMgSi₂O₇:Eu; Ba₂MgSiO₇:Eu; BaMg₂Si₂O₇:Eu; CaMgSi₂O₆:Eu; SrBaSiO₄:Eu; Sr₂Si₃O₈ × SrCl₂:Eu; Ba₅SiO₄Br₆:Eu; Ba₅SiO₄Cl₆:Eu; Ca₂MgSi₂O₇:Eu; CaAl₂Si₂O₈:Eu; Ca_1,5Sr_0,5MgSi₂O₇:Eu; (Ca,Sr)₂MgSi₂O₇:Eu; Sr₂LiSiO₄F:Eu; Sr₃Al₂O₆:Eu, Sr₃Al₂O₆:XY (X = Eu, Y = Dy), Sr₅Al₂O₈:Eu, Y₃Al₅O₁₂:Ce, Gd₃Al₅O₁₂:Ce, Lu₃Al₅O₁₂:Ce und (GdLu)₃Al₅O₁₂:Ce, Tb₃Al₅O₁₂:Ce, Tb₃Al₅O₁₂:XY (X = Ce, Y = Eu, Mn), Mg₂SiO₄:Mn²⁺, Dy³⁺ und M₃MgSi₂O₈ (M = Ca, Sr, Ba). Mg₂SiO₄:Mn²⁺,Dy³⁺; M₃MgSi₂O₈ (M = Ca, Sr, Ba). ZnMgSi₂O₆, CaMgSi₂O₆, MgSiO₃ (dotiert mit Eu, Mn, Dy) Sr₂MgSi₂O₇ (dotiert mit Eu, Dy) Sr₂M^IISi₂O₇:Ce3⁺ Sr₅SiO₄X₆:Eu²⁺ mit X = Halogenide Y₂SiO₅:X mit X = Tb und/oder Ce Y₂SiO₅:Ce³⁺, Sm³⁺
• 8. Wolframate und Molybdate: z. B. X₃WO₆ (X = Mg, Ca, Sr, Ba); X₂WO₄ (X = Li, Na, K, Rb, Cs); XMoO₄ (X = Mg, Ca, Sr, Ba) und MgWO₄, CaWO₄, CdWO₄, ZnWO₄; sowie Polymolybdate oder Polywolframate oder die Salze der entsprechenden Hetero- oder Isopolysäuren.
• 9. Germanate: z. B. Zn₂GeO₄.
• 10. Außerdem die folgenden Klassen: ALnO₂:Yb,Er (A = Li, Na; Ln = Gd, Y, Lu); LnAO₄:Yb,Er (Ln = La, Y; A = P, V, As, Nb); Ca₃Al₂Ge₃O₁₂:Er; Gd₂O₂S:Yb,Er; La₂S:Yb,Er, Ba₂ZnS₃:Ce.

When classified according to the host lattice type, the following preferred embodiments are also included:

• 1. halides: z. XY ₂ (X = Mg, Ca, Sr, Ba; Y = F, Cl, J); CaF ₂ : Eu (II); BaF ₂ : Eu; BaMgF ₄ : Eu; LiBaF ₃ Eu; SrF ₂ Eu; SrBaF ₂ Eu; CaBr ₂ Eu-SiO ₂ ; CaCJ ₂ : Eu; CaCJ ₂ : Eu-SiO ₂ ; CaCJ ₂ : Eu, Mn-SiO ₂ ; CaJ ₂ : Eu; CaJ ₂ : Eu, Mn; KMgF ₃ : Eu; SrF ₂ : Eu (II); BaF ₂ : Eu (II); YF ₃ ; NaYF ₄ ; MgF ₂ : Mn; MgF ₂ : Ln (Ln = lanthanide (s)). KBr: In ⁺ RbBr: Ga, CsBr: Ga, RbBr: Eu ^2+, CsBr: Eu ^2+, Cs ₂ NaYF _6: Ce ^3+, CsNaYF _6: Pr ³⁺ CaF _2: Eu ³⁺ (or Eu ²⁺ ), Sm ³⁺ ,
• 2. alkaline earth sulfates: z. XSO ₄ (X = Mg, Ca, Sr, Ba); SrSO ₄ : Eu; SrSO ₄ : Eu, Mn; BaSO ₄ : Eu; BaSO ₄ : Eu, Mn; CaSO ₄ ; CaSO ₄ : Eu; CaSO ₄ : Eu, Mn; and mixed alkaline earth sulfates, also in combination with magnesium, e.g. For example Ca, MgSO ₄ : Eu, Mn.
• 3. Phosphates and halophosphates: z. B. CaPO ₄ : Ce, Mn; Ca ₅ (PO ₄ ) ₃ Cl: Ce, Mn; Ca ₅ (PO ₄ ) ₃ F: Ce, Mn; SrPO ₄ : Ce, Mn; Sr ₅ (PO ₄ ) ₃ Cl: Ce, Mn; Sr ₅ (PO ₄ ) ₃ F: Ce, Mn; the latter also codoped with Eu (II) or codoped with Eu, Mn; α-Ca ₃ (PO ₄ ) ₂ : Eu; β-Ca ₃ (PO ₄ ) ₂ : Eu, Mn; Ca ₅ (PO ₄ ) ₃ Cl: Eu; Sr ₅ (PO ₄ ) ₃ Cl: Eu; Ba ₁₀ (PO ₄ ) ₆ Cl: Eu; Ba ₁₀ (PO ₄ ) ₆ Cl: Eu, Mn; Ca ₂ Ba ₃ (PO ₄ ) ₃ Cl: Eu; Ca ₅ (PO ₄ ) ₃ F: Eu ²⁺ X ³⁺ ; Sr ₅ (PO ₄ ) ₃ F: Eu ²⁺ X ³⁺ (X = Nd, Er, Ho, Tb); Ba ₅ (PO ₄ ) ₃ Cl: Eu; β-Ca ₃ (PO ₄ ) ₂ : Eu; CaB ₂ P ₂ O ₉ : Eu; CaB ₂ P ₂ O ₉ : Eu; Ca ₂ P ₂ O ₇ : Eu; Ca ₂ P ₂ O ₇ : Eu, Mn; Sr ₁₀ (PO ₄ ) ₆ Cl ₂ : Eu; (Sr, Ca, Ba, Mg) ₁₀ (PO ₄ ) ₆ Cl ₂ : Eu; LaPO ₄ : Ce; CePO ₄ ; LaPO ₄ : Eu; LaPO ₄ : Ce; LaPO ₄ : Ce, Tb; CePO ₄ : Tb; Zn ₃ (PO ₄ ) ₂ : Mn ²⁺ (Zn ₃ (PO ₄ ) ₂ : Mn ²⁺ , Al ³⁺ Zn ₃ (PO ₄ ) ₂ : Mn ²⁺ , Ga ³⁺ Sr ₃ (PO ₄ ) ₂ : Eu ²⁺ , Sr ₅ (PO ₄ ) ₃ : Eu ²⁺ , Sr ₂ PO ₄ : Eu ²⁺
• 4. Borates: z. B. LaBO ₃ ; LaBO ₃ : Ce; ScBO ₃ : Ce; YAIBO ₃ : Ce; YBO ₃ : Ce; Ca ₂ B ₅ O ₉ Cl: Eu; xEuO x yNa ₂ O x eg ₂ O ₃ . Sr ₂ BO ₃ X: Eu ²⁺ with X = Cl, Br and / or I Sr _{2 -x} (B ₅ O ₉ ) _{5-y / 2} X _y : D _x with X = halides and D = Eu ²⁺ , Ce ³⁺
• 5. Vanadates: z. B. YVO ₄ ; YVO ₄ : Eu; YVO ₄ : Dy; YVO ₄ : Sm; YVO ₄ : Bi; YVO ₄ : Bi, Eu; YVO ₄ : Bi, Dy; YVO ₄ : Bi, Sm; YVO ₄ : Tm; YVO ₄ Bi, Tm; GdVO ₄ ; GdVO ₄ : Eu; GdVO ₄ : Dy; GdVO ₄ : Sm; GdVO ₄ : Bi; GdVO ₄ : Bi, Eu; GdVO ₄ : Bi, Dy; GdVO ₄ : Bi, Sm; YVO ₄ : Eu; YVO ₄ : Sm; YVO ₄ : Dy.
• 6. Aluminates: z. For example, MgAl ₂ O ₄ : Eu; CaAl ₂ O ₄ : Eu; SrAl ₂ O ₄ Eu; BaAl ₂ O ₄ : Eu; LaMgAl ₁₁ O ₁₉ : Eu; BaMgAl ₁₀ O17: Eu; BaMgAl ₁₀ O ₁₇ : Eu, Mn; CaAl ₁₂ O ₁₉ : Eu; SrAl ₁₂ O ₁₉ : Eu; SrMgAl ₁₀ O ₁₇ : Eu; Ba (Al ₂ O ₃ ) ₆ : Eu; (Ba, Sr) MgAl ₁₀ O ₁₇ : Eu, Mn; CaAl ₂ O ₄ : Eu, Nd; SrAl ₂ O ₄ Eu, Dy; Sr ₄ Al ₁₄ O25: Eu, Dy. MAl ₂ O ₄ (M = Ca, Sr, Mg, Ba), especially BaAl ₂ O ₄ ; Sr ₅ Al ₈ O ₇ (doped with Eu and Dy). Aluminosilicates CaSrAlSiO ₇ and Ca ₂ Al ₂ SiO ₇ (also with Eu, Dy doping).
• 7. silicates: z. B. BaSrMgSi ₂ O ₇ : Eu; Ba ₂ MgSiO ₇ : Eu; BaMg ₂ Si ₂ O ₇ : Eu; CaMgSi ₂ O ₆ : Eu; SrBaSiO ₄ : Eu; Sr ₂ Si ₃ O ₈ × SrCl ₂ : Eu; Ba ₅ SiO ₄ Br ₆ : Eu; Ba ₅ SiO ₄ Cl ₆ : Eu; Ca ₂ MgSi ₂ O ₇ : Eu; CaAl ₂ Si ₂ O ₈ : Eu; Ca _1.5 Sr _0.5 MgSi ₂ O ₇ : Eu; (Ca, Sr) ₂ MgSi ₂ O ₇ : Eu; Sr ₂ LiSiO ₄ F: Eu; Sr ₃ Al ₂ O ₆ : Eu, Sr ₃ Al ₂ O ₆ : XY (X = Eu, Y = Dy), Sr ₅ Al ₂ O ₈ : Eu, Y ₃ Al ₅ O ₁₂ : Ce, Gd ₃ Al ₅ O ₁₂ : Ce, Lu ₃ Al ₅ O ₁₂ : Ce and (GdLu) ₃ Al ₅ O ₁₂ : Ce, Tb ₃ Al ₅ O ₁₂ : Ce, Tb ₃ Al ₅ O ₁₂ : XY (X = Ce, Y = Eu, Mn), Mg ₂ SiO ₄ : Mn ²⁺ , Dy ³⁺ and M ₃ MgSi ₂ O ₈ (M = Ca, Sr, Ba). Mg ₂ SiO ₄ : Mn ²⁺ , Dy ³⁺ ; M ₃ MgSi ₂ O ₈ (M = Ca, Sr, Ba). ZnMgSi ₂ O ₆ , CaMgSi ₂ O ₆ , MgSiO ₃ (doped with Eu, Mn, Dy) Sr ₂ MgSi ₂ O ₇ (doped with Eu, Dy) Sr ₂ M ^II Si ₂ O ₇ : Ce 3 ⁺ Sr ₅ SiO ₄ X ₆ : Eu ²⁺ with X = halides Y ₂ SiO ₅ : X with X = Tb and / or Ce Y ₂ SiO ₅ : Ce ³⁺ , Sm ³⁺
• 8. Tungstates and molybdate: z. B. X ₃ WO ₆ (X = Mg, Ca, Sr, Ba); X ₂ WO ₄ (X = Li, Na, K, Rb, Cs); X MoO ₄ (X = Mg, Ca, Sr, Ba) and MgWO ₄ , CaWO ₄ , CdWO ₄ , ZnWO ₄ ; and polymolybdates or polytungstates or the salts of the corresponding hetero- or isopolyacids.
• 9. Germanate: z. Zn ₂ GeO ₄ .
• 10. In addition, the following classes: ALnO ₂ : Yb, Er (A = Li, Na, Ln = Gd, Y, Lu); LnAO ₄ : Yb, Er (Ln = La, Y; A = P, V, As, Nb); Ca ₃ Al ₂ Ge ₃ O ₁₂ : He; Gd ₂ O ₂ S: Yb, He; La ₂ S: Yb, Er, Ba ₂ ZnS ₃ : Ce.

