CN102391874A - NaYF4-based fluorescent nano particles with double effects and preparation method thereof - Google Patents

NaYF4-based fluorescent nano particles with double effects and preparation method thereof Download PDF

Info

Publication number
CN102391874A
CN102391874A CN2011102816059A CN201110281605A CN102391874A CN 102391874 A CN102391874 A CN 102391874A CN 2011102816059 A CN2011102816059 A CN 2011102816059A CN 201110281605 A CN201110281605 A CN 201110281605A CN 102391874 A CN102391874 A CN 102391874A
Authority
CN
China
Prior art keywords
nayf
nano particle
kernel
fluorescent nano
hexanaphthene
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.)
Pending
Application number
CN2011102816059A
Other languages
Chinese (zh)
Inventor
陈风
步文博
施剑林
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.)
Shanghai Institute of Ceramics of CAS
Original Assignee
Shanghai Institute of Ceramics of CAS
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Shanghai Institute of Ceramics of CAS filed Critical Shanghai Institute of Ceramics of CAS
Priority to CN2011102816059A priority Critical patent/CN102391874A/en
Publication of CN102391874A publication Critical patent/CN102391874A/en
Pending legal-status Critical Current

Links

Images

Abstract

The invention relates to NaYF4-based fluorescent nano particles with double effects and a preparation method thereof. The NaYF4-based fluorescent nano particles at least comprise a kernel and a shell, wherein the kernel is NaYF4: Er/Yb/Gd or NaYF4: Er/Yb, and the shell is NaGdF4. By introducing different luminous ion pairs into different layers, the single-excitation multi-color luminescence function of the single fluorescent particles is realized, and the fluorescent particles have magnetic resonance imaging function; and meanwhile, by introducing a wrapping layer, surface defects of the particles are reduced, and the fluorescent strength of the particles is improved.

