IT201900005362A1 - NEEDLE OR CATHETER PROVIDED WITH A PLURALITY OF OPTICAL FIBERS - Google Patents

Description

NEEDLE OR CATHETER PROVIDED WITH A PLURALITY OF OPTICAL FIBERS

Field of the invention

The present invention relates to a needle or catheter for medical use comprising a plurality of optical fibers and to a device comprising said needle or catheter.

State of the art

In the medical sector there are numerous devices for diagnostic, therapeutic or surgical use. In order to diagnose, administer active ingredients and perform surgical interventions in a localized way, we try to reduce the size of medical devices as much as possible.

Each device performs a specific function. However, it would be particularly advantageous to have a single device which has adequately reduced dimensions to be able to carry out localized operations and which at the same time allows a plurality of operations to be carried out.

Summary of the invention

An object of the present invention is to provide a medical device of reduced dimensions to be able to locally perform a plurality of operations, for example diagnostic imaging, biochemical analyzes, release of drugs or active ingredients in general and surgical operations such as laser cuts or ablations.

In particular, an object of the present invention is to provide a needle or catheter, or a device comprising such a needle or catheter, which allows a plurality of operations to be performed.

Another purpose of the invention is to create a medical device that effectively allows you to perform diagnostics using SERS spectroscopy.

The present invention achieves at least one of these objects, and other objects which will be evident in the light of the present description, by means of a needle or a catheter for medical use comprising within it at least two different optical fibers, said at least two optical fibers being selected. between:

- a first optical fiber provided with at least one optical sensor, the optical sensor being able to be deformed when it comes into contact with a biological tissue;

- a second optical fiber functionalized with at least one particle of a polymeric gel comprising at least one photosensitive molecule and at least one biomolecule, in which the at least one particle of the polymeric gel is covalently linked to said second optical fiber;

- a third optical fiber, of the multimode type, having a core with a diameter between 100 and 1000 µm configured to confine laser light having a power density from 8 to 20 W / cm <2> and a wavelength between 800 nm and 10 µm; - a fourth optical fiber having an end provided with an optical transducer, the optical transducer being made, at least partially, of polymeric material capable of deforming when subjected to acoustic waves with a frequency between 1 and 100 MHz and an average intensity between 1 and 10 W / cm <2>;

- a fifth optical fiber having one end provided with a metal and / or polymeric coating, the fifth optical fiber comprising at least one diffraction grating; and / or in which the needle or catheter includes a plurality of fifth optical fibers inside.

According to one aspect, the invention comprises a medical device comprising at least a needle or a catheter according to any one of claims 1 to 7, and a body attached to said needle or catheter, the body preferably provided with at least a grip portion for be able to grasp the medical device.

According to one aspect, the invention comprises a system comprising a needle or a catheter according to any one of claims 1 to 7 or a medical device according to claim 8 or 9, comprising at least an optoelectronic interrogation unit adapted to be connected to at least one of said optical fibers for receiving data from the optical fiber to which it is connected;

and / or at least one lighting unit designed to be connected to said at least two optical fibers, configured to generate a beam of light that propagates from the inside of the optical fibers to which it is connected to the outside.

Advantageously, the first optical fiber is suitable for carrying out elastographic measurements of biological tissues; the second optical fiber is adapted to effect a release, for example a controlled release, of said at least one biomolecule, for example of one or more drugs or active ingredients; the third optical fiber is suitable for performing laser surgery operations, for example laser ablation; the fourth optical fiber is adapted to carry out diagnostic imaging, or imaging, in particular by ultrasonography; the fifth optical fiber is suitable for performing biochemical analyzes, for example for the detection of target proteins and / or diagnostics using SERS (Surface Enhanced Raman Scattering) spectroscopy.

Advantageously, the needle or the catheter, or a device that comprises the needle and / or the catheter, comprises a plurality of optical fibers, each of which being designed to perform at least one specific function, thus allowing to carry out simultaneously and directly in vivo inside the human or animal body, at least two operations including biochemical analyzes, controlled drug release, laser ablation, tissue imaging using SERS and / or ultrasound techniques, and elastographic investigations useful for positioning the needle and / or catheter in a precise space or biological compartment, ensuring minimum invasiveness and maximum effectiveness in terms of performance. Furthermore, given its compact size, the device can be integrated into robotic platforms for minimally invasive surgery.

Advantageously, moreover, the medical device is biocompatible, has no electrical contacts that can limit its in-vivo application, and does not generate unwanted electromagnetic interactions.

Advantageously, a robotic telemedicine system can be equipped with the needle or catheter according to the invention, or with a device including the needle or catheter.

According to one aspect, a plurality of fifth optical fibers is provided, alone or in combination with the other optical fibers, so as to be able to efficiently perform diagnostics by means of SERS spectroscopy. For example, nine or more fifth optical fibers may be provided.

Further features and advantages of the invention will become more evident in the light of the detailed description of exemplary, but not exclusive, embodiments.

The dependent claims describe particular embodiments of the invention.

Brief description of the figures

In the description of the invention, reference is made to the attached drawing tables, which are provided by way of non-limiting example, in which:

Fig. 1 schematically illustrates a perspective view of part of a needle comprising a plurality of optical fibers according to the invention;

Fig. 2a schematically illustrates a perspective view of part of an example of an optical fiber;

Fig.2b schematically illustrates a perspective view of part of another example of an optical fiber;

Fig.3a schematically illustrates a perspective view of part of another example of an optical fiber;

Fig.3b schematically illustrates a perspective view of part of another example of an optical fiber;

Fig. 4 schematically illustrates a side view of a device according to the invention;

Fig.5 schematically illustrates a section of the device of Fig.4;

Fig.5a illustrates an enlarged detail of Fig.5.

The same elements, or functionally equivalent elements, have the same reference number.

