Medical probe for optogenetics with VCSELs

Abstract

The invention relates to a medical probe (MP) for optogenetics comprising: a flexible substrate made of a two-dimensional conductive material (M2DS), a plurality of III-V semiconductor microlasers with vertical cavity and surface emission (µVL), called elementary lasers, comprising: an active layer (AL) arranged between a lower reflective layer (BBR) and an upper reflective layer (TBR), a lower semiconductor contact (BSCC) arranged between the lower reflective layer and the substrate and a lower metal contact (BMC) arranged on the substrate and connected to said lower semiconductor contact (BSCC) via said substrate (M2DS), an upper semiconductor contact (TSCC) arranged on the upper reflective layer (TBR), and an upper metal contact (TMC) connected to said upper semiconductor contact, the lower metal contacts of the elementary lasers being intended to be electrically connected to a common potential,a biocompatible encapsulation layer. Figure 5,

Description

Title of the invention: Medical probe for optogenetics with VCSELs FIELD OF THE INVENTION

[0001] The present invention relates to the field of optogenetics, and more particularly that of medical probes for its implementation. STATE OF THE ART

[0002] Optogenetics is a technique that consists of genetically modifying neurons or nerves, such as the auditory nerve, so that they become sensitive to light through the expression of a protein: opsin.

[0003] An example of application is hearing improvement.

[0004] A classic solution is to make cochlear implants (CIs), considered as the most efficient neuroprosthesis that allows patients suffering from neurosensory hearing loss to understand speech. By electrically stimulating the auditory nerve, cochlear implants constitute an interface that reconnects the patient's brain to the auditory scene. However, because it is difficult to concentrate the electrical current in conductive environments such as the cochlea, the accuracy of the electrical coding of sound and the quality of artificial hearing are limited.

[0005] The principle of hearing is briefly recalled. The sound wave represents an alternation of high and low pressure zones. The tympanic membrane vibrates in response to a sound wave. This vibration is amplified when it passes through the ossicles (malleus, incus and stapes).

[0006] The amplified vibration is picked up by the oval window, causing pressure waves in the fluid of the scala vestibuli and scala tympani of the cochlea, which are about 34 mm long. The function of the cochlea is to map sounds of different frequencies onto corresponding characteristic positions of the basilar membrane, as illustrated [Fig.l].

[0007] Stereocilia are actin-based protrusions on auditory and vestibular sensory cells that are necessary for hearing. They convert the physical force of sound into an electrical signal through mechanoelectrical transduction. Defective stereocilia homeostasis is one of the main causes of progressive age-related deafness.

[0008] Optogenetic stimulation of the cochlea is an interesting alternative approach for hearing restoration. Cochlear optogenetics promises improved spectral selectivity of artificial sound coding. It is based on the use of opsins injected into the cochlear branch of cranial nerve VIII, corresponding to the vestibulo-ocochlear nerve, and an optical device stimulating opsins. Opsins are light-sensitive proteins that ensure the conversion of a photon into an electrochemical signal.

[0009] The sensitivity curve of this opsin as a function of the wavelength of light excitation is given for example by the publication of Klapoetke et al "Independent optical excitation of distinct neural populations" Nat. Methods 11, 338-346 (2014). The normalized cumulative charge or NCC (for "Normalized cumulative charge") as a function of the wavelength X, which reflects the sensitivity of the opsin, is illustrated [Fig.2] for different types of opsin: Chrimson; VChRl; Chronos; ChR2; TsChR. For example, for Chrimson and its variants, the maximum sensitivity is at a wavelength of the order of 594 nm, and for TsChR the maximum sensitivity is at approximately 440 nm.

[0010] The publication by Keppeler et al “Multichannel optogenetic stimulation of the auditory pathway using microfabricated LED cochlear implants in rodents” Science Translational Medecine 12 (2020) describes an optical cochlear implant 35 (optogenetic) consisting of a flexible array of gallium nitride (GaN) micro-LEDs used for application in a mouse model, and illustrated [Fig.3]. The 50x50 pm2 LEDs 30 are arranged on a polyimide SubP substrate, at one of its ends 31, in a pitch of 350 pm. The part on which the LEDs 30 are arranged is intended to be inserted into the cochlear canal, the substrate must therefore be very flexible. The LEDs are powered via electrical tracks connected at the other end to wires 32 connected to a connection interface 33.Each LED is powered via two contacts, an n contact and a p contact, connected respectively to the electrical tracks 34n and 34p, the n contact being common to all the LEDs along a single track 34p. The substrate / LED assembly is encapsulated in a silicone layer 36 (see B of [Fig.3]).

[0011] The fabrication of 15 pm thick and highly flexible polyimide devices is made possible by a laser transfer process of GaN LEDs on sapphire to a polyimide on silicon support wafer. With this transfer process, the LEDs are positioned one by one on the substrate, which makes the fabrication of the implant long and expensive, and limits the number of emitters in the device. In addition, the large surface area of ​​the GaN-LEDs induces a large beam profile, which limits the number of optical emitters due to a risk of interaction between two neighboring optical emitters. In addition, the large surface area of ​​the GaN-LEDs increases the temperature inside the cochlea, which requires solutions to be found to dissipate the heat.

[0012] An alternative solution based on microOLED is described in the publication by Sheppard et al “Optogenetic stimulation probes with single-neuro resolution based on organic LED monolithically integrated on CMOS » Nature Electronics, Vol. 6 p 669-679 (2023). The device is illustrated [Fig.4]. The design and characterization of a silicon rod incorporating a high density of organic light sources. These microOLEDs of dimension 20 pm x 20 pm with a pitch of 25 pm have the advantage of being processed after the electronic driver. This is a so-called "above-IC" device, which means that the deposits and structuring are carried out after the chip (IC) production, on top, because the optical power of microOLEDs is low. Although very dim, it is validated that they can trigger an action potential associated with the opsin ChRmine which is two orders of magnitude more sensitive than the opsin ChrimsonR described by the publication of Klapoetke et al cited above, and sensitive to optical stimulation colored in orange.

