WO2018002043A2

WO2018002043A2 - A hybrid hyperthermia device, and methods using the same

Info

Publication number: WO2018002043A2
Application number: PCT/EP2017/065842
Authority: WO
Inventors: Josep NOGUÉS SANMIQUEL; Borja SEPÚLVEDA MARTÍNEZ; Alejandro GÓMEZ ROCA; José Luis TAJADA HERRAIZ; Elvira FANTECHI
Original assignee: Fundació Institut Català De Nanociència I Nanotecnologia; Consejo Superior De Investigaciones Cientificas (Csic); Institució Catalana De Recerca I Estudis Avançats
Priority date: 2016-06-27
Filing date: 2017-06-27
Publication date: 2018-01-04
Also published as: WO2018002043A3

Abstract

The present invention provides a hybrid hyperthermia system or device capable of generating, simultaneously or sequentially, optical and magnetic treatment by using materials with dispersed, embedded or anchored particles for applications where it is necessary to heat a specific area or material in a safer way, and for applications where it is necessary to characterize the properties of a specific area or material subjected to optical and/or magnetic heating. The invention is also directed to its uses for combined hyperthermia treatment, and for characterization of optical and magneto-optical properties of a specific area or material.

Description

A HYBRID HYPERTHERMIA DEVICE, AND METHODS USING THE SAME Field of the invention

The present invention relates to a hybrid hyperthermia system for use in the field of nanotechnology. In particular, the present invention relates to a magnetic and optical hyperthermia device using particles which is capable of generating an optical and magnetic effect, simultaneously or sequentially, at a specific area or material in need to be treated by heat.

The present invention also relates to the applications where it is necessary to heat a specific area or material to induce hyperthermia with safer conditions, and also to the applications where it is necessary to characterize the optical and magneto-optical properties of a specific area or material.

Background of the invention

Hyperthermia is a well-known therapeutic method in which malignant tumour, tissue or otherwise is heated to kill the malignant tumour cells, preferably without damaging the adjacent noncancerous cells.

In particular, magnetic hyperthermia is a method in which magnetic particles, such as magnetite (Fe₃04), are used as a heating element by means of application of alternating magnetic fields. When magnetic nanoparticles are exposed to an alternating magnetic field, they produce heat due to electromagnetic excitation (e.g., eddy current, hysteresis loss, Brownian relaxation, Neel relaxation, etc.). Typically, the alternating magnetic field has an amplitude of at least 1 Oe and a frequency of at least 50 kHz. Advantageously, the thermal treatment of a tumour improves the efficacy of other treatments (e.g., radiation, chemotherapy, or immunotherapy).

However, the heating or temperature rise in a tissue by magnetic hyperthermia is a complicated process that depends on numerous factors including the applied magnetic field, the number and magnetic properties of the particles, tissue thermal properties, among others. In order for hyperthermia to be effective, a certain thermal dosage equivalent cell exposure time must be achieved.

Some magnetic devices have been developed for inducing and controlling hyperthermia. However, there are magnetic devices which monitor temperature variations with temperature detectors such as thermocouples, which are invasive for in vivo situations, or optical fibres which are inserted in a liquid media to be treated in order to monitor the temperature variations. In addition, the heating process is very sensitive to the position of said temperature detectors inserted in the material, thereby changing the readings depending on their position. Furthermore, the optical fibre is limited to temperature sensing in liquid materials, such as colloidal dispersions.

Moreover, magnetic resonance thermometry is expensive and there is also the potential for the AC electromagnetic fields inducing hyperthermia to affect the imaging procedure, and much more significantly, the imaging electromagnetic fields from MRI could profoundly affect the hyperthermia process.

EP2192953 discloses hyperthermia devices and their uses with nanoparticles. The device consists of a generator of radiofrequency electromagnetic fields and a temperature detector. The device generates propagating electromagnetic waves, which can be absorbed by the nanoparticles to cause hyperthermia. Temperature variations are measured using an infrared thermometer. In this device there is not light source neither optical detector, so it cannot be employed for optical heating and neither to analyse simultaneously the optical or magneto- optical properties of the sample.

Alternative hyperthermia treatments have been also investigated. In this regards, optical hyperthermia is a method in which nanoparticles, carbon nanotubes, etc. are used as heating elements by means of optical absorption due to light excitation. For example, it is known that metal particles can display a pronounced optical resonance, thereby exhibiting strong optical absorption due to the collective electronic response of the material to light.

These particles, in addition to acting as light absorbers, may scatter light and thereby act as contrast agents as means for imaging the local environment in which they reside. However, particles need to be always optimised in terms of their morphology (size, size distribution, shape), crystallography (phase purity), magnetism (relaxation), optical properties (plasmon resonance) for effective temperature treatments.

US20020103517 discloses optically active nanoparticles for use in therapeutic and diagnostic methods. Particularly, nanoparticles composed of core and shell have been designed to induce local heating with light excitation. However, that hyperthermia method does not provide any information about the material properties thus treated.

KR20120043179 discloses the use of a combined hyperthermia using phototherapy and electromagnetic stimulus to treat lesion and alleviate pain. It is described a combined treatment apparatus using light therapy and a electromagnetic stimulation therapy comprises nanoparticles (1 1 1 ) which generates heat by light, a film (1 10) formed with transparent materials, and illuminator (120) which irradiates light on the film, an electromagnetic coil (131 ) which covers the illuminator, and a controller (140) which controls the illuminator and applies power to the electromagnetic coil. However, the apparatus disclosed does not disclose any component to measure the temperature of the medium that is going to be heated, neither any component to measure the properties of thus treated material.

Therefore, there is still the need to provide a device suitable for combined hyperthermia using safer actuation conditions, whose device is useful for hyperthermia in both liquid and solid materials, that is also useful for "in vivo" and "in vitro" applications, and which furthermore is useful for characterization of the optical and magneto-optical effects of the thus treated materials.

In view of the state of the art, there is also the need to provide a hyperthermia device that enables the analysis of the properties of a liquid or a solid material treated by magnetic and/or optic heating to better understand the hyperthermia treatment and thus to better control the same.

Summary of the invention

The present invention was made in view of the prior art described above, and the object of the present invention is to provide a hybrid hyperthermia system or device capable of generating, simultaneously or sequentially, optical and magnetic treatments by using particles for applications where it is necessary to heat a specific area or material in a safer way.