Description

NaYF with dual function 4Base fluorescent nano particle and preparation method thereof
Technical field
The present invention relates to the upconverting fluorescent material field, be specifically related to a kind of possess up-conversion fluorescence imaging and the double mode NaYF of nuclear magnetic resonance 4Base fluorescent nano particle and preparation method thereof.
Background technology
Early diagnosis of tumor presses for a kind of initiatively bioprobe of target of multiplex mode combination, efficient specificity that possesses.Fluorescence imaging and nuclear magnetic resonance at present is the diagnostic mode of tool potentiality.Research is expected to overcome the many weak points that exist in the present early diagnosis of cancer based on fluorescence/mr compound multi-mode probe, improves the diagnosis rate of clinical tumor.At present, the research emphasis of conventional fluorescent imaging field is based on the semiconductor-quantum-point that organic fluorescence is plain and contain heavy metal element.The former is not substituted by the latter because stability of photoluminescence is not good gradually.And the latter has also limited its further biologic applications because of the potential heavy metal toxicity.
Upconverting fluorescent material is one type of important rare earth (RE) luminescent material; It can convert the low frequency exciting light to high frequency emission light through multi-photon mechanism; Having near infrared excites; Emitted in ultraviolet-infrared the characteristics that wait multiband fluorescence has important use in fields such as solid statelaser, transmitter, solar cell and 3 D stereo demonstrations.
In recent years, the upconverting fluorescent material of nanoscale (upper conversion fluorescent nano particle) receives researchist's attention gradually in the application aspect the biomacromolecule detection as a kind of novel fluorescence affinity tag (probe).Than traditional fluorescent marker such as organic resorcinolphthalein and semiconductor-quantum-point etc., upper conversion fluorescent nano particle has as probe biomolecule that luminous intensity is high and stable, the tissue penetration degree of depth is big, background noise low and advantage such as the live body phototoxicity is low.For example, the exciting light of upper conversion fluorescent nano particle is a near infrared light, under this shooting conditions, can avoid the interference and the scattered light phenomenon of biological autofluorescence, thereby reduces detection background, improves signal to noise ratio.Therefore, upper conversion fluorescent nano particle all has extraordinary application prospect as fluorescent marker in biomacromolecule analysis and clinical medicine detection range.
In existing up-conversion fluorescence nano material, six side's phase NaYF 4Be the present best substrate material of luminescent properties in the report, through to NaYF 4In doping with rare-earth ions to (like Er 3+/ Yb 3+Tm 3+/ Yb 3+), can obtain the excellent fluorescent grain of luminescent properties.CN102140662 A discloses a kind of NaYF 4: Yb, Er upconverting fluorescent material and preparation method.Yet, nano NaY F 4Because the existence of surface imperfection, its luminous efficiency is starkly lower than body phase material usually, how to improve based on NaYF 4The luminescent properties of nano particle becomes an important subject of this area.
The foreign study personnel found to pass through to original luminous NaYF in 2009 4:Doped with rare-earth elements gadolinium ion in the Er/Yb nano particle, nano particle (Kumar, R.and Prasad, the P. N. that can realize having up-conversion fluorescence and nuclear magnetic resonance dual function smoothly Adv. Funct. Mater. 2009, 19, 853.).Lanthanide rare gadolinium ion (Gd for example 3+) have half-full 4f layer electronics, be to use T the most widely at present 1-MRI radiography is used ion.The T of clinical use 1Mostly-MRI contrast medium is Gd 3+Complex compound, its longitudinal relaxation rate ( r 1) be 3.8 mM -1s -1About.Through to NaYF 4Doped with rare-earth elements Gd ion in the matrix can make material have T 1-MRI radiography function, yet, present Gd 3+Adulterated NaYF 4That has reported in the structure is the highest r 1Value is merely 1.4 mM -1s -1(Park, Y. I. and Hyeon, T. Adv. Mater. 2009, 21,4467.), use the Gd agent well below clinical, therefore, demand urgently developing a kind of more efficiently based on NaYF 4Fluorescence/MR dual pattern nano biological molecular probe.
Summary of the invention
In the face of the problems referred to above that prior art exists, first aspect of the present invention provides a kind of NaYF with dual function 4The base fluorescent nano particle, said NaYF 4The base fluorescent nano particle comprises kernel and shell at least, and wherein said kernel is NaYF 4: Er/Yb/Gd or NaYF 4: Er/Yb, said shell are NaGdF 4
NaYF of the present invention 4The base fluorescent nano particle has nucleocapsid structure, and is right through introducing different light emitting ionics at different layers, realizes that the single of single fluorescent grain excites multicolor luminous function, and has nuclear magnetic resonance concurrently; Simultaneously, reduce the particulate surface imperfection, improved the particulate fluorescence intensity through introducing integument.
NaYF of the present invention 4The base fluorescent nano particle can comprise that also the middle layer forms three-decker, and said middle layer can be NaYF 4: Tm/Yb.
NaYF of the present invention 4In the base fluorescent nano particle, said shell NaGdF 4Mean thickness can be 0.2～4 nm, preferred 0.2～3.7 nm, more preferably 0.2～2.0 nm.Its corresponding longitudinal relaxation rate can be 1.18～6.18mM -1S- 1, preferred 2.18 ~ 6.18mM -1S- 1, more preferably 5.46 ~ 6.18mM -1S- 1
Through optimizing outermost layer NaGdF 4Thickness, can improve up-conversion fluorescence particulate longitudinal relaxation rate, realize near in addition surpass the purpose of the longitudinal relaxation rate value of clinical Gd agent.Prepared particulate relaxation rate is up to 6.18 mM -1s -1, be 44 times of similar structures of document reported first.The maximum relaxation rate of single particle is 1.4 * 10 5MM -1s -1
On the other hand, the present invention provides a kind of preparation to have the NaYF of dual function 4The method of base fluorescent nano particle comprises: muriate, NaOH and the NH of the rare earth ion that said kernel is comprised 4F elevated temperature heat in oleic acid and octadecylene mixed solution is decomposed, and then cleans, is dispersed in the hexanaphthene kernel preparation process as kernel; And the muriate of the rare earth ion that said shell is comprised, cyclohexane solution, NaOH and the NH of the kernel that will coat 4F elevated temperature heat in oleic acid and octadecylene mixed solution is decomposed the shell preparation process of then cleaning, being dispersed in hexanaphthene.
Wherein, said kernel preparation process can comprise: the aqueous chloride solution of the rare earth ion that said kernel is comprised adds in oleic acid and the octadecylene mixed solution, removes air and moisture, about 160 ℃, is incubated 60 minutes; Add and be dispersed with NaOH and NH 4The methanol solution of F heats up and removes methyl alcohol; And 290～300 ℃ of thermolysiss after 1.5 hours, cooling, carry out ultrasonic cleaning with absolute ethyl alcohol, hexanaphthene, alcohol successively, and centrifugal collection, products therefrom is dispersed in the hexanaphthene.
Said shell preparation process can comprise: the aqueous chloride solution of the rare earth ion that said shell is comprised adds in oleic acid and the octadecylene mixed solution, removes air and moisture, about 160 ℃, is incubated 60 minutes; Add the cyclohexane solution of the kernel that will coat, heat up and remove hexanaphthene; Add and be dispersed with NaOH and NH 4The methanol solution of F heats up and removes methyl alcohol; And 290～300 ℃ of thermolysiss after 1.5 hours, cooling, carry out ultrasonic cleaning with absolute ethyl alcohol, hexanaphthene, alcohol successively, and centrifugal collection, products therefrom is dispersed in the hexanaphthene.
Method of the present invention can also comprise preparation middle layer NaYF 4: the Tm/Yb step: the muriate of the rare earth ion that said middle layer is comprised, cyclohexane solution, NaOH and the NH of the kernel that will coat 4F elevated temperature heat in oleic acid and octadecylene mixed solution is decomposed, and then cleans, is dispersed in the middle layer preparation of hexanaphthene.
Said middle layer preparation process comprises: the aqueous chloride solution of the rare earth ion that said middle layer is comprised adds in oleic acid and the octadecylene mixed solution, removes air and moisture, about 160 ℃, is incubated 60 minutes; Add the cyclohexane solution of the kernel that will coat, heat up and remove hexanaphthene; Add and be dispersed with NaOH and NH 4The methanol solution of F heats up and removes methyl alcohol; And 290～300 ℃ of thermolysiss after 1.5 hours, cooling, carry out ultrasonic cleaning with absolute ethyl alcohol, hexanaphthene, alcohol successively, and centrifugal collection, products therefrom is dispersed in the hexanaphthene.
The employed raw material of the inventive method is inorganic salt, and the preparation process can not produce toxic gas.Prepared nano particle pattern is spherical, and the yardstick homogeneous is controlled, is six side's phase NaYF 4The NaYF that makes 4The base fluorescent nano particle has good up-conversion fluorescence emission and T 1-MRI weighting performance is expected in the early stage imaging of following tumour multi-mode, have a good application prospect.
Description of drawings
Figure 1A shows the NaYF of median size 18 nm of embodiment 1 preparation 4: Er/Yb/Gd low power TEM photo;
Figure 1B shows the NaYF of median size 18 nm of embodiment 1 preparation 4: Er/Yb/Gd high power TEM photo;
Fig. 2 A shows the NaYF of median size 22 nm of embodiment 2 preparations 4: Er/Yb/Gd NaYF 4: Tm/Yb low power TEM photo;
Fig. 2 B shows the NaYF of median size 26 nm of embodiment 2 preparations 4: Er/Yb/Gd NaYF 4: Tm/Yb high power TEM photo;
Fig. 3 A shows the NaYF of median size 26 nm of embodiment 3 preparations 4: Er/Yb/Gd NaYF 4: Tm/Yb NaGdF 4Low power TEM photo;
Fig. 3 B shows the NaYF of median size 26 nm of embodiment 3 preparations 4: Er/Yb/Gd NaYF 4: Tm/Yb NaGdF 4High power TEM photo;
Fig. 4 A shows the NaYF of the median size 24nm of embodiment 4 preparations 4: Er/Yb NaGdF 4Low power TEM photo;
Fig. 4 B shows the NaYF of median size 24 nm of embodiment 4 preparations 4: Er/Yb NaGdF 4High power TEM photo;
Fig. 5 A shows the NaYF of the median size 24.5nm of embodiment 5 preparations 4: Er/Yb NaGdF 4Low power TEM photo;
Fig. 5 B shows the NaYF of median size 24.5 nm of embodiment 5 preparations 4: Er/Yb NaGdF 4High power TEM photo;
Fig. 6 A shows the NaYF of the median size 25.8nm of embodiment 6 preparations 4: Er/Yb NaGdF 4Low power TEM photo;
Fig. 6 B shows the NaYF of median size 25.8 nm of embodiment 6 preparations 4: Er/Yb NaGdF 4High power TEM photo;
Fig. 7 A shows the NaYF of the median size 27.5nm of embodiment 7 preparations 4: Er/Yb NaGdF 4Low power TEM photo;
Fig. 7 b shows the NaYF of median size 27.5 nm of embodiment 7 preparations 4: Er/Yb NaGdF 4High power TEM photo;
Fig. 8 A illustrates the exemplary transmit spectrum of the nano particle of the present invention preparation, exciting light λ=980 nm wherein, and dotted line is NaYF 4: the fluorescence of Er/Yb/Gd, long and short dash line are NaYF 4: Er/Yb/GdNaYF 4: the fluorescence of Tm/Yb, solid line are NaYF 4: Er/Yb/Gd NaYF 4: Tm/Yb NaGdF 4Fluorescence;