All the aforementioned materials are also suitable for the production of nanoparticles that are not in the core-shell type, d. H. have only one phase ("full particles").

In the case of the nanoparticles according to the invention, it is further preferred that the doping concentration of the at least one second, different from the first, transition metal or lanthanide metal based on the molar amount of the first transition or lanthanide metal is between 0.01 and 25 mol%, preferably between 0.5 and 20 mol -%, more preferably between 1 and 10 mol%, particularly preferably between 2 and 7.5 mol%. The stated concentrations of the doping also apply in particular to the materials explicitly mentioned in the last paragraph.

In a further preferred embodiment, the surface of the shell is functionalized with functional groups, these functional groups being in particular selected from the group consisting of amino, carboxylate, carbonate, maleic, imine, imide, amide, aldehyde , Thiol, isocyanate, isothiocyanate, acylazide, hydroxyl, N-hydroxy-succinimidester-, phosphate, phosphonic acid, sulfonic acid, sulfonic acid chloride, epoxy, CC double bond-containing groups, such as. B. (meth) acrylic acid or (meth) acrylate or norbornyl groups.

Further preferred embodiments provide that the particle surface is surrounded by a shell of silica, polymer, aluminum oxide or polyethylene glycol, TiO ₂ , ZnO, ZrO ₂ , the surface of the PLS particle is chemically modified.

It is likewise advantageous if the surface has covalently or noncovalently bound compound molecules and / or reactive groups.

It is also possible that, as the connecting molecule, one or more chain-like molecules having a polarity or charge opposite to the surface of the nanoparticles non-covalently with the surface the particles are linked, the chain-like molecules may be anionic, cationic or zwitterionic detergents, acidic or basic proteins, polyamides or polysulfone or polycarboxylic acids.

It is furthermore advantageous if the surface and / or the connecting molecules connected to the surface of the nanoparticles have reactive neutral, charged or partially charged groups such as amino groups, carboxylic acid groups, thiols, thioethers, disulfides, imidazoles, guanidines, hydroxyl groups, indoles, vicinal diols, aldehydes, alpha-haloacetyl groups, N-maleimides, mercury organyls, aryl halides, acid anhydrides, isocyanates, isothiocyanates, sulfonic acid halides, imidoesters, diazoacetates, diazonium salts, 1,2-diketones, alpha-beta-unsaturated carbonyl compounds, azolides, silanes, phosphonic acids, phosphoric acid esters or derivatives thereof Carry groups, these reactive groups allow a chemical bond with other connection molecules or affinity molecules.

The nanoparticles according to the invention can likewise be provided with one or more affinity molecules or a plurality of affinity molecules coupled to one another, wherein the affinity molecules can bind to the particle surface on the one hand and bind to a biological or other organic substance on the other hand.

The affinity molecules can, for. As monoclonal or polyclonal antibodies, proteins, peptides, oligonucleotides, plasmids, nucleic acid molecules, oligo- or polysaccharides, haptens such as biotin or digoxin, or a low molecular weight synthetic or natural antigen.

It is also possible that the affinity molecule is covalently or non-covalently coupled to the particle through reactive groups on the affinity molecule and on the simple detection probe.