To solve this problem, the present invention provides in a first aspect, a hybrid hyperthermia system or device which uses particles in a material in need to be treated by heat, the device comprising:

- an electromagnetic actuator of tuneable intensity and frequency (ω) provided with an induction coil (L) and configured to generate a magnetic field on the material containing the particles by means of induction of an alternating magnetic field (H₍₀₎)), thereby the material rises its temperature (Ti) and/or the particles contained therein magnetically agitate (Ai),

- at least a light source (λι , λ₂, λ₃,..) provided with an emitted light intensity configured to illuminate the material containing the particles, being the material containing the particles capable of transmitting, reflecting or scattering the incident light, or absorbing the incident light thereby optically heating (T₂) the material containing the particles,

- a non-invasive temperature control means configured to measure temperature variations (ΔΤ) at the surface of the material containing the particles, wherein the temperature variations are a result of the magnetic heating (ΤΊ) generated by the alternating magnetic field and/or the optical heating (T₂) generated by the absorbed incident light, and

- optionally, an optical detector configured to measure the optical and magneto-optical effects of the material containing the particles by means of the light (λ) and the intensity of light transmitted, reflected and/or scattered by the material containing the particles, wherein the system or device further comprises support means for placing the material containing the particles, being the support means placed at a position in the device that allows the material containing the particles placed thereon be able to receive the magnetic field generated by the electromagnetic actuator simultaneously with the light emitted by the light source.

The energy for inductive magnetic heating and/or magnetic agitation is provided with alternating currents having frequencies between 1 Hz to 1 MHz.

Advantageously, the hybrid hyperthermia device according to this invention enables that the electromagnetic actuator and the light source may be used either separately or together.

The non-invasive temperature control means according to the present invention is able to detect the variations at the surface of the material when the temperature of the material changes and is able to work within high frequency magnetic fields, especially when the material is subjected to high frequency magnetic fields (1 OkH up to 1 MHz). Preferably, the non-invasive temperature control means is an infrared thermometer. The infrared thermometer detects the variations of the infrared radiation at the surface of the material when the temperature of the material changes.. This is an advantage with respect to fibre-optic thermometers that only work in liquid samples, since the optical fibre must be in contact to the material. Moreover, the cost of the infrared thermometer with respect to optical fibre thermometers is much lower. Other thermometers which have electric readout, such as thermocouples, cannot work inside high frequency magnetic fields, since this field will heat and destroy them, and therefore they are not suitable when a high frequency magnetic field is required according to a particular application. The infrared thermometer may be placed at a distance of the material containing the particles such that it is suitable to read infrared radiation variations at the material's surface. Usually said temperature sensors may pick up the infrared radiation at a distance of up to 30 cm and may measure temperatures between -30 and 900°C. Advantageously, the infrared thermometer can be used for measuring temperatures of a broad scope of materials, such as colloidal dispersions or solid materials, thereby providing a more versatile system or device and a more reliable reading system of the temperature variations.

The hybrid hyperthermia device comprises the following components: i) an electromagnetic actuator having an induction coil that generates a magnetic field with tuneable amplitude H and frequency ω, ii) at least one light source with tuneable intensity, iii) a non-invasive temperature control means and, optionally, iv) at least one optical detector, wherein such components have the meaning described herein.

In an embodiment, the hybrid hyperthermia system or device according to the present invention comprises an optical detector configured to measure the optical and magneto-optical effects of the material containing the particles by means of the light (λ) and the intensity of light (W-cnr²) transmitted, reflected and/or scattered by the material containing the particles.

Advantageously, this embodiment can be used in applications where it is necessary to analyse the magnetic and optical heating or to characterize the properties of a specific area or material subjected to optical and/or magnetic heating.

It is known that the optical properties of a material can vary with a magnetic field. It is also known that the optical and magneto-optical properties of a material are temperature dependent. Therefore, the same material can behave differently depending on the applied optical and magnetic treatment.

The authors of the present invention have designed a hybrid hyperthermia system or device that optionally further provides the analysis of combined optical and magneto-optic effects of a combined optical and magneto-optical actuation in a reliable, easy and secure way.

The optical detector may pick up measurements of the optical and magneto-optic effects resulting from a generated alternating magnetic field and/or resulting from irradiation with light, being tuneable the intensity of the emitted light. A low intensity causes an optical effect due to the transmission, reflection or scattering of light, and a high intensity in addition causes a heat treatment that is an optical heating due to the absorbance of the material.

The optical detector may detect and analyse both effects, allowing the system or device of this invention be able to characterize simultaneously or sequentially the properties of a material. The optical detector includes at least one of a photodiode, a spectrometer, a photon-counter or any other electronic instrument suitable to analyse a component of the light.

The hybrid hyperthermia system or device according to this invention provides access to the optical and magnetic properties of a material, simultaneously with an optical and magnetic actuation on the material. Advantageously, the hybrid hyperthermia system or device is further suitable for characterizing the optical and magnetic properties of a material by using the same intensity, or related, that the one used in the emitted light source, and by using the same intensity, or related, and the same frequency, and/or at higher harmonics, that the one applied for generating the alternating magnetic field.

Advantageously, the generated magneto-optic effects can provide information on the magnetic behaviour of the materials at the frequency and intensity of the magnetic actuation, and the generated optic effects may provide information on the optical behaviour of the materials at the intensity of optical actuation.

The voltage used to generate H is employed to trigger the acquisition of the optical detector, and for the analysis of the magneto-optic effects. All the components are controlled from a hardware and a software.

In a further preferred embodiment, the hybrid hyperthermia system or device further comprises at least a light polarizer capable of polarizing the light emitted by the light source and/or the light transmitted, reflected and/or scattered by the material containing the particles when it is illuminated by the light source, being the light polarizer operatively connected to the light source and/or to the optical detector.

A second aspect of this invention is an implementation of the hybrid hyperthermia system or device according to the first aspect of the present invention.

In this particular implementation, the hybrid hyperthermia system or device according to the first aspect can be used in an in vitro (ex vivo) method for inducing localized hyperthermia by combining optical and magnetic treatment at a specific area of a material containing particles in need to be treated by heat by exposing said material containing the particles to a light intensity emitted by a light source with a wavelength value which is selected within the wavelength range in which the material containing the particles has optical absorption in order to convert the incident light into heat, thereby heating the material containing the particles by optical heating, and simultaneously or sequentially to an alternating magnetic field generated by an electromagnetic actuator provided with an induction coil for magnetic heating and/or magnetic agitation.

Particularly, the optical and magnetic treatment can be a magnetic and optical hyperthermia, and/or a magnetic agitation and optical hyperthermia. The optical and magnetic treatment of a material containing particles in need to be treated by heat can be performed simultaneously or sequentially by using the hybrid hyperthermia system or device according to the first aspect. The combination of an optical heating and a magnetic agitation can be advantageous for applications wherein it is desired to improve the degradation of the material surrounding the particles, such as degradation and/or rupture of capsules containing the particles, or the degradation and/or rupture of extracellular or intracellular components. The magnetic agitation can also be advantageous for the detection of the viscosity and temperature variations around the particles caused by the magnetic and/or optical treatment.

