Medical probe for optogenetics with VCSELs

Abstract

The invention relates to a medical probe (MP) for optogenetics comprising: a flexible substrate made of two-dimensional conductive material (M2DS), a plurality of vertical cavity, surface-emitting III-V semiconductor microlasers (µVL), referred to as elementary lasers, comprising: an active layer (AL) disposed between a lower reflective layer (BBR) and an upper reflective layer (TBR), a lower semiconductor contact (BSCC) disposed between the lower reflective layer and the substrate and a lower metallic contact (BMC) disposed on the substrate and connected to said lower semiconductor contact (BSCC) via said substrate (M2DS), an upper semiconductor contact (TSCC) disposed on the upper reflective layer (TBR), and an upper metallic contact (TMC) connected to said upper semiconductor contact, the lower metallic 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 INVENTION

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

[0002] Optogenetics is a technique which 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 an application is the improvement of hearing.

[0004] A conventional solution is to create cochlear implants (CIs), considered the most effective neuroprosthesis enabling patients with sensorineural hearing loss to understand speech. By electrically stimulating the auditory nerve, cochlear implants provide an interface that reconnects the patient's brain to the auditory environment. However, because it is difficult to concentrate electrical current in conductive environments such as the cochlea, the accuracy of the electrical encoding of sound and the quality of the 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 captured by the oval window, which causes pressure waves in the fluid of the scala vestibuli and scala tympani of the cochlea, which is approximately 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. 1].

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

[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 vestibulocochlear nerve, and an optical device stimulating opsins. Opsins are light-sensitive proteins that convert a photon into an electrochemical signal.

[0009] The sensitivity curve of this opsin as a function of the wavelength of the light excitation is given, for example, in the publication by Klapoetke et al., "Independent optical excitation of distinct neural populations," Nat. Methods 11, 338-346 (2014). The normalized cumulative charge (NCC) as a function of wavelength X, which reflects the sensitivity of the opsin, is illustrated [Fig. 2] for different types of opsin: Chrimson; VChR1; Chronos; ChR2; TsChR. For example, for Chrimson and its variants, the maximum sensitivity is at a wavelength of approximately 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 Medicine 12 (2020), describes an optogenetic optical cochlear implant 35 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 end 31, with a 350 pm pitch. The portion on which the LEDs 30 are arranged is intended to be inserted into the cochlear duct; therefore, the substrate must be very flexible. The LEDs are powered via electrical traces connected at the other end to wires 32, which are connected to a connection interface 33.Each LED is powered via two contacts, an n contact and a p contact, connected respectively to electrical tracks 34n and 34p, the n contact being common to all LEDs via a single track 34p. The substrate / LED assembly is encapsulated in a silicone layer 36 (see B of [Fig.3]).

[0011] The fabrication of highly flexible, 15 µm thick polyimide devices is made possible by a laser transfer process of GaN LEDs on sapphire to a polyimide-on-silicon substrate. With this transfer process, the LEDs are positioned one by one on the substrate, making implant fabrication lengthy and expensive, and limiting the number of emitters in the device. Furthermore, the large surface area of ​​the GaN LEDs induces a large beam profile, which limits the number of optical emitters due to the risk of interaction between two neighboring optical emitters. In addition, the large surface area of ​​the GaN LEDs increases the temperature inside the cochlea, necessitating solutions for heat dissipation.

[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, pp. 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 20 µm x 20 µm microOLEDs with a 25 µm pitch have the advantage of being processed after the electronic driver. This is an "above-IC" device, meaning that the deposition and structuring are performed after the chip (IC) fabrication, on top of it, because the optical power of the microOLEDs is low. Although very dim, it has been validated that they can trigger an action potential associated with the ChRmin opsin, which is two orders of magnitude more sensitive than the ChrimsonR opsin described in the aforementioned publication by Klapoetke et al., and sensitive to orange-colored optical stimulation.

[0013] As before, a significant drawback of these emitters is their poor efficiency, which results in the conversion of the supply current into heat through the Joule effect. However, medical standards do not allow tissue heating to exceed 2°C, thus limiting the number of usable emitters. Furthermore, OLED technologies are sensitive to humidity, necessitating the use of a stack of atomic layer deposition (ALD) and parylene to ensure biocompatibility and limit moisture migration. The compatibility of these components with chronic use is not guaranteed.

