EP2616521A1 - Systèmes de particules, photostimulables, leur procédé de fabrication ainsi que leurs utilisations - Google Patents

Systèmes de particules, photostimulables, leur procédé de fabrication ainsi que leurs utilisations

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Publication number
EP2616521A1
EP2616521A1 EP11758394.8A EP11758394A EP2616521A1 EP 2616521 A1 EP2616521 A1 EP 2616521A1 EP 11758394 A EP11758394 A EP 11758394A EP 2616521 A1 EP2616521 A1 EP 2616521A1
Authority
EP
European Patent Office
Prior art keywords
nanoparticles
nanoparticle
groups
molecules
nanoparticles according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Application number
EP11758394.8A
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German (de)
English (en)
Inventor
Sofia Dembski
Carsten Gellermann
Albrecht Winnacker
Andres Osvet
Miroslaw Batentschuk
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Friedrich Alexander Univeritaet Erlangen Nuernberg FAU
Original Assignee
Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Friedrich Alexander Univeritaet Erlangen Nuernberg FAU
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Application filed by Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV, Friedrich Alexander Univeritaet Erlangen Nuernberg FAU filed Critical Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Publication of EP2616521A1 publication Critical patent/EP2616521A1/fr
Withdrawn legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/02—Use of particular materials as binders, particle coatings or suspension media therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y40/00—Manufacture or treatment of nanostructures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09C—TREATMENT OF INORGANIC MATERIALS, OTHER THAN FIBROUS FILLERS, TO ENHANCE THEIR PIGMENTING OR FILLING PROPERTIES ; PREPARATION OF CARBON BLACK  ; PREPARATION OF INORGANIC MATERIALS WHICH ARE NO SINGLE CHEMICAL COMPOUNDS AND WHICH ARE MAINLY USED AS PIGMENTS OR FILLERS
    • C09C1/00—Treatment of specific inorganic materials other than fibrous fillers; Preparation of carbon black
    • C09C1/28—Compounds of silicon
    • C09C1/30—Silicic acid
    • C09C1/3045—Treatment with inorganic compounds
    • C09C1/3054—Coating
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
    • C09K11/57—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing manganese or rhenium
    • C09K11/572—Chalcogenides
    • C09K11/574—Chalcogenides with zinc or cadmium
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
    • A61B2090/3937—Visible markers
    • A61B2090/3941—Photoluminescent markers
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2002/00—Crystal-structural characteristics
    • C01P2002/50—Solid solutions
    • C01P2002/52—Solid solutions containing elements as dopants
    • C01P2002/54—Solid solutions containing elements as dopants one element only
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2002/00—Crystal-structural characteristics
    • C01P2002/70—Crystal-structural characteristics defined by measured X-ray, neutron or electron diffraction data
    • C01P2002/72—Crystal-structural characteristics defined by measured X-ray, neutron or electron diffraction data by d-values or two theta-values, e.g. as X-ray diagram
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00—Particle morphology
    • C01P2004/01—Particle morphology depicted by an image
    • C01P2004/04—Particle morphology depicted by an image obtained by TEM, STEM, STM or AFM
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00—Particle morphology
    • C01P2004/30—Particle morphology extending in three dimensions
    • C01P2004/32—Spheres
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00—Particle morphology
    • C01P2004/60—Particles characterised by their size
    • C01P2004/62—Submicrometer sized, i.e. from 0.1-1 micrometer
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00—Particle morphology
    • C01P2004/60—Particles characterised by their size
    • C01P2004/64—Nanometer sized, i.e. from 1-100 nanometer

Definitions

  • the invention relates to stimulable, in particular photostimulable particle systems and their use as luminescent markers for biological and medical diagnostics, as optically detectable diffusion probe or as a substrate for the production of security systems, as a marker for the detection of plagiarisms and / or originals.
  • Luminescent nanoparticles 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 Base of polymers or oxidic materials, semiconductor NP (Quantum Dots, QDs) or NP based on inorganic phosphors doped with
  • the stimulating light and the fluorescence are effective at the same time.
  • the signal is weakened by stray light.