Description of exemplary embodiments of the invention

A needle 1 or a catheter for medical use is described comprising inside at least two different optical fibers,

said at least two optical fibers being preferably selected from:

- a first optical fiber 10 provided with at least one optical sensor 11, the optical sensor 11 being able to be deformed when it comes into contact with a biological tissue;

- a second optical fiber 20 functionalized with at least one particle, preferably a plurality of particles, of a polymeric gel comprising at least one photosensitive molecule and at least one biomolecule, in which the at least one particle of the polymeric gel is covalently linked to said second optical fiber 20;

- a third optical fiber 30, of the multimode type, having a core with a diameter between 100 and 1000 nm, configured to confine laser light having a power density in the range 8-20 W / cm <2> and a wavelength between 800 nm and 10 µm, the third optical fiber 30 being preferably configured to confine pulsed laser light having an energy up to 1 GW / cm <2> and / or continuous laser light having an energy up to 2 MW / cm <2>;

- a fourth optical fiber 40 having an end provided with an optical transducer 41, the optical transducer 41 being able to deform when subjected to acoustic waves with a frequency between 1 and 100 MHz and intensity, in particular medium intensity, between 1 and 10 W / cm <2>, preferably in which the optical transducer 41 is made, at least partially, of polymeric material, preferably with a low Young's modulus, for example between 0.5 and 1 GPa; the polymeric material preferably comprising p-xylene, such as for example parylene; - a fifth optical fiber 50 having one end provided with a metallic and / or polymeric coating 51 having a thickness between 100 nm and 10 µm, the fifth optical fiber 50 comprising at least a diffraction grating 511, 512; and / or in which the needle or catheter comprises a plurality of fifth optical fibers 50.

The first optical fiber 10 is suitable for carrying out elastographic measurements of biological tissues; the second optical fiber 20 is adapted to effect a release, for example a controlled release, of said at least one biomolecule, for example of one or more active principles; the third optical fiber 30 is adapted to perform laser surgery operations, for example laser ablation;

the fourth optical fiber 40 is adapted to carry out diagnostic imaging, or imaging, in particular by means of ultrasonography;

the fifth optical fiber 50 is adapted to perform diagnostics by means of SERS spectroscopy, for example diagnostic imaging, and / or biochemical analyzes, for example for the detection of target proteins.

Any combination of the first optical fiber 10, the second optical fiber 20, the third optical fiber 30, the fourth optical fiber 40 and the fifth optical fiber 50 can be provided inside the needle 1 or the catheter.

By way of non-limiting example, the needle 1 or the catheter may include inside:

- the first optical fiber 10 and the second optical fiber 20; or

- the first optical fiber 10 and the third optical fiber 30; or

- the first optical fiber 10 and the fourth optical fiber 40; or

- the first optical fiber 10 and the fifth optical fiber 50; or

- the second optical fiber 20 and the third optical fiber 30; or

- the second optical fiber 20 and the fourth optical fiber 40; or

- the second optical fiber 20 and the fifth optical fiber 50; or

- the third optical fiber 30 and the fourth optical fiber 40; or

- the third optical fiber 30 and the fifth optical fiber 50; or

- the fourth optical fiber 40 and the fifth optical fiber 50.

In some embodiments, the needle 1 or catheter comprises within it at least three different optical fibers, for example three different optical fibers, selected from said first optical fiber 10, said second optical fiber 20, said third fiber optical 30, said fourth optical fiber 40 and said fifth optical fiber 50.

In this case, by way of non-limiting example, the needle 1 or the catheter may include inside:

- the first optical fiber 10, the second optical fiber 20 and the third optical fiber 30; or - the first optical fiber 10, the second optical fiber 20 and the fourth optical fiber 40; or - the first optical fiber 10, the second optical fiber 20 and the fifth optical fiber 50; or - the first optical fiber 10, the third optical fiber 30 and the fourth optical fiber 40; or - the first optical fiber 10, the third optical fiber 30 and the fifth optical fiber 50; or - the first optical fiber 10, the fourth optical fiber 40 and the fifth optical fiber 50; or - the second optical fiber 20, the third optical fiber 30 and the fourth optical fiber 40; or - the second optical fiber 20, the third optical fiber 30 and the fifth optical fiber 50; or - the second optical fiber 20, the fourth optical fiber 40 and the fifth optical fiber 50; or - the third optical fiber 30, the fourth optical fiber 40 and the fifth optical fiber 50.

In some embodiments, the needle 1 or catheter comprises within it at least four different optical fibers, for example four different optical fibers, selected from said first optical fiber 10, said second optical fiber 20, said third fiber optical 30, said fourth optical fiber 40 and said fifth optical fiber 50.

In this case, by way of non-limiting example, the needle 1 or the catheter may include inside:

- the first optical fiber 10, the second optical fiber 20, the third optical fiber 30 and the fourth optical fiber 40; or

- the first optical fiber 10, the second optical fiber 20, the third optical fiber 30 and the fifth optical fiber 50; or

- the second optical fiber 20, the third optical fiber 30, the fourth optical fiber 40 and the fifth optical fiber 50; or

- the first optical fiber 10, the third optical fiber 30, the fourth optical fiber 40 and the fifth optical fiber 50; or

- the first optical fiber 10, the second optical fiber 20, the fourth optical fiber 40, and the fifth optical fiber 50.

In some embodiments, the needle 1 or catheter comprises inside said first optical fiber 10, said second optical fiber 20, said third optical fiber 30, said fourth optical fiber 40 and said fifth optical fiber 50.

In all embodiments, the needle 1 or catheter can optionally comprise within it a plurality of first optical fibers 10 and / or a plurality of second optical fibers 20 and / or a plurality of third optical fibers 30 and / or a plurality of fourth optical fibers 40 and / or a plurality of fifth optical fibers 50. For example, two or more fifth optical fibers can be provided, configured to perform SERS imaging, alone or in combination with the other optical fibers.

