DESCRIPTION OBJECT OF THE INVENTION

The present invention can be included in the technical field of nanotechnology.

More specifically, the invention aims at providing an overall solution to cover both the necessary apparatus and method of use thereof to obtain nanopartides sorted and separated according to their magnetic size, namely magnetic moment.

BACKGROUND OF THE INVENTION Nanopartides are microscopic particles with a dimension less than 100 nm and at present there is no evidence of the existence of any method or device to obtain nanopartides separated by their specific size and that size only, filling containers with nanopartides of a certain size only. Magnetic nanopartides are of great interest in many fields of physics and applications. At low temperatures showing quantum phenomena such as tunneling and magnetization at room temperature, its applications cover fields such as data storage, magnetic resonance imaging, magnetic fluids, permanent magnets, biosensors, drug delivery, security, and the magnetocaloric effect biomedicine.

The classification of bulk materials with respect to magnetic properties is usually based on their magnetic susceptibility (χ), defined as the ratio between the induced magnetization (M) and the applied magnetic field (H). In diamagnetic materials, magnetic dipoles are oriented antiparallel to H resulting in small negative susceptibility (-10-6 to -10-3) and the magnetization is not retained when the external field is removed. Paramagnetic materials possess permanent magnetic dipoles that align parallel to H and the susceptibility is positive. The temperature dependence of the paramagnetic susceptibility at low values of H follows the well known Curie-Weiss law. In the case of high values of H , the Curie- Weiss law is experimentally observed at high temperatures. For ferro-, ferri- and antiferromagnetic materials collective magnetism is crucial due to the fact that permanent magnetic dipoles show exchange interactions. This leads to the definition of a critical temperature (Curie temperature for ferromagnetic materials and Neel temperature for antiferromagnets) below which a spontaneous magnetization is exhibited. The susceptibilities of these materials depend on their atomic structures, temperature, and the external field H. In bulk materials and large magnetic particles there is a multidomain structure, where regions of uniform magnetization are separated by domain walls. If the particle size is decreased, there is a critical volume below which it costs more energy to create a domain wall than to withstand the external magnetostatic energy (applied field) of the single-domain state. Below this critical size, typically in the order of tens of nanometers, materials that exhibit collective magnetism become a single magnetic domain. This is observed for magnetic nanoparticles, and in particular for iron oxide systems developed for biomedical applications. For spherical magnetite particles, the critical diameter has been determined to be ca 120 nm. A single-domain particle is uniformly magnetized with all the spins aligned in the same direction. The magnetization can be reversed by spin rotation since there are no domain walls to move. This is the reason for the very high coercivity observed in small nanoparticles.

A characteristic property of a ferromagnetic particle is of nanometer size is not divided into magnetic domains, the particle is characterized by a single magnetic domain. Example of these are metal oxides particles and nanosized magnetic metals. The magnetic moment of single domain nanoparticles can switch between different orientations by thermal fluctuations. This effect is called superparamagnetism. The time between transitions superparamagnetic magnetic moment depends exponentially on the temperature and the particle diameter. When the particle is cooled, inversion of magnetic moment finally stops, the temperature at which this occurs is called blocking temperature.

The single domain magnetic nanoparticles with superparamagnetic properties such as spinels of iron and cobalt (CoFe204), Fe304 magnetite, the magnemite (y-Fe203), barium ferrites (BaFe03) and iron alloys platinum (FePt) are of great interest in various fields of science to find application as a fundamental part of permanent magnets, quantum computers, laser emission systems in the microwave region, data storage devices, etc.. The magnetic dipole interactions within the superparamagnetic nanopartide are weak which gives ownership to the nanopartide can be dispersed and stable in liquids, so that also the single domain magnetic nanoparticles are promising candidates existing within the area of the biomedicine and bioengineering as contrast agents in magnetic resonance imaging, biosensors, hyperthermia generators by applying alternating magnetic fields, etc. ... Moreover, the use of this type of magnetic nanoparticles can have an effect on phenomena transcendental guided and Targeting of drugs, both of promising future in cancer therapy, Alzheimer, etc. Hence the interest in these nanoparticles has increased dramatically in recent years.

