WO2009115176A2

WO2009115176A2 - Magnetic nanoparticles and method for the production thereof

Info

Publication number: WO2009115176A2
Application number: PCT/EP2009/001356
Authority: WO
Inventors: Achim Schwaemmle; Vera Goelden; Romain Dabre
Original assignee: Merck Patent Gmbh
Priority date: 2008-03-20
Filing date: 2009-02-26
Publication date: 2009-09-24
Also published as: EP2254838A2; DE102008015365A1; WO2009115176A3

Abstract

The present invention relates to magnetic nanoparticles, particularly magnetite particles having a diameter between 10 and 50 nm, and to a method for the production thereof.

Description

Magnetic nanoparticles and process for their preparation

The present invention relates to magnetic nanoparticles, in particular magnetite particles with a diameter between 10 and 50 nm and a method for their preparation.

Magnetic nanoparticles are used in a variety of different fields of application. For example, they play an important role in electronics in the field of information storage and sensor technology. For security applications, such as tamper-proof coding of products, documents, securities, etc., magnetic nanoparticles can be used as so-called security markers. In the form of so-called ferrofluids - stable liquid dispersions whose flow properties can be influenced by external magnetic fields - magnetic nanoparticles are used, among other things, in the construction of vibration dampers and tweeters. In molecular biology, biochemistry and diagnostics, magnetic micro- and nanoparticles have long been used as selective sorbents for the separation, enrichment or purification of biological molecules such as nucleic acids or proteins. A huge potential is predicted for magnetic materials in medicine. Magnetic nanoparticles are already being used as contrast agents in magnetic resonance imaging (MRI). Other potential uses include magnetic drug targeting, and hyperthermia treatment of diseased tissue, such as _x

Tumors.

For the applications described composite particles are usually used, which consist of a magnetic component (ferromagnetic or ferrimagnetic nanoparticles) and a functional component, such as a layer of silica or other metal oxide such as alumina, titania, or zirconia, a polymer such as Polystyrene, polymethacrylate, polyvinyl alcohol or polysiloxane, or a natural component such as dextran or chitosan. For chemical attachment of drug molecules, antibodies, oligonucleotides, etc., this coating can be modified with reactive groups, charge carriers or similar functionalities.

Iron oxides such as maghemite (γ-Fe ₂ Oa) or magnetite (Fe ₃ Ü 4) are preferred for most of the fields of use described above. Especially for applications in biotechnology and medicine, because of their non-toxic properties, iron oxides are preferred over other ferromagnetic or ferrimagnetic materials such as barium, zinc or cobalt ferrite, elemental cobalt, etc. In addition, maghemite and magnetite in nanoparticulate form are particularly easy due to a

Produce precipitation reaction. So in almost all relevant

Publications and patents Magnetite produced by precipitation from a strongly alkaline solution of Fe (II) and Fe (III) salts in a stoichiometric ratio of 1: 2. The method has been described by Massart (Massart, IEEE Trans. Magn. 1981, MAG-17, 1247) and is by far the most widely used method for the preparation of

Magnetite. The reaction conditions (temperature,

Concentrations, reaction time, type of liquor, etc.) can be varied widely, although little change is made in terms of yield, product purity and particle size. The particles produced in this way always have a very small size

Diameter (7-10 nm). Subsequent oxidation of the magnetite produces maghemite, which has similar magnetic properties.

The very small particle size of <10 nm results in the iron oxide being superparamagnetic, ie it shows its ferrimagnetic properties only in the presence of an external magnetic field and has no magnetic remanence. This is a general phenomenon of all ferri- and ferromagnetic materials at sufficiently low levels Particle sizes. It therefore results that the particle size is of the same order of magnitude as the Weiss domains, which can be regarded as the smallest elementary magnetic domains. In the case of magnetite, this order of magnitude is 20-30 nm. Thus, magnetite nanoparticles with a much larger diameter are no longer superparamagnetic. Superparamagnetism is a desirable or even indispensable feature in the majority of the applications described above, with the exception of information storage, since nanoparticles with remanent magnetism act as small permanent magnets and due to the magnetic field of the magnetic field

Attracting forces would aggregate. In particular, in vivo applications such as MRI, drug targeting or hyperthermia, such behavior could even have life-threatening effects.