Advantageously, with the hybrid hyperthermia system or device according to this invention the intensity of the magnetic fields required to achieve magnetic heating and the intensity of the light source required to achieve optical heating can be reduced, thus providing a system or device with safer actuation conditions for use in optical and magnetic hyperthermia.

The invention also provides an in vitro (ex vivo) method for inducing localized hybrid treatment at a specific area of a material in need to be treated by heat. This hybrid treatment consist of an optical and magnetic heating, and/or an optical heating together with a magnetic agitation.

The in vitro (ex vivo) method for inducing localized hybrid treatment to a material in need to be treated by heat comprises the steps of:

- dispersing, anchoring or embedding a plurality of particles having optical and magnetic properties in the material in need to be treated by heat,

- exposing said material containing the particles to a light intensity emitted by the light source at a wavelength value selected within the wavelength range in which the material has optical absorption to convert the incident light into heat, thereby heating the material containing the particles by optical heating,

- simultaneously or sequentially exposing said material containing the particles to an alternating magnetic field at a frequency and intensity to excite the particles by means of induction of the alternating magnetic field to generate heat, thereby heating the material containing the particles by magnetic heating, and/or magnetically agitating the particles contained therein and

- monitoring the temperature variations (ΔΤ) at the surface of the material containing the particles by means of the non-invasive temperature control means, and/or around the particles via optical analysis of the particle agitation in liquid.

In a preferred embodiment, when the hybrid hyperthermia system or device further comprises an optical detector, the method further comprises:

- processing the optical and magneto-optical data detected and analysed by means of the optical detector, and optionally at least a light polarizer, to monitor the hyperthermia treatment.

Advantageously, this preferred in vitro (ex vivo) method offers to the user a better and safer control of the hyperthermia treatment. Optical heating is proportional to the intensity of the absorbed light, and the required power of the light source for heating is very dependent on the area of the material that has to be heated.

A method as disclosed above for inducing localized optical and magnetic treatment to an in vitro or an in vivo material in need to be treated is also described herein.

The present invention also provides a hybrid hyperthermia system or device comprising an optical detector configured to measure the optical and magneto-optical effects of the material containing the particles by means of the light (λ) and the intensity of light (W-cnr²) transmitted, reflected and/or scattered by the material containing the particles.

In this particular embodiment, the hybrid hyperthermia system or device having an optical detector can be used in an extra-corporal method for optical and magneto-optical analysis or characterization of a material containing particles by exposing said material containing the particles to a light intensity emitted by a light source simultaneously or sequentially to an alternating magnetic field generated by an electromagnetic actuator provided with an induction coil to subject an optical and magnetic heating.

This particular embodiment is suitable for characterizing magnetic and optical heating in liquid, emulsion and solid materials, thereby allowing better understanding and optimizing the different mechanisms that contribute to the heating process.

The light intensity can be tuneable to be absorbed by the material or tuneable to be transmitted, reflected and/or scattered by the material, or both. One or additional light sources can be employed.

In this optical and magneto-optical characterization, the optical detector is required for measuring and analysing the reflected, transmitted and/or scattered light by the material with or without magnetic/optical heating. This information is used to determine the optical and morphological properties of the material, as for example, existence of optical resonances, optical absorbance, or hydrodynamic radius of the particles, and viscosity and/or local temperature of the liquid around the particles.

The material can be optically analysed with the same light source used for heating or with an additional light source. The analysis can be performed with the transmitted, reflected or scattered light by the sample, which is detected with an optical detector, typically a photodiode, a spectrometer or a photon-counting system. The optical analysis can also include polarizers to detect polarization dependent optical effects, which are especially important to detect the rotation in anisometric or optically anisotropic particles and to detect the magneto-optic activity of the sample.

Analysis of the transmitted/reflected light

In the presence of an alternating magnetic field at ω frequency, the dc component of the transmitted/reflected light intensity can be used to quantify the amount of light absorbed and scattered by the material. This information is useful to understand the optical absorbance and associated heating of the sample and to estimate the concentration of particles in colloidal dispersions. The components of the transmitted/reflected intensity at ω, 2ω, 3ω... frequencies can be used to retrieve the magneto-optic information of the material such as: i) the magneto- optic activity of the sample (Faraday and Kerr effects in transmission and reflection, respectively), ii) the mechanical rotation of colloids in liquid and/or iii) the formation of aggregated chains of particles. The magneto-optic measurements can therefore provide information of the magnetic properties of the material and the dynamics of the colloidal dispersions at the frequency of the magnetic actuation, which are relevant to understand and optimise the magnetic heating of the materials, and to measure the temperature variations.

Analysis of the scattered light

This information is particularly relevant when the material is a colloidal dispersion, because the correlation analysis of the scattered signal can be used to determine the hydrodynamic radius of the colloids and to detect their aggregation during the optical and magnetic actuation.

The invention also provides an extra-corporal method for optical and magneto-optical analysis or characterization of a material containing particles, wherein the material is subjected to an optical and/or magnetic heating.

In this particular application, the hybrid hyperthermia system or device comprises the optical detector.

The extra-corporal method for optical and magneto-optical analysis or characterization of a material containing particles comprises the steps of: a) - exposing said material containing the particles to a light intensity emitted by the light source, in which the light intensity may be tuneable to be absorbed by the material or tuneable to be transmitted, reflected and/or scattered by the material, or both. Additional light sources can be employed, b) - exposing said material containing the particles to an alternating magnetic field generated by the induction coil at a determined intensity and frequency, c) - measuring the temperature at the surface of the material by means of the noninvasive temperature control means, and d) - detection and analysis of the optical and magneto-optical effects by means of the optical detector and, optionally at least a light polarizer, to measure the intensity of the transmitted, reflected or scattered light by the material containing the particles, thereby providing the optical and magneto-optical properties of the material containing the particles, wherein the steps a) and b) are performed simultaneously to cause optical and magneto-optical effects on the material, and wherein the step d) is carried out at the temperature measured in step c), and at the same or related intensity of that of the emitted light source and at the same or related intensity and frequency, and/or at higher harmonics, of that of the alternating magnetic field.

The optical detector may include more than one electronic instrument suitable to analyse a component of the light. The optical detector may include a photodiode capable of analysing the light intensity of the transmitted, reflected or scattered light by the material containing the particles, an spectrometer capable of analysing the light spectrum of the transmitted, reflected or scattered light by the material containing the particles, a photon-counter capable of analysing scattered light by the material containing particles or other not listed here but within the scope of the general knowledge of a skill in this field.

The method as disclosed above for optical and magneto-optical analysis or characterization of a material in an extra-corporal or in an intra-corporal way is also described herein.