[0013] As previously, a significant drawback of these emitters is their poor efficiency, which induces a transformation of the supply current into heat by the Joule effect. However, medical standards do not allow tissue heating above 2°C, which limits the number of usable emitters. OLED technologies are also sensitive to humidity, which induces the use of a stack of atomic layer deposition (ALD) and parylene, to ensure biocompatibility and limit humidity migration. The compatibility of these components with chronic use is not guaranteed.

[0014] An aim of the present invention is to remedy the aforementioned drawbacks by proposing a medical probe for optogenetics having small emitters and with better performance than the optogenetic implants of the state of the art, and a parallel manufacturing process. DESCRIPTION OF THE INVENTION

[0015] The present invention relates to a medical probe for optogenetics comprising: - a flexible substrate made of two-dimensional conductive material, - a plurality of IILV vertical cavity surface emitting semiconductor microlasers, called elementary lasers, the elementary lasers being arranged on said substrate and integrated in an insulating layer, the elementary lasers having a maximum dimension of between 5 and 50 pm and comprising: • an active layer arranged between a lower reflective layer and an upper reflective layer, • a lower semiconductor contact disposed between the lower reflective layer and the substrate, and a lower metal contact disposed on the substrate and connected to said lower semiconductor contact via said substrate, • an upper semiconductor contact arranged on the upper reflective layer and an upper metal contact connected to said upper semiconductor contact, • the lower metal contacts of the elementary lasers being intended to be electrically connected to a common potential, - a biocompatible encapsulation layer.

[0016] According to a first embodiment, the two-dimensional material is graphene.

[0017] According to a second embodiment, the two-dimensional material is a dichal- cogenide or a trichalcogenide configured to be conductive.

[0018] According to one embodiment, the substrate has a ribbon shape on a part of which said elementary lasers of said plurality are arranged in a line, and the lower metal contacts of the elementary lasers are connected to a lower electrical track common to said elementary lasers of the line.

[0019] According to another embodiment, the elementary lasers of said plurality are arranged in a matrix, the lower semiconductor contacts of the elementary lasers of a row of the matrix being connected to a lower electrical track common to the elementary lasers of said row of the matrix, the lower electrical tracks associated with the rows being connected to each other.

[0020] According to a first variant, the lower and upper semiconductor contacts of an elementary laser are made of gallium nitride or a ternary material comprising gallium nitride.

[0021] According to an embodiment of the first preceding variant, the two-dimensional material is graphene and the lower semiconductor contact has a crystallographic growth axis along the

[1000] axis.

[0022] According to another embodiment of the first variant, the two-dimensional material is a dichalcogenide chosen from WS2, MoS2, ReS2 and the lower semiconductor contact has a crystallographic growth axis along the

[100] axis.

[0023] According to a second variant, the lower and upper semiconductor contacts of an elementary laser are made of gallium arsenide or a ternary material comprising gallium arsenide.

[0024] According to an embodiment of the second variant, the two-dimensional material is graphene, and the graphene substrate comprises housings in which the elementary lasers are arranged.

[0025] According to one embodiment, the active layer comprises multiple quantum wells or quantum dots.

[0026] According to one embodiment, the substrate made of two-dimensional material and the elementary lasers form a first structure, the probe comprising at least a second structure stacked on the first structure, elementary lasers of the two structures being arranged so that elementary lasers of the second structure do not obscure a beam emitted by elementary lasers of the first structure.

[0027] According to one embodiment, the elementary lasers in the second structure are configured to emit a wavelength different from an emission wavelength of the first structure.

[0028] According to one embodiment, one of the two structures is made up of elementary lasers comprising at least one layer of gallium nitride or a ternary material comprising gallium nitride, and the other structure is made up of elementary lasers comprising at least one layer of gallium arsenide or a ternary material comprising gallium nitride.

[0029] According to another aspect, the invention relates to a first method of manufacturing a medical probe for optogenetics comprising the steps of: Al having a first initial substrate comprising a semiconductor substrate, an insulating layer called a substrate, a metal layer and a graphene layer arranged on the metal layer, B1 depositing on the first initial substrate a first dielectric layer and a first resin layer, structuring the first resin layer so as to form a first mask having first openings, the first openings having a maximum dimension of between 5 and 50 pm, Cl etch the first dielectric layer down to the graphene layer by wet etching, so as to expose the graphene layer in the first openings, DI remove the first layer of resin, And to produce by epitaxy, in said first openings, a stack of semiconductor materials, the stack comprising a lower semiconductor contact made of gallium nitride epitaxially grown on the graphene layer, a lower reflective layer, an active layer, an upper reflective layer and an upper semiconductor contact made of gallium nitride, Fl depositing a second dielectric layer, structuring a second resin layer so as to form a second mask having second openings above each stack, etching the second dielectric layer and the upper semiconductor contact and removing the second resin layer, G1 removing the first and second dielectric layers by wet etching, so as to obtain stacks arranged on the first initial substrate, H1 deposit a lower metal contact on the graphene layer, deposit an insulating layer around the stacks and deposit an upper metal contact connected with the upper semiconductor contact, II remove the semiconductor substrate using the substrate insulating layer, J1 remove the metal layer. In addition, the stacks and the associated first and second metal contacts are configured to form vertical cavity, surface-emitting semiconductor microlasers inserted into the insulating layer, called elementary lasers, the graphene layer forming a flexible substrate, the elementary lasers being arranged on said flexible substrate. The method further comprises a step K1 of encapsulating the substrate and the elementary lasers with a biocompatible material.