Despite the simplicity of its preparation and superparamagnetism, the magnetite obtained via the Massart process and its variants has some disadvantages. Usually, other, non-magnetic iron oxides are formed as a by-product, such as α -Fβ ₂ θ ₃ (hematite) or FeOOH (goethite). These are difficult to separate and often cause the supernatant of a magnetically sedimented particle suspension is colored brownish-yellow. Furthermore, due to the high specific surface area, such small magnetite particles are considerably more sensitive to atmospheric oxygen and therefore, in a non-inert environment, are more prone to oxidation than larger particles. The main drawback, however, is the poor macroscopic magnetizability resulting from the small particle size, which manifests itself in the fact that the sedimentation of the particles in a magnetic field takes a very long time. On the one hand, this poor separability can be attributed to the low saturation magnetization resulting from the small extent of the elementary magnetic domains. Second, the sedimentation process is superimposed by Brownian motion, which becomes more apparent as the particle size decreases - A -

appears in appearance. As a remedy, stronger homogeneous magnetic fields could be used or special high field gradient separators, which were designed, for example, for use in wastewater treatment. For medical applications, however, such concepts are not or only partially usable.

The effect of poor magnetizability is e.g. long process times for .separations, low heat output in hyperthermia applications and poor dose availability with drug Q targeting.

It would therefore be advantageous for many applications to use particles that are larger and therefore better magnetizable. However, this is not feasible with the described precipitation method. Although particles with an average size of 20 nm could be produced by a specific variant of the Massart method (Goetze et al., J. Magn. Magn. Mater. 252, 359, 2002), this method is not particularly advantageous because the size distribution of the particles produced varies greatly (polydispersity). o As an alternative to the Massart method, only the oxidation method described for the first time by Sugimoto and Matijevic has prevailed so far (Sugimoto et al., J. Colloid Interface, pages 74, 227, 1979). Here, no stoichiometric mixture of Fe (II) and Fe (III) is used, but only a Fe (II) salt solution. Dark alkaline Fe (OH) _{2 is} initially precipitated from an Fe (II) salt solution in alkaline medium (so-called "green rust"), which is then oxidized by the addition of an oxidizing agent in the heat to very pure crystalline magnetite If nitrate is generally used, however, it is also possible in principle to use other oxidizing agents such as atmospheric oxygen 0. The particles which are obtained by this method can vary within certain limits by suitable choice of the reaction conditions. 200 nm However, much larger than the previously described and therefore not superparamagnetic. Being extremely magnetizable, they are ideal for adsorption and bioseparation tasks where 100% superparamagnetism is not required.

Numerous other synthetic approaches have been described in the literature. For example, it is possible to synthesize magnetic iron oxide nanoparticles by laser-induced pyrolysis of iron pentacarbonyl vapors into ethylene (Veintemillas-Verdaguer et al., Mater. Lett. 35, 227, 1998). Other authors describe the partial reduction of Fβ2θ ₃ nanoparticles with hydrogen. However, these methods have not yet become widely accepted because they are much more complicated to implement.

So far, there is no method that makes it possible to monodisperse iron oxide nanoparticles in a variable order of magnitude between 10 and 50 nm. In particular, the size range 20-40 nm is not accessible with the previous methods Massart and Matijevic. However, it is precisely this order of magnitude in which the transition from remanence to superparamagnetism should take place that is extremely interesting. It is expected that the magnetizability and thus the heating power in the alternating magnetic field which is so important for hyperthermia application can be substantially increased by using larger particles, without having to resort to non-superparamagnetic particles.