The reactive groups on the surface of the affinity molecule may be selected from amino groups, carboxylic acid groups, thiols, thioethers, disulfides, imidazoles, guanidines, hydroxyl groups, indoles, vicinal diols, aldehydes, alpha-haloacetyl groups, N-maleimides, mercury organyls, aryl halides, acid anhydrides, isocyanates , Isothiocyanates, sulfonic acid halides, imidoesters, diazoacetates, diazonium salts, 1,2-diketones, alpha-beta-unsaturated carbonyl compounds or azolides.

There may be a covalent or non-covalent, self-assembled compound between the PSL particle and the affinity molecule.

According to the invention, a stimulable nanoparticle system is also provided which contains a plurality of the aforementioned nanoparticles. The polydispersity of the nanoparticles in the nanoparticle system according to the invention is preferably between 0.1 and 10%, preferably between 1 and 3%.

• a) mindestens eine Sorte Ionen eines ersten Übergangsmetalls oder Lanthanidmetalls,
• b) mindestens eine Sorte Ionen eines zweiten, vom ersten verschiedenen Übergangsmetalls oder Lanthanidmetalls sowie
• c) für den Fall, dass die Schale Vanadate, Wolframate, Phosphate, Sulfide, Sulfate, Aluminate und/oder Halogenide enthalten soll Vanadat-, Wolframat-, Phosphat-, Sulfid- und/oder Halogenid-Ionen, insbesondere Fluorid- und Bromidionen,

beschichtet und die beschichteten Kernpartikel anschließend getempert werden.The invention also provides a process for producing a nanoparticle system as described above, wherein the amorphous core particles of silica or of a compound selected from the group consisting of silica, silicates, vanadates, tungstates, phosphates, oxides, sulfides, sulfates, aluminates and / or halides , such as As fluorobromides, a first Hauptgruppen-, transition or Lanthanidmetalls, with an average diameter between 10 and 290 nm by wetting with an aqueous solution containing

• a) at least one kind of ion of a first transition metal or lanthanide metal,
• b) at least one type of ion of a second, different from the first transition metal or lanthanide metal and
• c) in the event that the shell is to contain vanadates, tungstates, phosphates, sulfides, sulfates, aluminates and / or halides, vanadate, tungstate, phosphate, sulfide and / or halide ions, in particular fluoride and bromide ions,

coated and the coated core particles are then tempered.

In order to obtain the above-mentioned preferred concentrations of the dopants, the molar ratios of the second grade transition metal or lanthanide metal to the first grade transition or lanthanide metal are preferably adjusted accordingly.

• a) eine organische Carbonsäure mit mindestens zwei Säurefunktionalitäten, bevorzugt Zitronensäure, und/oder
• b) einen Alkohol mit mindestens zwei Alkoholfunktionalitäten, bevorzugt Polyethylenglykol und/oder Polypropylenglycol

enthalten.The aqueous solution used can be further additives, such as

• a) an organic carboxylic acid having at least two acid functionalities, preferably citric acid, and / or
• b) an alcohol having at least two alcohol functionalities, preferably polyethylene glycol and / or polypropylene glycol

contain.

The step of tempering is preferably carried out at temperatures between 500 to 1500 ° C, preferably 700 to 1300 ° C, more preferably at 800 to 1200 ° C, in particular at 1000 ° C to 1100 ° C.

It is likewise preferred if removal of the solvent, preferably by lyophilization of the particles, is carried out after wetting and before the sintering step.

A further preferred embodiment provides that after the tempering step, a chemical modification of the surface of the PSL particles and / or production of reactive groups on the surface of the particles and / or connection of one or more compound molecules with the surface of the PSL particles by covalent or non-covalent bond.

After the tempering step, further surface modification of the particles with an aminosilane compound and / or with an amino, carboxylate, carbonate, maleic, imine, imide, amide, aldehyde, thiol, isocyanate, isothiocyanate , Acylazid-, hydroxyl, N-hydroxy-succinimidester-, phosphate, phosphonic acid, sulfonic acid, sulfonic acid chloride, epoxy, cc double bond-containing, such as. B. (meth) acrylic acid or (meth) acrylate or norbornyl group-containing compound. For example, TRIAMO (N- [3 [trimethoxysilyl) propyl] diethylenetriamine) can be used for this purpose.

According to the invention, uses of the above-described nanoparticle system are also indicated. In particular, the nanoparticle systems according to the invention are suitable as a diagnostic agent and / or as a marker, in particular for biological or medical applications; as an optically detectable diffusion probe; in security systems; as a substrate for security systems and / or as markers for the detection of originals and / or plagiarisms and / or as contrast agents for biomedical applications and means for forensic investigations.

When using the nanoparticle system according to the invention, it is preferred if the nanoparticle system is brought into an electronically charged state with light having a wavelength between 100 and 800 nm, with X-rays and / or electron beams, and by means of a light pulse having a wavelength between 400 and 1600 nm for the stimulated emission of photons with a wavelength between 500 and 1600 nm is excited.

• a) eine Dauer zwischen 10 ns und 1 min, bevorzugt zwischen 100 ns und 100 μs, weiter bevorzugt zwischen 250 ns und 10 μs, insbesondere zwischen 500 ns und 3 μs aufweist und/oder
• b) eine Energiedichte zwischen 0,01 μJ/cm² und 100 μJ/cm², bevorzugt zwischen 0,1 μJ/cm² und 20 μJ/cm² besonders bevorzugt zwischen 1 μJ/cm² und 10 μJ/cm² aufweist.

The light pulse used to stimulate the emission preferably has the following characteristics:

• a) has a duration of between 10 ns and 1 min, preferably between 100 ns and 100 μs, more preferably between 250 ns and 10 μs, in particular between 500 ns and 3 μs, and / or
• b) has an energy density between 0.01 μJ / cm ² and 100 μJ / cm ² , preferably between 0.1 μJ / cm ² and 20 μJ / cm ^{2, more} preferably between 1 μJ / cm ² and 10 μJ / cm ² .

It can also be used continuous radiation for stimulation. It is preferred that the power density of the beam is between 0.01 W / cm ² and 100 W / cm ² , more preferably between 1 W / cm ² and 10 W / cm ² .

These luminescent particle systems are particularly suitable as photostimulable markers for biological and medical diagnostics, as optically detectable diffusion probes for the production of security systems and as markers for the detection of plagiarisms / originals.

The following examples illustrate the application potential of PLS particles.

The protein A may have special biological functionality, for example the ability to open the pores of the cell membrane. It should be clarified whether it differs from a protein B with regard to this function. For this purpose, one half of the nanoparticles to be added to a cell structure will be functionalized with protein A, the other half with protein B. The connection of Proteins to the nanoparticles are made by a corresponding surface modification of the particles - as described in more detail below. The first half (functionalized with A) is now additionally "marked" in such a way that it is made PSL-capable by charging. Then the cell assembly is exposed to all nanoparticles for the expected reaction time. If the PSL is subsequently triggered by the irradiation of IR light, the luminescence of the nanoparticles only shows the PSL-capable particles, ie only those that have been functionalized with protein A, since only these were charged. But if one stimulates the photoluminescence, then one sees both particle types, thus the B marked ones. Different spatial distributions of luminescence in PSL and photoluminescence (PL) excitation (in cell wall and cell interior) therefore indicate the different biological activity of the two proteins.

Another example is the charging of the messenger substance of a synapse fixed on a PSL-capable NP via a corresponding functionalization and the observation of the subsequent distribution and the temporal and spatial extension.

Such optical "tagging" allows diffusion and transport processes with very high spatial resolution in vivo and in vitro.

Particularly preferred examples of the materials which can be used according to the invention as shell are described below, but other materials than those explicitly mentioned here can also be used.