[0030] According to one embodiment, during step E1 the growth of the lower gallium nitride semiconductor contact by epitaxy on the graphene substrate takes place in a

[1000] direction.

[0031] According to one embodiment, in step C1 the wet etching of the first dielectric layer up to the graphene layer is of the BOE type for “Buffered Oxide Etching”.

[0032] According to another aspect, the invention relates to a second method of manufacturing a medical probe for optogenetics comprising the steps of: A2 having a second initial substrate comprising a gallium arsenide substrate, an insulating layer called a substrate, a metal layer and a first graphene layer arranged on the metal layer, B2 depositing on the second initial substrate a first dielectric layer and a first resin layer, structuring the first resin layer so as to form a first mask having first openings, the first openings having a maximum dimension of between 5 and 50 pm, C2 etch the first dielectric layer down to the graphene layer, D2 remove the first layer of resin, etch the graphene layer, etch the metal layer and etch the insulating substrate layer, so as to expose the gallium arsenide substrate in the first openings, E2 producing by epitaxy, in said first openings, a stack of semiconductor materials comprising a lower semiconductor contact in gallium arsenide epitaxially grown on the gallium arsenide substrate, a lower reflective layer, an active layer, an upper reflective layer and an upper semiconductor contact in gallium arsenide, F2 depositing a second dielectric layer and a second resin layer, structuring the second resin layer so as to form a second mask having second openings above each stack, etching the second dielectric layer, etching the upper semiconductor contact, and removing the second resin layer, G2 remove the first and second dielectric layers by wet etching, so as to obtain stacks arranged on the gallium arsenide substrate, H2 deposit a lower metal contact on the remaining graphene layer of each side of the stacks, deposit an insulating layer around the stacks and deposit an upper metal contact in contact with the upper semiconductor contact, 12 removing the gallium arsenide substrate using the substrate insulating layer, J2 removing the metal layer, and depositing a second graphene layer on the first graphene layer and the lower semiconductor contact, the first and second graphene layers collectively forming a flexible graphene substrate. In addition, the stacks and the associated first and second metal contacts are configured to form vertical cavity surface emitting (pVL) semiconductor microlasers inserted into the insulating layer, called elementary lasers, the elementary lasers being arranged on said graphene substrate, the graphene substrate comprising housings in which the elementary lasers are arranged. In addition, the method comprises a step K2 of encapsulating the substrate and the elementary lasers with a biocompatible material.

[0033] The following description presents several exemplary embodiments of the device of the invention: these examples are not limiting of the scope of the invention. These exemplary embodiments present both the essential characteristics of the invention as well as additional characteristics linked to the embodiments considered.

[0034] The invention will be better understood and other characteristics, aims and advantages thereof will appear during the detailed description which follows and with reference to the appended drawings given as non-limiting examples and in which:

[0035] The [Fig. 1] already cited illustrates the basic diagram of sound transmission by the cochlea.

[0036] The already cited [Fig.2] illustrates the normalized cumulative charge as a function of wavelength, for different types of opsin.

[0037] The [Fig.3] already cited illustrates an optical cochlear implant consisting of a flexible network of micro-LEDs based on gallium nitride for a mouse.

[0038] The [Fig.4] already cited illustrates an implant made up of microOLED on CMOS.

[0039] [Fig.5] illustrates an embodiment of a probe according to the invention in which the substrate has a ribbon shape.

[0040] [Fig.6] illustrates an embodiment of a probe according to the invention in which the elementary lasers are arranged in a planar matrix network.

[0041] [Fig.7] illustrates an embodiment of a probe according to the invention in which the graphene substrate comprises housings in which the GaAs-based elementary lasers are arranged.

[0042] [Fig.8] illustrates an embodiment of a probe according to the invention in which the 2D material substrate and the elementary lasers form a first structure SI, and the probe comprises at least a second structure S2 stacked on the first SI structure, the S2 structure having an architecture identical to the SI structure (substrate + elementary lasers).

[0043] [Fig.9] illustrates steps A1 to F1 of the method 100 according to the invention.

[0044] [Fig. 10] illustrates steps G1 to J1 of the method 100 according to the invention.

[0045] [Fig. 11] illustrates steps A2 to F2 of the method 100 according to the invention.

[0046] [Fig. 12] illustrates steps G2 to J2 of the method 100 according to the invention. DETAILED DESCRIPTION OF THE INVENTION

[0047] An embodiment of the MP medical probe according to the invention, suitable for producing a cochlear implant with a ribbon-shaped substrate and in-line emitters, is illustrated [Fig.5]. Part B is a top view in an XY plane of the probe according to the invention and part A is a profile view in an XZ plane (section along AA).

[0048] The design of the cochlear implant is facilitated by the fact that the topology of the cochlea is well known with its distribution of hair cells specific to sound frequencies. After recording and analyzing the frequency of an emitted sound, an emitter of the optical probe, whose location in the cochlea corresponds to this frequency, is switched on. It makes it possible to stimulate the cochlear branch of the VIII cranial nerve into which opsins have been injected and thus to generate an artificial sound perception.

[0049] However, the principle of stimulation of a neuron or a nerve by an optical device via opsin is applicable to any other application of optogenetics, by modifying the design of the device. The invention is thus applicable to other types of probes for optogenetics having different emitter arrangement geometries, for example a planar network, a rod, a tube obtained from a planar network (thanks to the flexible substrate) ... The probe according to the invention finds application for example for integration into the visual cortex for the restoration of sight or in the motor cortex for the compensation of motor handicaps.