The object of the present invention was therefore to provide a method with which nanoparticles can be prepared in a variable order of magnitude range between approximately 10 and 50 nm simply and as monodisperse as possible. It has been found that nanoparticles in a variable size range between about 10 and 50 nm can be prepared when a mixture of at least one Fe (II) salt and at least one Fe (III) salt is oxidized under alkaline conditions. According to the experience of the known processes, in which either a mixture of Fe (II) and Fe (III) salts is used (Massart method) or an oxidizing agent is used (method according to Matijevic et al.) Was to be expected that a combination would lead to completely uncontrollable reaction conditions. Surprisingly, however, it turned out that this combination provides an efficient and very easily controllable process for the production of nanoparticles.

The present invention therefore provides a process for producing nanoparticles, characterized by at least the following process steps: a) Preparation of a basic mixture comprising at least one Me (II) salt, a Me (III) salt and an oxidizing agent, wherein the molar ratio Me (II) to Me (III) in the mixture is between 100: 1 and 1: 1, 5, Me (II) is selected from the group Fe (II), Co (II), Cr (II) and / or Mn (II) and Me (III) is selected from the group Fe (III), Co (III), Cr (III) and / or Mn (III); b) optionally washing and / or isolating the resulting precipitate of nanoparticles

In a preferred embodiment, the mixture is tempered in a process step a2) after its preparation for at least one minute, typically at a temperature between 0 and 100 ⁰ C.

In a preferred embodiment, the mixture prepared in process step a) contains at least one Fe (II) salt and at least one Fe (III) salt. In a particularly preferred embodiment, the mixture prepared in process step a) contains Fe (II) sulfate and Fe (III) nitrate.

In a preferred embodiment, the mixture is generated in step a) by mixing a solution at least containing a Me (II) salt and a Me (III) salt with a basic solution containing at least one oxidizing agent.

In a preferred embodiment, the oxidizing agent used in step a) is a nitrate salt, such as potassium nitrate, sodium nitrate or ammonium nitrate.

In a preferred embodiment, in step a2) between 10 minutes and 4 hours at a temperature between 60 and 90 ⁰ tempered C.

In one embodiment of the method according to the invention, the surface of the nanoparticles obtained is completely or partially coated or derivatized in an additional process step.

The present invention also provides nanoparticles producible by the process according to the invention.

In a preferred embodiment, the nanoparticles have a diameter between 10 and 50 nm.

The present invention also provides for the use of the nanoparticles according to the invention in electronics, for example in the field of information storage and sensor technology, as security markers, as ferrofluids, for example in the construction of vibration dampers and tweeters, in molecular biology, biochemistry or diagnostics For example, as sorbents for the separation, enrichment or purification of biological molecules such as nucleic acids or proteins and in medicine, for example in magnetic resonance imaging (MRI) for magnetic drug targeting and hyperthermia treatment of diseased tissue.

The above-described embodiments of the present invention may be combined with each other to form embodiments having the features of two or more of the aforementioned embodiments.

Nanoparticles for the purposes of the present invention are particles which have a diameter of less than 80 nm, preferably a diameter of between 10 and 50 nm.

The nanoparticles prepared according to the invention are typically polyhedral, e.g. octahedral. The diameter of a nanoparticle is inventively determined so that a ball is placed around a particle on the surface as many corners of the particle are. The diameter of this hypothetical sphere then corresponds to the diameter of the particle.

In the method according to the invention for producing the nanoparticles, a basic mixture is produced which contains at least one Me (II) salt and one Me (III) salt and at least one oxidizing agent. A Me (II) salt according to the invention is a salt which contains at least one metal ion in the

Contains oxidation state (II). A Me (III) salt according to the invention is a salt which contains at least one metal ion in the oxidation state (III).

As Me (II) salt it is possible to use, for example, Fe (II), Co (II) Cr (II) or Mn (II) salts or mixtures thereof.