Therefore, in view the scope of the present application, the hybrid hyperthermia device can be implemented in different applications. Thus, although the specific term "device" has been generally used in the description, the skilled person in the art would directly and unambiguously derived that the invention covers a hybrid hyperthermia "system" implemented at such applications.

Definitions

According to the scope of the present invention, the term "hybrid" is intended to encompass the fact that the system or device according to the present invention is suitable for generating combined hyperthermia, that is, suitable for generating heat by combined, simultaneously or sequentially, magnetic hyperthermia and optical hyperthermia. Moreover, the term "hybrid" can be also intended to encompass the fact that the system or device according to the present invention is suitable for generating combined optical heating and magnetic agitation. Moreover, the term "hybrid" is also intended to encompass the fact that the system or device of this invention is suitable for generating hyperthermia resulting from optical and/or magnetic heating, optionally with magnetic agitation, and for analysing the optical and magneto-optical properties of a thus treated material.

Therefore, the hyperthermia system or device is hybrid in the sense of a combination of two types of hyperthermia treatments or a combination of optical hyperthermia and magnetic agitation, or a combination of a hyperthermia treatment and the characterization of the optical and/or magnetic properties of a material, which is illuminated at an intensity of light and, simultaneously or sequentially, exposed at an alternating magnetic field. Therefore, the system or device of this invention is also suitable for investigating the mechanisms and sources for heating the particles contained in a material in the application of hyperthermia treatments.

The term "particles" is intended to encompass particles, microparticles, and nanoparticles. Preferably, the particles are nanoparticles. Usually, the particle size is ranging from 1 nm to 1 cm, or from 1 nm to 100 nm, or from 10 nm to 200 nm. The particles may have optical properties, magnetic properties or both simultaneously. The particles may have different shapes including cylindrical, triangular, pyramidal, cubic, spherical, star shape, rod shape or a combination thereof. Any other shape is also contemplated into the scope of the present invention. The particles may be functionalised or coated with polymers, organic and/or inorganic molecules, or biomolecules. It is possible for a functionalised particle to be capable of binding to a particular type of cell and/or molecule, or other specific targets. The particles may be dispersed, anchored or embedded in a material. The particles may be embedded or anchored at the surface of nanocapsules, microcapsules, or vesicular systems.

The term "dispersed particles" is intended to mean particles heterogeneously distributed in a media, usually a liquid or an emulsion material, like in a colloid dispersion. The term "embedded particles" is intended to mean particles heterogeneously or homogeneously distributed in a media, usually a rigid or soft material. For dispersed and embedded particles in a material it is understood in three dimensions. Anchored particles is intended to mean particles uniformly or not uniformly distributed on the top of a material's surface, and therefore, they are distributed in two dimensions, and the surface can be planar or curved. When the anchored particles are distributed on the top of a surface and are close enough to each other, they can form a coating of particles on the surface of the material.

The term "optical particles" is intended to encompass the above "particles" which further are suitable for optical heating. The optical particles are particles which may convert the optical absorption into heat upon receiving an incident light. The oscillation of electrons of said particles stimulated by the incident light may cause an increase of the particle temperature, thereby also increasing the temperature in the surroundings of the particle. When the wavelengths of this incident light overlaps with the wavelength of the optical absorbance of the particle, then there is maximum optical absorption, thereby maximum optical heating. For biomedical applications, near infrared light is advantageous due to the lower absorption by the tissue and higher penetration.

The term "magnetic particles" is intended to encompass the above "particles" which further are suitable for magnetic heating and/or magnetic agitation. The magnetic particles are superparamagnetic or ferromagnetic particles. The magnetic particles may be heated by the mechanisms of hysteresis, Foucault currents, or friction and relaxation. The magnetic particles may be agitated by magnetic torques, i.e. by aligning their magnetic moment parallel to the magnetic field. The magnetic particles include particles which have known magnetic moments that, once exposed to an alternating magnetic field, the temperature of the magnetic particles increase and/or tend to be aligned their magnetic dipole moment parallel to the magnetic field.

The term "material" is intended to encompass living material or inert material. The living material includes a human, animal, or a biopsied thereof. The living material includes a cell culture or a tissue. The inert material means a non-living material. The inert material includes a non-cellular non-tissue material, a liquid or emulsion with dispersed colloids or a nanostructure, nanocapsule, microcapsule or a micelle, being the nanostructure, nanocapsule, microcapsule or micelle dispersed or embedded in a liquid or emulsion. When the material has superparamagnetic or ferromagnetic components and presents optical absorption, simultaneous or sequential optical heating and magnetic heating/agitation can be induced. Materials with low electrical resistance components can also be heated magnetically via eddy currents. Thus, the material in need to be treated by heat may be a liquid material, and emulsion material or a solid material, and the particles may be dispersed, anchored or embedded in the material.

The term "a light source" is intended to encompass at least a light source. A light source includes a source capable of emitting a light intensity within the range from close to zero, but different to zero, up to 100 W-cnr², preferably from 0.05 to 100 W-cnr², more preferably from 0.05 to 50 W-cnr². The light source includes a laser light source or another light source such as a LED. The light source of this invention may be selected from a monochromatic light source or a polychromatic light source. More than one light source may be combined. It is desirable to combine more than one light source to also combine the optical heating and the light analysis, as for example, one laser light source for optical heating and one white light source for spectral analysis.

The term "electromagnetic actuator" is understood as a solenoid/coil. The solenoid is a physical device capable of creating a highly uniform and intense alternating magnetic field inside, and very weak on the outside. According to this invention, the magnetic field "H" may have an amplitude value between close to zero, such as 0.01 Oe, to 700 Oe, which oscillates at a frequency "ω" between 1 Hz and 1 MHz. For magnetic heating the frequency of the magnetic field might preferably be between 10 kHz and 1 MHz, and more preferably between 100 kHz and 1 MHz. For magnetic agitation and for the detection and analysis of particles rotation in the liquid the magnetic field frequency might preferably be between 1 Hz and 10 kHz.

In a preferred embodiment, the electromagnetic actuator provided with a coil is associated to a resonant LC circuit. It is desirable a maximum amplitude of the magnetic field and a high frequency in order to achieve faster magnetic heating, and to better analyse the magneto-optic effects. The preferable frequency is the resonant frequency which can be tuned by means of modifying the capacitance I of the resonant LC circuit.

In a preferable embodiment of this invention, the electromagnetic actuator is further provided with cooling means, which are capable of keeping constant the temperature of the coil and/or keeping constant the temperature of the material containing the particles. Advantageously, the intrinsic heating of the coils is also avoided.