[0050] The MP medical probe for optogenetics according to the invention comprises a flexible M2DS substrate made of two-dimensional material, called 2D, configured to be conductive.

[0051] 2D materials have a planar structure and are composed of one to a few monolayers L, each monolayer comprising a few atomic planes (typically 1 to 20), the number of atomic planes being a function of the atomic structure. The chemical bonds within a monolayer are covalent. A two-dimensional material can be conductive or semiconducting, typically depending on the number of stacked monolayers.

[0052] According to one embodiment, the two-dimensional material is graphene. Graphene is naturally conductive and composed of a single atom, carbon, and the A monolayer comprises only one atomic plane, it is planar and made up of carbon atoms arranged in a hexagonal lattice. Graphene is flexible and the thickness T of such a substrate is typically between 0.3 and 20 nm depending on the number of stacked monolayers. The advantages of graphene are that the associated processes are mature and that it is non-toxic. It also has good lattice agreement with certain III-V semiconductors (see below).

[0053] According to another embodiment, the two-dimensional material is a dichalcogenide or a trichalcogenide configured to be conductive, having a thickness of between 0.3 and 20 nm.

[0054] The MP probe also comprises a plurality of IILV semiconductor microlasers with vertical cavity and emission by the pVL surface, called elementary lasers, and conventionally called VCSEL for Vertical Cavity Surface Emitting Laser. The elementary lasers pVL are arranged on the M2DS substrate and integrated in an IL insulating layer. The elementary lasers have a maximum dimension of between 5 and 50 pm. Maximum dimension is understood to mean the largest lateral dimension of the laser. Typically the lasers have a thickness (height) of the order of 0.5 to 5 pm.

[0055] An elementary laser of the probe according to the invention has a conventional layer structure and comprises an active layer AL arranged between a lower reflective layer BBR and an upper reflective layer TBR. It also comprises: - a lower semiconductor contact BSCC arranged between the lower reflective layer and the substrate and a lower metal contact BMC, - an upper semiconductor contact TSCC arranged on the upper reflective layer TBR and an upper metal contact TMC connected to the upper semiconductor contact.

[0056] In the configuration of the invention, the lower metal contact is arranged on the substrate M2DS and electrically connected to the lower semiconductor contact BSCC via the substrate which is conductive. However, for sufficient electrical connectivity, it is appropriate that the lower metal contact is not too far from the lower semiconductor contact.

[0057] Furthermore, the lower metal contacts of the elementary lasers are intended to be electrically connected to a common potential, typically a reference potential, a ground.

[0058] Conventionally for a probe having several emitters (see for example [Fig.3]), the lower and upper metal contacts are connected to associated electrical tracks, typically metallic, which carry the electrical signal for controlling the emitters.

[0059] The MP medical probe according to the invention is intended to be electrically connected to a power supply and control unit PU, connected to the tracks.

[0060] For the elementary VCSEL type lasers according to the invention, the lower metal contacts are electrically connected to each other via the conductive substrate, and are intended to be connected to the common potential typically via tracks connected, at the end of the probe, to the power supply and control unit.

[0061] Preferably, the lower semiconductor contacts are connected to one or more lower CMT electrical tracks (depending on the arrangement of the elementary lasers) arranged on the substrate.

[0062] Despite the conductive nature of the substrate, the lower metal contacts and the lower electrical tracks are necessary to carry the current flowing in the elementary lasers. There is typically a factor of at least 4 to 5 between the conductivity of a metal (gold, copper) and that of a 2D material.

[0063] The upper metal contacts are connected to upper electrical tracks TMT. For each laser, the upper electrical contact TMC is connected to an upper track TMT associated with the laser which carries the control signal of the elementary laser.

[0064] According to the embodiment, of [Fig.5] the substrate is in the form of a ribbon, on a part of which lasers are arranged in a line. The lower metal contacts of the plurality of lasers are connected to a lower electrical track CBMT common to the elementary lasers of the line, intended to be connected to the electrical ground of the device. This makes it possible to halve the number of electrical contacts. This geometry is well suited to a cochlear implant.

[0065] The MP probe also comprises a biocompatible, electrically insulating, transparent and long-term stable encapsulation layer, for example a medical grade silicone, which surrounds at least the portion of the probe intended to be inserted into the body.

[0066] The originality of the invention consists in the production of a medical probe for optogenetics comprising small-sized VCSELs on a graphene substrate which is thin and flexible, this structure having numerous advantages compared to existing probes.

[0067] First of all, the small size of the elementary lasers and the very directive nature of the emitted light beam ELB allows a very dense arrangement of the emitters on the 2D material substrate, with the limit of being able to pass the electrical wiring if necessary (typically the tracks have a width of a few microns). For in-line lasers such as in [Fig.5] part B, the lasers can be very close together because there are no tracks between two lasers. A dense arrangement allows the addressing of the target cells with a very good spatial resolution.

[0068] In addition, VCSELs have a much better quantum efficiency than LEDs (more of electrons transformed into photons), which induces a much lower generation of heat by Joule effect. This is very important for medical probes since the permissible heating of the device is very limited. It is therefore not necessary to provide an additional heat evacuation device, which also allows the densification of the emitters without excessive heat emission.

[0069] Finally, the 2D material substrate provides great flexibility to the device, allowing it to adapt to different environments of the human body.

