FR3138042A1 - Implantable illumination probe - Google Patents

Abstract

The invention relates to an illumination probe (1) intended to be implanted in a living being, comprising: A hollow housing (3) comprising a wall (30) having an internal face and an external face, in which a source is placed light capable of emitting light radiation, said housing (3) comprising an outlet (31) through which said light radiation is collected, An elongated waveguide (10) having a proximal end connected to said outlet (31) of the housing for collect the light radiation emitted by the light source and at least one implantable part made of transparent material, closed in a hermetic manner and ending in a distal end intended to come as close as possible to the tissues (2) to be treated, The light source comprising at least one radioluminescent source (4) capable of emitting said light radiation inside the housing (3). Figure to be published with the abstract: Figure 1

Description

Implantable illumination probe Technical field of the invention

The present invention relates to an illumination probe intended to be implanted at least partly in a living being to illuminate at least one internal zone of the living being.

State of the art

For the treatment of certain pathologies of a living being, it has been imagined to optically stimulate an internal area of a living being. For this, the devices used include a light source and are implanted at least partially or completely in the living being to illuminate the desired area.

In particular, we have noticed the benefit of such devices for illuminating/irradiating certain areas of the human brain.

However, given the risks associated with their implantation in the brain, these devices must be perfectly designed.

Patent application US2017281928A1 and patent US10213596B2 describe implantable illumination devices comprising a pulse generator (IPG for “Implantable Pulse Generator”) which powers a light source and a probe comprising a light guide, generally an optical fiber, responsible for bringing a light beam to the area to be treated. Patent application EP3723851A1 also provides certain improvements to known systems.

Previous solutions, however, have several drawbacks, including:

• The installation principle is quite damaging for the patient: it is necessary to make a first subclavicular implantation to position the battery, slide the cable subcutaneously over a long distance, make a substantial accommodation in the cranium for the source laser, and slide the optical fiber into a catheter inserted into the skull.
• The light emission is mainly localized at the end of the fiber, which does not easily illuminate a larger area.
• The device battery must be recharged regularly to keep the probe operating.

The aim of the invention is to propose an implantable illumination probe, the installation of which is less complex and less invasive for the patient than previous solutions, in which the emission of light can be carried out over a large area and which does not require regular battery charging.

This goal is achieved by an illumination probe intended to be implanted in a living being, comprising:

• A hollow housing comprising a wall having an internal face and an external face, in which is placed a light source capable of emitting light radiation, said housing comprising an outlet through which said light radiation is collected,
• An elongated waveguide having a proximal end connected to said outlet of the housing to collect the light radiation emitted by the light source and at least one implantable part made of transparent material, closed in a hermetic manner and ending in a distal end intended to come as close as possible to the tissues to be treated,
• The light source comprising at least one radioluminescent source capable of emitting said light radiation inside the housing.

According to one particular feature, the radioluminescent source is in the form of a capsule housed inside said housing and the internal face of the wall of the housing is covered with a reflective layer.

According to a particular embodiment, the capsule comprises a hermetically closed envelope, housing a radioactive source in gaseous form and provided with at least one layer to be excited of at least one radioluminescent material deposited on a surface exposed to said radioactive source .

According to another particular embodiment, the capsule comprises an envelope closed in a hermetic manner and housing a porous solid matrix whose pores define a surface carrying a layer of at least one radioluminescent material exposed to said radioactive source.

According to another alternative embodiment, the radioluminescent source comprises a deposit of a layer of a radioluminescent material produced on the internal face of the wall of the housing and a radioactive source in gaseous form enclosed in said housing.

According to one particular feature, the radioluminescent source comprises a radioactive source implanted in said wall of the housing and a deposit of a layer of a radioluminescent material produced on the internal face of the wall of the housing and exposed to said radioactive source.

According to another particularity, the radioluminescent material is a phosphor, a scintillator or a semiconductor material based on growth by epitaxy, or on quantum dots.

