Patent Application
20100167057
The present invention relates to magnetic nanoparticles, and magnetic and fluorescent nanocomposites, particularly those comprising maghemite, and methods of forming these particles.
Magnetic nanoparticles (MP), and nanocomposite of MP and quantum dots (QD), are useful in many different applications, such as bio-labeling, imaging, cell sorting or separation, drug targeting, and the like. MP having particle sizes less than 15 nm can display superparamagnetic characteristics and are useful in applications such as spintronics and magnetic resonance imaging. Nanocomposites of MP and QD (MQD) are both magnetic and fluorescent and are convenient to use when both these functionalities are needed.
One technique for forming MPs is to use iron pentacarbonyl (Fe(CO)3) or iron acetylacetonate, to form nanoparticles of iron oxide (γ-Fe2O3), also known as maghemite. However, the iron pentacarbonyl or iron acetylacetonate precursor is hazardous. Further, this technique uses trimethylamine N-oxide ((Me)3N(O)) as the oxidant, which is relatively expensive. Thus, it is desirable to provide a relatively less expensive and safer process for producing maghemite nanoparticles.
There have also been attempts to produce MQD. However, the reported fluorescence quantum yield of MQD is relatively low, in the range of about 3-18% in a growth solution. The fluorescence quantum yield is the ratio of the number of photons emitted to the number of photons absorbed. MQD with a low quantum yield has limited commercial application. It is desirable to produce MQD with a higher quantum yield.
In accordance with an aspect of the present invention, there is provided a method of forming maghemite, comprising oxidizing iron stearate (Fe(St)2) with methylmorpholine N-oxide (MNO), to form maghemite (γ-Fe2O3). The oxidation may comprise heating a mixture comprising iron stearate, MNO, a surfactant, and a solvent to maintain the mixture at a temperature of about 280 to about 320° C., such as about 300° C., for a sufficient period to form magnetic nanoparticles. The nanoparticles comprise the maghemite. After the heating, the mixture is cooled to limit growth in size of the nanoparticles. The mixture may be heated for a period of about 15 minutes to about 30 minutes, such as about 15 minutes. The mixture may be heated under an argon gas. The surfactant may comprise octadeylamine (ODA). The solvent may be octadecene (ODE). The weight ratio of iron stearate to MNO in the mixture may be about 1:1 to about 2:1, such as about 2.3:1. The weight ratio of iron stearate to the surfactant in the mixture may be about 2.3:1. The mixture may be cooled to a temperature of about 30 to about 40° C. After the cooling, the nanoparticles may be washed with a solution comprising cyclohexane and acetone.
In the method described in the preceding paragraph, the mixture may further comprise cadmium stearate (Cd(St)2). The surfactant may comprise trioctylphosphine oxide (TOPO). The cadmium stearate may be formed by reacting cadmium oxide (CdO) with a stearic acid. The mixture may initially comprise CdO and stearic acid, and the molar ratio of CdO to Fe(St)2 in the mixture may be from about 10:1 to about 2:1, such as from about 10:1 to about 5:1. Subsequent to the cooling, Selenium (Se) may be added to the mixture to react Cd(St)2 with Se to form CdSe quantum dots (QD); the nanoparticles and QD may be dissolved in a first solvent, and re-precipitated in a second solvent to form a nanocomposite comprising both the maghemite and the QD. The heating temperature may be about 300° C., and the cooling may comprise cooling the mixture to a temperature of about 280° C. The first solvent may be chloroform, and the second solvent may be methanol. The Se may be dissolved in trioctylphosphine (TOP) prior to being added to the mixture.
In accordance with a further aspect of the present invention, there is provided a composite comprising a particle comprising maghemite and a CdSe quantum dot and having an average particle size of less than 100 nm. The composite is magnetic and exhibits a fluorescence quantum yield of above 18%, such as about 42%. The average particle size may be less than about 10 nm. The composite may comprise a plurality of magnetic and fluorescent particles. The particles may be formed according to the method described in the preceding paragraph.
In accordance with another aspect of the present invention, there are provided nanoparticles comprising maghemite formed according to the method described in the preceding paragraphs under this section.
Other aspects and features of the present invention will become apparent to those of ordinary skill in the art upon review of the following description of specific embodiments of the invention in conjunction with the accompanying figures.