[0070] According to one embodiment, the elementary lasers are arranged according to a planar array in a matrix as illustrated [Fig.6]. Preferably, the elementary lasers of a line Li (index i) of the matrix are connected to an associated shared lower electrical track CBMTi

[0071] The elementary pVL laser is a vertical cavity surface emitting laser based on a stack of III-V semiconductor layers. Preferably it comprises a p-doped III-V contact, a p-doped III-V Bragg reflector, the active layer AL, an n-doped III-V Bragg reflector and a p-doped III-V contact.

[0072] According to one embodiment, the active layer AL of the laser contains multiple quantum wells MQW based on III-V semiconductors, the structure of which is an alternating stack of wells and barriers composed of IILV semiconductors. According to another embodiment, the active layer of the laser contains quantum dots QD which are based on IILV semiconductors.

[0073] According to a first variant of the probe according to the invention, the lower B SCC and upper TSCC semiconductor contacts of an elementary laser are made of gallium nitride GaN or a ternary material comprising gallium nitride. This family of GaN-based VCSELs emits an ELB light beam having a wavelength in a range from blue to green.

[0074] According to a second variant of the probe according to the invention, the lower B SCC and upper TSCC semiconductor contacts of an elementary laser are made of gallium arsenide (GaAs) or a ternary material comprising gallium arsenide. This family of GaAs-based VCSELs emits an ELB light beam having a wavelength in a range from orange to red or even infrared depending on the nature of the active layer.

[0075] As will be seen later, the steps of the method for manufacturing elementary lasers on a 2D material substrate which is graphene differ for the two families of IILV semiconductor laser components. This has the consequence that the GaAs-based pVL lasers are well arranged on the graphene substrate but the latter comprises housings in which the elementary lasers are arranged, as illustrated [Fig.7].

[0076] The two VCSEL families allow targeting two wavelength ranges different.

[0077] According to an illustrated embodiment [Fig.8], it is considered that the 2D material substrate and the elementary lasers form a first structure SI, and the MP probe comprises at least a second structure S2 stacked on the first structure SI, the structure S2 having an architecture identical to the structure SI (substrate + elementary lasers). It is then the assembly S1+S2 which is coated in an encapsulation layer. Preferably, elementary lasers of the two structures are arranged so that elementary lasers pVL2 of the second structure do not occlude a beam emitted ELB1 by elementary lasers pVL1 of the first structure as illustrated in part A of [Fig.8] (top view of the probe). Part B illustrates a profile view according to sections BB and CC.

[0078] Preferably, the elementary lasers in the second structure are configured to emit a wavelength X2 different from an emission wavelength XI of the first structure. This makes it possible to have a probe which can be located near the cells of interest and emit sometimes one color and sometimes another. Such a probe makes it possible, in combination with cells integrating an excitatory opsin (for example at XI) and an inhibitory opsin (for example at X2), to excite and inhibit the channels of the cells on command by switching on and off the associated emitters of the double-level probe.

[0079] According to an embodiment of the double-level probe of [Fig.8], one of the two structures is made up of elementary lasers comprising at least one layer of gallium nitride (family of components based on GaN) and the other structure is made up of elementary lasers comprising at least one layer of gallium arsenide (family of components based on GaAs).

[0080] According to an embodiment of an emitter according to the first variant, the lower semiconductor contact BSCC is made of n-doped gallium nitride and the upper semiconductor contact TSCC is made of p-doped gallium nitride. It is possible to reverse the dopings.

[0081] The lower and upper reflective layers BBR and TBR are for example an alternation of AlGaN and GaN layers, and the active layer AL comprises InGaN quantum multiwells separated by gallium nitride barriers.

[0082] Typically, the gallium nitride BSCC lower semiconductor contact has a Wurtzite crystallographic structure.

[0083] According to an embodiment of a probe according to the invention with emitters according to the first variant, the two-dimensional material is graphene and the lower semiconductor contact BSCC has a crystallographic growth axis along the

[1000] axis. For the production of such an emitter on graphene, the mesh agreement between GaN and graphene favors such a structure.

[0084] Conventionally, when the lower semiconductor contact is along the

[1000] axis and all the materials of the stack forming the VCSEL are based on GaN, these materials all have a growth axis along

[1000] .

[0085] According to another embodiment of an emitter according to the first variant, the two-dimensional material is a dichalcogenide or a trichalcogenide. Preferably, the material is a dichalcogenide chosen from WS2, MoS2, ReS2 and the lower semiconductor contact has a crystallographic growth axis along the

[100] axis. The aforementioned materials have the advantage of having an atomic lattice structure close to that of GaN and the structure of GaN along the

[100] axis is the most suitable for the growth of GaN on this type of material.

[0086] According to an embodiment of an emitter according to the second variant, the lower semiconductor contact BSCC and the upper semiconductor contact TSCC are made of GaAs or a ternary material comprising GaAs.

[0087] Preferably, one of the semiconductor contacts is n-doped and the other is p-doped.

[0088] For example, the lower reflective layer BBR is an alternation of two layers in AlGaAs and AlAs, the active layer AL comprises multiple quantum wells in GalnP separated by barriers in AlGalnP and the upper reflective layer TBR is an alternation of two layers in AlGaAs of different composition.

[0089] According to another aspect, the invention relates to a method 100 for manufacturing a medical probe for optogenetics with elementary lasers made from GaN (at least the lower semiconductor contact) on a substrate made of 2D graphene-type material. Graphene has the advantage of having a mature implementation method and of being non-toxic. It also has the advantage of having a mesh structure matched with that of GaN.

[0090] The method 100 according to the invention is illustrated [Fig.9] for steps A1 to F1 and [Fig. 10] for steps G1 to J1.