As Me (III) salt it is possible to use, for example, Fe (III), Co (III), Cr (III) or Mn (III) salts or mixtures thereof. Preferably, Me (II) salt and Me (III) salt have the same metal component. Particular preference is given to using one or more Fe (II) salts and one or more Fe (III) salts.

Preferred Fe (II) salts are Fe (II) sulfate, Fe (II) halides, especially Fe (II) chloride, Fe (II perchlorate, Fe (II) nitrate, Fe (II) carbonate, Fe (II) phosphate, Fe (II) arsenate, Fe (II) oxide, Fe (II) hydroxide, Fe (II) thiocyanate, Fe (II) acetylacetonate, and the Fe (II) salts of organic acids, in particular Fe (II) formate, Fe (II) II) acetate, Fe (II) citrate, Fe (II) oxalate,

Fe (II) fumarate, Fe (II) tartrate, Fe (II) gluconate, Fe (II) succinate, Fe (II) lactate ,. Particularly preferred is Fe (II) sulfate. The salts may contain other cations besides Fe, e.g. Ammonium, sodium or potassium.

Preferred Fe (III) salts are Fe (III) nitrate, Fe (III) sulfate, Fe (III) halides, especially Fe (III) chloride, Fe (III) perchlorate, Fe (III) phosphate, Fe (III) arsenate , Fe (III) oxide, Fe (III) hydroxide, Fe (III) thiocyanate, Fe (III) acetylacetonate, and the Fe (III) salts of organic acids, in particular Fe (III) formate, Fe (III) acetate, Fe (III) III) citrate, Fe (III) oxalate, Fe (II) fumarate, Fe (II) tartrate, Fe (II) gluconate, Fe (II) succinate, Fe (II) lactate.

Particularly preferred is Fe (III) nitrate. The salts may contain other cations besides Fe, e.g. Ammonium, sodium or potassium.

The Me (II) and Me (III) salts are typically used in the mixture in a concentration between 0.1 mmol / l and 5 mol / l. At higher concentrations, it may be due to the precipitating nanoparticles for

Clogging of the equipment come because of the high proportion of

Nanoparticles, the mixture is no longer sufficiently flowable.

Preferred concentration ranges are for Me (II) salts between 0.05 mol / l and 0.2 mol / l, for Me (III) salts between 0, 5 mmol and 0.1 mol / l, wherein in each case the molar ratio from Me (II) to Me (III) in the mixture must be between 100: 1 and 1: 1, 5. To prepare the mixture, the Me (II) salts and the Me (III) salts may be introduced together or separately. The Me-Saiz solutions should not be basic before preparation of the mixture, otherwise Me-hydroxides may form and precipitate. The pH is preferably

Value of Me salt solutions before mixing between 0 and 7.

As the oxidizing agent, it is possible to use all oxidizing agents which can be suitably metered stoichiometrically. Since this is often problematic in atmospheric oxygen, this is preferably not used as an oxidizing agent but largely eliminated, for example, by degassing the solutions used with nitrogen or noble gases. Suitable oxidizing agents are, for example, hydrogen peroxide, inorganic peroxo compounds such as peroxides, hydroperoxides, peroxodisulfates, peroxomonosulfates, peroxoborates, peroxochromates,

Peroxophosphates, peroxocarbonates, organic peroxo compounds such as acetone peroxide or peroxycarboxylic acids, chloramine T, chlorates, bromates, iodates, perchlorates, perbromates, periodates, permanganates, chromates, dichromates, hypochlorites, chlorine oxides or nitrates. Particularly preferred oxidizing agents according to the invention are nitrates, such as potassium nitrate, sodium nitrate or ammonium nitrate.