In some embodiments, at least two fifth optical fibers 50 may be provided, one of which is configured to perform biochemical analyzes and one or more other fifth optical fibers 50 configured to perform diagnostics by SERS spectroscopy.

For example, up to 20 optical fibers can be provided inside the needle 1. In some embodiments, it can also be provided that a catheter is arranged in the needle 1, and that one or more of said optical fibers 10 , 20, 30, 40, 50 are arranged in the catheter and / or that one or more of said optical fibers 10, 20, 30, 40, 50 are arranged in the lumen of the needle 1, in particular between the catheter and the internal wall needle 1.

For example, the first optical fiber 10 can be arranged in the catheter, and one or more of said second optical fiber 20, third optical fiber 30, fourth optical fiber 40 and fifth optical fiber 50 can be arranged in the lumen of the needle 1, in in particular between the catheter and the inner wall of the needle 1. Preferably, the tip of the first optical fiber 10 abuts with an end portion of the catheter.

With reference to the first optical fiber 10, the at least one optical sensor 11 is preferably an optical sensor 11 of the fiber Bragg grating type (FBG, indicated with the reference 11 in Fig.2a) or a Fabry-Perot optical cavity 112 (Fig.2b); or one or more FBGs and one or more Fabry-Perot optical cavities may be provided.

Advantageously, the optical sensor 11 allows you to perform real-time pressure measurements, in particular in a specific position in the human body reached for example through the needle 1.

One or more fiber Bragg gratings (FBGs) can be easily produced and integrated within the optical fiber 10, for example by means of a UV lithographic process. An FBG is typically a segment of optical fiber 10 having a periodic modulation of the refractive index along the axis of the core of the optical fiber 10. This grating substantially behaves like a band-pass filter in reflection and a band-eliminating filter in transmission. The peak in reflection is centered at the Bragg wavelength given by λB = 2 neff Λ where neff is the effective refractive index of the medium (for example of the biological tissue), and Λ is the period of the lattice. Since a longitudinal strain and a temperature variation modulate both n and Λ, the Bragg wavelength undergoes a shift following the perturbation caused by the environment outside the optical fiber 10. Preferably, the fiber Bragg grating (FBG) has a length, parallel to the longitudinal axis of the optical fiber 10, between 0.5 and 10 mm. When a plurality of FBGs are provided, the spacing between consecutive FBGs is preferably between 1 and 10 mm. The optical fiber 10 can optionally be provided (partially or completely) with an external coating that allows a coupling by interference with the needle 1.

In summary, the monitoring of pressure changes basically takes place in this way: as the needle 1 and / or the catheter is inserted inside the human body, the one or more FBG 11 undergo deformations, in particular compressions (due to a buckling, that is to a bending of the optical fiber 10) and of the extensions, as a function of the elasticity of the tissues that are crossed. The compressions and extensions of the one or more FBG 11 involve a shift of the Bragg wavelength towards shorter or longer wavelengths respectively. Such shifts can also be induced by a temperature variation. Since each shift in the Bragg wavelength is the sum of joint variations in strain and temperature, it is preferable to provide a temperature compensation for quasi-static and static pressure measurements. In addition or as an alternative to one or more FBG 11, one or more optical cavities of the Fabry-Perot 112 type can be provided (Fig.2b).

A Fabry-Perot optical cavity 112 is preferably an optical cavity comprising two parallel semi-reflective surfaces 113, 114 adapted to produce multiple reflections of the light beam passing through the optical fiber 10. One of the two surfaces 113, 114, preferably the terminal surface 114 , is a sensitive membrane that changes the optical thickness of the cavity under the effect of a pressure and / or a change in temperature. Consequently, the reflected signal reaching the optoelectronic interrogation unit (which for example comprises a spectrophotometer) connected to the optical fiber 10 will vary. The sensitive membrane 114 (which preferably extends perpendicular to the longitudinal axis of the optical fiber 10, and is separated from its tip) can be mounted directly on the end portion of the optical fiber 10 or can be supported by the outer lateral surface of the needle 1 or catheter.

With reference to the second optical fiber 20, advantageously, the functionalization with particles of a polymeric gel 21 comprising a photosensitive molecule and a molecule of interest, allows to release said molecule to the site of interest when illuminated with a beam of light suitable for causing the biomolecule is released from the polymer gel that comprises it.

By "photosensitive molecule" we mean a molecule or a particle capable of being excited by a light source and giving rise to chemical reactions of splitting chemical bonds, conformational changes and energy transfers. By photosensitive molecules we also mean the molecules that generate a photothermal effect; when we refer to a particle as a photosensitive molecule we mean a particle of any shape and size.

By "biomolecule", referring in particular to the second optical fiber 20, we mean a molecule for therapeutic or diagnostic use to be released to a site of interest. Advantageously, when the at least one polymer gel particle is irradiated by a beam of light, the at least one biomolecule is able to be released from the at least one polymer gel particle and to be conveyed in a human or animal tissue or compartment.

In particular, the second optical fiber 20 is adapted to be connected to a lighting unit (not shown) configured to generate a beam of light that propagates from the inside of the optical fiber 20 towards the outside. When the at least one particle is irradiated by the light beam, the at least one biomolecule is capable of being released by the particles and being conveyed in a human or animal tissue or compartment.

Preferably, the at least one particle of the polymer gel is covalently bonded on at least a part of the fiber surface by a covalent bond selected from a group consisting of an amide bond, an ester, ether and thioether bond, carbon-carbon bond, carbon-nitrogen bond, carbon-sulfur, carbon-phosphorus, carbon-oxygen, carbon-silicon.