  • the particle systems should be stimulated to stimulated emission by illumination with a targeted light pulse, which may preferably also be in the infrared light range, 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 having the features of claim 11, relating to a method for producing a corresponding nanoparticle system having the features of claim 12 and with respect to possible
  • a nanoparticle 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.
  • nanoparticles according to the invention are distinguished by the fact that, after being charged with light having a wavelength between 100 and 800 nm, with
  • X-ray and / or electron beams emitted by stimulated emission by a light pulse having a wavelength between 500 and 1600 nm photons with a wavelength between 400 and 1300 nm.
  • the duration of the light pulse which can be used for stimulated emission and for retrieving the light energy stored in the charged particle, can be very short, eg approx . 1 or less (A. Winnacker, "X-ray Imaging with
  • the stimulated emission can be used, for example, by using a laser pulse wherein the energy density of the stimulation laser is about 100 ⁇ / cm 2 or less (R. Schrisoning, R. Fasbender, P. Kersten, New High Speed Scanning Technique for Computed Radiography, Proc. SPIE 4682 (2002) 511-520), which provides tremendous advantages over the
  • the particle is characterized by energy storage and thus enabling a time shift between excitation (charge) and detection necessary for background-free detection.
  • excitation charge
  • detection detection necessary for background-free detection.
  • Markers that have been charged by exposure to ultraviolet or blue light, or an x-ray pulse prior to examination are marked. Stimulation of the sample with red or infrared (IR) light after minutes or even hours will cause emission in the visible or near-infrared region, ie shorter wavelengths than the excitation light wavelengths. 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 total stored energy (or, if necessary, only a part of it) can, at the desired later time, be retrieved with an infrared pulse.
  • NK nanocrystals
  • 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 re-emerges.It is known that NKs are charged for During optical excitation, NKs form electron-hole pairs whose recombination leads to light emission.
  • the spatial separation of charge carriers can be improved by the use of two-component semiconductor systems.
  • 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 become in the valence band of the other
  • Electron / holes also feasible on the nanoscale.
  • the targeted nanomarkers will be concerned with bringing these stored charge carriers to radiative recombination thermally or optically (PSL).
  • the nanoparticles Zn 2 Si0 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 charging 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).
  • the half life ti 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 transfer into the electronically charged state takes place by means of electromagnetic radiation, preferably by electromagnetic radiation having a wavelength 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”.
  • a stimulable nanoparticle which can be converted into an electronically charged state by light of a wavelength between 100 and 800 nm and / or with X-rays or electron beams, and by a light pulse can be excited with a wavelength of photons between 500 and 1600 nm for the emission of light of a wavelength between ⁇ 400 and 1300 nm.
  • a stimulable nanoparticle is further provided,
  • silica a compound selected from the group consisting of silica, silicates, vanadates, tungstates, phosphates, oxides, sulfides, sulfates, aluminates and / or halides, such. Fluorobromides, a first main group, transition or
  • 290 nm preferably between 10 and 260 nm, more 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.
  • To the compounds of a first main group metal Thus, among others, Ca and Sr compounds are to be counted.
  • 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.
  • the compound forming the core and / or the shell-forming compound or the shell-forming compound is independently selected from the group consisting of MgSiO 3 , Zn 2 SiO 4 ,
  • 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:
  • NaGd (W0 4 ) 2 Eu 3+
  • CaW0 4 Eu 3+ / Tb 3+
  • YV0 4 Eu 3+
  • Y 2 0 3 Eu 3+
  • GdV0 4 Eu 3+
  • CaP0 4 Ce 3+ / Tb 3+
  • ZnS Cu 1+ / Pb 2+
  • CaS Eu 2+ / Sm 3+
  • BaFBr Eu 2+
  • ZnMgSi 2 0 6 CaMgSi 2 0 6 and MgSi0 3
  • the last three mentioned silicates are doped with manganese, europium or dysprosium ions and Sr 2 MgSi 2 0 7 , which is doped with europium and / or dysprosium ions
  • the silicate Ca 0 , 2 Zn 0 , 9 g 0 , 9Si 2 0 6 doped with Eu 2+ , Dy 3+ and / or Mn 2+ .