Fig. 8 B illustrates the enlarged diagram of A part among Fig. 8 A;
Fig. 8 C illustrates the enlarged diagram of B part among Fig. 8 A;
Fig. 9 illustrates water-soluble NaYF 4: Er/Yb/Gd NaYF 4: Tm/Yb NaGdF 4The graphic representation of the longitudinal relaxation rate of nano particle, testing tool are clinical usefulness 3.0 T MRI;
Figure 10 illustrates water-soluble NaYF 4: Er/YbNaGdF 4The graphic representation of the longitudinal relaxation rate of (0.2 nm) nano particle, testing tool are clinical usefulness 3.0 T MRI;
Figure 11 illustrates water-soluble NaYF 4: Er/YbNaGdF 4The graphic representation of the longitudinal relaxation rate of (0.7 nm) nano particle, testing tool are clinical usefulness 3.0 T MRI;
Figure 12 illustrates water-soluble NaYF 4: Er/YbNaGdF 4The graphic representation of the longitudinal relaxation rate of (2.0 nm) nano particle, testing tool are clinical usefulness 3.0 T MRI;
Figure 13 illustrates water-soluble NaYF 4: Er/YbNaGdF 4The graphic representation of the longitudinal relaxation rate of (3.7 nm) nano particle, testing tool are clinical usefulness 3.0 T MRI.
Embodiment
With reference to Figure of description, and combine following embodiment to further specify the present invention, should be understood that Figure of description and following embodiment only are used to explain the present invention, and unrestricted the present invention.
The present invention is through nucleus assisting growth technology, and preparation has the upper conversion fluorescent nano particle of nucleocapsid structure, and it is right to introduce different light emitting ionics at the particulate different layers, below respectively with have three-decker and double-layer structure on the example that is prepared as describe.
One, the upper conversion fluorescent nano particle (NaYF that has three-decker 4: Er/YbGdNaYF 4: Tm/Yb NaGdF 4) preparation.
(1) kernel NaYF 4: the preparation of Er/YbGd
1) aqueous solution of rare earth chloride: take by weighing the muriate of an amount of yttrium (Y), ytterbium (Yb), erbium (Er) and gadolinium (Gd) respectively, subsequent use with deionized water dissolving.Rare earth chloride can adopt its hydrate commonly used separately (YCl for example here 36H 2O, YbCl 36H 2O, ErCl 36H 2O, GdCl 3XH 2O, the amount of the deionized water of employing can be dissolving said muriatic amount or excessive slightly.
2) in oleic acid and octadecylene mixed solution, add above-mentioned pre-configured aqueous solution of rare earth chloride, the oleic acid of employing and the volume ratio of octadecylene can be 1:2.Stirred about 1 hour under the room temperature.Logical argon gas certain hour (for example 5 minutes) then carries out removal process slowly to remove air.Dewater after the end, system temperature is raised to about 160 ℃ and is incubated certain hour, for example 60 minutes, obtains faint yellow clear liquor.Stop heating, system is cooled to room temperature (keeping logical argon gas therebetween) naturally.
3) take by weighing appropriate amount of NaOH and NH 4F is with an amount of methyl alcohol (for example 10mL) dissolving, ultra-sonic dispersion.Then it is added in the above-mentioned system carefully, stirred 2 hours under the room temperature; Then be warmed up to 80～100 ℃ and remove methyl alcohol, be incubated about 1 hour, finish up to the methyl alcohol removal.
4) after methyl alcohol had removed, system began to heat up, and at 290～300 ℃, condensing reflux kept 1.5 hours, reduced to room temperature then naturally with temperature-stable.
6) product cleaning: can carry out ultrasonic cleaning with absolute ethyl alcohol, hexanaphthene, alcohol successively, centrifugal collection, but repeated washing 4 times, final product disperses with cyclohexane solution, obtains colorless cleared solution.Product can be launched tangible green glow under the 980nm excitation light irradiation.
The preparation of (two) two layers of nucleocapsid structure: NaYF 4: Er/YbGdNaYF 4: Tm/Yb
1) aqueous solution of rare earth chloride: title takes by weighing an amount of yttrium (Y), ytterbium (Yb) respectively, reaches the muriate of thulium (Tm), and is subsequent use with deionized water dissolving.Rare earth chloride can adopt its hydrate commonly used separately, for example YCl here 36H 2O, YbCl 36H 2O, TmCl 36H 2O.The amount of the deionized water that adopts can be dissolving said muriatic amount or excessive slightly.
2) in oleic acid and octadecylene mixed solution, add above-mentioned pre-configured aqueous solution of rare earth chloride.The oleic acid that adopts and the volume ratio of octadecylene can be 1:2, stir about 1 hour under the room temperature.Logical argon gas certain hour (for example 5 minutes) then carries out removal process slowly to remove air.Dewater after the end, system temperature is raised to about 160 ℃, keeps certain hour, for example 60 minutes.Obtain faint yellow clear liquor.Stop heating, system is cooled to room temperature (keeping logical argon gas therebetween) naturally.
3) in system, add an amount of NaYF of preparation in advance 4: the Er/YbGd cyclohexane solution is as kernel.Stir after 30 minutes, be warming up to about 80 ℃ and remove cyclohexane solution;
4) take by weighing appropriate amount of NaOH and NH 4F uses an amount of dissolve with methanol, ultra-sonic dispersion.Then it is added in the above-mentioned system carefully, stirred about 2 hours under the room temperature; Be warmed up to 80～100 ℃ to remove methyl alcohol, kept about 1 hour, removed up to methyl alcohol.
5) after methyl alcohol had removed, system began to heat up, and at 290～300 ℃, condensing reflux kept 1.5 hours, reduced to room temperature then naturally with temperature-stable.
6) product cleaning: can carry out ultrasonic cleaning with absolute ethyl alcohol, hexanaphthene, alcohol successively, centrifugal collection, but repeated washing 4 times, final product disperses with cyclohexane solution, obtains colorless cleared solution.
(3) preparation of three-layer nuclear shell structure: NaYF 4: Er/YbGdNaYF 4: Tm/YbNaGdF 4
1) aqueous solution of rare earth chloride: take by weighing an amount of gadolinium muriate (GdCl for example 3XH 2O), subsequent use with the proper amount of deionized water dissolving.
) in oleic acid and octadecylene mixed solution, add above-mentioned pre-configured aqueous solution of rare earth chloride, stirred 1 hour under the room temperature.The oleic acid that adopts and the volume ratio of octadecylene can be 1:2.Logical argon gas certain hour (for example 5 minutes) then carries out removal process slowly to remove air.Dewater after the end, system temperature is raised to about 160 ℃, keeps certain hour, for example about 60 minutes.Obtain faint yellow clear liquor.Stop heating, system is cooled to room temperature (keeping logical argon gas therebetween) naturally.
3) in system, add an amount of NaYF of preparation in advance 4: Er/YbGdNaYF 4: the Tm/Yb cyclohexane solution is as kernel.Stir after 30 minutes, be warming up to 80 ℃ and remove cyclohexane solution;
4) take by weighing appropriate amount of NaOH and NH 4F uses an amount of dissolve with methanol, ultra-sonic dispersion.Then it is added in the above-mentioned system carefully, stirred 2 hours under the room temperature; Be warmed up to 80～100 ℃ to remove methyl alcohol, kept about 1 hour, removed up to methyl alcohol.
5) after methyl alcohol had removed, system began to heat up, and at 290～300 ℃, condensing reflux kept 1.5 hours, reduced to room temperature then naturally with temperature-stable.
6) product cleaning: can carry out ultrasonic cleaning with absolute ethyl alcohol, hexanaphthene, alcohol successively, centrifugal collection, but repeated washing 4 times, final product disperses with cyclohexane solution, obtains colorless cleared solution.
The NaYF that makes 4: Er/YbGdNaYF 4: Tm/YbNaGdF 4Exemplary transmit spectrum can be referring to accompanying drawing 8, its longitudinal relaxation rate can be referring to accompanying drawing 9.
The NaYF of embodiment 1 median size 18 nm 4: the preparation of Er/Yb/Gd:
Aqueous solution of rare earth chloride: the YCl that takes by weighing 1.3 mmol (394.368 mg) respectively 36H 2The YbCl of O, 0.36 mmol (139.4964 mg) 36H 2The ErCl of O, 0.04 mmol (15.2684 mg) 36H 2The GdCl of O and 0.3mmol (79.083) 3XH 2The O powder, subsequent use with 4 mL deionized water dissolvings.
In there-necked flask, add 15 mL oleic acid, 30 mL octadecylenes add the pre-configured above-mentioned muriatic aqueous solution then, stir 1 hour under the room temperature.Logical argon gas 5 minutes is removed a bottle air, and system begins to carry out removal process slowly then.Dewater finish after, system is raised to about 160 ℃, keeps 60 minutes.Obtain faint yellow clear liquor.Stop heating, let system be cooled to room temperature (keeping logical argon gas therebetween) naturally.
Take by weighing 200 mg NaOH, 296.3 mg NH 4F is with 10 mL dissolve with methanol, ultra-sonic dispersion.Then in the carefully adding system.Stirred 2 hours under the room temperature.After 2 hours, system begins to get into except that the methyl alcohol link.Be warmed up to 80～100 ℃, and kept 1 hour.Removed up to methyl alcohol.
After methyl alcohol has removed.Prolong is connected, and system begins to heat up, and last temperature-stable at 290～300 ℃, is kept 1.5 h.Naturally reduce to room temperature then.
Product cleaning: at first in system, add 20 mL absolute ethyl alcohols, stirring at room 30 minutes.Use 10000 r/min then, centrifugal 10 minutes; Add the hexanaphthene of 5～10 mL, ultrasonic, add the alcohol of 15 mL then, ultrasonic about 5 minutes, centrifugal collection.Repeated washing 4 times, final product disperses with cyclohexane solution, obtains to be colorless cleared solution.980 nm laser irradiation product down can have been launched tangible green glow.
Making average size of products is 18nm, and its low power and high power TEM photo are respectively shown in Figure 1A, 1B.
Embodiment 2 (the NaYF4:Er/Yb/Gd NaYF4:Tm/Yb preparations of median size 22 nm):
On embodiment 1 basis, proceed following steps:
Aqueous solution of rare earth chloride: the YCl that takes by weighing 0.747 mmol (226.61 mg) respectively 36H 2The YbCl of O, 0.25 mmol (96.8725 mg) 36H 2The TmCl of O, 0.003mmol (0.8258 mg) 36H 2The O powder, subsequent use with 4 mL deionized water dissolvings.
In there-necked flask, add 15 mL oleic acid and 30 mL octadecylenes, add pre-configured aqueous chloride solution then, stirred 1 hour under the room temperature.Logical argon gas 5 minutes is removed a bottle air, and system begins to carry out removal process slowly then.Dewater finish after, system is raised to about 160 ℃, keeps 60 minutes.Obtain faint yellow clear liquor.Stop heating, let system be cooled to room temperature (keeping logical argon gas) naturally.
The NaYF that in system, adds embodiment 1 preparation of 1mmol 4: the Er/YbGd cyclohexane solution is as the kernel of growth.Stir after 30 minutes, be warming up to 80 ℃ and remove cyclohexane solution.
Prepare 100 mg NaOH, 148.15 mg NH 4F is with the dissolve with methanol of 10 mL, ultra-sonic dispersion.In the carefully adding system, stirred 2 hours under the room temperature then.After 2 hours, system begins to get into except that the methyl alcohol link.Be warmed up to 80～100 ℃, kept 1 hour.Removed up to methyl alcohol.
After methyl alcohol has removed.Prolong is connected, and system begins to heat up, and last temperature-stable at 290～300 ℃, was kept 1.5 hours, reduces to room temperature then naturally.