ZnS: Cu ⁺ , Pb ²⁺

Zinc sulfide doped with Cu ⁺ and Pb ²⁺ is a phosphorescent phosphor [ S. Shionoya, World Cup Yen. Phosphorus Handbook. [Ed.] GHKG. sl: CRC Press, 1999. TZU] which also displays PSL (photostimulable luminescence) and is used as a storage phosphor for the visualization of infrared (IR) lasers [ www.phosphor-technology.com ]. Accordingly, a ZnS: Cu ⁺ , Pb ²⁺ marker charged with UV or blue light can be made to glow in the visible region of the spectrum after an interval of time by an IR pulse. The luminescence mechanisms of ZnS are particularly well studied: Cu ⁺ : green luminescence with a broad band at λ _max. = 520 nm is a donor-acceptor emission, wherein both inserted by manufacturing Cl ^- and Al ^{3 +} ions can be used as donors.

Different lattice defects in ZnS can localize electrons and holes and thus contribute to phosphorescence. The duration of the afterglow can be significantly increased by the creation of deep traps with co-ions.

The PSL in ZnS: Cu ⁺ , Pb ²⁺ comes about through the liberation of electrons from the trap [ DE Mason. Rev. Modern Phys. 1965, vol. 37, p. 743 ; R. Scheps, F. Hanson. J. Appl. Phys. 1985, Vol. 57, p. 610 ]. The traps are stable at room temperature, thus the IR-stimulated luminescence can be observed even after several hours [ M. Sidran. Appl. Optics. 1969, Vol. 8, p. 79 ; E. Bulur, HY Göksü. phys. stat. Sol. A. 1997, Vol. 161, p. R9 ].

ZnS: Eu, Mn

The UV-excited luminescence of nanocrystalline ZnS: Eu, Mn is also sensitive to IR light [Chen, W. U.S. Patent 7,126,136 Oct. 24 2006]. This effect is associated with a charge transfer Eu ³⁺ + Mn ²⁺ ↔ Eu ²⁺ + Mn ³⁺ between the two dopant ions and proves that Eu and Mn also act as traps for charge carriers.

CaS: Eu, Sm

The material system CaS shows a very good agreement with the requirement profile: Eu, Sm, an effective IR converter with fast reaction time [ Y. Tamura, A. Shibukawa. Jap. J. Appl. Phys. 1993, Vol. 32, 7, pp. 3187-3196 ]. The emission maximum lies in the red spectral range, the stimulation spectrum extends from 900 to 1500 nm. CaS, however, is slightly soluble in water, but this disadvantage can be overcome by sheathing the CaS microparticles with SiO ₂ , TiO _2. C. Guo, B. Chu, M. Wu, Q. Su. J. Lumin. 2003, Vol. 105, 2-4, pp. 121-126 ], or CaF ₂ [ C.-F. Guo, B.-L. Chu, J. Xu, Q. Su. Cehm. Res. Chinese U. 2004, Vol. 20, 3, pp. 253-257 ] become. The PSL mechanism is well-informed in this material system and should be given as an example a bit more detailed here:
The current models of charge, storage of energy and charge carriers and of stimulated emission are essentially based on a stimulated emission model developed in the late 1950s in SrS: Eu, Sm [ SP cellar, GD Pettit. Phys. Rev. 1958, Vol. 111, 6, pp. 1533-1539 ; SP cellar. Phys. rev. 1959, vol. 113, 6, p. 1415 ; SP Keller, JE Mapes, and G. Cheroff. Phys. Rev. 1957, Vol. 108, 3, pp. 663-676 ]. It has been modified by the newer authors [ Y. Tamura, A. Shibukawa. Jap. J. Appl. Phys. 1993, Vol. 32, 7, pp. 3187-3196 ; Y. Tamura. Jap. J. Appl. Phys. 1994, Vol. 33, pp. 4640-4646 ; J. Wu, D. Newman, IVF Viney. Appl. Phys. B. 2004, Vol. 79, pp. 239-243 ; J. Wu, D. Newman, and IVF Viney. J. Lumin. 2002, Vol. 99, 3, pp. 237-245 ; M. Danilkin, et al. Radiation Measurements. 1995, Vol. 24, 4, pp. 351-354 ; M. Weidner, A. Osvet, G. Schierning, M. Batentschuk, A. Winnacker. Journal of Applied Physics. 2006. Vol. 100, 7, p. 073701 ]. By irradiation with high-energy light (blue, UV), part of the Eu ²⁺ ions can be ionized to Eu ³⁺ . These Eu ions in trivalent valence state are called hole traps. The electrons excited into the conduction band are attached to Sm ³⁺ ions (Sm ³⁺ ions are reduced to Sm ²⁺ ). The resulting electron traps or hole traps (Eu ³⁺ ) are stable at room temperature, some of the charge carriers are stored in the traps for several hours.

When the charged CaS: Eu, Sm is stimulated with low-energy IR light in the range of 900-1500 nm, the red luminescence of Eu ^{2+ is shown} . By stimulating light the electrons stored at the Sm ²⁺ can be excited back into the conduction band and recombine with a hole stored at the Eu ³⁺ . As a result, the Eu ³⁺ ions are returned to the bivalent valence state. The resulting Eu ²⁺ is in the excited state and changes to the ground state, emitting the characteristic luminescence.

Zn ₂ SiO ₄ : Mn ²⁺ and ZnMgSi ₂ O ₆ : Mn ²⁺ , Eu ²⁺ , Dy ³⁺

Optoelectronics use numerous silicate-based phosphors, including one of the oldest phosphors, Zn ₂ SiO ₄ doped with Mn ²⁺ , which has both phosphorescence and PSL properties. The usual way of preparation is the solid-state synthesis [ S. Shionoya, World Cup Yen. Phosphorus Handbook. [Ed.] GHKG. sl: CRC Press, 1999. TZU ]. The green luminescence (λ _max = 520 nm) of the manganese in α-Zn ₂ SiO ₄ (Willemite) and the red-orange (λ _max = 600 nm) in β-Zn ₂ SiO ₄ is due to the intraionic dd junctions in Mn ²⁺ . In Zn ₂ SiO ₄ : Mn at least two types of traps were found from which the electrons can return to the Mn ion through tunneling, which in turn leads to phosphorescence [ P. Thioulouse, IF Chang, EA Giess. J. Electrochem. Soc. 1983, Vol. 130, p. 2065 ]. Also, irradiation with a He-Ne laser (633 nm) leads to the liberation of the stored electrons from the traps and subsequent PSL in the region of the emission of Mn ²⁺ ions. The PSL effect has also been observed in Ga-doped zinc silicates [ H. Hess. phys. status solidi (a). 1984, Vol. 85, p. 543 ].

Over MgSiO ₃ and ZnMgSi ₂ O ₆ , both doped with Mn ²⁺ , Eu ²⁺ , Dy ³⁺ , was reported in [ XJ. Wang, D. Jia, WM Yen. J. Lumin. 2003, Vol. 102-103, pp. 34-37 ] or in [D. Scherman, M. Bessodes, C. Chaneac, DL Gourier, JP. Jolivet, Q. le Masne, S. Maitrejean, F. Pelle. Patent application WO 2007/048856 A1 , published 03.05.2007. Q. le Masne, C. Chanéac, J. Seguin, F. Pellé, S. Maîtrejean, JP. Jolivet, D. Gourier, M. Bessodes. PNAS 2007, Vol. 104, p. 9266 ] reports. These phosphors emit in the red region (λ _max. = 650 nm) and show a long-lived (several hours) phosphorescence. A shift of the emission spectrum in the near-infrared can be achieved with a partial replacement of Zn and Mg by Ca [D. Scherman, M. Bessodes, C. Chaneac, DL Gourier, JP. Jolivet, Q. le Masne, S. Maitrejean, F. Pelle. Patent application WO 2007048856 A1 , published 03.05.2007. Q. le Masne, C. Chanéac, J. Seguin, F. Pellé, S. Maîtrejean, JP. Jolivet, D. Gourier, M. Bessodes. PNAS 2007, Vol. 104, p. 9266 ].