In another embodiment, the electromagnetic actuator is enclosed in a support structure, such as a cage, that has transparent apertures to enable the transmission of light emitted by the light source inside the magnetic actuation region, i.e., the material is placed in a position inside or next to the electromagnetic actuator to be suitable to receive the alternating magnetic field and at the same region to be suitable to receive the light, thereby the material can be simultaneously optically and magnetically treated. The term "treated" includes a heat treatment, and/or a light or magnetic treatment with an intensity of the incident light or magnetic field as reduced as to minimize or to eliminate optical or magnetic heating.

The term "non-invasive temperature control means" is understood as any mean to detect temperature variations. Particularly, the non-invasive control temperature means is able to detect the variations of an infrared radiation at the surface of the material when the temperature of the material changes and is able to work within high frequency magnetic fields. Preferably, the non-invasive control temperature control means is an infrared thermometer which allows to detect the temperature variations generated by combined optical and magnetic hyperthermia. The non-invasive temperature control means can be a thermocouple to detect temperature variations when the alternating magnetic field is within 1 Hz to 10 kHz (low frequency magnetic fields) to generate a magnetic agitation.

Brief Description of the Drawings

Figure 1 depicts a schematic view of the hybrid hyperthermia system or device according to the present invention showing the components for combined optical heating and magnetic heating/agitation, and for the detection of temperature variations.

Figure 2 depicts a schematic view of the hybrid hyperthermia system or device of this invention showing the components for analysing the transmitted intensity and magneto-optic Faraday effects, represented by solid and dashed arrows.

Figure 3 depicts a schematic view of the hybrid hyperthermia system or device of this invention showing the components for optical characterization of the scattered light, represented by solid and dashed arrows.

Figure 4 depicts a schematic view of the hybrid hyperthermia system or device of this invention showing the components for analysing the reflectance and the magneto-optic polar (left) and longitudinal (right) Kerr effects, represented by solid and dashed arrows.

Figure 5 depicts a graph of the voltage signal (V_w) of a photodiode versus the voltage applied in the coil (Vr_w) to generate the magnetic field (H) according to Example 1 . The graph shows the magnetic hysteresis loop of iron/gold nanoparticles.

Figure 6 depicts a graph of the temperature (°C) versus time (s) in the surface of a colloidal dispersion of iron/gold nanoparticles in water heated by combination of light and magnetic fields, acquired by the infrared thermometer according to Example 1 .

Figure 7 depicts a graph of the phase variation of particle rotation versus time (s) of cobalt/gold nanoparticles in water heated by light, detected by the analysis of the intensity of the transmitted light in the presence of a magnetic field of 600 Hz and 20 Oe, and compared to the temperature measured by the IR thermometer.

Detailed Description of the Invention

Hereinafter, the best mode for carrying out the present invention is described in detail. The magnetic heating is based on hysteresis losses and viscous loses in magnetic particles induced in alternating magnetic fields. Eddy currents in metal materials can also induce heating. The magnetic agitation is based on magnetic torque that tends to align the magnetic moment of the particles parallel to the alternating magnetic field. The alternating magnetic field is generated by the coil when the material is placed inside or next to the coil.

In the presence of an alternating magnetic field, the amplitude of the DC component of the detected reflected, transmitted or scattered light is used to determine the optical properties of the material at the given temperature. Since the optical properties are wavelength dependent, the light source can be monochromatic or polychromatic, and the detector can analyse the intensity or the spectrum of the reflected, transmitted or scattered light by the sample.

The magneto-optic effects are determined by the intensity variations of the reflected, transmitted or scattered light at the frequency (or higher harmonics) of the alternating magnetic field at the given temperature. Since the magneto-optical properties are wavelength dependent, the light source can be monochromatic or polychromatic, and the detector can analyse the intensity or the spectrum of the reflected, transmitted or scattered light by the sample. The intensity variations can be detected for example via FFT analysis of the detected light intensity or with a lock-in amplifier.

Some magneto-optic effects induce changes in the polarization of the reflected, transmitted or scattered light, as for example the Faraday rotation of the polarization of the transmitted light by the sample. Polarizers and additional optical and electronic instruments such as elasto- optic modulators can be introduced to detect such polarization based magneto-optic effects.

The Faraday Effect is a rotation of the polarization plane of the transmitted light through the sample that is proportional to the magnetization M of the sample. The Faraday effect is used to obtain the hysteresis loop M(H) of the sample and the temporal evolution of M, which will depend on the temperature T. The transmittance provides information related to the optical absorption of the material, which is related to the optical heating.

The Kerr effect in the polar and longitudinal configurations is a rotation of the polarization plane of the reflected light by the sample that is proportional to the magnetization M of the sample. In the polar Kerr effect, the magnetic field is applied perpendicular to the sample. In the longitudinal Kerr effect the magnetic field is in the plane of the sample and in the incidence plane of the light. The Kerr effect is used to obtain the hysteresis loop M(H) of the sample and the temporal evolution of M, which will depend on the temperature T. The reflectance provides information related to the optical absorption of the material, which is related to the optical heating. The alternating magnetic field can also induce the agitation or rotation of the particles in the solution. When the particles are optically anisotropic, i.e. their scattering and/or absorption changes with the polarization of the incident light, then the transmitted, reflected or scattered light will suffer an intensity modulation when the incident light is linearly polarized. When the magnetic field oscillates at frequency w, the intensity modulation will generally have a 2ω frequency and possibly also higher harmonics. The phase difference between the applied magnetic field and the rotation of the particles, and consequently, the modulated transmitted, reflected or scattered light is highly dependent on the magnetic field amplitude and frequency, as well as the size, shape and mass of the particles, and the viscosity of the liquid. For a given type of particle and a fixed magnetic field amplitude and frequency, the phase difference between the magnetic field and the optical modulation can be used to monitor the viscosity changes in the liquid around the particles. When the viscosity of the liquid decreases as the temperature increases, the quantification of the phase change can be used as local thermometer to monitor the temperature variations around the particles. The same light source that is employed for optical heating can also be simultaneously or sequentially used to monitor the temperature increase around the particles, i.e. inside the liquid. This method to detect the temperature variations has the advantage of providing a temperature measurement inside the liquid, contrary the IR thermometer that measures at the surface of the liquid. This feature enables faster and more accurate detection of the temperature variations around the particles.

When there is not magnetic field, there is not magnetic heating and the magneto-optic effects cannot be detected.

Optical heating of the material is induced by a light beam when the sample has optical absorption. The absorbed light is transformed into heat. The light beam is generated by a light source, typically a laser, which is directed to the material.

If the intensity of the light beam is low, the optical heating is not sufficient for practical photothermal applications. However, such light typically a laser or LED can be used to determine optical and magnetic properties of the material.