Product cleaning: at first in system, add 20 mL absolute ethyl alcohols, stirring at room 30 minutes.Use 10000 r/min, centrifugal 10 minutes; The hexanaphthene that adds 5～10 mL then, and ultrasonic adds the alcohol of 15 mL, and ultrasonic about 5 minutes, centrifugal collection.Repeated washing 4 times, last product disperses with cyclohexane solution, obtains to be colorless cleared solution.
Making average size of products is 22nm, and its low power and high power TEM photo are respectively shown in Fig. 2 A, 2B.
Embodiment 3 (the NaYF of median size 26 nm 4: Er/Yb/Gd NaYF 4: Tm/Yb NaGdF 4Preparation):
On embodiment 2 bases, proceed following steps:
Aqueous solution of rare earth chloride: the GdCl that takes by weighing 1 mol (263.61 mg) 3XH 2The O powder, subsequent use with 4 mL deionized water dissolvings.
In there-necked flask, add 15 mL oleic acid, 30 mL octadecylenes, add pre-configured aqueous chloride solution then, stirred 1 hour under the room temperature.Logical argon gas 5 minutes is removed the air in the bottle, and system begins to carry out removal process slowly then.Dewater finish after, system is raised to about 160 ℃, keeps 60 minutes.Obtain faint yellow clear liquor.Stop heating, let system be cooled to room temperature (keeping logical argon gas) naturally.
The NaYF that in system, adds embodiment 2 preparations of 1 mmol 4: Er/YbGdNaYF 4: the Tm/Yb cyclohexane solution is as the kernel of growth.Stir after 30 minutes, be warming up to 80 ℃ and remove cyclohexane solution.
Prepare 100 mg NaOH, 148.15 mg NH 4F is with the dissolve with methanol of 10 mL, ultra-sonic dispersion.In the carefully adding system, stirred 2 hours under the room temperature then.
After 2 hours, system begins to get into except that the methyl alcohol link.Be warmed up to 80～100 ℃, kept 1 hour.Removed up to methyl alcohol.
After methyl alcohol has removed.Prolong is connected, and system begins to heat up, and final temp is stabilized in 290～300 ℃, keeps 1.5 hours.Naturally reduce to room temperature then.
Product cleaning: at first in system, add 20 mL absolute ethyl alcohols, stirring at room 30 minutes.Use 10000 r/min then, centrifugal 10 minutes; Add the hexanaphthene of 5～10 mL, ultrasonic, add the alcohol of 15 mL, ultrasonic about 5 minutes, centrifugal collection.Repeated washing 4 times, final product disperses with cyclohexane solution, obtains to be colorless cleared solution.
Making average size of products is 26nm, and its low power and high power TEM photo are respectively shown in Fig. 3 A, 3B.
Two, the conversion fluorescent nano particle (NaYF that has double-layer structure 4: preparation Er/Yb NaGdF).
(1) kernel NaYF 4: the preparation of Er/Yb
1) aqueous solution of rare earth chloride: take by weighing an amount of yttrium (Y), ytterbium (Yb), and the muriate of erbium (Er) respectively, subsequent use with deionized water dissolving.Rare earth chloride can adopt its hydrate commonly used separately, for example (YCl here 36H 2O, YbCl 36H 2O, ErCl 36H 2O.The amount of the deionized water that adopts can be dissolving said muriatic amount or excessive slightly.
2) in oleic acid and octadecylene mixed solution, add above-mentioned pre-configured aqueous solution of rare earth chloride, the oleic acid of employing and the volume ratio of octadecylene can be 1:2.Stirred about 1 hour under the room temperature.Logical argon gas certain hour (for example 5 minutes) then carries out removal process slowly to remove air.Dewater after the end, system temperature is raised to about 160 ℃ and is incubated certain hour, for example 60 minutes, obtains faint yellow clear liquor.Stop heating, system is cooled to room temperature (keeping logical argon gas therebetween) naturally.
3) take by weighing appropriate amount of NaOH and NH 4F is with an amount of methyl alcohol (for example 10mL) dissolving, ultra-sonic dispersion.Then it is added in the above-mentioned system carefully, stirred 2 hours under the room temperature; Be warmed up to 80～100 ℃ to remove methyl alcohol, be incubated about 1 hour, removed up to methyl alcohol.
4) after methyl alcohol had removed, system began to heat up, and at 290～300 ℃, condensing reflux kept 1.5 hours, reduced to room temperature then naturally with temperature-stable.
5) product cleaning: can carry out ultrasonic cleaning with absolute ethyl alcohol, hexanaphthene, alcohol successively, centrifugal collection, but repeated washing 4 times, final product disperses with cyclohexane solution, obtains colorless cleared solution.Product can be launched tangible green glow under the 980nm excitation light irradiation.
(2) two layers of nucleocapsid NaYF 4: Er/Yb NaGdF 4Preparation
1) aqueous solution of rare earth chloride: take by weighing an amount of gadolinium muriate (GdCl for example 3XH 2O), subsequent use with the proper amount of deionized water dissolving.
2) in oleic acid and octadecylene mixed solution, add above-mentioned pre-configured aqueous solution of rare earth chloride, stirred 1 hour under the room temperature.The oleic acid that adopts and the volume ratio of octadecylene can be 1:2.Logical argon gas certain hour (for example 5 minutes) then carries out removal process slowly to remove air.Dewater after the end, system temperature is raised to about 160 ℃, keeps certain hour, for example about 60 minutes.Obtain faint yellow clear liquor.Stop heating, system is cooled to room temperature (keeping logical argon gas therebetween) naturally.
3) in system, add an amount of NaYF of preparation in advance 4: the Er/Yb cyclohexane solution is as kernel.Stir after 30 minutes, be warming up to 80 ℃ and remove cyclohexane solution.
4) take by weighing appropriate amount of NaOH and NH 4F uses an amount of dissolve with methanol, ultra-sonic dispersion.Then it is added in the above-mentioned system carefully, stirred 2 hours under the room temperature; Be warmed up to 80～100 ℃ to remove methyl alcohol, kept about 1 hour, removed up to methyl alcohol; After methyl alcohol had removed, system began to heat up, and at 290～300 ℃, condensing reflux kept 1.5 hours, reduced to room temperature then naturally with temperature-stable.
5) product cleaning: can carry out ultrasonic cleaning with absolute ethyl alcohol, hexanaphthene, alcohol successively, centrifugal collection, but repeated washing 4 times, final product disperses with cyclohexane solution, obtains colorless cleared solution.
Embodiment 4 (the NaYF of median size 24 nm 4: Er/Yb NaGdF 4, preparation NaGdF 4Layer thickness is 0.2 nm):
The preparation of kernel: NaYF 4: Er/Yb
Aqueous solution of rare earth chloride: the YCl that takes by weighing 1.6 mmol (458.376 mg) respectively 36H 2The YbCl of O, 0.36 mmol (139.4964 mg) 36H 2The ErCl of O and 0.04 mmol (15.2684 mg) 36H 2The O powder, subsequent use with 4 mL deionized water dissolvings.
In there-necked flask, add 15 mL oleic acid and 30 mL octadecylenes, add above-mentioned pre-configured aqueous chloride solution then, stirred 1 hour under the room temperature.Logical argon gas 5 minutes is removed the air in the bottle, and system begins to carry out removal process slowly then.Dewater finish after, system is raised to about 160 ℃, keeps 60 minutes.Obtain faint yellow clear liquor.Stop heating, let system be cooled to room temperature (keeping logical argon gas) naturally.
Take by weighing 200 mg NaOH and 296.3mg NH 4F is with the dissolve with methanol of 10 mL, ultra-sonic dispersion.Then in the carefully adding system.Stirred 2 hours under the room temperature.
After 2 hours, system begins to get into except that the methyl alcohol link.Be warmed up to 80～100 ℃, kept 1 hour.Removed up to methyl alcohol.
After methyl alcohol has removed.Prolong is connected, and system begins to heat up, and last temperature-stable at 290～300 ℃, was kept 1.5 hours.Naturally reduce to room temperature then.
Product cleaning process: at first in system, add 20 mL absolute ethyl alcohols, stirring at room 30 minutes.Use 10000 r/min then, centrifugal 10 minutes; Add the hexanaphthene of 5～10mL, ultrasonic, add the alcohol of 15 mL, ultrasonic about 5 minutes, centrifugal collection.Repeated washing 4 times, final product disperses with cyclohexane solution, obtains to be colorless cleared solution.980 nm laser irradiation product down can have been launched tangible green glow.
The preparation of two layers of nucleocapsid structure: NaYF 4: Er/YbNaGdF 4
Aqueous solution of rare earth chloride: take by weighing 0.337 mol GdCl 3XH 2The O powder, subsequent use with 4 mL deionized water dissolvings.
In there-necked flask, add 15 mL oleic acid, 30 mL octadecylenes add pre-configured aqueous chloride solution then, stir 1 hour under the room temperature.Logical argon gas 5 minutes is removed the air in the bottle, and system begins to carry out removal process slowly.Dewater finish after, system is raised to about 160 ℃, keeps 60 minutes.Obtain faint yellow clear liquor.Stop heating then, let system be cooled to room temperature (keeping logical argon gas) naturally.
In system, add about 1 mmol NaYF of preparation in advance 4: the Er/Yb cyclohexane solution is as the kernel of growth.Stir after 30 minutes, be warming up to 80 ℃ and remove cyclohexane solution.
Take by weighing 33.7 mg NaOH and 49.92 mg NH4F, with the dissolve with methanol of 10 mL, ultra-sonic dispersion.Then in the carefully adding system.Stirred 2 hours under the room temperature.
After 2 hours, system begins to get into except that the methyl alcohol link.Be warmed up to 80～100 ℃, kept 1 hour.Removed up to methyl alcohol.
After methyl alcohol has removed.Prolong is connected, and system begins to heat up, and last temperature-stable at 290～300 ℃, and is kept 1.5h.Naturally reduce to room temperature.Product cleaning process: at first in system, add 20 mL absolute ethyl alcohols, stirring at room 30 minutes.Use 10000 r/min then, centrifugal 10 minutes; Add the hexanaphthene of 5～10 mL, ultrasonic, add the alcohol of 15 mL then, ultrasonic about 5 minutes, centrifugal collection.Repeated washing 4 times, last product disperses with cyclohexane solution, obtains to be colorless cleared solution.
Making average size of products is 24 nm, and the mean thickness of shell is 0.2 nm, and its low power and high power TEM photo are respectively shown in Fig. 4 A, 4B; Its longitudinal relaxation rate can be referring to accompanying drawing 10.
Embodiment 5 (the NaYF of median size 24.5 nm 4: Er/Yb NaGdF 4Preparation, NaGdF 4Layer thickness is 0.7 nm):
The preparation of kernel: NaYF 4: Er/Yb
Aqueous solution of rare earth chloride: the YCl that takes by weighing 1.6 mmol (458.376 mg) respectively 36H 2The YbCl of O, 0.36 mmol (139.4964mg) 36H 2The ErCl of O and 0.04 mmol (15.2684 mg) 36H 2The O powder, subsequent use with 4 mL deionized water dissolvings.
In there-necked flask, add 15 mL oleic acid, 30 mL octadecylenes add the above-mentioned in advance aqueous chloride solution that configures then, stir 1 hour under the room temperature.Logical argon gas 5 minutes is removed the air in the bottle, and system begins to carry out removal process slowly.Dewater finish after, system is raised to about 160 ℃, keeps 60 minutes.Obtain faint yellow clear liquor.Stop heating then, let system be cooled to room temperature (keeping logical argon gas) naturally.
Take by weighing 200 mg NaOH and 296.3 mg NH 4F is with the dissolve with methanol of 10 mL, ultra-sonic dispersion.In the carefully adding system, stirred 2 hours under the room temperature then.
After 2 hours, system begins to get into except that the methyl alcohol link.Be warmed up to 80～100 ℃, kept 1 hour.Removed up to methyl alcohol.
After methyl alcohol has removed.Prolong is connected, and system begins to heat up, and last temperature-stable at 290～300 ℃, was kept 1.5 hours.Naturally reduce to room temperature then.