From the biological point of view, the fact that this type of magnetic nanoparticles can be produced with a uniform size ranging from a few nanometers to tens, confers a comparable dimension to a biological entity such as a virus (20-450 nm), protein (5-50 nm) or a gene (2 nm wide and 10-100 nm long). Is the magnetic nanoparticle size which therefore determines the biological application. The opposite is the guiding and focusing magnetic particles comprising a drug, the larger the better the response to external fields.

Current methods of production of magnetic nanoparticles either physical (laser, plasma, flame) or chemical provide a size distribution of nanoparticles not acceptable for demanding applications today. Chemical methods are the most accurate in size and shape of the magnetic nanoparticles reaching size distributions of 10% [DR Shivang and G. Xiaohu, monodisperse magnetic nanoparticles for Biodetection, imaging and drug delivery: a versatile and Evolving Technology, Nanobiotechnology 1 , 583-609, (2009)].

So there is a need for isolation, sorting and/or separating methods of obtaining magnetic nanoparticles with magnetic moments controlled extremely narrow size distributions (AR / R <5%, where R is the radius of the nanoparticle).

All of this said, it's well known that large magnetic particles split into magnetic domains in order to decrease their magnetostatic energy. The thickness, δ, of the domain wall where occurs the rotation of spins from one domain to another is given by 5~a(J/D)1/2, where J and D are exchange and anisotropy energies per lattice site, respectively, and a is the lattice spacing. For practical reasons it is assumed that energy anisotropy can also be expressed as KV, K being the so called anisotropy constant -which depends on the material and size- and V~R3 the volume of the particle. Thus if we have a particle of a size R « δ is a sufficient condition for the particle to consist of a single domain. The total energy of a single domain particle depends on the exchange interaction, type of crystal field anisotropy, dipolar forces and the shape of the particle. In general single domain particles are very complex objects because, for example, the exchange interactions at the surface are different from the exchange in the bulk and in addition the magnetic anisotropy at the surface differs from the anisotropy in the bulk as a consequence of the different symmetry in the local arrangement of atoms. In the case of cobalt iron oxide which are a very good example of the particles of interest in this work, the energy of the exchange interaction per atom, greatly exceeds the energy of the magnetic anisotropy per atom. Consequently an accepted way to simplify the problem is to assume that the effective exchange interaction at all atomic sites is sufficiently large to make the particle uniformly magnetized. This is true for most nanoparticles having a size less than 20 nm. In this case the low energy dynamics of such particles, reduces to uniform rotation of the total magnetic moment. The magnetic moment of single domain particles, however, is not necessarily frozen in a certain direction. At the nanometer scale, thermal fluctuations may make it flip between different orientations. This effect is called superparamagnetism. The time between superparamagnetic transitions of the magnetic moment depends exponentially on the temperature and the diameter of the particle. When the particle is cooled down, the flipping of its magnetic moment eventually stops. The temperature at which this happens is called the Blocking temperature, which depends on the resolution time of the used experimental method and it is proportional to the volume and the magnetic anisotropy constant of the particle. Studies of superparamagnetism date back to the work of Louis Neel in 1930s and continue until this day. Most of the experiments, however, have been performed with particles embedded in a solid matrix. In such studies one usually deals with a broad size distribution of nanoparticles.

An interesting and a relatively new problem in single domain particles is the study of their properties when the exchange length, lexc exceeds the characteristic length size, I, of the particles. However we are far from having a good answer to the open question of the size dependence of the exchange energy of nanoparticles measured by its Curie temperature, Tc, as a function of the ratio lexc/l. Moreover, we may enter in the very interesting regime of values of I for which the reduction in the value of J is such that the magnetic moment of the particle is blocked just at Tc. In this case, it can be of great importance the study of this effect and the temperature range of the spin fluctuations. That is, in the region close to the magnetic ordering transition when lexc/l <1 the correlation length of the spin fluctuations may have a strong effect on the variation of the order parameter M on T below Tc, as well as in the shift of Tc. Usually in bulk materials these fluctuations determining the shift in the ordering temperature are determined by Monte Carlo simulation. In nanomagnets of size I, it has been suggested that the variation in Tc is given by ΔΤο=(β/Ι)λ, β being a constant for the correlation length of bulk phase at a temperature away from the ordering temperature and λ is the shift exponent. Magnetic single-domain nanoparticles possess another important property, the anisotropy energy, which refers to the preference of the magnetization to lie along particular directions (with respect to the crystallographic directions) within the nanoparticles. These directions minimize the magnetic energy and are called anisotropy directions or easy axes. The magnetic energy of a nanoparticle increases with the tilt angle between the magnetization vector and the easy directions.