Preferably, the at least one particle of the polymer gel has a hydrodynamic radius in the range of 0.01 and 5 µm.

Preferably, the at least one polymer gel particle has a hydrodynamic radius in the range from 0.1 to 2.5 µm and the polymer gel is a microgel.

Preferably, the at least one polymer gel particle has a hydrodynamic radius in the range from 0.010 to 0.050 µm and the polymer gel is a nano-freeze. Preferably, the at least one polymer gel particle is obtained from the polymerization of one or more monomers selected from the group consisting of: acrylic monomers, vinyl monomers, stimulus-responsive monomers and bioinert monomers.

Preferably, said acrylic monomers comprise or consist of carboxylic and / or amino functional groups, preferably selected from the group consisting of acrylic acid, methacrylic acid, fumaric acid, maleic acid, butylmethylacrylate (nBuMA), dimethylaminoethyl acrylate (DMAEA), acrylamide (AAm ), aminoethyl methacrylate (Aema), dimethylaminoethyl (meth) acrylate (DMAEMA), N- (3-aminopropyl) methacrylamide (Apma), and polyethyleneimine (PEI).

Preferably, said bioinert monomers are selected from the group consisting of monomers derived from ethylene glycol, preferably polyethylene glycol acrylates, polyethylene glycol methacrylates, polyethylene glycol functionalized with acrylamides, polyethylene glycol functionalized with methacrylamides, oligo (ethylene glycol) acrylate (OEGA), oligo (ethylene glycol) acrylate (OEGA), oligo (ethylene glycol) acrylate (OEGA) ethylene glycol) methacrylate (OEGMA), oligo (ethylene glycol) diacrylate (OEGDA), N-alkyl acrylamide, vinyl caprolactone (VCL), and hydroxy-ethyl methacrylate.

Preferably, said stimulus-responsive monomers are (N-isopropylacrylamide) and derivatives of aminoethyl-methacrylate.

Preferably, said at least one photosensitive molecule is selected from the group consisting of:

- azobenzene or its derivatives,

- a nitrobenzyl derivative,

- a fluorophore, preferably a derivative of malachite and carbocyanins, - a particle of gold and / or silver; And

- a particle with a high refractive index.

Preferably, the at least one biomolecule of the second optical fiber 20 is selected from the group consisting of growth factors, neuroprotective molecules, active molecules for the regeneration of the central nervous system, drugs and prodrugs and their combinations, antineoplastic agents, biological response modifiers, hormones, vitamins, peptides, enzymes, antiviral agents, radioactive compounds, monoclonal antibodies, genetic material and cells.

Preferably, at least one particle of said polymeric gel is covalently bonded to the tip and / or to the cladding of the second optical fiber 20.

With reference to the fifth optical fiber 50, as already mentioned, it has one end provided with a metallic and / or polymeric coating 51.

Preferably, the coating 51 has a thickness comprised between 10 nm and 10 µm. This thickness is measured parallel to the longitudinal axis of the optical fiber 50. Preferably, when the coating 51 is metallic it has a thickness of 10 to 100 nm; when the coating 51 is polymeric, it has a thickness from 100 nm to 10 µm. The fifth optical fiber 50 comprises a diffraction grating 511, 512.

In a first variant (Fig. 3a) said coating 51 comprises said diffraction grating 511 preferably having a period from 50 nm to 5 µm, preferably said diffraction grating (511) comprising either being formed by a plurality of holes or by a plurality of pillars.

In a second variant (Fig. 3b), said diffraction grating 512 is a fiber Bragg grating, preferably having a period from 10 to 1000 µm.

These variants will be further described below.

In both variants, the coating 51 optionally comprises at least one biomolecule, preferably at least one protein, for example an antibody or a bio-receptor, or at least a nucleic acid, such as an aptamer or an anti-miRNA. The coating 51 adheres to an end portion of the optical fiber 50, preferably to the portion of the optical fiber which is known in the art as "tip" and / or to the end portion of the optical fiber 50 which comprises the tip. The tip of the optical fiber is typically the end surface of the optical fiber which is transverse, for example orthogonal, to the lateral surface of the optical fiber, the lateral surface being typically cylindrical.

Preferably, the coating 51 substantially forms a biological recognition system. Preferably, the coating 51 is substantially a layer, comprising biological material capable of recognizing and binding to other target molecules, in particular for specific recognition.

The coating 51 of the fifth optical fiber 50, for biochemical analysis, comprises or is substantially formed of functional materials preferably having a nanometric structure, which by trapping the light at a specific resonance wavelength give rise to strong localizations of the electromagnetic field and therefore to strong light-matter interaction. This interaction underlies the conversion of the biological event (for example a binding or molecular bond between a biomarker and its antibody) into a measurable signal. In fact, the transduction mechanism takes place thanks to the presence of superficial resonant phenomena (i.e. which occur on the surface of the tip, generally on areas of the order of fractions of a square millimeter), typically but not exclusively of a plasmon nature, which interacting with the biological layers to be analyzed allow the detection of bio-markers and their quantization through spectral measurements in reflection. The biological recognition system is able to interact, for example, with the biomarker to be quantized and determine the specificity of the sensor. The signal resulting from the interaction between the biological recognition system and the analyte will be of the luminous type and will be recorded by the optical fiber 50. Various types of chemical protocols can be used to immobilize the biological system on the optical fiber 50, depending on the the nature of the deposited layer and the substrate.