Product cleaning: at first in system, add 20 mL absolute ethyl alcohols, stirring at room 30 minutes.Use 10000r/min then, centrifugal 10 minutes; Add 5～10 mL hexanaphthenes, and ultrasonic, add the alcohol of 15 mL then, ultrasonic about 5 minutes, centrifugal collection.Repeated washing 4 times, last product disperses with cyclohexane solution, obtains to be colorless cleared solution.980 nm laser irradiation product down can have been launched tangible green glow.
The preparation of two layers of nucleocapsid structure: NaYF 4: Er/Yb NaGdF 4:
Aqueous solution of rare earth chloride: take by weighing 0.08 mol GdCl 3XH 2The O powder, subsequent use with 4 mL deionized water dissolvings.
In there-necked flask, add 15 mL oleic acid and 30 mL octadecylenes, add above-mentioned pre-configured aqueous chloride solution then, stirred 1 hour under the room temperature.Logical argon gas 5 minutes is removed the air in the bottle, and system begins to carry out removal process slowly.Dewater finish after, system is raised to about 160 ℃, keeps 60 minutes.Obtain faint yellow clear liquor.Stop heating then, let system be cooled to room temperature (keeping logical argon gas) naturally.
In system, add about 1 mmol NaYF of preparation in advance 4: the Er/Yb cyclohexane solution is as the kernel of growth.Stir after 30 minutes, be warming up to 80 NaYF 4: Er/Yb removes cyclohexane solution.
Take by weighing 8 mg NaOH and 11.85 mg NH4F, with the dissolve with methanol of 10 mL, ultra-sonic dispersion.Then in the carefully adding system.Stirred 2 hours under the room temperature.
After 2 hours, system begins to get into except that the methyl alcohol link.Be warmed up to 80～100 ℃, kept 1 hour.Removed up to methyl alcohol.
After methyl alcohol has removed.Prolong is connected, and system begins to heat up, and last temperature-stable at 290～300 ℃, and was kept 1.5 hours.Naturally reduce to room temperature then.
Product cleaning process: at first in system, add 20 mL absolute ethyl alcohols, stirring at room 30 minutes.Use 10000 r/min then, centrifugal 10 minutes; Add the hexanaphthene of 5～10 mL then, ultrasonic, add the alcohol of 15 mL then, ultrasonic about 5 minutes, centrifugal collection.Repeated washing 4 times, last product disperses with cyclohexane solution, obtains to be colorless cleared solution.
Making average size of products is 24.5 nm, and the mean thickness of shell is 0.7nm, and its low power and high power TEM photo are respectively shown in Fig. 5 A, 5B; Its longitudinal relaxation rate can be referring to accompanying drawing 11.
Embodiment 6 (the NaYF of median size 25.8 nm 4: Er/Yb NaGdF 4Preparation, NaGdF 4Layer thickness is 2.0 nm):
The preparation of kernel: NaYF 4: Er/Yb:
Aqueous solution of rare earth chloride: the YCl that takes by weighing 1.6 mmol (458.376 mg) respectively 36H 2The YbCl of O, 0.36 mmol (139.4964 mg) 36H 2The ErCl of O and 0.04 mmol (15.2684 mg) 36H 2The O powder, subsequent use with 4 mL deionized water dissolvings.
In there-necked flask, add 15 mL oleic acid and 30 mL octadecylenes, add above-mentioned pre-configured aqueous chloride solution then, stirred 1 hour under the room temperature.Logical argon gas 5 minutes is removed the air in the bottle, and system begins to carry out removal process slowly.Dewater finish after, system is raised to about 160 ℃, keeps 60 minutes.Obtain faint yellow clear liquor.Stop heating then, let system be cooled to room temperature (keeping logical argon gas) naturally.
Take by weighing 200 mg NaOH and 296.3 mg NH 4F is with 10 mL dissolve with methanol, ultra-sonic dispersion.Then in the carefully adding system.Stirred 2 hours under the room temperature.
After 2 hours, system begins to get into except that the methyl alcohol link.Be warmed up to 80～100 ℃, kept 1 hour.Removed up to methyl alcohol.
After methyl alcohol has removed.Prolong is connected, and system begins to heat up, and last temperature-stable at 290～300 ℃, was kept 1.5 hours.Naturally reduce to room temperature then.
Product cleaning process: at first in system, add 20 mL absolute ethyl alcohols, stirring at room 30 minutes.Use 10000 r/min then, centrifugal 10 minutes; The hexanaphthene that adds 5～10 mL then, and ultrasonic adds the alcohol of 15 mL, and ultrasonic about 5 minutes, centrifugal collection.Repeated washing 4 times, final product disperses with cyclohexane solution, obtains to be colorless cleared solution.980 nm laser irradiation product down can have been launched tangible green glow.
Two layers of nucleocapsid structure NaGdF 4Preparation:
1) aqueous solution of rare earth chloride: take by weighing 0.02 mol GdCl 3XH 2The O powder, subsequent use with the 4mL deionized water dissolving.
In there-necked flask, add 15 mL oleic acid and 30mL octadecylene, add pre-configured aqueous chloride solution then, stirred 1 hour under the room temperature.Logical argon gas 5 minutes is removed the air in the bottle, and system begins to carry out removal process slowly.Dewater finish after, system is raised to about 160 ℃, keeps 60 minutes.Obtain faint yellow clear liquor.Stop heating then, let system be cooled to room temperature (keeping logical argon gas) naturally.
In system, add above-mentioned about 1 mmol NaYF of preparation in advance 4: the Er/Yb cyclohexane solution is as the kernel of growth.After stirring 30 min, be warming up to 80 degree and remove cyclohexane solution.
Take by weighing 2 mg NaOH and 2.96 mg NH4F, with the dissolve with methanol of 10 mL, ultra-sonic dispersion.Then in the carefully adding system.Stirred 2 hours under the room temperature.
After 2 hours, system begins to get into except that the methyl alcohol link.Be warmed up to 80～100 ℃, kept 1 hour.Removed up to methyl alcohol.
After methyl alcohol has removed.Prolong is connected, and system begins to heat up, and final temp is stabilized in 290～300 ℃, keeps 1.5 hours.Naturally reduce to room temperature then.
Product cleaning process: at first in system, add the absolute ethyl alcohol of 20 mL, stirring at room 30 minutes.Use 10000 r/min then, centrifugal 10 minutes; The hexanaphthene that adds 5～10 mL then, and ultrasonic adds the alcohol of 15 mL, and ultrasonic about 5 minutes, centrifugal collection.Repeated washing 4 times, final product disperses with cyclohexane solution, obtains to be colorless cleared solution.
Making average size of products is 25.8 nm, and the mean thickness of shell is 2.0 nm, and its low power and high power TEM photo are respectively shown in Fig. 6 A, 6B; Its longitudinal relaxation rate can be referring to accompanying drawing 12.
Embodiment 7 (the NaYF of median size 27.5 nm 4: Er/Yb NaGdF 4Preparation, NaGdF 4Layer thickness is 3.7 nm):
The preparation of kernel: NaYF 4: Er/Yb
Aqueous solution of rare earth chloride: the YCl that takes by weighing 1.6 mmol (458.376 mg) respectively 36H 2The YbCl of O, 0.36 mmol (139.4964 mg) 36H 2The ErCl of O and 0.04 mmol (15.2684 mg) 36H 2The O powder, subsequent use with 4 mL deionized water dissolvings.
In there-necked flask, add 15 mL oleic acid and 30 mL octadecylenes, add pre-configured aqueous chloride solution then, stirred 1 hour under the room temperature.Logical argon gas 5 minutes is removed the air in the bottle, and system begins to carry out removal process slowly.Dewater finish after, system is raised to about 160 ℃, keeps 60 minutes.Obtain faint yellow clear liquor.Stop heating then, let system be cooled to room temperature (keeping logical argon gas) naturally.
Take by weighing 200 mg NaOH and 296.3 mg NH 4F is with the dissolve with methanol of 10 mL, ultra-sonic dispersion.Then in the carefully adding system.Stirred 2 hours under the room temperature.
After 2 hours, system begins to get into except that the methyl alcohol link.Be warmed up to 80～100 ℃, kept 1 hour.Removed up to methyl alcohol.
After methyl alcohol has removed.Prolong is connected, and system begins to heat up, and last temperature-stable at 290～300 ℃, was kept 1.5 hours.Naturally reduce to room temperature then.
Product cleaning process: at first in system, add 20 mL absolute ethyl alcohols, stirring at room 30 minutes.Use 10000 r/min then, centrifugal 10 minutes; Add the hexanaphthene of 5～10mL, ultrasonic, add the alcohol of 15mL, ultrasonic about 5 min, centrifugal collection then.Repeated washing 4 times, final product disperses with cyclohexane solution, obtains to be colorless cleared solution.980 nm laser irradiation product down can have been launched tangible green glow.
Two layers of nucleocapsid structure NaYF 4: Er/Yb NaGdF 4Preparation:
1) preparation of rare earth chloride: take by weighing 0.004 mol GdCl 3XH 2The O powder, subsequent use with 4 mL deionized water dissolvings.
In there-necked flask, add 15 mL oleic acid, 30 mL octadecylenes add pre-configured aqueous chloride solution then, stir 1 hour under the room temperature.Logical argon gas 5 minutes is removed the air in the bottle, and system begins to carry out removal process slowly then.Dewater finish after, system is raised to about 160 ℃, keeps 60 minutes.Obtain faint yellow clear liquor.Stop heating then, let system be cooled to room temperature (keeping logical argon gas) naturally.
In system, add about 1 mmol NaYF of preparation in advance 4: the Er/Yb cyclohexane solution is as the kernel of growth.Stir after 30 minutes, be warming up to 80 ℃ and remove cyclohexane solution.
Take by weighing 0.4 mg NaOH and 0.592 mg NH 4F is with the dissolve with methanol of 10mL, ultra-sonic dispersion.Then in the carefully adding system.Stirred 2 hours under the room temperature.
After 2 hours, system begins to get into except that the methyl alcohol link.Be warmed up to 80～100 ℃, kept 1 hour.Removed up to methyl alcohol.
After methyl alcohol has removed.Prolong is connected, and system begins to heat up, and final temp is stabilized in 290～300 ℃, keeps 1.5 hours.Naturally reduce to room temperature then.
Product cleaning process: at first in system, add 20 mL absolute ethyl alcohols, stirring at room 30 minutes.Use 10000 r/min then, centrifugal 10 minutes; The hexanaphthene that adds 5～10 mL, and ultrasonic adds the alcohol of 15 mL, and ultrasonic about 5 minutes, centrifugal collection.Repeated washing 4 times, final product disperses with cyclohexane solution, obtains to be colorless cleared solution.
Making average size of products is 27.5 nm, and the mean thickness of shell is 37nm, and its low power and high power TEM photo are respectively shown in Fig. 7 A, 7B; Its longitudinal relaxation rate can be referring to accompanying drawing 13.
The present invention preparation has the upper conversion fluorescent nano particle of nucleocapsid structure, and is right through introducing different light emitting ionics at different layers, and that can realize single fluorescent grain singlely excites multicolor luminous function; Simultaneously, reduce the particulate surface imperfection, improved the particulate fluorescence intensity through introducing integument.The second, through optimizing outermost layer NaGdF 4Thickness, improve up-conversion fluorescence particulate longitudinal relaxation rate, realize near in addition surpass the purpose of the longitudinal relaxation rate value of clinical Gd agent.Prepared particulate relaxation rate is up to 6.18 mM -1s -1, be 44 times of similar structures of document reported first.The maximum relaxation rate of single particle is 1.4 * 10 5MM -1s -1
Raw material used in the present invention is inorganic salt, and the preparation process can not produce toxic gas.Prepared nano particle pattern is spherical, and the yardstick homogeneous is controlled, is six side's phase NaYF 4This material has good up-conversion fluorescence emission and T 1-MRI weighting performance is expected in the early stage imaging of following tumour multi-mode, have a good application prospect.