In the case of nanoparticles of iron cobalt oxide, the energy per atom exchange interaction is far superior to the magnetic anisotropy energy per atom. Therefore, an accepted way to simplify the problem is to assume that the effective exchange interaction at all atomic sites is large enough so that the particle is uniformly magnetized. This is true for the majority of nanoparticles with a size of less than 20 nm, in this case, the dynamics of such low energy particles is reduced to the uniform rotation of the overall magnetic moment. Moreover, in the scientific world is well known the first experiment conducted in 1922 on the deflection of particles, and helped lay the experimental basis of quantum mechanics called Stern-Gerlach experiment in honor of its creators. Said Stern-Gerlach experiment shows how it is possible to send a beam of silver atoms through an inhomogeneous magnetic field wherein said magnetic field intensity increases in the direction perpendicular to the beam is sent and separate them depending on their value of their magnetic moment.

The Stern-Gerlach experiment shows that all particles are deflected either up or down but both groups with the same intensity. Also particles must have values of positive and negative spin or spin or, without further intermediate values to determine the magnetic moment m of the atom that is of the order of magnitude of the Bohr magneton mB.

Ten years ago the nanoparticles produced in laboratories/commercially available had a size distribution exceeding 30%. This translates into 100% difference in volume. Since superparamagnetic properties depend on the volume exponentially, and so their properties, this means that at a given temperature some of the nanoparticles in such a sample would flip their magnetic moment in a nanosecond, while other would be blocked forever.

Particles of different size would also have very different response to the magnetic field and very different Brownian motion, the latter being crucial for biomedical applications and biosensor applications. In recent years chemical methods have been developed that permit narrowing the size distribution. Monodispersity within 10% has been reported by some researchers [D.R. Shivang and G. Xiaohu, Monodisperse magnetic nanoparticles for biodetection, imaging, and drug delivery: a versatile and evolving technology, Nanobiotechnology 1 , 583-609 (2009)]. Even in this case, however, the volume distribution would be as large as 30%, still resulting in exponentially different dynamics and properties. Besides, if the particles are chemically coated (or functionalized), which is often the case for biomedical applications, they do not exhibit direct correlation between the volume and the magnetic moment. This inhibits applications that are based on the response to the magnetic field, what often makes the method useless. Modern methods used to obtain monodisperse arrays of nanoparticles employ chemical processes that control the size of the particles but not their magnetic moments. The aim, therefore, is to obtain magnetic nanoparticles with extremely narrow size distributions (AR/R<5%, R being the radius of the nanoparticle) and controlled magnetic moment. State-of-the-art methods for nanoparticle manufacturing only uses bottom-up approaches to get the desired materials. Chemical methods are the most size- and shape-sensitive, but, on the contrary, they have the lowest efficiency.

Pyrolisis based methods, either laser or flame assisted in its multiple variants allow for higher throughput, but lower control on size and aggregation, being the laser methods more precise, but less productive.

State-of the art chemical processes, with very low productivity, reach dispersion in particle diameter down to 20%.

DESCRIPTION OF THE INVENTION The present invention overcomes the drawbacks posed above, by combining the use of a wide dispersed and cheap raw material, and the use of the machine to post-process it and get finely classified magnetic nanoparticles with a diameter dispersion lower than 5%.

Both the system and method of the invention are based on the fact of blocking the movement of the magnetic moment of nanoparticles MNP's flying through a chamber by both magnetic and temperature means, using the values of blocking temperatures and permanent and variable gradient magnetic fields.