Advantageously, the optical fiber 50 is sensitive, and therefore capable of detecting, to local changes (for example of a few tens of nanometers) in the refractive index of the environment surrounding the optical fiber 50 which occur on their sensitive surface, in particular on the surface of the coating 51. In fact, a variation of the boundary conditions (for example a variation of the material deposited in the immediate vicinity of the sensitive area) induces a variation of the reflected signal. By monitoring the variations of a characteristic parameter of said material, for example the resonance wavelength, it is possible to obtain information on the quantity and type of material deposited (there is therefore a transduction mechanism). For example, fiber transducers work in reflection: the signal emitted by the source propagates in the optical fiber 50 and is reflected at the tip after interacting with the biological recognition system, ie with the coating 51. The transducers are designed in such a way as to present typically a resonance (ie a minimum or a maximum of reflected intensity) at a particular wavelength. In the absence of links between the biomolecule of the coating 51, for example a bioreceptor, and the target molecule, this resonance does not undergo any shift. Therefore, by monitoring the variation over time of the resonance wavelength, a constant or substantially constant signal is obtained which forms the so-called "baseline". Following the molecular binding, the resonance wavelength of the diffraction grating 511, 512 undergoes a shift due to surface refractive index modifications; such a shift, for example, is proportional to the concentration of target molecule present in the tissue or biological liquid.

By way of non-limiting example, to obtain selective recognition, the surface of the optical fiber 50 is treated in such a way that only the target molecule (and not the other molecules present in the solution or biological tissue) is immobilized and therefore detected by the transducer ( the transducer preferably comprises the optical fiber 50 and the diffraction grating 511 or 512). Preferably, the treatment of the sensitive area of the fiber transducers takes place through a functionalization which includes two sequential steps:

a) chemical functionalization: which includes a treatment of the surface of the transducer so that it presents functional groups suitable for the subsequent coupling phase with the biomolecule, i.e. with the biomolecular recognition element (ERB). , carboxylic, amine, thiol groups, or as cationic and anionic sites; b) biological functionalization: after phase a), the biomolecule is immobilized, which can be, for example, a macromolecular bio-receptor or a synthetic receptor. For this purpose, well-established coupling techniques can be used, for example techniques that lead to the formation of a covalent bond between the biomolecule and the coating, and / or techniques that lead to supramolecular interactions between the biomolecule and the coating.

With particular reference to Fig. 3a, in a first exemplary variant, the coating 51 is a metallic or polymeric coating. For example, the coating 51 comprises one or more layers, in particular nanometric layers, of metallic material, for example comprising gold. Preferably, the external surface of the covering 51 has a plurality of surface features 511, preferably periodic or substantially periodic, preferably with a square or substantially square lattice. Features 511 form a diffraction grating. Such characteristics 511 are for example protrusions, in particular nanometric protrusions or holes, in particular holes of nanometric diameter. For example, the protrusions are formed by a plurality of pillars and the holes are made in a sheet, for example of gold.

The metallic coating 51 is provided at least on the tip of the optical fiber 50.

The metallic coating 51 supports a localized plasmon resonance whose coupling wavelength is sensitive to morphological changes on the sensor surface.

Preferably, the period of the posts or holes is between 50 nm and 5 µm, for example between 100 nm and 1 µm, and / or the radius of the posts or holes is between 10 nm and 0.5 µm and / or the thickness of the coating 51 is comprised between 10 and 100 nm. With “period” we mean in particular the center-to-center distance between each pillar (or hole) and the pillars (or holes) immediately consecutive to it.

The selection of these parameters is made according to the maximization of the surface sensitivity (in particular to maximize the resonance shift per nm of biological material deposited on the surface) leaving a good visibility (minimum-maximum excursion of the reflected light intensity) of the resonance .

With particular reference to Fig.3b, in a second variant, the fifth optical fiber 50 comprises a diffraction grating 512 having a period comprised between 10 and 1000 µm, and said coating 51 is preferably metallic.

In particular, the diffraction grating 512 is of the "long-pitch grating" (LPG) type. The diffraction grating 512 is inscribed within the core 52 of the optical fiber 50, for example by periodic modulation of the core 52.

This modulation is for example obtained through a periodic variation of the refractive index of the core 52, for example by local exposure to UV light or by variations in the dimensions of the core 52.

The length of the period of the diffraction grating 512 allows the coupling between the fundamental core mode and the co-propagating cladding modes. The transmission spectrum of the diffraction grating 512 is typically formed by several attenuation bands, each of which is linked to a different cladding mode.

The diffraction grating 512 is particularly sensitive to various parameters, such as temperature, bending, strain and refractive index of the environment outside the optical fiber 50. Given its sensitivity to the refractive index, the diffraction grating 512 is particularly suitable for use as a chemical and biological sensor, for example for biological analyzes of the label-free type.

In both variants (Fig. 3a and 3b), the terminal portion (which includes the tip) of the optical fiber 50 is covered by the coating 51. Optionally, in the second variant (Fig. 3b) a polymeric coating 54 is also provided on the surface external lateral surface of the optical fiber 50, in particular on the external lateral surface of the cladding 53, adjacent to the tip. Preferably, said polymeric coating 54 comprises said at least one biomolecule.

The fifth optical fiber 50 is preferably configured to perform, in addition or as an alternative to performing biochemical analyzes, diagnostics using SERS (Surface Enhanced Raman Scattering) spectroscopy. The fifth optical fiber 50 can therefore comprise or not comprise said at least one biomolecule.

In some embodiments, at least two fifth optical fibers 50 may be provided, one of which is configured to perform biochemical analyzes and one or more other fifth optical fibers 50 configured to perform diagnostics by SERS spectroscopy. With the exception of the at least one biomolecule (which may not be present), the other characteristics of the fifth optical fiber 50 configured to perform SERS spectroscopy are the same or substantially the same as previously described with reference to Figs.3a and 3b.