According to another particularity, the probe comprises a layer of a dielectric material deposited under the radioluminescent source.

According to another particularity, the layer of radioluminescent material is nanostructured.

According to another particularity, the radioluminescent source comprises fluorescent quantum dots.

According to another particularity, the radioactive source is based on tritium.

Brief description of the figures

Other characteristics and advantages will appear in the detailed description which follows with reference to the appended drawings in which:

• There schematically shows the illumination probe according to the invention and illustrates its operating principle;
• There schematically shows the principle of producing a radioluminescent source that can be used in the illumination probe of the invention;
• Figures 3A and 3B show two alternative embodiments of the housing used in the illumination probe of the invention;
• Figures 4A and 4B represent two alternative embodiments of the wall of the housing which is used in the illumination probe of the invention;

Detailed description of at least one embodiment

The invention relates to an implantable illumination probe 1 as shown in the .

The probe 1 makes it possible in particular to achieve illumination (for example in the near infrared or with any other wavelength depending on the treatment envisaged – neuroprotection, optogenetic type treatment) of the targeted tissues 2 (for example SNc, hippocampus, striatum, etc.). ) while minimizing medical risks during its implantation. It can be used in particular in the treatment of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, etc.

Tissue illumination 2 can have different objectives depending on the application: neuroprotection, optogenetics, stimulation, etc. Several targets are concerned, for example: the substantia nigra compacta (SNc) which degenerates in Parkinson's disease, the hippocampus, the main nucleus implicated in the onset of Alzheimer's disease, the striatum for Huntington's disease.

The invention uses the principle of radioluminescence. Radioluminescence is a form of luminescence produced by the radioactive disintegration of a body (a permanent phenomenon that does not require an external energy source). It is implemented by exposing a radioluminescent material to a radioactive source.

Luminescence includes fluorescence (radiative de-excitation phenomenon from a singlet excited state) and phosphorescence (radiative de-excitation phenomenon from a triplet excited state). The wavelength of the emitted light depends on the radioluminescent material used.

In the context of the invention, in a non-limiting manner, the radioactive source used is advantageously tritium, which can be used in different forms.

As a reminder, tritium is a radioisotope of hydrogen and decays into a helium atom, an electron with an average energy of 5.7 keV and an antineutrino, according to the following relationship:

The radioluminescent material used can be a scintillator or a phosphor, such as classically zinc sulphide which emits in the green, or a semiconductor material (III-V material, quantum dots) whose nature and geometry influence in particular the emission wavelength. When the electron produced during decay interacts with such a material, it can emit light.

The aim of the invention is to optimally use the light produced to treat areas of the brain.

The implantable probe 1 comprises a waveguide 10 in the form of a flexible elongated rod, having a proximal end, for example located outside the living being and a distal end intended to be as close as possible to tissues to be treated. Its distal end advantageously has an atraumatic profile. The waveguide 10 is chosen sufficiently long so that its distal end can reach the area of interest to be treated in the body (for example an area in the brain).

The waveguide advantageously has a circular cross section. For example, the diameter of the waveguide section can range from 1 to 3 mm, preferably 1.3 mm to be compatible with standard tools used in neurosurgery.

The waveguide 10 can be in the form of an optical fiber made of silicone or polyurethane.

The probe 1 also comprises a hollow housing 3 materialized by a wall 30 having an internal face and an external face. The housing 3 is closed hermetically and has an outlet 31 to which the waveguide 10 is connected, via its proximal end.

This housing 3 is intended to contain a radioluminescent source 4. The radiation emitted by the radioluminescent source 4 is collected at the outlet 31 of the housing 3 and intended to propagate along the waveguide 10 to its distal end .

The outlet 31 of the housing 3 is advantageously covered on its internal face with a layer 310 of a specular reflective material ( And ).

It should be noted that it would be possible to provide a box 3 with several outputs, a separate waveguide 10 being connected to each output.