Claims (13)

1. NaYF with dual function 4The base fluorescent nano particle is characterized in that said NaYF 4The base fluorescent nano particle comprises that at least kernel and shell are two-layer, and wherein said kernel is NaYF 4: Er/Yb/Gd or NaYF 4: Er/Yb, said shell are NaGdF 4
2. NaYF according to claim 1 4The base fluorescent nano particle is characterized in that said NaYF 4The base fluorescent nano particle also comprises the middle layer, and said middle layer is NaYF 4: Tm/Yb.
3. NaYF according to claim 1 4The base fluorescent nano particle is characterized in that said shell NaGdF 4Mean thickness be 0.2～4 nm.
4. NaYF according to claim 3 4The base fluorescent nano particle is characterized in that said shell NaGdF 4Mean thickness be 0.2～3.7 nm.
5. NaYF according to claim 4 4The base fluorescent nano particle is characterized in that said shell NaGdF 4Mean thickness be 0.2～2.0 nm.
6. NaYF according to claim 1 4The base fluorescent nano particle is characterized in that said NaYF 4The longitudinal relaxation rate of base fluorescent nano particle is 1.18～6.18mM -1S- 1
7. NaYF according to claim 6 4The base fluorescent nano particle is characterized in that said NaYF 4The longitudinal relaxation rate of base fluorescent nano particle is 2.18 ~ 6.18mM -1S- 1
8. NaYF according to claim 7 4The base fluorescent nano particle is characterized in that said NaYF 4The longitudinal relaxation rate of base fluorescent nano particle is 5.46 ~ 6.18mM -1S- 1
9. one kind prepares the described NaYF with dual function of claim 1 4The method of base fluorescent nano particle is characterized in that, comprising:
Muriate, NaOH and the NH of the rare earth ion that said kernel is comprised 4F elevated temperature heat in oleic acid and octadecylene mixed solution is decomposed, and then cleans and be dispersed in the hexanaphthene kernel preparation process as kernel; And
The muriate of the rare earth ion that said shell is comprised, cyclohexane solution, NaOH and the NH of the kernel that will coat 4F elevated temperature heat in oleic acid and octadecylene mixed solution is decomposed, and then cleans and be dispersed in the shell preparation process of hexanaphthene.
10. method according to claim 9 is characterized in that, said kernel preparation process comprises:
The aqueous chloride solution of the rare earth ion that said kernel is comprised adds in oleic acid and the octadecylene mixed solution, removes air and moisture, about 160 ℃, is incubated 60 minutes;
Add and be dispersed with NaOH and NH 4The methanol solution of F then heats up and removes methyl alcohol; And
290～300 ℃ of thermolysiss after 1.5 hours, cooling, carry out ultrasonic cleaning with absolute ethyl alcohol, hexanaphthene, alcohol successively, centrifugal collection, and products therefrom is dispersed in the hexanaphthene.
11. method according to claim 9 is characterized in that, said shell preparation process comprises:
The aqueous chloride solution of the rare earth ion that said shell is comprised adds in oleic acid and the octadecylene mixed solution, removes air and moisture, about 160 ℃, is incubated 60 minutes;
Add the cyclohexane solution of the kernel that will coat, then heat up and remove hexanaphthene;
Add and be dispersed with NaOH and NH 4The methanol solution of F then heats up and removes methyl alcohol; And
, cool off, carry out ultrasonic cleaning with absolute ethyl alcohol, hexanaphthene, alcohol successively after 1.5 hours 290～300 ℃ of thermolysiss, centrifugal collection, products therefrom is dispersed in the hexanaphthene.
12. method according to claim 9 is characterized in that, said NaYF 4The base fluorescent nano particle also comprises the middle layer, and said middle layer is NaYF 4: Tm/Yb, said method also comprises:
The muriate of the rare earth ion that said middle layer is comprised, cyclohexane solution, NaOH and the NH of the kernel that will coat 4F elevated temperature heat in oleic acid and octadecylene mixed solution is decomposed, and then cleans, is dispersed in the middle layer preparation of hexanaphthene.
13. method according to claim 12 is characterized in that, said middle layer preparation process comprises:
The aqueous chloride solution of the rare earth ion that said middle layer is comprised adds in oleic acid and the octadecylene mixed solution, removes air and moisture, about 160 ℃, is incubated 60 minutes;
Add the cyclohexane solution of the kernel that will coat, then heat up and remove hexanaphthene;
Add and be dispersed with NaOH and NH 4The methanol solution of F then heats up and removes methyl alcohol; And
, cool off, carry out ultrasonic cleaning with absolute ethyl alcohol, hexanaphthene, alcohol successively after 1.5 hours 290～300 ℃ of thermolysiss, centrifugal collection, products therefrom is dispersed in the hexanaphthene.
CN2011102816059A 2011-09-21 2011-09-21 NaYF4-based fluorescent nano particles with double effects and preparation method thereof Pending CN102391874A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN2011102816059A CN102391874A (en) 2011-09-21 2011-09-21 NaYF4-based fluorescent nano particles with double effects and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN2011102816059A CN102391874A (en) 2011-09-21 2011-09-21 NaYF4-based fluorescent nano particles with double effects and preparation method thereof