The optical fiber 50 is preferably also suitable for the recognition of high resolution tumor tissues based on SERS technology. In particular, the SERS effect can be exploited, i.e. the intensification and amplification of the Raman signal of the molecules characterizing the biological tissue to be inspected. As for the SERS, the intensification and amplification of Raman scattering is due to the interaction between the electromagnetic wave associated with the laser used and a metal substrate on which the analyte is placed. In fact, the amplification of the electromagnetic field is due to the plasmonic resonances generated by the metal surface, for example of the gold nanostructures present on the optical fiber. The optical fiber 50 can scan directly onto fabric.

With particular reference to Figures 4, 5 and 5a, a medical device 100 is illustrated comprising a needle 1 as described above, for example comprising inside it at least two different optical fibers, said at least two optical fibers being selected from said first fiber optical 10, said second optical fiber 20, said third optical fiber 30, said fourth optical fiber 40 and said fifth optical fiber 50. It should be noted that the medical device 100 can also comprise a catheter inserted in the needle 1, as described above.

The medical device 100 comprises a body 6 bound to the needle 1. The needle 1 is preferably metallic.

The body 6 is preferably provided with at least one gripping portion 61 in order to be able to grip the medical device 100. The gripping portion 61 is for example an external surface, preferably cylindrical, of the body 6.

Preferably, inside the needle 1 is provided said fourth optical fiber 40 and one or more of said first optical fiber 10, second optical fiber 20, third optical fiber 30, and fifth optical fiber 50.

When a catheter (not shown) is inserted into the needle 1, the fourth optical fiber 40 is preferably arranged between the inner wall of the needle 1 and the catheter.

The medical device 100 also comprises at least one piezoelectric crystal 3 connected to the needle 1, preferably by means of an acoustic adapter 2;

and at least one power supply cable 7, connected to the at least one piezoelectric crystal 3 in order to electrically power the piezoelectric crystal 3, in particular to be able to generate ultrasounds. Preferably, the power supply cable 7 extends partly inside the body 6, and partly outside the body 6, and at least the external part is arranged inside an electrically insulating sheath 8.

Preferably, the acoustic adapter 2 is arranged between the needle 1 and the piezoelectric crystal 3. Preferably, the acoustic adapter 2 is directly connected to the piezoelectric crystal 3 and / or the needle 1 is directly connected to the acoustic adapter 2.

The acoustic adapter 2 is preferably made of a material suitable for adapting the acoustic impedance between the piezoelectric crystal 3 and the needle 1. For example, the acoustic adapter 2 is made of metal, preferably steel.

Preferably, the acoustic adapter 2 comprises a through hole crossed by the fourth optical fiber 40.

Preferably, the acoustic adapter 2 is of a truncated cone shape, tapered towards the needle 1.

Preferably, the piezoelectric crystal 3 comprises a through hole crossed by the fourth optical fiber 40.

Preferably, the through hole of the piezoelectric crystal 3 is coaxial or substantially coaxial to the through hole of the acoustic adapter 2.

Preferably, the piezoelectric crystal 3 is annular in shape.

Preferably, a support 4, also called backing medium or material, is provided, fixed to the piezoelectric crystal 3, preferably directly fixed to the piezoelectric crystal 3.

The support 4 is able to attenuate the vibrations, in particular the undesired vibrations, of the piezoelectric crystal 3 and is preferably also able to increase the acoustic frequency band of the piezoelectric crystal 3.

The support 4 is made for example of plastic. The support 4 is also provided with a through hole crossed by the fourth optical fiber 40.

Preferably, the piezoelectric crystal 3 is arranged between the support 4 and the acoustic adapter 2.

Preferably, the support 4 is arranged, at least partially, in a seat. For example, the support 4 is wedged in said seat and / or fixed to said seat by means of fixing means. Said seat is part, for example, of a body 5 constrained to the body 6 or said seat may be part of the body 6 itself.

The body 5 is also provided with a through hole crossed by the fourth optical fiber 40.

Preferably, a casing 12 is provided, for example a hollow body, in which the acoustic adapter 2, the piezoelectric crystal 3 and, when provided, the support 4 and at least part of the body 5 are housed, in particular the part that defines said seat for support 4.

The casing 12 preferably comprises a flange 121, for example an annular flange.

The envelope 12 is provided at one end with an opening crossed by the needle 1 and therefore also by the fourth optical fiber 40.

Note that the further optical fiber, or further optical fibers, also pass through the opening of the casing 12 and the through holes of the acoustic adapter 2, of the piezoelectric crystal 3 and of the support 4 and of the body 5.

The fourth optical fiber 40 is constrained to the body 6 by means of fixing means 14, 15, schematically illustrated in Fig.3.

For example, the fastening means 14, 15 can be arranged at one end of the body 6 opposite the needle 1.

Preferably, the fastening means comprise a clamp 15 which clamps the fourth optical fiber 40. In particular, the fourth optical fiber 40 passes through the clamp 15 and exits from the body 6. Preferably, the fastening means also comprise a ring nut 14, arranged around the gripper 15, preferably made of electrically insulating material. Optionally, the ferrule 15 is adapted to act on the clamp 15 so as to be able to tighten and widen it, in order to be able to clamp and release the fourth optical fiber 40.

The other optical fiber, or the other optical fibers, are preferably bound to the body 6 in the same way as the fourth optical fiber 40.

As already mentioned, the fourth optical fiber 40 is particularly suitable for carrying out diagnostic imaging, for example ultrasound scans.

Advantageously, the ultrasounds produced by the piezoelectric crystal 3 can be transmitted to the needle 1 connected to the piezoelectric crystal 3.

Advantageously, by means of the fourth optical fiber 40 inserted in the needle 1 or in the catheter, an ultrasound investigation, in particular the generation of ultrasounds and the detection of ultrasounds, can be performed in any point of the human or animal body accessible through a needle. 1. In fact, the generator and the detector are made of optical fiber, whose dimensions are much smaller than the lumen of the needle 1. The optical fiber 40 allows to carry out in vivo investigations using the piezoelectric crystal 3 and using the needle 1 as a physical means to guide the ultrasounds generated in the body and emit them in the anatomical area of interest and vice versa.