Several distinct embodiments can be envisaged:

As shown on the , on the and on the , a first embodiment consists of producing the radioluminescent source 4 in the form of a capsule 40 which is housed inside the housing 3.

The capsule 40 comprises a hermetic envelope 400 having at least one transparent wall.

The capsule 40 is for example filled with the radioactive source 401 based on tritium. The radioluminescent material 402 is deposited or applied to at least part of the internal surface of the envelope 400 of the capsule (as in the appended figures), or even to the external surface of the radioactive source.

In a non-limiting manner, the capsule 40 may have a circular section having an external diameter ranging from 300 μm to 1 mm. The length of the capsule can be from a few millimeters to several centimeters. The capsule may have a larger or smaller size.

The tritium placed in the hermetic envelope 400 of the capsule can in particular be stored using different solutions.

A first solution is to place the tritium in gaseous form inside the envelope of the capsule, as illustrated in the .

A second solution would be to incorporate the tritium into a matrix, for example styrene, as carried out in "Preparation of tritiated polystyrene coated radioluminescent phosphor, Journal of Radioanalytical and Nuclear Chemistry, Vol. 254, No. 1 (2002) 209–211 " .

Another solution is to incorporate tritium into nanodiamonds or nanometric arrangements of carbon atoms, as described in the publication referenced “Using hydrogen isotope incorporation as a tool to unravel the surfaces of hydrogen-treated nanodiamonds, Nanoscale, 2019, 11, 8027-8036 » .

Tritium can also be incorporated into a solid matrix, for example titanium, as described in the publication https://link.springer.com/content/pdf/10.1007/s10971-019-05022-2.pdf .

The matrix can be adapted so as to increase its effective contact surface with the tritium. The radioluminescent material can then be deposited in a way that is compatible with the size of the pores or cells of the titanium. For example, one can use porous titanium, for example with an average pore opening of 20 µm, and use a radioluminescent material whose grain size is much smaller, for example 5 µm, in order to fill these pores and thus maximize light output.

The matrix itself can be radioluminescent: for example, it can be a bar or a cylinder of semiconductor material epitaxied on a substrate whose emission wavelength is in the red. The "tritiation" of this semiconductor makes it a source of light, by excitation of the semiconductor material by electrons resulting from the radioactive disintegration of the incorporated tritium.

It is also possible to deposit quantum dots on the solid matrix incorporating tritium. Quantum dots are assemblies of atoms; the size and nature of these assemblies determines the emission wavelength. The emission of electrons from the tritium incorporated in the titanium excites the quantum dots which emit light.

In this first embodiment, as shown in the , the internal face of the wall of the housing 3 is covered with a layer 32 of a reflective material, advantageously diffusive and non-specular.

According to this first embodiment, the light radiation emitted by the capsule 40 propagates throughout the internal volume of the housing, by successive reflections against its internal face. The light radiation is captured at the output 31 of the housing 3 and is propagated along the waveguide 10 to the distal end (see ). The reflective layer 310 deposited on the internal face at the outlet 31 of the housing 3 makes it possible to collect the beam and convey it to the waveguide 10.

According to a second alternative embodiment illustrated by the , the internal face of the housing 3 is directly covered with a layer 33 of the radioluminescent material.

According to this second embodiment, the radioactive source 34 in gaseous form can be placed in the internal volume of the housing 3, thus interacting directly with the radioluminescent material present on the internal face of the housing. Alternatively, the radioactive source 34 in gaseous form can be directly implanted in the wall 30 of the housing 3, the latter being chosen sufficiently porous. The principles of storage of the radioactive source, described above for the capsule can be used in a similar manner for deposition on the internal face of the casing.

According to one particular feature, it is possible to ensure that the light radiation is emitted discontinuously over time. For this, the radioluminescent source 4 can integrate nanoparticles to modulate the emission of light.

In the two embodiments described, the housing 3 functions as an integrating sphere, that is to say it allows multiple reflections in its internal volume, before collection at the outlet 31 of the housing 3.