SrAl ₂ O ₄ : Eu ²⁺ , Dy ³⁺ and Sr ₃ Al ₂ O ₆ : Eu ²⁺ , Dy ³⁺

Have alkaline earth aluminates, prepared as doped powders, ceramics or single crystals, the properties necessary for the objectives of the project. The most widely used luminescent substance in this group is SrAl ₂ O ₄ : Eu ²⁺ , Dy ³⁺ , which has become clearly superior to the previously used ZnS: Cu, Co due to its excellent and long-lasting phosphorescence. As a material showing effective green luminescence (λ _max = 520 nm), SrAl ₂ O ₄ : Eu ²⁺ has been known since 1966 [H. Long. U.S. Patent 3,294,699 ] and has been systematically investigated by Blasse and Bril [ G. Blasse, A. Bril. Philips Res. Rep. 1968, Vol. 23, p. 201 ]. The phosphorescence of SrAl ₂ O ₄ : Eu ²⁺ is formed after prolonged irradiation with UV light [ V. Abbruscato. J. Electrochem. Soc. 1971, vol. 118, 6, p. 930 ]. In [ T. Matsuzawa, Y. Aoki, N. Takeuchi, Y. Murayama. J. Electrochem. Soc. 1996, vol. 143, 8, p. 2670 ] it has been shown that the phosphorescence of SrAl ₂ O ₄ : Eu ²⁺ can be substantially improved by co-doping with trivalent rare earth ions (SE). In [ H. Aizawa, T. Katsumata, J. Takahashi, K. Matsunaga, S. Komuro, T. Morikawa. Rev. Sci. Inst. 2003, Vol. 74, 3, P. 1344 ] it was found that the maximum storage efficiency of SrAl ₂ O ₄ : Eu is achieved by doping with Dy ³⁺ . A model for the phosphorescence of CaAl ₂ O ₄ : Eu ²⁺ , SE ³⁺ , is presented in [ T. Aitasalo, P. Deren, J. Hölsä, H. Jungner, J.-C. Krupa, M. Lastusaari, J. Legendziewicz, J. Niittykoski, W. Strek. J. Sol. St. Chem. 2003, Vol. 171, pp. 114-122 ], in which oxygen and calcium vacancies are proposed as traps for electrons and holes. The trapped charge carriers can also be stimulated with light in Sr (Ca) Al ₂ O ₄ : Eu, Dy (PSL) [ W. Jia, H. Yuan, S. Halmstrom, H. Liu, WM Yen. J. Lumin. 1999, Vol. 83/84, p. 465 ], [ T. Aitasalo, J. Hölsa, H. Jungner, M. Lastusaari, J. Niittykoski. J. Lumin. 2001, Vol. 94/95, p. 59 ]. An effective emission under direct excitation and phosphorescence in the red spectral range (broad spectrum with λ _max = 612 nm) was observed in microcrystalline (d ₅₀ ≈ 1 μm) [ Ping Zhang, Mingxia Xu, Zhentai Theng, Lan Liu, Lingxia Li. J. Sol-Gel Sci. Techn. 2007, Vol. 43, p. 59-64 ] and nanocrystalline (d ₅₀ ≈ 80-100 nm) [ Ping Zhang, Mingxia Xu, Zhentai Theng, Bo Sun, Yanhui Zhang. Mat Sci. and Engineering B 2007, Vol. 136, pp. 159-164 ] Sr ₃ Al ₂ O ₆ : Eu ²⁺ , Dy ³⁺ powder detected. The PSL of this composition has not been reported in the literature.

Example of the preparation of a SiO ₂ @Zn ₂ SiO ₄ : Mn ²⁺ core-shell nanoparticle system.

The synthesis of luminescent core-shell nanoparticles was carried out in a two-step process: coating of the silica cores and sintering of the coated nanoparticles. For this purpose, quasi-monodisperse silica cores of different particle sizes (D = 75, 110, 140, 260 nm) according to a modified method according to Stoeber et al. ( W. Stoeber, A. Fink, E. Bahn, J. Colloid Interface Sci. 1968, 26, 62 ; C. Gellermann, W. Storch, H.Walter, J. Sol-Gel Sci. Technol. 1997, 8, 173 ) Prepared by the hydrolysis of TEOS (Si (OEt) ₄ in alcohol in the presence of water and ammonia. The particle size of the silica colloids was carried concentration of the reactants and the temperature During the particle growth adjusted. The isolation of the silica particles obtained was purified by distilling off the solvent, and by washing the particles three times with ethanol.

The obtained silica cores showed a spherical morphology and a narrow size distribution (polydispersity between 1 to 3%). In the first step, the cores were annealed with Zn ₂ SiO ₄ : Mn ²⁺ precursors using a modified Pechini sol-gel process (see, e.g. US 3,330,697 ) at room temperature. The doping concentration of Mn ²⁺ was varied between 1 mol% and 20 mol%, based on Zn ²⁺ in Zn ₂ SiO ₄ . The amount of starting material was calculated to give a shell thickness of 5 nm. The starting materials for the shell were dissolved in a water-ethanol solution in the presence of nitric acid, citric acid as a chelating agent and polyethylene glycol (PEG) as a cross-linking agent. The network formation after chelation of Zn ²⁺ and Mn ²⁺ ions led to a stabilization of the metal ions and to a homogeneous distribution in the shell material on the surface of the silica core. The silica cores used ensured a spherical shape of the resulting core-shell nanoparticles and simultaneously served as a source of silicate for the resulting Zn ₂ SiO ₄ shell. In the final step, the nanoparticles were heated to a temperature between 800 ° C and 1100 ° C and held there for a short time to crystallize. Because of their specific surface area and strong interaction between the nanoparticles, they tend to coagulate and form aggregates during the final thermal treatment. To reduce particle agglomeration during annealing, pretreatment of the coated nanoparticles was accomplished by flash freezing followed by lyophilization. Lyophilization involves the sublimation of water under vacuum conditions from the frozen sample. This pre-treatment leads to a loose storage of the nanoparticles side by side and prevents the melting of the particles during the temperature treatment. Dispersion tests were performed to determine the amount of isolated particles as well as the fraction of non-redispersible aggregates. Despite the spray-drying of the particle samples, a fraction of non-redispersible aggregates was obtained, which were sorted out by selective sedimentation. Table 1 shows the degree of aggregation correlated with particle size. The amount of non-redispersible aggregates increases as the primary particle size decreases. Samples of SiO ₂ @Zn ₂ SiO ₄ : Mn ² Core-shell Nanoparticles ^(a) Particle diameter ^{( b )} [nm] Amount of aggregates [wt-%] 80 @ 10 75 ± 15 53 110 @ 5 115 ± 1 29 140 @ 5 123 ± 1 14 260 @ 5 240 ± 6 - (a) Sample designation consists of the diameter of the silica core (determined by dynamic light scattering (DLS)) and the shell desired in the synthesis
(b) Determined by DLS

To avoid aggregation, the sintering temperature is also of great importance. Observations on nanoparticles of the same size show that the amount of non-redispersible aggregates increases with increasing temperature. In the case of a nanoparticle with a core diameter of 75 nm, an increase in the aggregate fraction of up to 90% by weight was observed at temperatures above 1100 ° C. These results demonstrate the importance of choosing the synthesis parameters in accordance with particle size and the importance of further optimizing the manufacturing process for making aggregate-free nanoparticles.

1 shows a TEM image of SiO ₂ cores (d = 140 nm, 1a ) and core-shell nanoparticles sintered at 900 ° C ( 1b SiO ₂ @Zn ₂ SiO ₄ : Mn ²⁺ core-shell particles with a Mn ²⁺ doping concentration of 5 mol%). After coating the silica cores with a Zn ₂ SiO ₄ : Mn ₂ layer, the resulting core-shell nanoparticles still retain their spherical shape. However, no increase in the diameter of the nanoparticles was found for core-shell nanoparticles compared to pure silica cores. This is due to the shrinkage of the silica core during sintering at high temperatures. Because of the different electron permeability of the core and the material of the shell, the core-shell structure of the SiO ₂ @Zn ₂ SiO ₄ : Mn ²⁺ nanoparticle can be clearly recognized (see 1b ).