  • CaS Ln (with Ln, Ce, Sm, Eu), Silicates Zn 2 Si0 4 doped with Mn or Lnl, Ln2 (with Ln (l, 2): Ce 3+ , Eu 3+ , Tb 3+ , Sm 3+ , as an alternative
  • ZnS Cu, Pb and different calcium phosphates.
  • luminescent materials which are suitable for core and / or shell are, for example: (very hygroscopic); CsI: Tl; CsI: Na; LiF: Mg;
  • BaMgAli 0 Oi 7 Eu
  • BaMgAl 2 0 3 Eu
  • Ba 2 P 2 O 7 Ti
  • MgSiO 3 Mn; 3.5MgO x 0.5MgF 2 x Ge0 2 : Mn; MgW0 4 : Sm;
  • MgW0 4 Pb; 6MgO x As 2 0 5 : Mn; (Zn, Mg) F 2 : Mn; (Zn 4 Be) S0 4 : Mn; Zn 2 Si0 4 : Mn; Zn 2 Si0 4 : Mn, As; Zn 3 (PO 4 ) 2 : Mn; CdB0 4 : Mn;
  • (Ca, Sr) S Bi; CaW0 4 : Pb; CaW0 4 : Sm; CaSO 4 : A (A Mn, lanthanide); 3Ca 3 (PO 4 ) 2 x Ca (F, Cl) 2 : Sb, M n ; CaSiO 3 : Mn, Pb; Ca 2 Al 2 Si 2 O 7 : Ce; (Ca, Mg) Si0 3: Ce; (Ca, Mg) Si0 3 : Ti; 2SrO x 6 (B 2 O 3 ) x SrF 2 : Eu; 3Sr 3 (PO 4 ) 2 CaCl 2 : Eu; A 3 (P0 4 ) 2
  • Gd 2 0 2 S Tb
  • Gd gB 5 Oi 0 Ce, Tb
  • LaOBr Tb
  • La 2 0 2 S Tb
  • CaCJ 2 Eu; CaCJ 2 : Eu-Si0 2 ; CaCJ 2 : Eu, Mn-Si0 2 ;
  • CaJ 2 Eu
  • CaJ 2 Eu, Mn
  • KMgF 3 Eu
  • SrF 2 Eu (II)
  • RbBr Ga, CsBr: Ga, RbBr: Eu 2+, CsBr: Eu 2+,
  • BaS0 4 Eu, Mn; CaSO 4 ; CaS0 4 : Eu; CaSO 4 : Eu, Mn; and mixed alkaline earth sulfates, also in combination with magnesium, eg Ca, MgS0 4 : Eu, Mn. 3. phosphates and halophosphates: eg CaP0 4 : Ce, Mn; Ca 5 (PO 4 ) 3 Cl: Ce, Mn; Ca 5 (PO 4 ) 3 F: Ce, Mn; SrP0 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
  • Bai 0 (PO 4 ) 6 Cl Eu, Mn
  • Ca 2 Ba 3 (P0 4 ) 3 C1 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 Eu, Mn;
  • LaP0 4 Ce; CeP0 4 ; LaP0 4 : Eu; LaP0 4 : Ce; LaP0 4 : Ce, Tb;
  • Zn 3 (PO 4 ) 2 Mn 2+ (Zn 3 (PO 4 ) 2 : Mn 2+ , Al 3+ Zn 3 (PO 4 ) 2 : Mn + , Ga 3+ Sr 3 (PO 4 ) 2 : Eu 2+ , Sr 5 (P0 4 ) 3 : Eu 2+ , Sr 2 P0 4 : Eu 2+
  • YB0 3 Ce; Ca 2 B 5 0 9 Cl: Eu; xEuO x yNa 2 0 x eg 2 0 3 .
  • Vanadates eg YV0; YV0 4 : Eu; YV0 4 : Dy; YV0 4 : Sm;
  • YV0 4 Bi; YV0 4 : Bi, Eu; YV0 4 : Bi, Dy; YV0 4 : Bi, Sm;
  • YV0 4 Tm; YV0 4 Bi, Tm; GdV0 4 ; GdV0 4 : Eu; GdV0 4 : Dy;
  • GdV0 4 Sm; GdV0: Bi; GdV0 4 : Bi, Eu; GdV0 4 : Bi, Dy;
  • GdV0 4 Bi, Sm; YV0 4 : Eu; YV0 4 : Sm; YV0 4 : Dy.