[0091] It comprises a first step A1 consisting of having a first initial substrate IS1 comprising a semiconductor substrate SS, such as silicon, an insulating layer called substrate ILS, typically dielectric, a metal layer ML, for example made of copper or nickel and a graphene layer GS arranged on the metal layer. Graphene is not soluble in these metals. Typically the graphene layer has grown on the metal layer by a chemical vapor deposition or CVD technique (for "Chemical Vapor Deposition") using CH4-H2.

[0092] Then, in a step B1, a first dielectric layer (DL1), typically SiO2 or Si3N4, and a first resin layer RL1 are deposited on the first initial substrate IS1, and the first resin layer RL1 is typically structured by photolithography so as to form a first mask M1 having first openings Op1. The first openings have a maximum dimension between 5 and 50 pm.

[0093] In a step C1, the first dielectric layer DL1 is etched down to the graphene layer by wet etching, so as to expose the graphene layer in the first openings. Here, we stop at a layer of 2D material of atomic thickness, and the integrity of the graphene layer must be preserved. We cannot use dry ion etching (or RIE for "Reactive Ion Etching"), for example based on chlorine, which is necessarily partly mechanical and would risk damaging the graphene. Only wet etching can be used for this step. Preferably, according to one embodiment, we use a buffered hydrofluoric acid (HF) type etching such as BOE for "Buffered Oxide Etching" because graphene resists this type of etching.

[0094] In a step D1, the first layer of resin is removed, for example by chemical attack with 2-propanol.

[0095] Locations are then available in which the VCSELs are grown. Thus, in a step El, a stack of semiconductor materials is produced by epitaxy, typically by MOCVD (for "MetalOrganic Chemical Vapor Deposition") or GSMBE (for "Gas Source Molecular Beam Epitaxy") in the first openings Opl. The stack Emp comprises a lower semiconductor contact BSCC made of gallium nitride (or a GaN-based ternary) epitaxied on the graphene layer, a lower reflective layer BBR, an active layer AL, an upper reflective layer TBR and an upper semiconductor contact TSCC made of gallium nitride (or a GaN-based ternary).

[0096] According to a preferred embodiment, the epitaxy of GaN on graphene is carried out along the crystallographic axis

[1000] , because there is a good lattice agreement. Preferably the lower semiconductor contact BSCC has a Wurtzite crystallographic structure.

[0097] Thus, in places where the graphene is exposed, VCSELs are grown, all isolated from each other, with a common mass. Thanks to this technology called SAG (for Selective Area Growth), the semiconductor grows on the graphene and not elsewhere, which makes it possible to define the geometry of the laser without chlorine etching (just the etching of the dielectric layer and the contact to let the light out).

[0098] In a step F1, a second dielectric layer DL2 (for example made of SiO2 or Si3N4) is deposited and a second resin layer RL2 is structured, typically by photolithography, so as to form a second mask M2 having second openings Op2 above each stack. Then the second dielectric layer DL2 is etched, typically by fluorine RIE, and the upper semiconductor contact is etched, typically by chlorine RIE etching. Finally, the second resin layer RL2 is removed. The emission surface of the VCSEL is exposed. for the passage of the emitted light. The graphene layer is protected by the DL2 layer.

[0099] In step G1, the first and second dielectric layers DL1 and DL2 are removed by wet etching, so as to obtain stacks arranged on the first initial substrate. The etching is wet here for the same reasons as previously, i.e. to avoid damaging the graphene layer.

[0100] In step H1, a lower metal contact BMC is then deposited on the graphene layer, which is therefore connected to the lower semiconductor contact via the conductive graphene layer, and an insulating layer IL is deposited around the stacks. An upper metal contact TMC is also deposited, connected to the upper semiconductor contact TSCC, so that emission from the upper surface of the VCSEL can take place. At this stage, the elementary lasers are finished. It is also at this stage that the lower track(s) CBMT and the upper track(s) TMT are produced for the connection.

[0101] In a step II, the semiconductor substrate SS is removed using the insulating substrate layer ILS, preferably by mechanical cleavage. The presence of the insulating substrate layer ILS helps in the decoupling between the graphene layer and the metal layer ML.

[0102] Then, in a step Jl, the metal layer ML is removed, for example by chemical attack based on FeCl3 when the layer ML is made of copper.

[0103] The stacks and the associated first and second metal contacts are configured to form vertical cavity semiconductor microlasers with surface emission pVL inserted in the insulating layer, called elementary lasers. The graphene layer forms a flexible substrate GS, the elementary lasers being arranged on this flexible substrate.

[0104] The method 100 further comprising a step Kl of encapsulating the substrate and the elementary lasers with a biocompatible material.

[0105] The method 100 according to the invention thus makes it possible to produce in parallel a large number of elementary lasers on a flexible graphene substrate, in one go and without a transfer process.

[0106] The elementary lasers are all at the same mass due to the conductivity of graphene.

[0107] According to another aspect, the invention relates to a method 200 for manufacturing a medical probe for optogenetics with elementary lasers made from GaAs on a substrate made of 2D graphene-type material. The method 200 according to the invention is illustrated [Fig. 11] for steps A2 to E2 and [Fig. 12] for steps G2 to J2.

[0108] Process 200 has some different steps than process 100 because GaAS is not mesh-matched with 2D materials such as graphene or dichal-cogenides.

[0109] In a first step A2, a second initial substrate IS2 is provided comprising a gallium arsenide substrate GAS, an insulating layer called an ILS substrate, a metal layer ML (for example copper or nickel) and a first graphene layer GL1 arranged on the metal layer.

[0110] In a step B2, a first dielectric layer DL1 and a first resin layer RL1 are deposited on the second initial substrate, the first resin layer is structured so as to form a first mask M1 having first openings Op1. The first openings have a maximum dimension of between 5 and 50 pm.