The hybrid hyperthermia system or device of this invention, which is used together with a plurality of particles, comprises the elements shown in Figures 1 to 4 which are included below. Figures 1 to 4 also depict a simultaneous magnetic and optical heating and their effects, represented by solid and dashed arrows, temperature monitoring and Figures 2 to 4 show in addition detection of the optical and magneto-optical effects of the material.

In Figures 1 to 4, an electromagnetic actuator 1 is provided with a coil 1 1 to generate the alternating magnetic field Η(ω), which is based on a resonant LC circuit. The coil 1 1 is internally refrigerated to keep controlled temperature. The electromagnetic actuator enables modifying both the resonant frequency of the LC circuit by changing the capacitance of the circuit, and the intensity of the applied magnetic field. The electromagnetic actuator 1 1 is enclosed in a cage (not showed) that has transparent apertures to enable the transmission of light inside the magnetic actuation region, where the sample S is placed.

An alternating magnetic field Η(ω) is generated. The alternating magnetic field can have a single frequency or multiple frequencies. The frequency typically ranges from 1 Hz to 1 MHz, and the amplitude from 0 to 700 Oe. For magnetic heating in biomedical applications it is important to control the product Η-ω, to be within the recommended safety values for humans.

A light source 2 which is suitable for: i) inducing optical heating in the sample, and ii) analysing the optical and magneto-optical properties of the material. Additional light sources (λι , λ₂, λ₃, ..) can be employed to combine optical heating and light treatment.

At least one light beam is incident to the sample S. The light beam can be polarized using a polarizer 6 as it is shown in the figures 2 to 4. For efficient optical heating the wavelength of the light, laser 2, should be chosen in the wavelength range that maximises the optical absorption of the material. Optical heating is proportional to the intensity of the light beam.

An infrared thermometer 3 to measure the temperature increase of the surface of the material during the actuation of the alternating magnetic field and/or the light source.

The infrared thermometer 3 detects the temperature variations of the sample S caused by the light and/or alternating magnetic field actuation.

An optical detector 4 to measure the intensity variations or the spectrum of the transmitted, reflected or scattered light by the material. The optical detector can typically be a photodiode to analyse light intensity, or a spectrometer to analyse light spectrum. Other types of detectors, such a photon-counters can be employed to analyse the scattered light by the material, which has much lower intensity. The optical detector can include additional electronic instruments such as an amplifier to amplify the power of a signal and to convert it into voltage.

The optical detector 4 detects the transmitted (fig. 2), reflected (fig.4), or scattered (fig. 3) light by the sample. The optical detector 4 also detects the intensity variations (fig.3) of the scattered light by the sample.

The detector 4 can detect the light from the light beam used for heating or from an additional light source 2 with low intensity that will not cause appreciable heating in the material. The signal of the optical detector 4 is analysed to determine the optical and/or magneto-optical characteristics of the sample at the given temperature.

At least a light polarizer 6 to polarize the light emitted by the light source. A polarizer 6 can also be introduced before the detector 4 to polarize the transmitted, reflected and/or scattered light by the sample. The support means for placing the material are disposed inside or next to the induction coil of the magnetic actuator, where the magnetic field (H) is generated. The support means may be, for example, a glass slide, a polymer film or a tissue.

Examples

Hereinafter, the present invention is described in more detail and specifically with reference to the Examples and Figures, which however are not intended to limit the present invention.

Example 1 : Combined magnetic heating/agitation and optical heating, and detection of the temperature variations in the surface of the material (Figure 1)

For combined optical heating and magnetic agitation the sample S is placed next to the coil 1 1 , the amplitude of the magnetic field H is 20 Oe and oscillates at frequency ω of 200 Hz. The laser beam emitted by a laser 2 has a wavelength of 808 nm. The laser 2 intensity incident on the sample is lo = 2 W-cnr². The sample S is an emulsion with dispersed Fe₂0₃ nanoparticles embedded inside biodegradable polymer nanocapsules. The laser light induces optical heating in the nanoparticles and the alternating magnetic field induces the magnetic agitation. The combination of both effects accelerates the degradation of the biodegradable polymer. The temperature variation at the surface of the sample is detected with an IR thermometer.

For combined optical heating and magnetic heating the sample S is placed next to the coil 1 1 , the amplitude of the magnetic field H is 200 Oe and oscillates at frequency ω of 200 kHz. The laser beam emitted by a laser 2 has a wavelength of 808 nm. The laser 2 intensity incident on the sample is lo = 2 W-cnr². The sample S is an emulsion with dispersed Fe₂0₃ nanoparticles embedded inside biodegradable polymer nanocapsules. The laser light induces optical heating in the nanoparticles and the alternating magnetic field induces magnetic heating. The combination of both effects accelerates the degradation of the biodegradable polymer and increases the local temperature locally with more efficiency. The temperature variation at the surface of the sample is detected with an IR thermometer. Example 2: Simultaneous Magnetic and optical heating, detection of transmittance and magneto optic Faraday Effect in the transmitted light, and detection of the scattered intensity and magneto-effects in the scattered light The sample S is placed inside the coil 1 1 , the amplitude of the magnetic field H is 200 Oe and oscillates at frequency ω of 200 kHz. The laser beam emitted by a laser 2 has a wavelength of 785 nm. The laser 2 is linearly polarized by the polarizer 6 and intensity incident on the sample is lo = 10 W-crrr².

The sample S is a colloidal dispersion of iron/gold nanoparticles with a concentration of 50 μg/mL in water. The total volume of the sample is 500 μΙ_. The temperature varies from 20⁵C to 40⁵C.

Acquisition of the optical transmittance and magneto-optic Faraday Effect in the transmitted light (Figure 2):

To acquire the Faraday Effect, the transmitted light through the sample S passes through a polarizer 6 that is rotated an angle Θ from 70 to 85 degrees with respect to the polarization of the incident light. The light transmitted through the polarizer 6 is detected with an optical detector which in this case is a photodiode 4.

The current signal of the photodiode 4 can be amplified and is converted into voltage.

The amplified temporal variation of the voltage signal V(t) of the photodiode 4 is acquired and digitalized. To synchronize the acquisition of V(t) with the applied magnetic field H, the voltage applied in the coil Vr(t) to generate H is acquired. Vr(t) is proportional to H(t). Vr(t) is used to trigger the acquisition of the signal of the photodiode V(t).

The hysteresis loop of the sample S is obtained by plotting V(t) versus Vr(t), see Figure 5, since V(t) is proportional to M in the sample, and Vr is proportional to the applied H. Figure 6 depicts the temperature (°C) versus time (s) acquired by the infrared thermometer 3.

In addition, Fast Fourier Transform of the digitalized voltage signal V(t) is performed. The dc component of the FFT (Vdc) provides the optical signal, in this case Vdc/(Vo sin0) gives the transmittance through the sample S, where Vo is the acquired voltage without sample.