To achieve the desired product -magnetic nanoparticles with extremely narrow distribution (AR/R<5%, R being the radius of the nanoparticle) and controlled magnetic moment- a new physical method based upon separation of nanoparticles on their magnetic moments is presented. The first method of that kind was proposed to elucidate the existence of the intrinsic magnetic moment of electrons, the so called spin, by Stern and Gerlach at the dawn of quantum physics in the earliest 1920s. The idea of the Stern-Gerlach experiment is the following: Interaction of the magnetic moment of the particle with a magnetic field gradient creates the force that attracts the particle into the region with either higher or weaker field, depending on the orientation of its magnetic moment with respect to the field. Thus, particles in a beam passing through the gradient of the magnetic field will be deflected differently depending on the direction and absolute value of their magnetic moment. The Stern-Gerlach set-up may also allow to test the prediction of quantum mechanics that the Χ,Υ,Ζ components of the magnetic moment could not be measured simultaneously. More recently the Stern-Gerlach set-up was applied to the size separation of atomic clusters of magnetic materials. In Stern-Gerlach experiments with atomic clusters the final separation of the clusters was done with the help of a mass spectrometer. This step will not be needed in the described apparatus as it will deal with the separation of NPs having hundreds of thousands of atoms as compared to a few dozen or a few hundred atoms in the experiments with atomic clusters. The machine will be fed with a large sample of NPs synthesized by mostly chemical methods in comparison with samples having much smaller numbers of atomic clusters prepared by laser vaporization. This will result in much larger flow of NPs and will make temperature control less challenging than in experiments with atomic clusters. On top of that, the collection and manipulation of the nanoparticles has never been addressed before as, typically, the few hundred atoms thrown impact on a screen and are lost. Therefore, novel collection methods are to be introduced in the machine.

It is important to mention that the deflection of a magnetic particle in a Stern-Gerlach setup is proportional to the ratio of its magnetic moment and its mass or, which is almost the same, to the ratio of the magnetic moment and the volume of the particle. For uncoated magnetic nanoparticles these two quantities are roughly proportional to each other. Thus, the difference in the deflection of blocked nanoparticles could only result from a small deviation from this proportionality. However, the situation changes for superparamagnetic nanoparticles that flip their magnetic moments during the flight through the field gradient. Clearly, the particles that flip their moment many times will be only weakly deflected compared to the deflection of blocked particles. In general the effective magnetic moment of the superparamagnetic particle during its flight through the field gradient strongly depends on the size of the particle, magnetic field, and temperature. The proposed method of separation of nanoparticles on size, shape, and magnetic moments is based upon this effect.

Since a property of small ferromagnetic particles is that below a certain size they do not split into magnetic domains, i.e. such a particle is a uniformly magnetized single domain particle (SDP). Nanometric particles of magnetic metals and oxides are SDP; they are small magnets with certain location of the north and south magnetic poles.

In the absence of the external magnetic field, the energy of a SDP does not change if its magnetic poles are interchanged. Consequently, there is the same probability of finding the particle in either state. For a particle of volume V, these two equivalent but opposite orientations of the magnetic moment are separated by an energy barrier, U, that depends linearly on the volume, U = K V, via a constant K, called magnetic anisotropy constant, that varies for each material. The overbarrier transition probability at temperature T decreases exponentially with the ratio U/kBT, where kB is the Boltzman's constant and kBT is the thermal energy. That is, Γ = Γ0 exp(-U/T), where Γ0 is the so-called attempt frequency and is of the order of 1 GHz.

If the thermal energy is larger than the barrier height, the magnetic moment oscillates rapidly between the two orientations, which corresponds to the superparamagnetic behaviour.

If T decreases or U increases, the magnetic moment becomes frozen in a particular direction. This means that we can keep the temperature constant and change the volume of the particle to shift the value of the frequency for overbarrier transitions from 1 Hz, corresponding to large particles, to 1 GHz, corresponding to very small particles.

The blocking temperature, TB, is usually defined as the temperature at which the inverse of the overbarrier frequency equals the experimental resolution time, t. Taking into account the exponential dependence of the overbarrier frequency on the ratio between the volume of the particles and the temperature, it is verified that TB oc K V.