  • aluminates eg MgAl 2 O 4 : Eu; CaAl 2 0 4 : Eu; SrAl 2 0 4 Eu;
  • BaAl 2 0 4 Eu; LaMgAluOig: Eu; BaMgAli 0 Oi 7 : Eu; BaMGalioOi 7 : Eu, Mn; CaAli 2 0 19 : Eu; SrAli 2 0i 9 : Eu;
  • BaMg 2 Si 2 O 7 Eu
  • CaMgSi 2 0 6 Eu
  • SrBaSi0 4 Eu
  • Sr 2 Si 3 O 8 x SrCl 2 Eu
  • Ba 5 Si0 4 Br 6 Eu
  • Ba 5 Si0 4 Cl 6 Eu
  • Mg 2 Si0 4 Mn 2+ , Dy 3+ ;
  • Mg, Ca, Sr, Ba and MgW0 4 , CaW0 4 , CdW0 4 , ZnW0 4 ; and polymolybdates or polytungstates or the salts of the corresponding hetero- or isopolyacids.
  • germanates eg Zn 2 Ge0 4 .
  • La 2 S Yb, Er, Ba 2 ZnS 3 : Ce.
  • Amount of the first transition or Lanthanidmetalls 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 indicated concentrations of
  • 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-succinimide ester, phosphate, phosphonic acid, sulfonic acid, sulfonyl chloride, epoxy, CC double bond-containing groups such as (meth) acrylic acid or (meth) acrylate or norbornyl groups.
  • 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.
  • the surface has covalently or noncovalently bound compound molecules and / or reactive groups.
  • the connecting molecule one or more chain-like molecules having a polarity or charge opposite to the surface of the nanoparticles are non-covalently bonded to the surface of the particles
  • the chain-shaped molecules are anionic, cationic or zwitterionic detergents, acidic or basic proteins, Polyamides or polysulfone or polycarboxylic acids may be.
  • 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, imido esters, diazoacetates, diazonium salts, 1,2-diketones, alpha-beta-unsaturated carbonyl compounds, azolides, silanes, phosphonic acids, phosphoric acid esters or derivatives of said groups, said reactive groups allowing chemical bonding with further compound molecules or affinity molecules.
  • reactive neutral, charged or partially charged groups such as amino groups, carboxylic acid groups,
  • the nanoparticles of the invention may be oriented ⁇ equipped also with one or more affinity molecules or a plurality of mutually coupled affinity molecules, which affinity molecules can on the one hand bind to the particle surface and on the other hand to bind to a biological or other organic substance.
  • the affinity molecules can e.g. 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.
  • 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 imido esters, diazoacetates, diazonium salts, 1,2-diketones, alpha-beta-unsaturated carbonyl compounds or azolides.
  • Nanoparticle system 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 process for the preparation of a nanoparticle system described above is also disclosed in which amorphous core particles
  • Transition metal or lanthanide metal Transition metal or lanthanide metal
  • vanadium, tungstate, phosphate, sulfide and / or halide ions in particular fluoride and bromide ions, be coated with olframates, phosphates, sulfides, sulfates, aluminates and / or halides and then the coated core particles are tempered become.
  • the molar ratios of the second grade of transition metal or lanthanide metal to the first grade of transition metal or lanthanide metal are preferably set accordingly.
  • the aqueous solution used can be further additives, such as
  • an organic carboxylic acid having at least two acid functionalities, preferably citric acid, and / or
  • an alcohol having at least two alcohol functionalities preferably polyethylene glycol and / or polypropylene glycol
  • 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.
  • 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.
  • 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.
  • the nanoparticle system 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.
  • the light pulse used to stimulate the emission preferably has the following characteristics:
  • 500 ns and 3 s and / or b) has an energy density between 0.01 pJ / cm 2 and 100 pj / cm 2 , preferably between 0.1 pJ / cm 2 and 20 pj / cm 2, more preferably between 1 pj / cm 2 and 10 pj / cm 2 .