A device comprising the optical fiber 40 arranged in the needle 1 is particularly suitable, for example, as a support and integration to traditional ultrasound probes, for example where the need arises to inspect a region inside the body with a resolution equal to or greater than that typically used for superficial tissues or in other application scenarios based on the use of acoustic waves.

The optical transducer 41 of the fourth optical fiber 40 is preferably an acoustic sensor, in particular an ultrasound receiver.

The optical transducer 41 can be made both on the tip of the optical fiber (for example by modifications of the geometry of the fiber itself, or by integrating other materials), and along the axis, in the internal region, i.e. the core (for example by alterations of the refractive index).

The optical transducer 41 integrated on the tip of the optical fiber 40, thanks to essentially interferometric mechanisms, traps the electromagnetic radiation at certain wavelengths, thus providing a particular pattern of the spectrum of the radiation reflected by them. By way of example, an optical transducer 41 can be a resonant cavity of the Fabry-Perot type or a diffraction grating, which are able to work as an ultrasound receiver thanks to the variations that an acoustic field can induce to its geometry (and , indirectly, of the refractive index due to acousto-optic effect), consequently causing a variation in the reflected spectrum. By detecting these changes it is possible to have information regarding the variations in the pressure incident on the optical transducer 41.

A Fabry-Perot resonant cavity can for example be made on the tip of the optical fiber 40, for example, by depositing a polymeric film on it, so as to obtain two partially reflecting discontinuity surfaces: one between the fiber and the film, the the other between the film and the external material with which it is in contact. The polymeric film preferably has a thickness of between 1 and 100 µm. Preferably, the polymeric film comprises or consists of p-xylene, for example it is made of parylene. This structure acts as a selective reflector in wavelength thanks to the interferometric effects that arise between the different components reflected by the two surfaces. In other words, the reflected intensity at a given wavelength takes on a value that depends on the geometric and optical parameters of the structure built on the tip of the fiber. The spectrum of the reflected field can be engineered by possibly integrating multiple films of different materials such as metal mirrors. The transduction mechanism is essentially entrusted to changes in the thickness of the polymer film and / or changes in refractive index due to the acousto-optic effect.

A variant of the use of Fabry-Perot cavities, as previously anticipated, can be the use of diffraction gratings, for example made on dielectric diffraction gratings capable of determining an interference between the diffractive orders and the modes guided in the dielectric layer, thus trapping the field inside it at certain wavelengths. Also this type of device can be implemented on the tip of the optical fiber 40, and can therefore be able to work in reflection. A diffraction grating is determined, in general, by the alternation of refractive index, therefore it can be made, for example, by integrating on the tip of the optical fiber 40 periodic or completely dielectric structures with particular geometries (for example given by the alternation of ridge and groove), or given by the alternation of dielectric materials and materials with different refractive index between them (for example metals).

An advantage of a diffraction grating compared to a Fabry-Perot cavity lies in the greater number of degrees of freedom, since in addition to defining the materials and thicknesses, it is possible to act on the geometry of the diffraction grating, in order to obtain the particular spectrum desired. Furthermore, by using periodic structures, the transduction mechanism can be entrusted not only to variations in the thickness of the slab, but also to variations in other parameters such as the period or the filling factor of the lattice. By acting on its geometry, it is possible to determine field distributions (such as that due to surface plasmon resonance, if metallic materials are also used) that are particularly sensitive to variations in the thickness of the dielectric slab.

An alternative to the use of integrated devices on the tip of the optical fiber (i.e. the aforementioned diffraction grating and Fabry-Perot cavity) is to use longitudinal sensors, such as Bragg grating (FBG) or long-pitch grating (LPG, ie diffraction gratings with a period between 10 and 1000 µm). This type of device can be achieved by periodically altering the refractive index of the core of the optical fiber 40, resulting in a particular trend of the spectrum. FBGs and LPGs are also capable of working as a wavelength selective reflector, and therefore can be used for sonic detections since the incident acoustic wave can modify the period and the effective refractive index of the device and , consequently, the reflected spectrum.

The invention also includes a system comprising a needle 1 or a catheter as described above, or a medical device 100 as described above. The system includes at least one optoelectronic interrogation unit (not shown) capable of being connected to at least one of said optical fibers to receive data from the optical fiber to which it is connected;

and / or at least one lighting unit (not shown) capable of being connected to said at least two optical fibers, configured to generate a beam of light that propagates from the inside of the optical fibers to which it is connected to the outside.

Depending on the optical fibers of which the system is provided, the first optical fiber 10, the fourth optical fiber 40 and the fifth optical fiber 50 can be connected to the optoelectronic interrogation unit; and the first optical fiber 10, the second optical fiber 20, the third optical fiber 30, the fourth optical fiber 40 and the fifth optical fiber 50 can be connected to the lighting unit.

Note that the same unit can also function as an optoelectronic interrogation unit and as a lighting unit.

When the fourth optical fiber 40 is provided, preferably, the optoelectronic interrogation unit can comprise a monochromatic source, or a broadband source or a source adjustable over a wavelength range, for example between 500 nm and 2 µm . In the case of the monochromatic source, by appropriately choosing the wavelength of the source, for example a value selected in the range between 500 nm and 2 µm, the intensity at the output of the optical fiber 40 will be modulated by the variations in the intensity of the field acoustic that you want to reveal.

In the case of a broadband source, for example 500 nm and 2 µm, the variations of the spectrum can be monitored to then extract the desired information by post-processing.