Publications (1)

Publication Number Publication Date
CN102391874A true CN102391874A (en) 2012-03-28

Family

ID=45859260

Family Applications (1)

Application Number Title Priority Date Filing Date
CN2011102816059A Pending CN102391874A (en) 2011-09-21 2011-09-21 NaYF4-based fluorescent nano particles with double effects and preparation method thereof

Country Status (1)

Country Link
CN (1) CN102391874A (en)

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102925157A (en) * 2012-11-27 2013-02-13 哈尔滨工业大学 Preparation method of NaY(98-X)% F4:X%Yb, 2%Er@NaDyF4 in core-shell structure
CN102936500A (en) * 2012-12-10 2013-02-20 哈尔滨工程大学 Core-shell-structure photomagnetic double-function nano composite material and preparation method thereof
CN103007295A (en) * 2012-11-07 2013-04-03 中国科学院上海硅酸盐研究所 Medical imaging material, and preparation method and application thereof
CN103450875A (en) * 2013-08-30 2013-12-18 中国科学院化学研究所 800-nanometer continuous laser excited rare earth upconversion nanoparticles (UCNPs), and preparation method and application thereof
CN103484120A (en) * 2013-09-02 2014-01-01 中国科学院生态环境研究中心 Synthesis method of RE-doped upconversion fluorescence nano material
CN103525397A (en) * 2013-10-10 2014-01-22 哈尔滨工业大学 Preparation method of nanocrystal with core-shell-shell structure
CN103553081A (en) * 2013-10-10 2014-02-05 哈尔滨工业大学 Preparation method for monodisperse Er-Ho codoped core-shell-structured nanometer crystal
CN103623437A (en) * 2013-12-01 2014-03-12 中国科学院上海硅酸盐研究所 Nano probe material for imaging, and preparation method and application thereof
CN103865538A (en) * 2014-02-23 2014-06-18 复旦大学 Up/down conversion dual-mode fluorescent nanomaterial for Nd<3+> sensitization and synthesis method thereof
CN104445373A (en) * 2014-12-05 2015-03-25 合肥工业大学 Preparation method of sub-10-nanometer NaGdF4 nanocrystal
CN104818023A (en) * 2015-03-19 2015-08-05 合肥工业大学 Rare earth luminescent material preparation method containing crystal defect repair technology and product thereof
CN104992842A (en) * 2015-07-24 2015-10-21 哈尔滨汇工科技有限公司 Method of preparing dye-sensitized solar cell photo anode material capable of absorbing near infrared sunlight in multiple bands
CN106075474A (en) * 2016-06-06 2016-11-09 合肥工业大学 Water solublity NaYF4: Yb, Er@NaGdF4core-shell nano crystalline substance and preparation method thereof and the application in nuclear magnetic resonance, NMR
CN107418553A (en) * 2017-04-17 2017-12-01 华南农业大学 A kind of up-conversion luminescent material of core shell structure and preparation method thereof
CN108735902A (en) * 2017-04-20 2018-11-02 丛聪 Flexible all band photoelectric material, photoelectric device and its manufacturing method
CN108728078A (en) * 2018-07-12 2018-11-02 段涛 A kind of NaYF4:The preparation method and applications of Gd/Tm/Er@CdTe
CN108956556A (en) * 2018-05-18 2018-12-07 复旦大学 A kind of luminescence probe and time-resolved fluorescence detection system
TWI668018B (en) * 2018-01-11 2019-08-11 國立陽明大學 Lanthanide-doped fluoride nanocomposites and production method,applications
CN111320199A (en) * 2020-03-24 2020-06-23 福建师范大学 Anti-counterfeiting fluoride nanoparticle composite material and preparation method thereof
CN112451485A (en) * 2020-12-07 2021-03-09 南京大学 Nano micelle activated by short-time near-infrared illumination for rapid drug release
CN112704745A (en) * 2021-01-08 2021-04-27 中国科学院精密测量科学与技术创新研究院 NaErF4@NaGdF4Application of core-shell nanoparticles in preparation of multi-modal contrast agent
CN113567412A (en) * 2021-08-30 2021-10-29 华南师范大学 Near-infrared excited total internal reflection fluorescence correlation spectroscopy dynamics detection device and method
CN113604212A (en) * 2021-08-27 2021-11-05 湖北工业大学 Up-conversion and down-conversion rare earth doped nano material with high fluorescence intensity and preparation method thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HAI-SHENG QIAN ET AL.: "Synthesis of Hexagonal-Phase Core-Shell NaYF4 Nanocrystals with Tunable Upconversion Fluorescence", 《LANGMUIR》 *
KEITH A.ABEL ET AL.: "Hard Proof of the NaYF4NaGdF4 Nanocrystal CoreShell Structure", 《JOURNAL OF AMERICAN CHEMISTRY SOCIETY》 *