  • 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 .
  • luminescent particle systems are particularly suitable as photostimulable markers for biological and medical diagnostics, as optically detectable diffusion probes for the production of
  • 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 is with regard to this
  • 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 binding of proteins to the nanoparticles is carried out by an appropriate 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
  • Another example is the charging of the messenger substance of a synapse fixed to a PSL-capable NP via appropriate functionalization and the observation of the subsequent distribution and the temporal and spatial extension.
  • optical "tagging” allows diffusion and transport processes with very high spatial resolution in vivo and in vitro.
  • Zinc sulfide doped with Cu + and Pb 2+ is a phosphorescent phosphor [S. Shionoya, WM Yen.
  • 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 a time interval by an IR pulse.
  • the PSL in ZnS: Cu + , Pb 2+ comes about through the release of electrons from the traps [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 a few hours [. Sidran. Appl. Optics. 1969, Vol. 8, p. 79; E. Bulur, HY Göksü. phys.
  • the materials 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 is slightly water-soluble, but this disadvantage can be overcome by sheathing the CaS microparticles with Si0 2 , Ti0 2 [C. Guo, B. Chu, M. Wu, Q. Su. J. Lumin.
  • Hole traps (Eu 3+ ) are stable at room temperature, some of the charge carriers are stored in the traps for several hours.
  • the red luminescence of Eu 2+ is shown .
  • 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+ .
  • 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 SiQ 4 Mn 2+ and ZnMgSi 2 Q 6 : Mn 2+ , Eu 2+ , Dy 3+
  • Optoelectronics use numerous silicate-based phosphors, including one of the oldest phosphors, Zn 2 Si0 4 doped with n 2 + , which has both phosphorescence and PSL properties.
  • the usual method of preparation is solid-state synthesis [p. Shionoya, WM Yen. phosphorus
  • alkaline earth aluminates prepared as doped powders, ceramics or single crystals suitable for the
  • the most widely used phosphor in this group is SrAl 2 0 4 : Eu 2+ , Dy 3+ , which has become clearer than previously used due to its excellent and long-lasting phosphorescence
  • the particle size of the silica colloids was adjusted by concentration of the reactants and the temperature during particle growth. Isolation of the resulting silica particles was achieved by distilling off the solvent and washing the particles three times with ethanol.
  • the resulting silica cores showed a spherical morphology and a narrow size distribution (polydispersity between 1 and 3%).
  • the cores were treated with Zn 2 Si0 4 : Mn 2+ precursors using a modified Pechini sol gel.
  • Zn 2+ and Mn 2+ ions resulted in a stabilization of the metal ions and 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 served as a silicate source for the resulting Zn 2 Si0 4 shell 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.
  • 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 pretreatment leads to a loose storage of the nano- Particles side by side and prevents the melting of the particles during the temperature treatment.
  • Dispersion tests were carried out 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.
  • Sample designation is composed of the diameter of the silica core (determined by dynamic light scattering (DLS)) and the shell desired in the synthesis (b) Determined by DLS
  • Si0 2 @Zn 2 Si0 4 Mn 2+ core-shell particles with a Mn 2+ doping concentration of 5 mol%).
  • 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 on the
  • the enveloping Zn 2 Si0 layer is continuous, but not of constant thickness. This can be explained by the fact that the Si0 2 core is responsible not only 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 the ZnSiO: Mn 2+ layer is. Obviously, the ZnSi0 4 : Mn 2+ shell does not form uniformly on the surface of the silica cores. Structural properties of Si0 2 @Zn 2 Si0 4 : Mn 2+ core-shell nanoparticles
  • the sintering temperature plays an important role, not only in the formation of aggregates during the
  • Chelatleiter and polymerization are stabilized, homogeneously distributed in the starting solution and adsorbed on the colloidal silica particles to form a gel layer (1).
  • Heating of the coated particles at 800 ° C causes the formation of a Mn + - doped ZnO shell (2).