The amount of oxidizing agent typically depends on the amount of metal salt to be oxidized. If the Me (III) salt content is very low, then the oxidizing agent is preferably used in an approximately equimolar amount to the Me (II) salt. If a high proportion of Me (III) salt is present, the proportion of oxidizing agent is correspondingly reduced. When using mild oxidants such as nitrate, the oxidizing agent can also be used in excess, without further oxidation of the precipitated product takes place. The oxidizing agent may be added individually to prepare the mixture, or may be preliminarily mixed with the Me salts or the base.

The mixture prepared in the process of the invention must be basic, i. have a pH> 7, so that the formed

Nanoparticles are precipitated. The pH of the mixture is preferably between pH 9 and 13, more preferably between pH 11 and 12. To this end, at least one base is added to the mixture, which makes the pH of the mixture rapidly correspondingly alkaline. Suitable are all strong bases, e.g. Alkali or alkaline earth hydroxides, amines or ammonia. Preference is given to using sodium hydroxide as the base.

The basic mixture containing at least one Me (II) salt, a Me (III) salt and an oxidizing agent, wherein the molar ratio of Me (II) to Me (III) in the mixture is between 100: 1 and 1: 1, 5, Me (II) is selected from the group consisting of Fe (II), Co (II), Cr (II) and / or Mn (II) and Me (III) is selected from the group Fe (III), Co (II) III), Cr (III) and / or Mn (III) can be prepared in any way, in particular so as to ensure that the Me salts have not been previously in contact with a base or basic solution. Typically, however, in order to achieve a particularly rapid mixing of all components, all components are previously dissolved. For this purpose, preferably a solution containing at least one Me (II) salt and a Me (III) salt (Me salt solution) is prepared and a basic solution. The oxidizing agent may be added to the Me salt solution or, preferably, the basic solution.

The solvent is typically water or mixtures of water with water-soluble organic solvents. Preferably, water is used as the solvent. Furthermore, the solutions may contain additives, such as surface-active substances. In order to additionally influence the properties of the nanoparticles, it is also possible to add to the mixture other constituents, such as, for example, other metal salts, metals, pigments or organic compounds.

The mixture of the individual components (Me salts, oxidizing agents,

Base) is then carried out by mixing the solutions in which the components are contained. This can be done in a batch process in a stirred tank or a corresponding apparatus. Preferably, the mixture is carried out in a continuous process. For this purpose, typically two streams of liquid are generated, which are introduced into each other and mixed. This can e.g. using a static mixer or preferably a simple T or Y piece. The flow rates for continuous mixing are typically between 50 and 150 mL / min, but can be arbitrarily increased or decreased depending on the size of the system.

The preparation of the mixture is typically carried out at temperatures between 0 and 100 ⁰ C, preferably between 10 and 60 ⁰ C, particularly preferably at room temperature.

By preparing the basic mixture containing at least one Me (II) salt, a Me (III) salt and an oxidizing agent, wherein the molar ratio of Me (II) to Me (III) in the mixture is between 100: 1 and 1 : 1, 5, Me (II) is selected from the group Fe (II), Co (II), Cr (II) and / or Mn (II) and Me (III) is selected from the group Fe (III) , Co (III), Cr (III) and / or Mn (III), forms a precipitate of the nanoparticles. After the preparation of the mixture, it is preferably tempered to complete the precipitation of the nanoparticles and their growth in size.

The tempering can be carried out in a batch process in a stirred tank or a corresponding other temperature-controlled apparatus. In a continuous process, the mixture is for example in a Tempering vessel (eg a temperature-controlled stirred tank) or preferably converted into a residence loop. Length and diameter as well as the flow rate can be used to precisely define the dwell time and is the same for the entire mixture.

The tempering is typically carried out at temperatures between 0 and 100 ⁰ C, preferably between 20 and 100 ⁰ C _{1, more} preferably between 60 and 90 ⁰ C.

Depending on the temperature (lower temperatures require a longer tempering time), the tempering time is typically between one minute and one day, preferably between 10 minutes and 4 hours, particularly preferably between 20 minutes and one hour.