[0111] In a step C2, the first dielectric layer is etched down to the graphene layer. The etching here can be dry or wet, because the graphene layer GL1 will be removed.

[0112] In a step D2, the first layer of resin is removed, the graphene layer is etched, for example with chlorine RIE etching, the metal layer is etched, typically by IBE (for “Ion Beam Etch”). The insulating substrate layer is also etched, for example with fluorine RIE etching so as to expose the GaAs substrate in the first openings Opl.

[0113] Thus, in the places where the GAS substrate is bare, VCSELs are grown, all isolated from each other, typically with a common mass (see below). The GaAs material does not grow on the graphene because it is not adapted to the graphene mesh. In the 200 process, which is always of the SAG type in the Opl openings, the graphene becomes a growth mask.

[0114] In a step E2, a stack of semiconductor materials is produced by epitaxy, typically MOCVD or GSMBE, in the first openings Op1, comprising a lower semiconductor contact BSCC in gallium arsenide (or in a ternary material based on GaAs) epitaxially grown on the gallium arsenide substrate GAS, a lower reflective layer BBR, an active layer AL, an upper reflective layer TBR and an upper semiconductor contact TSCC in gallium arsenide.

[0115] As in method 100, in a step F2, a second dielectric layer DL2 and a second resin layer RL2 are deposited, the second resin layer RL2 is structured so as to form a second mask M2 having second openings Op2 above each stack, the second dielectric layer is etched, the upper semiconductor contact is etched and the second resin layer is removed.

[0116] In a step G2, the first and second dielectric layers are removed by wet etching, so as to obtain stacks arranged on the gallium arsenide GAS substrate. Wet etching is used here so as not to degrade the graphene remaining on each side of the stack.

[0117] In a step H2, the lower metal contact BMC is deposited on the remaining graphene layer on each side of the stacks, an insulating layer IL is deposited around the stacks and an upper metal contact TMC is deposited in contact with the upper semiconductor contact TSCC. It is also at this stage that the lower track(s) and the upper track(s) for the connection are produced.

[0118] In a step 12, the gallium arsenide substrate GAS is removed using the insulating substrate layer ILS, preferably by mechanical cleavage.

[0119] In a step J2, the metal layer ML is removed and a second graphene layer GL2 is deposited on the first graphene layer GL1 and the lower semiconductor contact, the first and second graphene layers collectively forming a flexible graphene substrate GS.

[0120] This second graphene layer ensures the strength and flexibility of the graphene substrate and the injection of the current. The stacks and the associated first and second metal contacts are configured to form vertical cavity semiconductor microlasers with surface emission pVL inserted in the insulating layer, called elementary lasers. The elementary lasers are arranged on the graphene substrate GS, and here the graphene substrate comprises housings in which the elementary lasers are arranged.

[0121] The method 200 further comprising a step K2 of encapsulating the substrate and the elementary lasers with a biocompatible material.

[0122] Thus, in this process, the graphene is etched down to GaAs, the laser component is grown on a GaAs GAS substrate, and then the component is peeled off from the GAS substrate using the substrate insulating layer.

Claims

Claims

1. Medical probe (MP) for optogenetics comprising: - a flexible substrate made of two-dimensional conductive material (M2DS), - a plurality of III-V semiconductor microlasers with vertical cavity and surface emission (pVL), called elementary lasers, the elementary lasers being arranged on said substrate and integrated in an insulating layer (IL), the elementary lasers having a maximum dimension of between 5 and 50 pm and comprising: • an active layer (AL) arranged between a lower reflective layer (BBR) and an upper reflective layer (TBR), • a lower semiconductor contact (BSCC) arranged between the lower reflective layer and the substrate and a lower metal contact (BMC) arranged on the substrate and connected to said lower semiconductor contact (BSCC) via said substrate (M2DS), • an upper semiconductor contact (TSCC) arranged on the upper reflective layer (TBR),and an upper metal contact (TMC) connected to said upper semiconductor contact, • the lower metal contacts of the elementary lasers being intended to be electrically connected to a common potential, - a biocompatible encapsulation layer.,

2. Medical probe (MP) according to the preceding claim in which the two-dimensional material is graphene.

3. A medical probe (MP) according to claim 1 wherein the two-dimensional material is a dichalcogenide or a trichalcogenide configured to be conductive.

4. Medical probe according to one of the preceding claims in which the substrate has a ribbon shape on a part of which said elementary lasers of said plurality are arranged in line, the lower metal contacts of the elementary lasers being connected to a lower electrical track (CBMT) common to all elementary lasers of the line.

5. Medical probe according to one of claims 1 to 3 in which the elementary lasers of said plurality are arranged in a matrix, the lower semiconductor contacts of the elementary lasers of a row of the matrix being connected to a lower electrical track common to the elementary lasers of said row of the matrix, the lower electrical tracks associated with the rows being connected to each other.

6. Medical probe according to one of the preceding claims in which the lower and upper semiconductor contacts of an elementary laser are made of gallium nitride (GaN) or a ternary material comprising gallium nitride.

7. A medical probe according to claim 6 wherein the two-dimensional material is graphene and the lower semiconductor contact has a crystallographic growth axis along the [1000] axis.

8. A medical probe according to claim 6 wherein the two-dimensional material is a dichalcogenide selected from WS2, MoS2, ReS2 and the lower semiconductor contact has a crystallographic growth axis along the [100] axis.

9. Medical probe according to one of claims 1 to 5 in which the lower and upper semiconductor contacts of an elementary laser are made of gallium arsenide (GaAs) or a ternary material comprising gallium arsenide.

10. Medical probe according to the preceding claim in which the two-dimensional material is graphene, and in which the graphene substrate comprises housings in which the elementary lasers are arranged.