Cited By (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103007295A (en) * 2012-11-07 2013-04-03 中国科学院上海硅酸盐研究所 Medical imaging material, and preparation method and application thereof
CN102925157A (en) * 2012-11-27 2013-02-13 哈尔滨工业大学 Preparation method of NaY(98-X)% F4:X%Yb, 2%Er@NaDyF4 in core-shell structure
CN102936500A (en) * 2012-12-10 2013-02-20 哈尔滨工程大学 Core-shell-structure photomagnetic double-function nano composite material and preparation method thereof
CN103450875B (en) * 2013-08-30 2015-03-25 中国科学院化学研究所 800-nanometer continuous laser excited rare earth upconversion nanoparticles (UCNPs), and preparation method and application thereof
CN103450875A (en) * 2013-08-30 2013-12-18 中国科学院化学研究所 800-nanometer continuous laser excited rare earth upconversion nanoparticles (UCNPs), and preparation method and application thereof
CN103484120A (en) * 2013-09-02 2014-01-01 中国科学院生态环境研究中心 Synthesis method of RE-doped upconversion fluorescence nano material
CN103525397A (en) * 2013-10-10 2014-01-22 哈尔滨工业大学 Preparation method of nanocrystal with core-shell-shell structure
CN103553081A (en) * 2013-10-10 2014-02-05 哈尔滨工业大学 Preparation method for monodisperse Er-Ho codoped core-shell-structured nanometer crystal
CN103623437B (en) * 2013-12-01 2015-08-19 中国科学院上海硅酸盐研究所 A kind of imaging nano-probe material and its preparation method and application
CN103623437A (en) * 2013-12-01 2014-03-12 中国科学院上海硅酸盐研究所 Nano probe material for imaging, and preparation method and application thereof
CN103865538A (en) * 2014-02-23 2014-06-18 复旦大学 Up/down conversion dual-mode fluorescent nanomaterial for Nd<3+> sensitization and synthesis method thereof
CN104445373A (en) * 2014-12-05 2015-03-25 合肥工业大学 Preparation method of sub-10-nanometer NaGdF4 nanocrystal
CN104818023A (en) * 2015-03-19 2015-08-05 合肥工业大学 Rare earth luminescent material preparation method containing crystal defect repair technology and product thereof
CN104992842A (en) * 2015-07-24 2015-10-21 哈尔滨汇工科技有限公司 Method of preparing dye-sensitized solar cell photo anode material capable of absorbing near infrared sunlight in multiple bands
CN104992842B (en) * 2015-07-24 2017-05-31 哈尔滨汇工科技有限公司 A kind of multiband absorbs the preparation method of near-infrared sunshine dye-sensitized solar cell anode material
CN106075474B (en) * 2016-06-06 2019-03-08 合肥工业大学 Water-soluble NaYF4:Yb,Er@NaGdF4Core-shell nano crystalline substance and preparation method thereof and the application in nuclear magnetic resonance
CN106075474A (en) * 2016-06-06 2016-11-09 合肥工业大学 Water solublity NaYF4: Yb, Er@NaGdF4core-shell nano crystalline substance and preparation method thereof and the application in nuclear magnetic resonance, NMR
CN107418553A (en) * 2017-04-17 2017-12-01 华南农业大学 A kind of up-conversion luminescent material of core shell structure and preparation method thereof
CN107418553B (en) * 2017-04-17 2019-11-08 华南农业大学 A kind of up-conversion luminescent material of nucleocapsid structure and preparation method thereof
CN108735902A (en) * 2017-04-20 2018-11-02 丛聪 Flexible all band photoelectric material, photoelectric device and its manufacturing method
TWI668018B (en) * 2018-01-11 2019-08-11 國立陽明大學 Lanthanide-doped fluoride nanocomposites and production method,applications
CN108956556A (en) * 2018-05-18 2018-12-07 复旦大学 A kind of luminescence probe and time-resolved fluorescence detection system
CN108728078A (en) * 2018-07-12 2018-11-02 段涛 A kind of NaYF4:The preparation method and applications of Gd/Tm/Er@CdTe
CN108728078B (en) * 2018-07-12 2021-04-16 杭州启幸生物科技有限公司 Preparation method and application of NaYF4 Gd/Tm/Er @ CdTe
CN111320199B (en) * 2020-03-24 2022-08-19 福建师范大学 Anti-counterfeiting fluoride nanoparticle composite material and preparation method thereof
CN111320199A (en) * 2020-03-24 2020-06-23 福建师范大学 Anti-counterfeiting fluoride nanoparticle composite material and preparation method thereof
CN112451485A (en) * 2020-12-07 2021-03-09 南京大学 Nano micelle activated by short-time near-infrared illumination for rapid drug release
CN112451485B (en) * 2020-12-07 2022-03-18 南京大学 Nano micelle activated by short-time near-infrared illumination for rapid drug release
CN112704745A (en) * 2021-01-08 2021-04-27 中国科学院精密测量科学与技术创新研究院 NaErF4@NaGdF4Application of core-shell nanoparticles in preparation of multi-modal contrast agent
CN113604212A (en) * 2021-08-27 2021-11-05 湖北工业大学 Up-conversion and down-conversion rare earth doped nano material with high fluorescence intensity and preparation method thereof
CN113604212B (en) * 2021-08-27 2023-11-07 湖北工业大学 Up-and-down conversion rare earth doped nano material with high fluorescence intensity and preparation method thereof
CN113567412A (en) * 2021-08-30 2021-10-29 华南师范大学 Near-infrared excited total internal reflection fluorescence correlation spectroscopy dynamics detection device and method

Similar Documents

Publication Publication Date Title
CN102391874A (en) NaYF4-based fluorescent nano particles with double effects and preparation method thereof
Yao et al. Upconversion luminescence nanomaterials: A versatile platform for imaging, sensing, and therapy
Cao et al. Wide-range and highly-sensitive optical thermometers based on the temperature-dependent energy transfer from Er to Nd in Er/Yb/Nd codoped NaYF4 upconversion nanocrystals
Zhong et al. A mini-review on rare-earth down-conversion nanoparticles for NIR-II imaging of biological systems
Zhang et al. Upconversion luminescence and discussion of sensitivity improvement for optical temperature sensing application
Tu et al. Europium-activated luminescent nanoprobes: From fundamentals to bioapplications
Resch-Genger et al. Perspectives and challenges of photon-upconversion nanoparticles-Part I: routes to brighter particles and quantitative spectroscopic studies
CN104804741B (en) Single-emission up-conversion nano fluorescent probe and synthetic method thereof
CN102140344B (en) Two-mode nanometer fluorescence labelling material based on rare earth doped sodium gadolinium fluoride core-shell structure and preparation method thereof
Escudero et al. Luminescent rare-earth-based nanoparticles: a summarized overview of their synthesis, functionalization, and applications
Das et al. Rare-earth-doped and codoped Y 2O 3 nanomaterials as potential bioimaging probes
CN102268259B (en) Luminescent centre regionally doped rare earth upconversion luminescent material and preparation method thereof
CN103589432B (en) Rear-earth-doped lithium lutetium fluoride nano material and its preparation and application
Fang et al. Surface-protected high-efficiency nanophosphors via space-limited ship-in-a-bottle synthesis for broadband near-infrared mini-light-emitting diodes
CN105802627B (en) Composite nano materials and its preparation of long afterglow are changed in a kind of near infrared light excitation
CN113817469B (en) Ultra-bright monochromatic up-conversion nano probe for excitation/emission in biological window and preparation method and application thereof
CN106867509A (en) A kind of Nd3+Conversion nano crystalline substance material and preparation method thereof and water detect application on sensitization nucleocapsid
CN105505392B (en) Rare earth oxyfluoride nano material and its preparation method and application
Kuang et al. Fine-tuning Ho-based red-upconversion luminescence by altering NaHoF4 core size and NaYbF4 shell thickness
CN102134253A (en) Photoluminescent nano particle as well as preparation method and application thereof
Jain et al. Rare-earth-doped Y3Al5O12 (YAG) nanophosphors: synthesis, surface functionalization, and applications in thermoluminescence dosimetry and nanomedicine
CN102925155B (en) Near infrared fluorescent probe substrate material of rare earth ion nano alkali metal rare earth fluoride and preparation method of near infrared fluorescent probe substrate material
Prasad et al. Up-conversion luminescence and EPR properties of KGdF4: Yb3+/Tm3+ nanophosphors
Karthickraja et al. Fabrication of Nd3+ and Yb3+ doped NIR emitting nano fluorescent probe: a candidate for bioimaging applications
Wang et al. Multifunctional near-infrared (NIR) phosphors with NIR I and NIR II luminescence for biological detection

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C02 Deemed withdrawal of patent application after publication (patent law 2001)
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20120328