After tempering, the resulting nanoparticles can optionally be washed, filtered, centrifuged, or otherwise purified or isolated. Typically, it is washed several times with deionized water.

In the same way, the nanoparticles can be subjected to further derivatization reactions directly or after washing or isolation. For example, the particles are wholly or partly coated with a layer of silicon dioxide (WO 98/31461) or another inorganic oxide (EP 0343934), a polymer such as polystyrene (US 4421660), polymethacrylate (Horäk et al., Biotechnol , 447, 2001), polyvinyl alcohol (WO 97/04862) or polysiloxane (US 4985166) or a natural component such as dextran (US 4452773) or chitosan (US 5864025). For chemical attachment of drug molecules, antibodies, oligonucleotides, etc., this coating with reactive groups, charge carriers or the like

Functionalities have been modified (Liu et al., Colloids & Surfaces A 238, 127, 2004). The application of graft polymers, for example according to EP 0 337 144, WO 98/01480 or WO 2000/011043 is possible.

Also, a direct derivatization of nanoparticles with functional

Molecules, e.g. Silanes bearing reactive groups, charge carriers or similar functionalities are possible (Kobayashi et al., J. Colloid

Interface Be. 141, 505, 1991). Also, the aggregation tendency of the nanoparticles may be e.g. are reduced by the adsorption of surface-active molecules (Badescu et al., J. Magn., Magn., Mater., 202, 197, 1999).

10

Magnetite particles are preferably produced by the method according to the invention. Depending on their size, these have superparamagnetic properties. Subsequent oxidation of the magnetite nanoparticles produces maghemite particles that have similar magnetic properties. (Cornell, Schwertman, The Iron Oxides, Wiley-VCH, 2003, p. 402)

The nanoparticles obtained by the process according to the invention typically have a diameter of <80 nm; Preferably, they have a diameter between 10 and 50 nm. Since the nanoparticles are obtained very monodisperse by the preparation according to the invention, usually no further classification of the particles is necessary.

By choosing the molar ratio between Me (II) and Me (III) salts,

The size of the nanoparticles obtained in a very narrow range Zo _{O (_} can be set. The larger the percentage of Me (III) is selected to the total metal content, are the smaller the nanoparticles obtained.

The present invention also provides the use of the nanoparticles according to the invention in electronics, for example in the field of information storage and sensor technology, as security markers, as ferrofluids, for example, in the construction of vibration dampers and tweeters, in molecular biology, biochemistry or diagnostics, for example as sorbents for the separation, enrichment or purification of biological molecules such as nucleic acids or proteins and in medicine, for example in magnetic resonance imaging (MRI) for magnetic drug targeting and for hyperthermia treatment of diseased tissue.

Even without further explanation, it is assumed that a specialist can use the above description to the greatest extent. The preferred embodiments and examples are therefore to be considered as merely illustrative, in no way limiting as in any way limiting disclosure. 5 The complete disclosure of all applications, patents and publications mentioned above and below, in particular of the corresponding applications DE 102008015365.6 filed on 20.03.2008, is incorporated by reference into this application. 0

Examples

Example 1: Comparative Example: Continuous Production of Magnetite-5 Nanoparticles with an Average Particle Size of about 80 nm Analogously to Suqimoto et al. J. Colloid Interface Sei. 74, 227. 1979

In each case 2.5 liters of glass bottles are charged with 1.5 L of deionised water. The dissolved oxygen in the air is largely expelled by introducing nitrogen _Q. Subsequently, in the one

Initial vessel 38.2 g of iron (II) sulfate heptahydrate (497 mmol) of water were dissolved, in the second 45.9 g of potassium nitrate (454 mmol) and 56 g Sodium hydroxide (1.4 mol). The two solutions are pumped with the help of two Büchi piston pump with a flow rate of 100 mL / min in a T-piece, which serves as a static mixer. The exiting mixture is passed into a 200 m long residence section (Teflon tube with an inner diameter of 4 mm), which in a