The FFT component at ω frequency V1 ω is used to acquire the amplitude of the magneto-optic Faraday Effect, which is monitored over time to detect the variations of M with T.

Acguisition of the intensity and magneto-optic effects in the scattered light (figure 3):

To acquire the scattered light the optical detector, which in this case is photomultiplier tube 4, is placed at and angle that cannot detect the transmitted or reflected light, but only the light scattered by the sample S. The acquired intensity is digitalized and analysed via autocorrelation function: _{2 (} . (/(*)/(* + Τ))

^{5 W, r} <Ι(ί))² where g^g; CT) is the autocorrelation function at a particular wave vector q, and delay time τ, and / is the intensity. The angular brackets <> denote the expected value operator.

The autocorrelation analysis is used to determine the hydrodynamic radius of the colloids and the variations of the intensity at the 1/rrelated to the frequency ro of the applied magnetic field.

Example 3: Simultaneous Magnetic and optical heating, detection of reflectance and magneto-optic Kerr effect in the reflected light, and detection of the scattered intensity and magneto-effects in the scattered light (Figure 4)

The sample S is placed inside the coil 1 1 , the amplitude of the magnetic field H is 200 Oe and oscillates at frequency ω of 200 kHz. The laser beam emitted by a laser 2 has a wavelength of 785 nm. The laser 2 is linearly polarized by using a polarizer 6 and the incident intensity on the sample is lo = 10 W-cnr².

The sample S is a solid. The sample is composed of a monolayer of iron/gold nanoparticles adhered on a solid support (glass slide or polymer film) with a surface concentration of 15 nanoparticles/μΓΤΐ². The total area of the sample is larger than the size of the light beam. The temperature varies from 20⁵C to 80⁵C.

Acquisition of the optical reflectance and magneto-optic Kerr effect in the reflected light (figure 4):

To acquire the Kerr effect, the reflected light through the sample S passes through a polarizer 6 that is rotated an angle Θ from 70 to 85 degrees with respect to the polarization of the incident light. The light transmitted through the polarizer 6 is detected with a photodiode 4. The analysis of the signal is identical to the case of the Faraday rotation.

Example 4: Simultaneous optical heating, and detection of the local temperature variation around the particles via analysis of the particle rotation in the liquid (Figure 2)

The sample S is placed inside the coil 1 1 , the amplitude of the magnetic field H is 20 Oe and oscillates at frequency ω of 600 Hz. This magnetic field induces the rotation of the particles in the liquid. The laser beam emitted by a laser 2 has a wavelength of 808 nm. The laser 2 is linearly polarized by using a polarizer 6 and the incident intensity on the sample is initially lo = 0.1 W-cnr², and at the time 300 s, the intensity in increased to Ih = 1 W-cnr².

The sample S is colloidal dispersion of CoAu nanoparticles with high optical anisotropy at 808 nm wavelength. The temperature at the surface of the liquid detected with the IR thermometer varies from 27.3⁵C to 32.5⁵C when the light increases from lo to Ih.

Determination of the temperature variation around the CoAu nanoparticles using the intensity modulation in the transmitted light (figure 7):

To detect the temperature variations, the transmitted light through the sample is detected with an optical detector 4 such as a photodiode, and the polarizer before the detector is either removed or parallel to the polarizer 6 after the laser. The voltage to generate the magnetic field is used to trigger the acquisition of the intensity variations. A FFT analysis of the acquired transmitted intensity is used to extract the amplitude and phase of the light intensity modulation at the frequency 2ω (1200 Hz). The heating generated by the laser around the particles when the laser intensity increases to Ih induces a reduction of the viscosity around the particles, which reduces the dephasing between the magnetic field and the rotation of the particles. The phases variation in 2ω can therefore, be used to monitor the temperature variations induced by the light source in the liquid around the particles.

As described above in detail, the hybrid hyperthermia system or device according to this invention has at least one of the following advantages:

- The optical and magnetic properties of the materials which are temperature dependent may be detected and analysed with the hybrid hyperthermia device of this invention. For example, there can be phase transitions at a specific temperature that can modify the optical and/or magnetic properties of the materials, or the change of the magnetic character of the ferromagnetic materials at the Curie temperature.

- The magnetic properties of the materials which are frequency dependent may be detected and analysed with the hybrid hyperthermia device of this invention. The hysteresis loops can increase their area as the frequency increases. The area of the hysteresis loop is related to the capacity of the magnetic material to generate heat via hysteresis loses.

- The optical properties which are wavelength dependent, such as the absorption of the material and the related temperature increase upon illumination which depends on the wavelength may be detected and analysed with the hybrid hyperthermia device of this invention. For example, for efficient optical heating, the wavelength should be selected at the spectral region with maximum absorption of the material.

- The optical properties which can vary with the magnetic field (with both amplitude and frequency) may be detected and analysed with the hybrid hyperthermia device of this invention. For example, the generation of magneto-optic effects (Faraday or Kerr), or changes in the orientation or distribution of nanoparticles in a fluid in a presence of a magnetic field (alignment of easy magnetization axis of the particles parallel to the magnetic field direction, or formations of chains or aggregates in the presence of a magnetic field) depend on the amplitude and frequency of the magnetic fields.

- The Kerr and Faraday magneto-optic effects which provide information related to the magnetic properties of the material may be detected and analysed with the hybrid hyperthermia device of this invention. Other magneto-optic effects which can provide information on the orientation and distribution of the nanoparticles are also possible to be detected and analysed.

- The properties of the medium surrounding the nanoparticles which can also change with temperature may be detected and analysed with the hybrid hyperthermia device of this invention. For example, the refractive index of the medium in contact to the nanoparticles can change with the temperature. The coatings that the nanoparticles can have can also change with the temperature and with magnetic agitation, for example dehybridization of DNA chains, thermally responsive polymers, such as PNIPAAm, degradation of biodegradable polymers, rupture of vesicular systems. These changes can be optically detected. As the viscosity of the liquid around the particles also changes with the temperature, optical analysis of the magnetic rotation of the particles in the liquid can be employed to monitor the temperature variations around the particles, as the ones induced by optical or magnetic heating.

With the hybrid hyperthermia system or device of this invention it is offered a new way to understand and optimise the properties of the materials for optical and/or magnetic thermal applications, which allows to simultaneously analyse the optical and magneto-optical properties and the temperature of the material while magnetic and/or optical heating is induced, since such properties might change with the temperature.

It is a matter of course that the features mentioned above and those explained below can be used in other combinations in addition to those described, on in isolation, without departing from the scope of the invention.