11. A medical probe according to any preceding claim wherein the active layer comprises multi-quantum wells (MQWs) or quantum dots (QDs).

12. Medical probe according to one of the preceding claims in which the substrate made of two-dimensional material and the elementary lasers form a first structure (SI), the probe comprising at least one second structure (S2) stacked on the first structure (SI), elementary lasers of the two structures being arranged so that elementary lasers (pVL2) of the second structure do not obscure a beam emitted (ELB1) by elementary lasers (pVLl) of the first structure.

13. Medical probe according to the preceding claim in which the elementary lasers in the second structure are configured to emit a wavelength (X2) different from an emission wavelength (XI) of the first structure.

14. Medical probe according to the preceding claim in which one of the two structures consists of elementary lasers comprising at least one layer of gallium nitride or a ternary material comprising gallium nitride, and the other structure consists of elementary lasers comprising at least one layer of gallium arsenide or a ternary material comprising gallium nitride.

15. Method (100) for manufacturing a medical probe for optogenetics comprising the steps of: A1 providing a first initial substrate (IS1) comprising a semiconductor substrate (SS), an insulating layer called substrate (ILS), a metal layer (ML) and a graphene layer (GS) arranged on the metal layer, B1 depositing on the first initial substrate a first dielectric layer (DL1) and a first resin layer (RL1), structuring the first resin layer so as to form a first mask (Ml) having first openings (Opl), the first openings having a maximum dimension of between 5 and 50 μm, C1 etching the first dielectric layer down to the graphene layer by wet etching, so as to expose the graphene layer in the first openings, D1 removing the first resin layer, E1 producing by epitaxy, in said first openings (Opl),a stack of semiconductor materials, the stack comprising a lower semiconductor contact (BSCC) made of gallium nitride epitaxially grown on the graphene layer, a lower reflective layer (BBR), an active layer (AL), an upper reflective layer (TBR) and an upper semiconductor contact (TSCC) made of gallium nitride, F1 depositing a second dielectric layer (DL2), structuring a second resin layer (RL2) so as to form a second mask (M2) having second openings (Op2) above each stack, etching the second dielectric layer and the upper semiconductor contact and removing the second resin layer, G1 removing the first and second dielectric layers by etching, wet, so as to obtain stacks arranged on the first initial substrate, H1 depositing a lower metal contact (BMC) on the graphene layer, depositing an insulating layer around the stacks and depositing an upper metal contact (TMC) connected with the upper semiconductor contact (TSCC), H1 removing the semiconductor substrate (SS) using the substrate insulating layer (ILS), J1 removing the metal layer (ML), the stacks and the first and second associated metal contacts being configured to form vertical cavity and surface emitting semiconductor microlasers (pVL) inserted in the insulating layer, called elementary lasers, the graphene layer forming a flexible substrate (GS), the elementary lasers being arranged on said flexible substrate, the method further comprising a step Kl of encapsulating the substrate and the elementary lasers with a biocompatible material.

16. Method according to the preceding claim in which during step E1 the growth of the lower semiconductor contact in gallium nitride by epitaxy on the graphene substrate takes place in a direction [1000],

17. Method according to one of claims 15 or 16 in which in step C1 the wet etching of the first dielectric layer up to the graphene layer is of the BOE type for “Buffered Oxide Etching”.

18. Method (200) for manufacturing a medical probe for optogenetics comprising the steps of: A2 providing a second initial substrate (IS2) comprising a gallium arsenide substrate (GAS), an insulating layer called substrate (ILS), a metal layer (ML) and a first graphene layer (GL1) arranged on the metal layer, B2 depositing on the second initial substrate a first dielectric layer (DL1) and a first resin layer (RL1), structuring the first resin layer so as to form a first mask (Ml) having first openings (Opl), the first openings having a maximum dimension of between 5 and 50 μm, C2 etching the first dielectric layer down to the graphene layer, D2 removing the first resin layer, etching the graphene layer, etching the metal layer and etching the insulating substrate layer, so as to expose the gallium arsenide substrate in the first openings, E2 producing by epitaxy, in said first openings (Opl), a stack of semiconductor materials comprising a lower semiconductor contact (BSCC) in gallium arsenide epitaxially grown on the gallium arsenide substrate, a lower reflective layer (BBR), an active layer (AL), an upper reflective layer (TBR) and an upper semiconductor contact (TSCC) in gallium arsenide, F2 depositing a second dielectric layer (DL2) and a second resin layer (RL2), structuring the second resin layer (RL2) so as to form a second mask (M2) having second openings (Op2) above each stack, etching the second dielectric layer, etching the upper semiconductor contact, and removing the second resin layer, G2 removing the first and second dielectric layers by wet etching, so as to obtain stacks arranged on the gallium arsenide substrate, H2 deposit a bottom metal contact (BMC) on the remaining graphene layer on each side of the stacks, deposit an insulating layer around the stacks and deposit a top metal contact (TMC) in contact with the top semiconductor contact (TSCC), 12 remove the gallium arsenide (GAS) substrate using the substrate insulating layer (SIL), J2 removing the metal layer (ML), and depositing a second graphene layer (GL2) on the first graphene layer and the lower semiconductor contact, the first and second graphene layers collectively forming a flexible graphene substrate (GS), the stacks and the associated first and second metal contacts being configured to form vertical cavity surface emitting semiconductor microlasers (pVL) inserted in the insulating layer, called elementary lasers, the elementary lasers being arranged on said graphene substrate, the graphene substrate comprising housings in which the elementary lasers are arranged, the method further comprising a step K2 of encapsulating the substrate and elementary lasers with a biocompatible material.

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