Thermostat is heated to 75 ⁰ C. The residence time in the thermostat is therefore about 12 minutes. The mixture is collected in a 5 L glass bottle and allowed to cool there. For working up the black precipitate is sedimented by means of a permanent magnet (Bakker, 200 mT) and the clear

Poured off supernatant. The precipitate is stirred up with 3 L of demineralized water and the sedimentation repeated several times in the manner described until the electrical conductivity of the supernatant has dropped to a value of <200 μS. Subsequently, the product is characterized as follows: 1. Drying of a sample of about 0.5 g in a vacuum oven at 100 ⁰ C and determining the specific surface A _{sp of} the magnetite by the method of Brunauer, Emmett and Teller (BET). Based on the specific surface area and specific gravity of magnetite p = 5 g / mL, the average particle diameter D can be approximated: D = 6 / (pA _sp )

2. Making a scanning electron micrograph for visual characterization.

3. Carrying out a magnetization measurement by means of a SQUID magnetometer.

Results: specific. Surface: 15 m ² / g calculated average particle size: 79 nm magnetic remanence: 25 emu / g Since only iron (II) salt was used for the precipitation (0% Fe (III), the product corresponds to the magnetite produced by the Matijevic method.

Example 2 Continuous Production of Maqnetite Nanoparticles with an Average Particle Size of about 46 nm

The experimental setup described in Example 1 is maintained. However, in addition to 128.4 g of iron (II) sulfate heptahydrate (462 mmol), 9.9 g of iron (III) nitrate nonahydrate (24 mmol) are weighed into the one receiver vessel. Instead of 45.9 g, only 35 g of potassium nitrate (346 mmol) are weighed into the second receiving vessel. The total amount of iron ions (Fe (II) + Fe (III)) remains the same overall. The amount of nitrate is slightly reduced because a little less iron needs to be oxidized. The percentage of Fe (III) in relation to the total iron content is 5%. The experiment is carried out as described in Example 1.

Results: specific. Surface area: 26 m ² / g Calculated mean particle size: 46 nm Magnetic remanence: 25 emu / g

Example 3 Continuous Production of Magnetite Nanoparticles with an Average Particle Size of about 28 nm

Procedure as described in Example 2, but with 124.3 g of iron (II) sulfate heptahydrate (447 mmol), 20.1 g of iron (III) nitrate nonahydrate (50 mmol) and 24.2 g of potassium nitrate (239 mmol). The percentage of Fe (III) in relation to the total iron content is 10%. Results: specific. Surface: 43 m ² / g calculated mean particle size: 28 nm magnetic remanence: 6 emu / g

Example 4 Continuous Production of Magnetite Nanoparticles with an Average Particle Size of about 21 nm

Procedure as described in Example 2, but with 117.4 g of iron (II) sulfate heptahydrate (422 mmol), 30.2 g of iron (III) nitrate nonahydrate (75 mmol) and 13 g of potassium nitrate (129 mmol). , The percentage of Fe (III) in relation to the total iron content is 15%.

Results: specific. Surface area: 57 m ² / g Calculated mean particle size: 21 nm Magnetic remanence: 5 emu / g

Example 5 Continuous Production of Maqnetite Nanoparticles with an Average Particle Size of about 18 nm

Procedure as described in Example 2, but with 110.5 g of iron (II) sulfate heptahydrate (397 mmol), 40.2 g of iron (III) nitrate nonahydrate (99 mmol) and 2 g of potassium nitrate (20 mmol). , The percentage of Fe (III) in relation to the total iron content is 20%.