Claims

1. A hybrid hyperthermia device using particles in a material in need to be treated by heat, the device comprising:

- an electromagnetic actuator (1 ) of tuneable intensity and frequency (ω) provided with an induction coil (1 1 ) and configured to generate a magnetic field on the material containing the particles by means of induction of an alternating magnetic field (H₍₀₎)), thereby the material rises its temperature (ΤΊ) and/or the particles contained therein magnetically agitate (Ai),

- at least a light source (2) provided with an emitted light intensity configured to illuminate the material containing the particles, being the material containing the particles capable of transmitting, reflecting or scattering the incident light, or absorbing the incident light thereby optically heating (T₂) the material containing the particles,

- a non-invasive temperature control means (3) configured to measure temperature variations (ΔΤ) at the surface of the material containing the particles, wherein the temperature variations are a result of the magnetic heating (ΤΊ) generated by the alternating magnetic field and/or the optical heating (T₂) generated by the absorbed incident light, and

- optionally, an optical detector (4) configured to measure the optical and magneto- optical effects of the material containing the particles by means of the light (λ) and the intensity of light transmitted, reflected and/or scattered by the material containing the particles, wherein the system or device further comprises support means (5) for placing the material containing the particles, being the support means placed at a position in the device that allows the material containing the particles placed thereon be able to receive the magnetic field generated by the electromagnetic actuator simultaneously with the light emitted by the light source.

2. Hybrid hyperthermia device according to claim 1 , wherein the device further comprises at least a light polarizer (6) capable of polarizing the light emitted by the light source and/or the light transmitted, reflected and/or scattered by the material containing the particles, being the light polarizer (6) operatively connected to the light source (2) and/or to the optical detector (4).

3. Hybrid hyperthermia device according to claim 1 , wherein the electromagnetic actuator (1 ) is associated to a resonant LC circuit having a resonance frequency ranging from 1 Hz and 1 MHz, tuneable by means of modifying the capacitance (C) of the resonant LC circuit.

4. Hybrid hyperthermia device according to any one of previous claims, wherein the electromagnetic actuator (1 ) is further provided with cooling means capable of keeping constant the temperature of the coil and/or keeping constant the temperature of the material containing the particles.

5. Hybrid hyperthermia device according to any one of previous claims, wherein the electromagnetic actuator (1 ) is arranged in a structure provided with transparent apertures to enable the transmission of the light emitted by the light source inside an area where the alternating magnetic field is generated, thereby the material containing the particles being simultaneously optically and magnetically treated.

6. Hybrid hyperthermia device according to claim 1 , wherein the light source (2) is selected from a monochromatic light source or a polychromatic light source, and wherein the intensity of emitted light ranges from close to zero, but different to zero, up to 100 W-crrr².

7. Hybrid hyperthermia device according to claim 1 , wherein the non-invasive temperature control means is an infrared thermometer (3) and it is placed at a distance of the material containing the particles suitable to read infrared radiation variations at the material surface.

8. Hybrid hyperthermia device according to claim 1 , wherein the optical detector (4) includes at least one of a photodiode, an spectrometer, a photon-counter or other electronic instrument suitable to analyse a component of the light.

9. Hybrid hyperthermia device according to claim 1 , wherein the support means (5) for placing the material containing the particles are disposed inside or next to the induction coil (1 1 ) of the electromagnetic actuator (1 ), where the alternating magnetic field (H) is generated.

10. Use of a hybrid hyperthermia device according to any one of claims 1 to 9 in an in vitro (ex vivo) method for inducing localized hybrid hyperthermia at a specific area of a material in need to be treated by heat by exposing said material containing the particles to a light intensity emitted by a light source with a wavelength value which is selected within the wavelength range in which the material containing the particles has optical absorption in order to convert the incident light into heat, thereby heating the material containing the particles by optical heating, and simultaneously or sequentially to an alternating magnetic field generated by an electromagnetic actuator provided with an induction coil for magnetic heating and/or magnetic agitation.

11. Use of a hybrid hyperthermia device according to any one of claims 1 to 9, the hybrid hyperthermia device comprising an optical detector, in an extra-corporal method for optical and magneto-optical characterization of a material containing particles by exposing said material containing the particles to a light intensity emitted by a light source, simultaneously or sequentially to an alternating magnetic field generated by a electromagnetic actuator provided with an induction coil.

12. Use according to claim 1 1 , wherein the optical and magneto-optical characterization is carried out by the optical detector by using the same or related light intensity of that of the emitted light source and using the same or related intensity and frequency and/or at higher harmonics of that of the applied alternating magnetic field.

13. Use according to claim 10, wherein the in vitro (ex vivo) method for inducing localized hybrid hyperthermia at a specific area of a material in need to be treated by heat comprises the steps of:

- dispersing, anchoring or embedding a plurality of particles having optical and/or magnetic properties in the material in need to be treated by heat,

- exposing said material containing the particles to a light intensity emitted by a light source at a wavelength value which is selected within the wavelength range in which the material has optical absorption to convert the incident light into heat, thereby heating the material containing the particles by optical heating,

- simultaneously or sequentially exposing said material containing the particles to an alternating magnetic field at a frequency and intensity to excite the particles to generate heat, thereby heating the material containing the particles by magnetic heating or to generate magnetic agitation, and

- monitoring the temperature variations at the surface of the material containing the particles by means of the infrared thermometer and/or around the particles via optical analysis of the particle agitation in liquid.

14. Use according to claim 1 1 , wherein the extra-corporal method for optical and magneto- optical characterization of a material containing particles comprises the steps of: a) - exposing said material containing the particles to a light intensity emitted by a light source, in which the light intensity may be tuneable to be absorbed by the material or tuneable to be transmitted, reflected and/or scattered by the material; b) - exposing said material containing the particles to an alternating magnetic field generated by an induction coil at a determined amplitude and frequency, c) - measuring the temperature at the surface of the material by means of the infrared thermometer, and d) - detection and analysis of the optical and magneto-optical effects using an optical detector, and optionally at least a light polarizer, to measure the intensity of the transmitted, reflected or scattered by the material containing the particles, thereby providing the optical and magneto-optical properties of the material containing the particles, wherein the steps a) and b) are performed simultaneously to cause optical and magneto-optical effects on the material, and wherein the step d) is carried out at the temperature measured in step c) and at the same or related intensity of that of the emitted light source and at the same or related intensity and frequency, and/or at higher harmonics, of that of the alternating magnetic field.

15. Use according to claims 1 1 or 14, wherein the optical detector includes at least one of a photodiode capable of analysing the light intensity of the material containing particles, a spectrometer capable of analysing the light spectrum of the material containing particles, a photon-counter capable of analysing scattered light by the material containing particles or other electronic instrument suitable to analyse a component of the light.