The enveloping Zn ₂ SiO ₄ layer is continuous, but not of constant thickness. This can be explained by the fact that the SiO ₂ core is not only used as a matrix for the morphological properties such. As the spherical shape, but also as a source for the formation of the silicate during the growth of ZnSiO ₄ : Mn ²⁺ layer is responsible. Obviously, the ZnSiO ₄ : Mn ²⁺ shell does not form uniformly on the surface of the silica cores.

Structural properties of SiO ₂ @Zn ₂ SiO ₄ : Mn ²⁺ core-shell nanoparticles

The sintering temperature plays an important role, not only in the formation of aggregates during particle production, but also in the structural properties of the Mn ²⁺ -doped zinc orthosilicate ( M. Takesue, K. Shimoyama, S. Murakami, Y. Hakuta, H. Hayashi, RL Smith Jr., J. Supercrit. Fluids, 2007, 43, 214 ). To study the effects of temperature on the formation of the crystalline phase of the nanoparticle shell, samples were sintered at various temperatures between 800 and 1100 ° C and analyzed by XRD. 2 shows the change of the crystalline phase, which was obtained as a function of the sintering temperature. 2 shows XRD diffraction patterns of the SiO ₂ @Zn ₂ SiO ₄ : Mn ²⁺ core-shell nanoparticles annealed at different temperatures (d = 75 nm, doping concentration of Mn ²⁺ : 5 mol%). The bottom line indicates the line positions of the α-Zn ₂ SiO ₄ lattice [PDF 37-1485; Circles] and the ZnO lattice [PDF 36-1451; Asterisk].

All samples show the formation of a crystalline layer around the amorphous silica core. The XRD analysis shows, however, that at 800 ° C mainly a ZnO phase is formed. In the case of SiO ₂ @Zn ₂ SiO ₄ : Mn ²⁺ nanoparticle samples sintered at 900 ° C, the formation of two phases was detected: ZnO and α-Zn ₂ SiO ₄ . The intensities of reflections of the willemite increase with increasing firing temperature, and a predominant α-Zn ₂ SiO ₄ phase is observed in samples that are heat treated at 1100 ° C. In addition, no influence of the Mn ²⁺ concentration on the formation of the crystalline shell structure was observed. On the one hand, these results show the importance of the shell-forming temperature treatment, which consists only of a pure zinc-silicate phase. On the other hand, these results can be used to understand the phase-forming process during shell growth. The mechanisms of phase formation of the crystalline shell may be as in 3 be summarized represented. According to the in 3 proposed formation of the core-shell-structured SiO ₂ @Zn ₂ SiO ₄ : Mn ²⁺ nanoparticles are in a first step Zn ²⁺ and Mn ²⁺ , which are stabilized by chelation and polymerization, homogeneously distributed in the starting solution and the colloidal silica Particles are adsorbed to form a gel layer ( 1 ). Heating of the coated particles at 800 ° C causes the formation of a Mn ²⁺ -doped ZnO shell ( 2 ). The Zn ₂ SiO ₄ phase begins to form when heated at 900 ° C ( 3 ). Further elevation of the temperature to 1100 ° C induces the formation of pure Mn ²⁺ -doped α-Zn ₂ SiO ₄ (Willemite) ( 4 ).

In the first step of the Pechini process, the starting materials are dissolved in the reaction solution. Zn ²⁺ and Mn ²⁺ ions are stabilized by citric acid (chelation) and polymerized by reactions of the remaining carboxylic acid groups with PEG (polyesterification). This ensures a homogeneous Distribution of metal cations in the polymeric network and subsequent adsorption of metal ions on the silica core surface (see step ( 1 ) in 3 ). During the temperature treatment, the organic components decompose; the reaction takes place on the interface between SiO ₂ and Zn ²⁺ and Mn ²⁺ . A temperature of about 800 ° C is needed to form a zinc oxide phase (see step ( 2 ) in 3 ). A further increase in the temperature leads to the transformation of ZnO into the Zn ₂ SiO ₄ phase (see step ( 3 ) in 3 ). At temperatures between 900 and 1000 ° C coexist ZnO and Zn ₂ SiO ₄ in a mixed crystal system. The transformation of the ZnO phase into zinc silicate proceeds by further diffusion of ZnO into the silica matrix ( C. Xu, J. Chun, K. Roh, DE Kim, Nanotechnology 2005, 16, 2808 ). The reaction along the interface between ZnO seed crystals and the silica surface can be represented by the following equation (1): 2ZnO + SiO ₂ → Zn ₂ SiO ₄ (1)

The XRD results prove that the arrangement of the zinc silicate phase is formed by reshaping the ZnO phase formed at the beginning of the sintering process ( 2 ) progresses. The formation of the pure Zn ₂ SiO ₄ shell takes place at temperatures of 1100 ° C. (see step ( 4 ) in 3 ).

Optical properties of SiO ₂ @Zn ₂ SiO ₄ : Mn ₂ core-shell nanoparticles

The UV-excited photoluminescence spectra of the particles are dominated by a strong green emission band with a maximum around 525 nm ( 4 ). 4 shows the photoluminescence spectra of SiO ₂ @Zn ₂ SiO ₄ : Mn ²⁺ nanoparticles, which at 1100 ° C ( 1 ), 1000 ° C ( 2 ) and 900 ° C ( 3 ) were annealed. The measurements were carried out at 300 K with an excitation at 260 nm. The doping concentrations amount to 5 mol% ( 1 . 2 ) and 1 mol% ( 3 ).

This corresponds to the ⁴ T ₁ (G ⁴⁾ - ⁶ A ₁ emission of Mn ²⁺ ions in α-Zn ₂ SiO _4, which are localized in the substitutive tetragonal Zn sites, resulting in the formation of the α-willemite structure approved ( ALN Stevels, AT Vink, J. Lumin. 1974, 8, 443 ). A slight shift of the maximum wavelength with increasing Mn ²⁺ concentration is related to the relative population of the two non-equivalent Zn sites. The decrease in luminescence in lightly doped samples is exponential, with a lifetime of approximately 20 ms, which is typical for forbidden dd junctions. 5 shows the photoluminescence decay of the SiO ₂ @Zn ₂ SiO ₄ : Mn ²⁺ nanoparticles containing 1 mol% ( 1 ), 5 mol% ( 2 ) and 20 mol% ( 3 ) Are Mn ²⁺ -doped, at pulsed excitation at 260 nm, at room temperature. The emission maximum was detected at 525 nm. As in 5 The samples doped with 1 mol% still show an exponential decay. A slight non-exponential decay of the 5 mol% sample demonstrates concentration quenching according to Inoue et al. ( Y. Inoue, T. Toyoda, J. Morimoto, J. Mater. Sci. 2008, 43, 378 ) and Sohn et al. ( K.-S. Son, B. Cho, HD Park, Mater. Lett. 1999, 41, 303 ) quenching starts at 6 to 7 mol%; it is possible that the inhomogeneous distribution of Mn ²⁺ ions in the samples also leads to quenching at lower concentrations. A stronger quenching effect is observed for samples doped with a nominal 20 mol%.

The photoluminescence spectra as well as the decay curves are measured at 260 nm excitation, which leads to a transfer of the electrons of Mn ²⁺ ground state into the conduction band of Zn ₂ SiO ₄ and a subsequent recombination. It is also possible to excite the luminescence in band between 340 nm and 399 nm, which excited the transition from the ⁶ A ₁ (S) ground state of the Mn ²⁺ ions to the ⁴ E ( ⁴ D) and ⁴ T ₂ ( ⁴ D) States corresponds.