A magnetic dipole is properly modeled as a current loop having a current I and an area a. Such a current loop has a magnetic moment of: m=la; where the direction of m is perpendicular to the area of the loop and depends on the direction of the current using the right-hand rule. In this model it is easy to see the connection between angular momentum and magnetic moment which is the basis of the Einstein-de Haas effect "rotation by magnetization" and its inverse, the Barnett effect or "magnetization by rotation". Rotating the loop faster (in the same direction) increases the current and therefore the magnetic moment, for example.lt is sometimes useful to model the magnetic dipole similar to the electric dipole with two equal but opposite magnetic charges (one south the other north) separated by distance d. As a matter of fact, this simplification is very useful in many calculations of the demagnetizing factor of permanent magnets.

This variable, the magnetic moment, is used by the invention as the dimension as"magnetic size" being this dimension the variable setting the sizes for separation; hence the magnetic nanoparticles are separated by their magnetic moment; namely magnetic size. Said size distributed magnetic nanoparticles are suitable for different applications, Depending on the size and subsequent change in magnetic properties, the magnetic nanoparticles are used in different applications as described below. Since the relaxation time of magnetic nanoparticles can be modified by changing the size of the nanoparticles or using different kinds of materials, magnetic nanoparticles have been and will be very useful in many applications, from biomedical to data-storage systems. Size selection and classification is, therefore, a huge leap forward into the improvement of research activities and accuracy and performance of their applications.

SPM NPs sortened by size are ideal platforms for drug delivery. On targeted delivery, SPM NPs have distinct advantages over the other polymer based delivery systems:

The pathway of the drug can be readily tracked in the biological systems through SPM NPs by MRI.

The drug-NPs can be guided or held in place by an external magnetic field.

Under an alternate magnetic field, the SPM NPs act as a heater and can trigger controlled drug release. It's crucial to precisely control the size in order to guide and activate the NP's with the less amount of external energy possible. On the other hand, it is important to control the size to allow the NP's to go through the reticuloendothelial system (RES).

By separating the MNP's according to their magnetic moments (sizes), a new and extraordinary application can be introduced into the scientific research and drug development:

1. Each NP size can be functionalized with a certain drug. Applying different alternating magnetic frequencies to the size-segregated MNP's, each frequency will trigger the delivery of the drug attached to the specific NP size. With this method, one could selectively choose the time and length of the drug delivery treatment, either by manually turning on the magnetic system, or connecting it to external controller devices such as a mobile phone with an application that could be supervised either by the doctor or the patient.

2. Each NP size can be functionalized with different drugs. Therefore, by the application of different alternating magnetic field frequencies, a certain mix of drugs can be delivered selectively, in a timely manner, selectable by the doctor.

One of the major applications of magnetic particles in biomedicine is in magnetic separation. It is possible to separate a specific substance from a mixture of substances, from proteins, to viruses and DNA. The separation time is one of the important parameters in the magnetic separation method. In order to optimize this parameter, it is very important to know the magnetic properties of the magnetic-particle system as well as of the magnets that are being used in the separation system. A size-selected material, will be, then, much more efficient than the current methods.

Magnetic nanoparticles with long relaxation times (thermally blocked nanoparticles) with stable remanent magnetization can be used as information carriers in magnetic identification and data-storage systems where it is crucial to have small regions of magnetic material. The two directions of the magnetic moments (the remament magnetization) of the magnetic nanoparticles gives the zeros (0) and ones (1 ) that make it possible to store information on a hard disk in a computer or in other types of media. The directions of the magnetic moment of the nanoparticles must be stable with time, otherwise information would be lost. Research into using magnetic nanoparticles for information storage is evolving rapidly. A narrow sized material, will here improve the amount of information per surface, as you can be very specific in the type of particle to use, reducing noise to signal ratio.