In the figures, which illustrate, by way of example only, embodiments of the present invention,
In brief overview, it is discovered that maghemite can be conveniently formed by oxidizing iron stearate with methylmorpholine N-oxide. The resulting maghemite may be in the form of nanoparticles and may have a nanocrystal structure.
For forming the desired maghemite nanocrystals, a surfactant, such as octadeylamine (ODA), is also mixed with the reactants. The ODA can provide a ligand source to cap the surface of formed nanocrystals and reduce undesired aggregation and over-growth of the particles.
For the oxidation reaction to proceed at a suitable rate, the reaction temperature may be maintained within a range from about 280 to about 320° C. For forming nanoparticles with a desired size distribution, the reaction temperature may be selected and maintained for a sufficient period of time to allow the particles to form and grow in size. After the selected period of heating, the mixture may be cooled to limit growth in size of the nanoparticles.
In an exemplary process, a mixture including iron stearate (Fe(St)2), methylmorpholine N-oxide (MNO), octadecyl amine (ODA), and a solvent is heated to, and maintained at, a temperature of about 300° C., for about 15 to about 30 minutes. The solvent may be a non-coordinating organic solvent such as octadecene (ODE). After heating, the mixture is cooled to a lower temperature, e.g., in the range of about 30 to about 40° C. The cooled mixture contains magnetic nanoparticles that include maghemite (γ-Fe2O3). The nanoparticles may be extracted from the mixture by washing the mixture and the nanoparticles therein with a solution of cyclohexane and acetone (their volume ratio may be from about 1:3 to about 1:5. In one embodiment, the volume ratio of cyclohexane to acetone may be 3:2. In different embodiments, a different washing solution may be used. For example, chloroform and methanol may be used.
For forming iron oxide particles, the weight ratio of iron stearate to MNO in the reaction mixture may be about 1:1 to about 2:1, such as about 2.3:1, and the weight ratio of iron stearate to ODA in the reaction mixture may be about 2.3:1. With a higher concentration of ODA in the reaction mixture, the quality of the nanocrystals formed may be improved.
In different embodiments, another long chain amine may be used as the surfactant instead of ODA. For example, hexadeylamine (HDA) may be used as the surfactant.
As can be appreciated, the reagents used in this process, including MNO, are non-toxic and are relatively inexpensive.
Conveniently, the above process can be integrated with a process for forming quantum dots to produce magnetic quantum dots (MQDs) in an integrated process. In an exemplary embodiment of the present invention, the integrated process may be performed as follows.
Suitable amounts of Cadmium stearate (Cd(St)2) and trioctylphosphine oxide (TOPO) may be additionally added to the initial mixture discussed above before the mixture is heated to the selected temperature, such as about 300° C. The Cd(St)2 added to the mixture may be formed by reacting cadmium oxide (CdO) with a stearic (octadecanoic) acid, and may be formed in situ within the mixture by adding CdO to the initial mixture and heating the mixture to about 150° C. In one embodiment, the initial molar ratio of CdO to Fe(St)2 in the mixture may vary from about 10:1 to about 5:1. In another embodiment, the molar ratio of CdO to Fe(St)2 in the mixture may vary from about 5:1 to about 2:1.
For the synthesis of bifunctional Fe2O3—CdSe MQDs, excess surfactants (such as ODA and TOPO) are added. As both ODA and TOPO can serve as a surfactant, in some applications, only one surfactant such as TOPO may be sufficient and ODA may be omitted.
After the mixture has been heated to the selected temperature such as about 300° C. and then cooled back to about 280° C., selenium (Se) is added to the cooled mixture to react with the Cd(St)2 to form CdSe quantum dots. Se may be dissolved in trioctylphosphine (TOP) before being added to the mixture. The cooled mixture contains nanoparticles and quantum dots, which are dissolved in a first solvent such as chloroform and are then re-precipitated in a second solvent such as methanol.
In different embodiments, chloroform may be replaced by another solvent such as toluene, cyclohexane, or the like; and methanol may be replaced by another solvent such as acetone, ethanol or the like.
The dissolution and re-precipitation cycle may be repeated a number of times, such as two to three times. The final precipitation contains nanocomposite of maghemite and CdSe QD.