When the fourth optical fiber 40 is provided, preferably, the lighting unit is in particular configured for a photo-acoustic generation which can take place, for example, by means of an elastic-type mechanism which is triggered following the absorption of a electromagnetic radiation from a solid structure. This solid structure can be made on the tip of the optical fiber 40. By means of the solid structure, the optical field that propagates within the optical fiber 40 itself can be exploited. The generation of an acoustic field can, in particular, take place in the thermo-elastic regime or in the plasma (or ablative) regime. In thermoelastic conditions, the power absorbed by the solid structure is transformed into heat, thus causing a thermal expansion of the material, thanks to which the propagation of mechanical waves is triggered. If the absorbed energy reaches a certain threshold, the expulsion of electrons and ions can be favored, and therefore the formation of a plasma near the point of incidence. This mechanism overlaps with the thermo-elastic one. In plasma mode, in order to vibrate said solid structure, and therefore generate a series of pulses, it is preferably provided that the lighting unit includes a pulsed source, in order to activate the mechanism for each incident pulse.

In any case, preferably, the solid structure made on the tip of the fourth optical fiber 40 for the generation of acoustic waves can, at the same time, efficiently absorb the incident electromagnetic radiation, and has a high coefficient of thermal expansion. For this purpose, the solid structure is preferably made of metal.

To obtain both the above characteristics, photo-acoustic generators (ie said solid structure) can be made on the tip of the optical fiber 40 by integrating different materials together. By way of example, the solid structure can include metal spheres of nanometric dimensions (with a diameter for example between 10 and 50 nm) inside polymeric layers, exploiting the high absorption coefficient of the metal, and the high expansion thermal insulation of polymers. A further example, said solid structure is a periodic metallodielectric structure, capable of supporting surface plasmonic modes, to which the temperature increase is entrusted, and consequently the thermal expansion of the dielectric. It should be clear that in any case the realization of said solid structure is not limited to the use of metals and polymers, but other materials or metamaterials can also be used.

Claims (10)

CLAIMS 1. Needle (1) or catheter for medical use comprising inside at least two different optical fibers, said at least two optical fibers being selected from: - a first optical fiber (10) provided with at least one optical sensor (11), the optical sensor (11) being adapted to be deformed when it comes into contact with a biological tissue; - a second optical fiber (20) functionalized with at least one particle of a polymeric gel comprising at least one photosensitive molecule and at least one biomolecule, in which the at least one particle of the polymeric gel is covalently linked to said second optical fiber (20); - a third optical fiber (30), of the multimode type, having a core with a diameter between 100 and 1000 µm configured to confine laser light having a power density from 8 to 20 W / cm <2> and a wavelength between 800 nm and 10 µm; - a fourth optical fiber (40) having an end provided with an optical transducer (41), the optical transducer (41) being made, at least partially, of polymeric material able to deform when subjected to acoustic waves with a frequency between 1 and 100 MHz and average intensity between 1 and 10 W / cm <2>; - a fifth optical fiber (50) having one end provided with a metal and / or polymeric coating (51), the fifth optical fiber (50) comprising at least one diffraction grating (511, 512); and / or in which the needle or catheter includes a plurality of fifth optical fibers (50). 2. Needle (1) or catheter according to claim 1, comprising at least three different optical fibers or at least four different optical fibers, selected among said first optical fiber (10), said second optical fiber (20), said third optical fiber (30), called fourth optical fiber (40) and said fifth optical fiber (50). 3. Needle (1) or catheter according to any one of the preceding claims, comprising said first optical fiber (10), said second optical fiber (20), said third optical fiber (30), said fourth optical fiber (40) and said fifth optical fiber (50). 4. Needle (1) or catheter according to any one of the preceding claims, wherein said optical sensor (11) of the first optical fiber (10) is of the fiber Bragg grating type or a Fabry-Perot optical cavity. Needle (1) or catheter according to any one of the preceding claims, wherein said third optical fiber (30) is configured to confine pulsed laser light having an energy of up to 1 GW / cm <2> and / or continuous laser light having an energy up to 2 MW / cm <2>. Needle (1) or catheter according to any one of the preceding claims, wherein said coating (51, 54) of the fifth optical fiber (50) comprises at least one biomolecule, preferably at least one protein or at least one nucleic acid. Needle (1) or catheter according to any one of the preceding claims, wherein said coating (51) comprises said diffraction grating (511) preferably having a period from 50 nm to 5 µm, preferably said diffraction grating (511) comprising either being formed by a plurality of holes or by a plurality of pillars; or in which said diffraction grating (512) is a fiber Bragg grating, preferably having a period from 10 to 1000 µm. Medical device (100) comprising at least a needle (1) or a catheter according to any one of the preceding claims, and a body (6) attached to said needle (1) or catheter, the body (6) preferably provided with at least a gripping portion (61) for grasping the medical device (100). 9. Medical device () according to claim 8 comprising said needle (1) and said fourth optical fiber (40) inserted in the needle (1), the medical device (100) further comprising - at least one piezoelectric crystal (3) connected to the needle (1), preferably by means of an acoustic adapter (2); - and at least one power supply cable (7), connected to at least one piezoelectric crystal (3) to be able to power it electrically to generate ultrasounds; and preferably in which the medical device (100) comprising a support (4) connected to the at least one piezoelectric crystal (3), designed to attenuate the vibrations of the at least one piezoelectric crystal (3); and / or in which said fourth optical fiber (40) is constrained to the body (6) by means of fixing means (14, 15). System comprising a needle (1) or a catheter according to any one of claims 1 to 7 or a medical device (100) according to claim 8 or 9, comprising at least an optoelectronic interrogation unit adapted to be connected to at least one of said optical fibers to receive data from the optical fiber to which it is connected; and / or at least one lighting unit designed to be connected to said at least two optical fibers, configured to generate a beam of light that propagates from the inside of the optical fibers to which it is connected to the outside.