Surface modification of the SiO ₂ @Zn ₂ SiO ₄ : Mn ²⁺ core-shell nanoparticles

Regarding the use of SiO ₂ @Zn ₂ SiO ₄ : Mn ²⁺ core-shell nanoparticles as luminescent markers in biological and medical diagnostic systems, further surface modification of zinc silicate coated nanoparticles with amino and carboxyl functionalities for further attachment of biomolecules has been demonstrated , Surface analogues of Zn ₂ SiO ₄ and SiO ₂ demonstrate the possibility of transferring the functionalization methods for silica particles to the zinc silicate surfaces. The nanoparticles were modified by covalent attachment of the aminosilane N- [3- (trimethoxysilyl) propyl] diethylenetriamine (TRIAMO) via the silanization method (see also Van Blaaderen, A .; Vrij, A., J. Colloid Interface Sci. 1993, 156, 1 and Waddell, TG; Leyden, DE; DeBello, MT, J. Am. Chem. Soc., 1981, 103, 5303 ). The success of the surface modification was determined by measurements of the ζ-potential as a function of the pH-value (see 6 ). 6 shows the ζ potential of unmodified and functionalized SiO ₂ @Zn ₂ SiO ₄ : Mn ²⁺ nanoparticles as a function of the pH before functionalization ( 1 ) and after Surface modification with amine ( 2 ) and carboxyl ( 3 ) Functionalities. The diagram shows the shift of the electrical point after modification with amino and carboxyl functionalities.

This measurement clearly showed the change in surface properties due to the reaction with TRIAMO. The isoelectric point (IEP) obtained at a pH of 3.1 for the initial unmodified SiO ₂ @Zn ₂ SiO ₄ : Mn ²⁺ core-shell nanoparticle is close to the values for pure silica particles were reported ( T. Schiestel, H. Brunner, GEM Tovar, J. Nanosci. Nanotechnol. 2004, 4, 504 ). The shift of the isoelectric point to pH 7 after amino functionalization showed the successful binding of the aminosilane to the surface of the nanoparticles. Succinic anhydride was used to introduce carboxyl groups onto the particle surface in an analogous manner ( X. Zhao, LR Hilliard, SJ Mechery, Y. Wang, RP Bagwe, S.Jin, W. Tan, Proc. Nat. Acad. Sci. USA 2004, 101, 15027 ), the isoelectric point of 3.5 found for the carboxylic acid-modified nanoparticles, suggests that the cyclic anhydride molecules had reacted with the amino groups via a ring-opening reaction to form an amide functionality, resulting in spacer elongation and the introduction of Carboxyl functionalities in place of the amine on the surface of the nanoparticles suggests. The terminal carboxyl groups, which are directed into the surrounding solution, stabilize the nanoparticles in an aqueous environment and allow immobilization on amine-containing biomolecules, such. For example, proteins. Thus, surface-modified luminescent SiO ₂ @Zn ₂ SiO ₄ : Mn ²⁺ core-shell nanoparticles can be used directly in a variety of biological and medical diagnostic applications.

As discussed above, redispersible core-shell-structured luminescent nanoparticles having particle sizes in the range of 10 and 290, preferably 75 and 260 nm, are successfully via a sol-gel process performed by a sintering step at high temperatures to manufacture. The crystal structures of the shell and the photoluminescence intensity of the core-shell nanoparticles can be adjusted by selecting the sintering conditions and varying the concentration of the metal used for the doping, for example Mn ²⁺ . At temperatures above 800 ° C., preferably 900 ° C., the shell forms, which preferably represents α-Zn ₂ SiO ₄ , which is characterized by a long lifetime of the emission of luminescence, for example Mn ²⁺ at a wavelength of 525 nm.

The successful additional functionalization of nanoparticle surfaces suggests that, in principle, conventional silanization methods can be used to modify Zn ₂ SiO ₄ : Mn ²⁺ -based nanoparticles. According to the present invention, nanoparticles of controlled particle size, morphology, crystal structure and optical properties can be prepared, as well as the aggregation of the nanoparticles and their agglomeration can be controlled. Moreover, the present invention offers considerable potential applications of the luminescent nanoparticles in various biotechnological applications.

example

Preparation of monodisperse silica cores:

Monodisperse silica cores were prepared by the modified Stoeber method ( W. Stoeber, A. Fink, E. Bohn, J. Colloid Interface Sci. 1968, 26, 62 and C. Gellermann, W. Storch, H. Wolter, J. Sol-Gel Sci. Technol. 1997, 8, 173 ) produced. In a typical synthesis, 225 grams of TEOS was hydrolyzed in 4.5 liters of ethanol in the presence of 225 ml of ammonium hydroxide. The resulting clear, colorless mixture was then aged at room temperature for 3 days. The isolation of the resulting silica cores was accomplished by distilling off the solvent and then washing three times with ethanol.

Preparation of SiO ₂ @Zn ₂ SiO ₄ Core Shell Nanoparticles:

The surface coating with an Mn ²⁺ -doped zinc silicate layer was carried out by a modified Pechini process ( DY Kong, M. Yu, CK Lin, XM Liu, J. Lin, J. Fang, J. Electrochem. Soc. 2005, 152, H146 ) accomplished. In a typical reaction, 31.2 g (142 mmol) of Zn (O ₂ C ₂ H ₄ ) .2H ₂ O and 1.29 g (7.47 mmol) of Mn (O ₂ C ₂ H ₄ ) ₂ (doping concentration of 5 mol%) in a solution of 1.07 1 of ethanol and 133 ml of water (ethanol / water = 8/1 vol / vol). After adding 20 ml of nitric acid, the reaction mixture was sonicated to dissolve the starting materials. Subsequently, 62.6 g (298 mmol) of citric acid monohydrate as a chelating agent and 63.1 g (5.49 to 7.43 mmol) of PEG (MW = 10000) as cross-linking agent were added. The reaction mixture was stirred and sonicated for 2 h. A dispersion of monodisperse silica cores was added to the above solution. The resulting suspension was stirred for 3 h at room temperature. The reaction mixture was subsequently centrifuged and the precipitate freeze-dried. The lyophilized nanoparticle powder was heated to 100 ° C for 1 hour in an oven and sintered at the required temperatures (800 to 1100 ° C) at a heating rate of 200 K / h, keeping it at the sintering temperature for 15 minutes.

Surface modification:

The following steps were carried out in an argon atmosphere. 5.73 ml of ammonium hydroxide and 44.6 μl (173 μmol) of TRIAMO were added to a dispersion of 1.00 g of the core-shell nanoparticles in ethanol prepared by a coating process mentioned above. The solution was stirred for 16 h at room temperature. The amino-functionalized nanoparticles were centrifuged off and washed three times with ethanol. To form the carboxyl functionalities on the nanoparticle surface, 100 mg of the amino-functionalized nanoparticles were transferred to THF (70 ml). 6 ml succinic anhydride solution in THF (2 mol / l) was added to the nanoparticle suspension with sonication. The suspension was stirred for 16 h at room temperature. The resulting carboxyl-modified nanoparticles were washed three times thoroughly in deionized water.

Example of use:

In this case, Zn ₂ SiO ₄ : Mn ₂₊ (5 mol%) of PSL was measured.

The sample was irradiated with a xenon flash lamp through 260 nm interference filters for 1 minute.
Repetition rate 10 Hz, pulse energy 18 microjoules, pulse duration 4 microseconds, irradiated area approx. 1.5 cm ² . Absorbed dose about 7 mJ / cm ² .

For stimulation, a red LED with the wavelength 640 nm was used.
Power density approx. 2.5 mW / cm ² .

The picture also shows afterglow (phosphorescence). Even after a few minutes, if afterglow is already gone, you can measure PSL.