The composite may contain particles formed of maghemite and CdSe quantum dots. The average particle size may be less than 100 nm (thus referred to as nanoparticles). Depending on the exact steps taken and the reagents used, the average particle size may be less than about 10 nm. The particle sizes may be controlled by adjusting the reaction temperature and reaction (growth) time. Techniques for controlling the sizes of the particles and the quantum dots can be readily understood and developed by those skilled in the art. For example, the reactions may be carried out in a Schlenk™ line which has three or five manifolds to control Ar purging and create vacuum inside the reaction flask. For further details of exemplary size control techniques, see, e.g., C. B. Murray, D. J. Norris, M. G. Bawendi, J. Am. Chem. Soc., 1993, 115, 8706-8715; M. A. Hines, P. Guyot-Sionnest, J. Phys. Chem., 1996, 100, 468-471; B. O. Dabbousi, J. Rodriguez-Viejo, F. V. Mikulec, J. R. Heine, H. Mattoussi, R. Ober, K. F. Jensen, M. G. Bawendi, J. Phys. Chem. B, 1997, 101, 9463-9475; D. V. Talapin, A. L. Rogach, A. Komowski, M. Haase, H. Weller, Nano Lett., 2001, 1, 207-211; X. Peng, Chem. Eur. J., 2002, 8, 334-339; C. B. Murray, C. R. Kagan, M. G. Bawendi, Ann. Rev. Mater. Sci., 2000, 30, 545-610, the entire contents of each of which are incorporated herein by reference.
The composite is both magnetic and exhibits a fluorescence quantum yield of above 18%, such as up to about 42%.
Conveniently, in the processes described above it is not necessary to use iron pentacarbonyl (Fe(CO)5) or iron acetylacetonate as the precursor, which can be hazardous. Further, bi-functional magnetic quantum dots (MQDs) containing fluorescent quantum dots (QDs) and γ-Fe2O3 magnetic nanoparticles (MPs) can be conveniently synthesized in a single reaction container. The MNO conveniently serves as an oxidizing agent in both the formation of the MPs and the QDs. It is not necessary to use the more expensive oxidant trimethylamine N-oxide (Me)3N(O)). The exemplary embodiment described herein can also be conveniently adapted to produce the nanocrystals in large quantities.
The above process can be modified to form MQDs that contain other QDs than CdSe. For example, the process may be adapted to produce nanoparticles that contain other semiconducting nanoparticles or QDs, such as CdTe, CdS, or the like, and the MPs. The process may also be modified to make the MQDs water soluble using a suitable technology, such as that described in S. T. Selvan, P. K. Patra, C. Y. Ang, J. Y. Ying, Angew. Chem. Int. Ed. 2007, vol. 46, pp. 2448-2452, the entire content of which is incorporated herein by reference.
Advantageously, the quantum yield in the exemplary processes described herein can be as high as about 42% and various desirable magnetic properties may be obtained.
Nanocomposites of MPs and QDs have applications in various applications such as biolabeling/imaging, cell sorting/separation, and drug targeting. MPs with sizes of less than about 15 nm can display superparamagnetic characteristics, which may be useful for applications such as spintronics and magnetic resonance imaging (MRI).
Sample γ-Fe2O3.MPs were synthesized according to the synthesis route schematically shown in
Fe(St)2 (3.73 g), ODA (1.61 g), MNO (1.61 g) and ODE (90 mL) were mixed in a 250 mL container. The container was pumped to near vacuum and purged with argon for 15 to 30 minutes. The mixture in the container was next heated under argon to 300° C., and kept at this temperature for about 15 minutes. After the heating was terminated, the resulting mixture solution, which was of a brownish black color, was cooled to 30 to 40° C. Particles in the mixture were washed/purified with a mixture of cyclohexane/acetone (with a volume ratio of 1:5) in three centrifugation-redispersion cycles. The wet precipitate extracted from the mixture solution was stored in a glove box under vacuum. The total weight of the dried magnetic particles was 2.03 g.
The formed samples were examined using the X-ray diffraction (XRD) technique. Representative XRD measurement results are shown in
The samples were also examined by transmission electron microscope (TEM), which showed that the MPs were monodispersed with an average particle diameter of about 6 nm. Representative TEM images of the samples at different magnification factors are shown in
Sample Fe2O3CdSe MQDs were synthesized according to synthesis route schematically shown in
Cadmium stearate (Cd(St)2) was prepared according to the procedure described in L. Qu and X. Peng, “Control of Photoluminescence Properties of CdSe Nanocrytals in Growth,” J. Am. Chem. Soc., 2002, vol. 124, pp. 2049-2055, and Z. A. Peng and X. Peng, “Formation of High-Quality CdTe, CdSe, and CdS Nanocrystals Using CdO as Precursor,” J. Am. Chem. Soc., 2001, vol. 123, pp. 183-184, the entire contents of each of which are incorporated herein by reference.