In the two embodiments described above, it is possible to enhance the electromagnetic field emitted by the radioluminescence. One of the options is for example to deposit a dielectric material on a metal layer (deposited on the internal face of the wall 30 of the housing 3 or on the external face of the capsule 40). As shown on the , it may involve associating on the face 30 to be treated, a metallic layer 35 and a dielectric layer, under the layer 36 of radioluminescent material. It may also involve carrying out nanostructuring (reference 37) of the layer 36 of deposited radioluminescent material ( ).

The radioluminescent source may contain phosphors or quantum dots emitting at several wavelengths (for example 670 and 810 nm, of which these wavelengths are known to be beneficial for neurodegenerative diseases).

Several capsules, emitting at different lengths can be placed in the housing.

It is also possible to combine the two embodiments of Figures 3A and 3B. A capsule 40 is inserted inside the housing 3 capable of luminescing at a first wavelength. The internal wall of the housing 3 also integrates a radioluminescent material capable of luminescing at a second wavelength and excitable by the first wavelength by photoluminescence. The internal volume of the housing is for its part filled with the radioactive source, for example tritium in gaseous form.

According to one particular feature, the housing 3 of the probe 1 is positioned outside the body of the living being, for example fixed subclavicularly, the waveguide 10 having a part deployed subcutaneously and a part implanted for example intracerebral.

The invention has numerous advantages, including:

• Long-lasting autonomy (1/2 life at 12.3 years for tritium), without using an electrical power source;
• Simplicity in installation and operation;
• The possibility of choosing the wavelength and possibly using several waveguides and several distinct wavelengths;

Claims (11)

Illumination probe (1) intended to be implanted in a living being, comprising:

• A hollow housing (3) comprising a wall (30) having an internal face and an external face, in which is placed a light source capable of emitting light radiation, said housing (3) comprising an outlet (31) through which said radiation bright is collected,
• An elongated waveguide (10) having a proximal end connected to said outlet (31) of the housing to collect the light radiation emitted by the light source and at least one implantable part made of transparent material, closed hermetically and ending by a distal end intended to come as close as possible to the tissues (2) to be treated,
• Characterized in that the light source comprises at least one radioluminescent source (4) capable of emitting said light radiation inside the housing (3).

Probe according to claim 1, characterized in that the radioluminescent source (4) is in the form of a capsule (40) housed inside said housing and in that the internal face of the wall of the housing is covered with a reflective layer (32). Probe according to claim 2, characterized in that the capsule (40) comprises a hermetically closed envelope (400), housing a radioactive source (401) in gaseous form and provided with at least one layer to be excited of at least a radioluminescent material (402) deposited on a surface exposed to said radioactive source (401). Probe according to claim 2, characterized in that the capsule (40) comprises a hermetically closed envelope and housing a porous solid matrix whose pores define a surface carrying a layer of at least one radioluminescent material exposed to said radioactive source. Probe according to claim 1, characterized in that the radioluminescent source (4) comprises a deposit of a layer (33) of a radioluminescent material produced on the internal face of the wall (30) of the housing (3) and a source radioactive (32) in gaseous form enclosed in said casing. Probe according to claim 1, characterized in that the radioluminescent source (4) comprises a radioactive source implanted in said wall (30) of the housing (3) and a deposit of a layer of a radioluminescent material produced on the internal face of the wall of the housing and exposed to said radioactive source. Probe according to one of claims 3 to 6, characterized in that the radioluminescent material is a phosphor, a scintillator or a semiconductor material based on growth by epitaxy, or on quantum dots. Probe according to claim 5 or 6, characterized in that it comprises a layer of a dielectric material deposited under the radioluminescent source. Probe according to one of claims 5 or 6, characterized in that the layer (36) of radioluminescent material is nanostructured. Probe according to one of Claims 1 to 9, characterized in that the radioluminescent source (4) comprises fluorescent quantum dots. Probe according to one of claims 1 to 10, characterized in that the radioactive source (111) is based on tritium.