The magnetic nanoparticles in biosensor applications can be used to study how the Brownian relaxation (random particle rotation) time changes when biomolecules are bound to the surface of the particles. This goal can be achieved using magnetic-induction techniques to study the changes in Brownian relaxation. The orientation of the magnetic moment of the particle must change at the same rate as the rotation time of the particle itself. The orientation of the magnetic moments in the single domains must then be constant, which means that the total magnetic particle, which can contain several single domains locked in a solid matrix, must contain thermally-blocked single domains. This puts a lower limit to the sizes of the nanoparticles. For single domains of maghemite, this size lies at a domain diameter of approximately 15 nm at room temperature. Therefore, selecting the material by size is critical. There are other biosensor systems that use the magnetic detection of magnetic particles. These biosensor systems use SQUIDs (Superconducting Quantum Interference Devices) or sensitive GMR (Giant Magnetic Sensors) to detect the presence of magnetic particles. The sizes of the single domains are dependent on the technique used, and it is possible to find both superparamagnetic as well as thermally blocked particles in these applications. Using exact size of particles means that the detection precision will be very high as the aim is clearly delimited. Another advantage of the use of size separated magnetic nanopartides is the possibility to use each size of separation to detect, in parallel, different antigens or substances in the same analysis. As the AC magnetic susceptibility changes radically with the size, each nanoparticle size could be bound to a specific antigen, so that in the same analysis a multiple set of antibodies could be detected just by the measurement of the frequency change of the imaginary part of the AC susceptibility.

If an AC magnetic field with a specific frequency and amplitude is applied, it is possible for the magnetic nanopartides to absorb energy, which increases the local temperature around the nanoparticle system. This is used in in-vivo applications in medicine to destroy tumor cells. In such cases, magnetic nanopartides made of materials with Curie temperatures around 42 °C (the temperature at which the tumor cells are destroyed) are preferred. Overheating problems can be avoided with these materials. The nanoparticle system then works as a thermostat. Under a fast switching magnetic field, a group of superparamagnetic NPs can become ferromagnetic with their magnetization direction switching quickly along the field directions. The frictions caused by the physical rotation of a NP -Brownian relaxation- and the magnetization reversal within the NP -Neel relaxation- lead to the loss of magnetic energy and the generation of thermal energy. The heating power of these NPs is directly related to A ^» f, where A is the ferromagnetic hysteresis area and f is the frequency of the alternating magnetic field. Used for cancer therapy, this magnetic heating technique has long been known as magnetic fluid hyperthermia (MFH). To maximize the NP heating power, the hysteresis area A must be as large as possible. However, hyperthermia limitations require that the product Hmax* f should be below 5x109 Α·η 1 · s-1 with f being above 50 kHz To ensure optimum MFH effect under the common hyperthermia conditions, magnetic NPs should have small He, large susceptibility, and high Ms. The NP heating efficiency is measured by the specific absorption rate (SAR, W ^» g-1 ). For practical therapeutic applications with minimized side effects, it is critically important to obtain optimum heating efficiency to reach the desired hyperthermia temperature at 41-46 °C, not thermo ablation at greater than 50 °C.

In all of these cases, it is important to fully understand the magnetic properties of the particle systems. Sizes of the nanoparticles are chosen to be thermally blocked or superparamagnetic depending on whether the nanoparticles are free to rotate or are locked in a solid matrix; furthermore the size of the magnetic nanoparticle is critical, in order to get the maximum heat dissipation, with the minimum frequency possible in order not to surpass the limit given before. In another biomedical application, MRI is known to be one of the most powerful noninvasive imaging techniques utilized in clinical medicine. It is based on the principle that protons align and precess along an applied magnetic field. Upon applying a transverse radiofrequency pulse, these precessed protons are perturbed from the magnetic field direction. The subsequent process, through which the pulsing field is turned off to allow protons to return to their original state, is referred to as relaxation. Two independent relaxation processes, longitudinal relaxation (T1 -recovery) and transverse relaxation (T2- decay), are used to generate a bright and a dark MR image respectively.

The longitudinal relaxation is primarily a measure of the dipolar coupling of the proton moments to their surroundings whereas transverse relaxation is driven by the loss of phase coherence in the precessing protons due to their magnetic interaction with each other and with other fluctuating moments in the tissue. Upon accumulation in tissues, SPM NPs are magnetically saturated in the normal range of magnetic field strengths in MRI scanner and establish a substantial locally perturbing dipolar field, which leads to a marked shortening of T2 ^* along with a less marked reduction of T1. Thus SPM NPs are a good candidate for T2 contrast agent to provide a dark image and the contrast enhancement is proportional to the magnetization magnitude..