The trace is in 7 shown.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

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Claims (27)

Photo-stimulable nanoparticles, which can be converted into an electronically charged state by supplying energy and can be induced to emit electromagnetic radiation by means of stimulation by electromagnetic radiation. Nanoparticle according to Claim 1, characterized in that the half-life t _{1/2 of} the spontaneous decay of the charged state is at least 1 s, preferably at least 1 min., Particularly preferably at least 30 min. Nanoparticles according to one of the preceding claims, characterized in that the conversion into the electronically charged state by means of electromagnetic radiation, preferably by electromagnetic radiation having a wavelength between 100 to 1600 nm, in particular UV radiation, and / or by X-radiation and / or by electron beams he follows. Nanoparticle according to one of the preceding claims, characterized in that the electromagnetic radiation used to stimulate the emission has a wavelength between 200 to 2000 nm, preferably between 400 to 1600 nm. Nanoparticle according to one of the preceding claims, characterized in that the wavelength of the emission between 200 to 4000 nm, preferably 400 to 1600 nm. Nanoparticles according to one of the preceding claims, characterized in that the particle size is between 2 to 1000 nm. Nanoparticle according to one of the preceding claims, characterized in that the nanoparticle is present as a core-shell nanoparticle. Photo-stimulable nanoparticles according to one of the preceding claims, comprising a) an amorphous core of silica or a compound selected from the group consisting of silica, silicates, vanadates, tungstates, phosphates, oxides, sulfides, sulfates, aluminates and / or halides, such as. Fluorobromides, a first main group, transition or lanthanide metal, b) a stimulable shell containing at least one compound selected from the group consisting of silica, silicates, vanadates, tungstates, phosphates, oxides, sulfides, sulfates, aluminates and / or halides, such as. Fluorobromides, a first main group, transition or lanthanide metal doped with transition metal or lanthanide metal ions of at least one second grade of a transition metal or lanthanide metal other than the first main group metal, transition metal or lanthanide metal. characterized by a diameter of the silica core between 10 and 290 nm, preferably between 10 and 260 nm, particularly preferably between 10 and 50 nm or 75 and 260 nm. Nanoparticle according to claim 8, characterized in that the second type of transition metal or lanthanide metal ions used for doping is selected from the group consisting of Pb ²⁺ , Mn ²⁺ , Cu ⁺ , Dy ³⁺ , Sm ³⁺ , Eu ^{2 +} , Eu ³⁺ , Tb ³⁺ , La ³⁺ , Ce ³⁺ , Pr ³⁺ , Nd ³⁺ , Gd ³⁺ , Ho ³⁺ , Er ³⁺ , Tm ³⁺ , Yb ³⁺ , Lu ³⁺ and / or combinations thereof. Nanoparticle according to one of claims 8 to 9, characterized in that the at least one compound is selected from the group consisting of Sr (Ca) Al ₂ O ₄ , MgSiO ₃ , ZnSiO ₄ , ZnMgSi ₂ O ₆ , Sr ₂ MgSiO ₇ , YVO ₄ , GdVO ₄ , NaGd (WO ₄ ) ₂ , CaWO ₄ , Y ₂ O ₃ , LaPO ₄ , ZnS, CaS, BaFBr and / or combinations thereof. Nanoparticles according to one of the preceding claims, characterized by a surface functionalization, preferably an amino, carboxylate, carbonate groups, maleic, imino, imide, amide, aldehyde, thiol, isocyanate, isothiocyanate, acyl azide, hydroxyl -, N-hydroxy-succinimidester-, phosphate, phosphonic acid, sulfonic acid, sulfonic acid chloride, epoxy, cc double bond-containing, such. B. (meth) acrylic acid or (meth) acrylate or norbornyl groups-containing functionalization. Nanoparticle according to one of the preceding claims, characterized in that the particle surface with a shell of silica, polymer, alumina, titania, zinc oxide, zirconia or polyethylene glycol is surrounded. Nanoparticle according to one of the preceding claims, characterized in that the surface of the PLS particle is chemically modified and / or has covalently or non-covalently bound compound molecules and / or reactive groups. Nanoparticles according to one of the preceding claims, characterized in that one or more chain-like molecules having a polarity or charge opposite to the surface of the nanoparticles are connected non-covalently to the surface of the particles as the connecting molecule. Nanoparticles according to one of the preceding claims, characterized in that the chain-like molecules are anionic, cationic or zwitterionic detergents, acidic or basic proteins, polyamides or polysulfone or polycarboxylic acids. Nanoparticles according to one of the preceding claims, characterized in that the surface and / or the compound molecules connected to the surface of the nanoparticles reactive neutral, charged or partially charged groups, such as amino groups, carboxylic acid groups, thiols, thioethers, disulfides, imidazoles, guanidines, hydroxyl groups, Indoles, vicinal diols, aldehydes, alpha-haloacetyl groups, N-maleimides, mercury organyls, aryl halides, acid anhydrides, isocyanates, isothiocyanates, sulfonic acid halides, imidoesters, diazoacetates, diazonium salts, 1,2-diketones, alpha-beta-unsaturated carbonyl compounds, azolides, silanes, Phosphonic acids, phosphoric acid esters or derivatives of said groups wear, these reactive groups allow chemical bonding with other connection molecules or affinity molecules. Nanoparticles according to one of the preceding claims, characterized in that they are equipped with one or more affinity molecules or more affinity molecules coupled to one another, wherein the affinity molecules can bind on the one hand to the particle surface and on the other hand bind to a biological or other organic substance. Nanoparticles according to one of the preceding claims, characterized in that the affinity molecules are monoclonal or polyclonal antibodies, proteins, peptides, oligonucleotides, plasmids, nucleic acid molecules, oligo- or polysaccharides, haptens, such as biotin or digoxin, or a low molecular weight synthetic or natural antigen. Nanoparticle according to one of the preceding claims, characterized in that the affinity molecule is covalently or non-covalently coupled to the particle by reactive groups on the affinity molecule and on the simple detection probe. Nanoparticles according to one of the preceding claims, characterized in that the reactive groups on the surface of the affinity molecule are amino groups, carboxylic acid groups, thiols, thioethers, disulfides, imidazoles, guanidines, hydroxyl groups, indoles, vicinal diols, aldehydes, alpha-haloacetyl groups, N-maleimides, Mercury organyls, aryl halides, acid anhydrides, isocyanates, isothiocyanates, sulfonic acid halides, imidoesters, diazoacetates, diazonium salts, 1,2-diketones, alpha-beta-unsaturated carbonyl compounds or azolides. Nanoparticles according to one of the preceding claims, characterized in that a covalent or non-covalent, self-assembled compound exists between the PSL particle and the affinity molecule. Photo-stimulable nanoparticle system containing nanoparticles according to one of the preceding claims with a preferred polydispersity of the nanoparticles between 0.1 and 10%, preferably between 1 and 3%. Photo-stimulable nanoparticle system according to the preceding claim in the form of a solution, a dispersion or a suspension. Photo-stimulable nanoparticle system according to one of the two preceding claims, containing further additives, in particular stabilizers. A method of making a photo-stimulable nanoparticle system according to any one of the preceding claims, wherein amorphous core particles of silica or of a compound selected from the group consisting of silica, silicates, vanadates, tungstates, phosphates, oxides, sulfides, sulfates, Aluminates and / or halides, such as. B. fluorobromides, a first main group, transition or Lanthanidmetalls, with an average diameter between 10 and 290 nm by wetting with an aqueous solution containing a) at least one kind of ions of a first transition metal or lanthanide metal, b) at least one sort of ions c) in the event that the shell should contain vanadates, tungstates, phosphates, sulfides, sulfates, aluminates and / or halides, vanadate, tungstate, phosphate, sulfide and / or halide -Ions, in particular fluoride and bromide ions, coated and the coated core particles are then tempered. Method according to the preceding claim, characterized in that the aqueous solution additionally a) an organic carboxylic acid having at least two acid functionalities, preferably citric acid, and / or b) an alcohol having at least two alcohol functionalities, preferably polyethylene glycol and / or polypropylene glycol contains. Use of a nanoparticle system according to one of Claims 22 to 23 as a diagnostic agent and / or as a marker, in particular for biological or medical applications; as an optically detectable diffusion probe; in security systems; as a substrate for security systems and / or as a marker for the detection of originals and / or plagiarism and / or as a contrast agent for biomedical examinations and / or as a means for forensic investigations, wherein preferably the nanoparticle system with light of a wavelength between 100 and 800 nm, with X-ray - And / or electron beams is converted into an electronically charged state, and is excited by means of a light pulse having a wavelength between 400 and 1600 nm for the stimulated emission of photons having a wavelength between 400 and 1500 nm.

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