Results: specific. Surface: 65 m ² / g calculated average particle size: 18 nm magnetic remanence: 2 emu / g Example 6 Continuous Production of Magnetite Nanoparticles with a Mean Particle Size of about 14 nm

Procedure as described in Example 2, but with 104 g of iron (II) - sulfate heptahydrate (374 mmol), 50.2 g of iron (III) nitrate nonahydrate (124 mmol) and 0 g of potassium nitrate (0 mmol). The percentage of Fe (III) in relation to the total iron content is 25%.

Results: specific. Surface: 82 m ² / g calculated average particle size: 14 nm magnetic remanence: <1 emu / g

Example 7 Continuous Production of Magnetite Nanoparticles with an Average Particle Size of about 13 nm

Procedure as described in Example 5, but with 96.7 g of iron (II) - sulfate heptahydrate (348 mmol) and 60.2 g of iron (III) nitrate nonahydrate (149 mmol). The percentage of Fe (III) in relation to the total iron content is 30%.

Results: specific. Surface area: 89 m ² / g calculated mean particle size: 13 nm magnetic remanence: not measured

Example 8 Continuous Production of Magnetite Nanoparticles with an Average Particle Size of about 11 nm Procedure as described in Example 5, but with 90.1 g of iron (II) - sulfate heptahydrate (324 mmol) and 70.3 g of iron (III) nitrate nonahydrate (174 mmol). The percentage of Fe (III) in relation to

Total iron content is 35%.

Results: specific. Surface area: 111 m ² / g calculated mean particle size: 11 nm magnetic remanence: <1 emu / g

Example 9 Continuous Production of Maqnetite Nanoparticles with an Average Particle Size of about 8 nm

Procedure as described in Example 5, but with 69.1 g of iron (II) - sulfate heptahydrate (248 mmol) and 100.4 g of iron (III) nitrate nonahydrate (248 mmol). The percentage of Fe (III) in relation to the total iron content is 50%

Results: specific. Surface area: 155 m ² / g calculated average particle size: 8 nm magnetic remanence: <1 emu / g

Claims

claims

1. A process for the preparation of nanoparticles, characterized by at least the following process steps: a) Preparation of a basic mixture containing at least one

Me (II) salt, a Me (III) salt, and an oxidizing agent, wherein the molar ratio of Me (II) to Me (III) in the mixture is between 100: 1 and 1: 1.5; Me (II ) is selected from the group Fe (II), Co (II), Cr (II) and / or Mn (II) and Me (III) is selected from the group Fe (III), Co (III), Cr (III ) and / or Mn (III); b) Optional washing and / or isolation of the resulting nanoparticles.

2. The method according to claim 1, characterized in that the mixture is tempered in a process step a2) after the preparation for at least one minute.

3. The method according to any one of claims 1 or 2, characterized in that the mixture prepared in process step a) contains at least one Fe (II) -SaiIz and at least one Fe (III) -SaiIz.

4. The method according to one or more of claims 1 to 3, characterized in that the mixture prepared in step a) contains Fe (II) sulfate and Fe (III) nitrate.

5. The method according to one or more of claims 1 to 4, characterized in that the mixture is produced in step a) by mixing a solution containing at least one Me (II) salt and a Me (III) salt is treated with a basic solution containing at least one oxidizing agent.

6. The method according to one or more of claims 1 to 5, characterized in that a nitrate salt is used as the oxidizing agent in step a).

7. The method according to one or more of claims 2 to 6, characterized in that in step a2) between 10 minutes and 24 hours at a temperature between 60 and 90 ⁰ tempered C.

8. The method according to one or more of claims 1 to 6, characterized in that the surface of the resulting nanoparticles is completely or partially coated or derivatized in an additional process step.

9. nanoparticles producible by the process according to one or more of claims 1 to 8.

10. nanoparticles according to claim 9, characterized in that they have a diameter between 10 and 50 nm.

11. Use of the nanoparticles according to claim 9 or 10 in the

Electronics, as security markers, as ferrofluids, in molecular biology, biochemistry or diagnostics, as well as in medicine.