Again, size distribution is in order to supply the proper material for each application. The availability of size-classified MNPs allows the manufacturing of rare earth (or conventional) permanent magnets (of extensive application in many devices) of very high performance and low weight, due to the use of single domain nanoparticles, of exact size for the application. On the one hand, this helps to reach maximum remanence and coercivity values, and on the other hand, because of the use of the exact size material, will reduce the weight of the magnet, by using only active material and rare earth consumption.

Regarding the present invention, the use of monodispersed MIOP's offers a powerful tool for the removal as one can be very specific in the process, because the size controlled particles can be easily moved with the optimal magnetic field, and their presence can be monitored and tracked in a simply manner, as their relaxation frequency will be fixed on a certain value thanks to the single magnetic moment value.

Both the method and the device hereby described may be used for sorting and separating MNP ^' s as platforms for drug delivery. On targeted delivery, SPM MNP ^' s have distinct advantages over the other polymer based delivery systems: the pathway of the drug can be readily tracked in the biological systems through SPM NPs by MRI; the drug-NPs can be guided or held in place by an external magnetic field; and under an alternate magnetic field, the MNP ^' s act as a heater and can trigger controlled drug release.

Such applications require a precise control of the size in order to guide and activate the MNP ^' s with the less amount of external energy possible. On the other hand, it is important to control the size to allow the NP's to go through the reticuloendothelial system (RES).

By separating the MNP ^' s according to their magnetic moments (sizes), each MNP size can be functionalized with a certain drug. Applying different alternating magnetic frequencies to the size-segregated MNP's, each frequency will trigger the delivery of the drug attached to the specific NP size. With this method, one could selectively choose the time and length of the drug delivery treatment, either by manually turning on the magnetic system, or connecting it to external controller devices such as a mobile phone with an application that could be supervised either by the doctor or the patient.

Each MNP size can be functionalized with different drugs. Therefore, by the application of different alternating magnetic field frequencies, a certain mix of drugs can be delivered selectively, in a timely manner; being said drugs, and timeframe, trigger and release selectable by the doctor.

One of the major applications of magnetic particles in biomedicine is in magnetic separation. It is possible to separate a specific substance from a mixture of substances, from proteins, to viruses and DNA. The separation time is one of the important parameters in the magnetic separation method. In order to optimize this parameter, it is very important to know the magnetic properties of the magnetic-particle system as well as of the magnets that are being used in the separation system. A size- selected material, will then, is much more efficient than the current methods.

DESCRIPTION OF THE FIGURES

To complement the description being made and with the object of assisting in a better understanding of the characteristics of the invention according to a preferred example of practical embodiment thereof, accompanying as an integral part of said description, a set of drawings where with an illustrative and not limiting character, represent the following:

Figure 1.-Depicts and illustration showing the device of the invention. Figure 2.- Shows a detailed view of the device of the invention.

PREFERRED EMBODIMENT

One of the aspects of this is invention is related to a device (1 ) for separating magnetic nanoparticles [MNP's] by magnetic size being the magnetic size a magnetic moment and collected in collecting means comprising compartments for allocating MNP's, being each compartment associated with at least one MNP's collection container, which is arranged in parallel and respectively presenting a series of caps with an arrangement of a labyrinth structure defined by each of them to prevent the MNP's from coming out of the compartment once they have entered the same. In an alternative embodiment of the invention the collecting means comprise at least one tray with a liquid like distilled water or a volatile liquid like alcohol, or a mix of both, once the MNP's are collected we need a postprocessing device to evaporate the liquid where the MNP's are, then once the liquid is removed by evaporation the MNP's are available for their use. Said device, depicted in figure 1 , comprises at least one gun (2) with a series of concentric tubes made of non magnetic material like aluminum, stainless steel, epoxy resin or PTFE type. Said gun (2)is intended for firing the MNP's into a chamber (3) where said MNP's will be separated by their magnetic moment. Basically the MNP's with a certain size distribution are housed in a cartridge (4) which is associated or connected with the gun (2), in said cartridge (4) the MNP ^' s are stirred by means of means for generating ultrasound waves arranged so that ultrasound waves affect at least part of the flow of MNP's comprised in the cartridge (4) stirring said MNP's by means of the incidence of the ultrasound waves avoiding agglomeration of MNP's. Once the MNP's are ready by setting a working temperature of the MNP's for choose the classification range, a control unit, used to set the temperature as well and associated with each element of the device (1 ) to send operational commands and actuate each element to perform the separation, triggers gas injection means to inject gas at a certain pressure Pi generating a shot of MNP's through the gun (2) thus generating the flow of MNP's by the insertion of pressurized gas, said gas and the rest of the flows running the device (1 ) are controlled by means of a series of valves distributed along a flow passage areas of MNP's, valves designed to control and manage the flow working in the discharge of the MNP load from the cartridge (4) in continuous flow, in order to avoid MNP collisions.