Sample magnetic fluorescent nanocomposites were synthesized with iron stearate (Fe(St)2), ODA and trioctylphosphine oxide (TOPO) using octadecene (ODE) as solvent and methylmorpholine N-oxide (MNO) as oxidant.
CdO (0.05 g) and stearic acid (0.46 g) were mixed in a container. The container was pumped to near vacuum for about 20 minutes. The mixture in the container was next heated under argon to 200° C. to form cadmium stearate, in accordance with procedure described above. The mixture was cooled down to about room temperature. Fe(St)2 (0.05 g), ODA (8.71 g), TOPO (8 g) and MNO (0.012 g) were added into the container to form a further mixture. The new mixture was heated to 300° C., and kept at that temperature for about 15 minutes. The mixture was cooled to 280° C., and Se (0.32 g) dissolved in TOP (9.6 mL) was injected quickly into the container. Quantum dots and particles were allowed to grow in the mixture (a hot growth solution). For different samples, the growth period varied from 1 to 30 minutes. Aliquots were taken from the samples after the desired growth period. The hot growth solution was quenched in chloroform, followed by mixing with methanol (to form precipitation) and/or magnetic harvesting. The cycle of precipitation by mixing with methanol and redispersion in chloroform was repeated twice. The resulting precipitate was dried in a glove box.
The magnetic and optical properties of the sample nanocomposites were adjusted by varying the molar ratio of CdO to Fe(St)2 from about 5:1 to about 2:1. Representative TEM images of the samples obtained with different molar ratios are shown in
Addition of methanol destabilized the suspension, and both QDs and MPs were attracted to a magnet placed close to the suspension. When methanol was added, both the MPs and QDs were believed to be aggregated and separated by the magnet due to either heterodimer or network structure, or hydrophobic bilayer formation utilizing the interaction between ODA and TOPO. The aggregated particles that were both fluorescent and magnetic were re-dispersed in chloroform. The emission peaks of the solution became broader with growth time increased from 1-12 min to 25-30 min during the synthesis process, indicating particle aggregation induced by bilayer formation.
Magnetic properties of the sample particles were measured using a MPMS™ R2 magnetometer (by Quantum Design Co.™), which is a superconducting quantum interference device (SQUID). Representative measurement results of the field-dependent magnetization are shown in
Representative zero-field-cooled (ZFC) and field-cooled (FC) magnetization curves measured at 200 Oe are shown in
The measurement results indicated that the samples exhibited behavior characteristic of superparamagnetism with distinct blocking temperatures TB of 24 K and 38 K for Fe2O3 MPs and Fe2O3—CdSe MQDs, respectively.
The variations in the observed magnetic parameters were consistent with an increase in the effective magnetic anisotropy density (Keff) of the Fe2O3 nanoparticles when CdSe QDs were anchored onto their surface to form hybrids (as indicated by
Some of the measured absorption spectra of the sample MQDs formed with a CdO/Fe(St)2 molar ratio of about 5:1 after the respective growth period are shown in
The d-spacing values of the sample MPs and MQDs were measured. The measured results are listed in Table I, in comparison with values for maghemite and magnetite, which are obtained from JCPDS (Joint Committee on Powder Diffraction Standards).
Table I compares d-spacing values of as-synthesized iron oxide nanocrystals with those of the maghemite (γ-Fe2O3) and magnetite (Fe3O4) references from JCPDS.
As can be appreciated from the Table I, the d-spacing values of the sample iron oxide nanocrystals are close to the values of the γ-Fe2O3 reference material.
Other features, benefits and advantages of the embodiments described herein not expressly mentioned above can be understood from this description and the drawings by those skilled in the art.
Of course, the above described embodiments are intended to be illustrative only and in no way limiting. The described embodiments are susceptible to many modifications of form, arrangement of parts, details and order of operation. The invention, rather, is intended to encompass all such modification within its scope, as defined by the claims.
This application claims the benefit of U.S. provisional application No. 60/929,438, filed Jun. 27, 2007, the contents of which are incorporated herein by reference.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/SG2008/000229 | 6/27/2008 | WO | 00 | 12/23/2009 |
| Number | Date | Country | |
|---|---|---|---|
| 60929438 | Jun 2007 | US |