  • the Zn 2 Si0 4 phase begins to form with tempering at 900 ° C (3). Further elevation of the temperature to 1100 ° C induces the formation of pure Mn 2+ -doped a-Zn 2 Si0 4
  • the starting materials are dissolved in the reaction solution.
  • Zn 2+ and Mn 2+ ions are stabilized by citric acid (cholate formation) and polymerized by reactions of the remaining carboxylic acid groups with PEG (polyesterification).
  • PEG polymerification
  • This ensures a homogeneous distribution of the metal cations in the polymeric network and the subsequent adsorption of metal ions on the silica core surface (see step (1) in FIG. 3).
  • the organic components decompose; the reaction takes place on the interface between Si0 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 Figure 3).
  • FIG. 4 shows the photoluminescence spectra of FIG
  • Si0 2 @Zn 2 Si0 4 Mn 2+ nanoparticles annealed at 1100 ° C (1), 1000 ° C (2), and 900 ° C (3).
  • the measurements were carried out at 300 K with an excitation at 260 nm.
  • the doping concentrations are 5 mol% (1, 2) and 1 mol% (3). This corresponds to the Ti ( 4 G) - ⁇ emission of the Mn 2+ ions in a-Zn 2 Si0 4 , which are substituted in the tetragonal Zn atoms. Sites are confirmed, which confirms the formation of the a-Willemite structure (ALN Stevels, AT Vink, J. Lumin 1974, 8, 443).
  • FIG. 5 shows the photoluminescence decay of FIG
  • Si0 2 @Zn 2 Si0 4 Mn 2+ nanoparticles doped with 1 mol% (1), 5 mol% (2) and 20 mol% (3) n 2+ in the case of pulsed excitation 260 nm, at room temperature. The emission maximum was detected at 525 nm. As shown in Figure 5, those doped with 1 mol%
  • quenching begins 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 from Mn 2+ ground state into the conduction band of Zn 2 Si0 4 and a subsequent recombination. It is also possible to excite the luminescence in band between 340 nm and 399 nm, which is the transition from the 6 Ai (S) ground state of Mn 2+ - Ions corresponding to 4 E ( 4 D) and 4 T 2 (D) excited states.
  • FIG. 6 shows the ⁇ potential of unmodified and functionalized Si0 2 @Zn 2 Si0 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.
  • IEP isoelectric point
  • the shell forms, which is preferably a-Zn 2 Si0 4 , which is characterized by a long lifetime of the emission of luminescence, for example Mn 2+ at a wavelength of 525 nm.
  • nanoparticles of controlled oxidation-semiconductor oxide suggest that, in principle, conventional silanization methods can be used to modify Zn 2 Si0 4 : Mn 2+ -based nanoparticles.
  • nanoparticles of controlled oxidation-semiconductor oxide suggest that, in principle, conventional silanization methods can be used to modify Zn 2 Si0 4 : Mn 2+ -based nanoparticles.
  • nanoparticles of controlled silanization methods can be used to modify Zn 2 Si0 4 : Mn 2+ -based nanoparticles.
  • Particle size, morphology, crystal structure and optical properties are produced, as well as the aggregation of the nanoparticles and their agglomeration can be controlled.
  • the present invention offers considerable potential applications of the luminescent nanoparticles in various biotechnological applications.
  • the resulting suspension was stirred for 3 h at room temperature.
  • the reaction mixture was then centrifuged and the precipitate was 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.
  • the sample was irradiated with a xenon flash lamp through 260 nm interference filters for 1 minute.
  • a red LED with the wavelength 640 nm was used.
  • the measurement curve is shown in FIG. 7.

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Abstract

L'invention concerne des systèmes de particules, stimulables, en particulier photostimulables, ainsi que leur utilisation en tant que marqueur luminescent pour le diagnostic biologique et médical, en tant que sonde de diffusion optiquement détectable ou en tant que substrat pour la fabrication de systèmes de sécurité, en tant que marquage pour l'identification de plagiats et/ou d'originaux.
EP11758394.8A 2010-09-14 2011-09-14 Systèmes de particules, photostimulables, leur procédé de fabrication ainsi que leurs utilisations Withdrawn EP2616521A1 (fr)

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