The gun (2) is operative to fire the MNP's generating a flow of nanoparticles comprising at least one MNP at certain speed through a conduit that leads to a chamber (3), said chamber (3) has a trumpet-shaped proximal end diameter of the duct coinciding with that part which flared distal end and a larger diameter than that of the proximal end, when the MNP's are passing through the conduit they are under the influence of a permanent magnetic field generated by means of first means for generating magnetic fields (5), being the MNP's affected by said permanent magnetic field before entering the chamber (3) the MNP's getting polarized in their easy axis. Once the MNP's are inside the chamber (3) they are affected by a variable gradient magnetic field generated by second means for generating magnetic fields (6) for generating a variable magnetic field in the chamber (3) producing a force proportional to the magnetic moment of each MNP, the field strength and the field gradient. Once the MNP's have been affected by the permanent magnetic field and once still under the effect of the variable gradient magnetic field, the temperature inside the chamber (3) is varied so some of the MNP's will be blocked and act as superparamagnetic, while some other will be unblocked and their trajectories won't be affected by the variable magnetic field, as their magnetic moments will be freely rotating between their easy axis, and the net force will be cero acting this step as a separation inducer to fine tune the classification process per each size, then we only have to collect the MNP's coming out from the variable magnetic field magnet distributed by its magnetic size (magnetic moment associated to some properties of the MNP material, size, geometry, etc) in the compartments of the collecting means where the MNP's may be cooled down by cooling means furnished with cryogenic elements adapted to provide a temperature (being said temperature of around 2K) to either the cooling vessels housing the MNP's collected before they are launched again by the gun (2), or to the cartridge (4) but always before they are launched by the gun (2),. Said cooling means may be preferably arranged next to the gun (2) so we can control the temperature of the MNP's before they are launched thus helping the separation process by setting blocking temperatures.

In an alternative embodiment the device (1 ) may comprise a vacuum system connected at least to the chamber (3) and in order to generate a vacuum therein to carry out the separation in vacuum conditions if needed.

In yet an alternative embodiment of the invention the method may be repeated using the collected MNP's as a source since the collector container fits the gun (2) and is used as the cartridge (4) using the MNP's comprised with a size distribution therein as a source for the flow of MNP's. Then we need to set setting a new working temperature, in order to discriminate certain sizes by their blocking temperature and repeat the procedure described above with this new temperature and the MNP's coming from a previous separation, this is intended to refine the process.

Once the MNP's are separated and collected, we now have MNP's with a determined size, and that size only in respective in the compartments of the collecting means; as the skilled person may appreciate the Superparamagnetic (SPM) Nanoparticles (NPs) have been considered as attractive magnetic probes for biological imaging and therapeutic applications. In normal biological conditions, these SPM NPs are not subject to strong magnetic interactions in the dispersion due to the randomization of their magnetization and are readily stabilized in physiological conditions. Under an external magnetic field, however, they exhibit a magnetic signal far exceeding that from any of the known biomolecules and cells. This makes SPM NPs readily identified by a magnetic sensing device from the ocean of biomolecules. At a core diameter at less than 20 nm and overall hydrodynamic diameter at less than 50 nm, these NPs have the size that is comparable to the nuclear pore size (~50 nm) and is much smaller than a cell (normally 10-30 mm). So the device (1 ) and the method hereby described may be useful to provide this application with MNP's of the size required.