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

[0015] The present invention relates to a medical probe for optogenetics comprising: - a flexible substrate made of a two-dimensional conductive material, - a plurality of vertical cavity, surface-emitting IILV semiconductor microlasers, referred to as elementary lasers, the elementary lasers being arranged on said substrate and integrated into an insulating layer, the elementary lasers having a maximum dimension between 5 and 50 pm and comprising: • an active layer positioned 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 metallic contact disposed on the substrate and connected to said lower semiconductor contact via said substrate, • an upper semiconductor contact disposed on the upper reflective layer and an upper metallic contact connected to said upper semiconductor contact, • the lower metallic 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 of a ternary material comprising gallium nitride.

[0021] According to an embodiment of the first variant above, 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 selected from WS2, MoS2, ReS2 and the lower semiconductor contact has a crystallographic growth axis along the

[100] axis.

[0023] According to a second embodiment, the lower and upper semiconductor contacts of an elementary laser are made of gallium arsenide or of 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 includes housings in which the elementary lasers are arranged.

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

[0026] According to one embodiment, the two-dimensional material substrate and the elementary lasers form a first structure, the probe comprising at least a second structure stacked on top of the first structure, elementary lasers of both 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 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.

[0029] According to another aspect, the invention relates to a first method for manufacturing a medical probe for optogenetics comprising the steps of: To have a first initial substrate comprising a semiconductor substrate, an insulating layer called the substrate layer, a metallic layer and a graphene layer placed on the metallic layer, B1 deposit on the first initial substrate a first dielectric layer and a first resin layer, structure the first resin layer so as to form a first mask with first openings, the first openings having a maximum dimension between 5 and 50 pm, First, etch the first dielectric layer down to the graphene layer by wet etching, so as to expose the graphene layer in the first openings; second, remove the first resin layer. To achieve by epitaxy, in the said first openings, a stack of semiconductor materials, the stack comprising a lower semiconductor contact of gallium nitride epitaxially on the graphene layer, a lower reflective layer, an active layer, an upper reflective layer and an upper semiconductor contact of gallium nitride, To deposit a second dielectric layer, structure a second resin layer to form a second mask with second openings above each stack, etch the second dielectric layer and the upper semiconductor contact, and remove the second resin layer. G1 remove the first and second dielectric layers by wet etching, so as to obtain stacks arranged on the initial first substrate, H1 deposit a lower metallic contact on the graphene layer, deposit an insulating layer around the stacks and deposit an upper metallic contact connected with the upper semiconductor contact, II remove the semiconductor substrate using the substrate insulating layer, J1 remove the metallic layer. Furthermore, the stacks and their associated first and second metallic contacts are configured to form vertical-cavity, surface-emitting semiconductor microlasers embedded in the insulating layer, referred to as elemental lasers. The graphene layer forms a flexible substrate, and the elemental lasers are arranged on this flexible substrate. The process further includes a step K1 of encapsulating the substrate and the elemental lasers with a biocompatible material.

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

[1000] .

[0031] According to one embodiment, in step Cl 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 for manufacturing a medical probe for optogenetics comprising the steps of: A2 to have a second initial substrate comprising a gallium arsenide substrate, an insulating layer called the substrate layer, a metallic layer and a first graphene layer placed on the metallic layer, B2 deposit on the second initial substrate a first dielectric layer and a first resin layer, structure the first resin layer so as to form a first mask with initial openings, the initial openings having a maximum dimension 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 metallic layer and etch the insulating substrate layer, so as to expose the gallium arsenide substrate in the first openings, E2 to create by epitaxy, in the said first openings, a stack of semiconductor materials comprising a lower semiconductor contact of gallium arsenide epitaxially on the gallium arsenide substrate, a lower reflective layer, an active layer, an upper reflective layer and an upper semiconductor contact of gallium arsenide, F2 deposits a second dielectric layer and a second resin layer, structures the second resin layer to form a second mask with second openings above each stack, etches the second dielectric layer, etches the upper semiconductor contact, and removes 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 deposits a lower metallic contact on the remaining graphene layer of On each side of the stacks, deposit an insulating layer around the stacks and place a top metallic contact in contact with the top semiconductor contact. 12. Remove the gallium arsenide substrate using the substrate insulating layer. J2. Remove the metallic layer and deposit a second graphene layer onto the first graphene layer and the lower semiconductor contact. The first and second graphene layers collectively form a flexible graphene substrate. Furthermore, the stacks and the associated first and second metallic contacts are configured to form vertical cavity surface-emitting (pVL) semiconductor microlasers embedded in the insulating layer, referred to as elemental lasers. The elemental lasers are arranged on the graphene substrate, which includes housings in which the elemental lasers are arranged. The process also includes a step K2 of encapsulating the substrate and the elemental lasers with a biocompatible material.

[0033] The following description presents several embodiments of the device of the invention: these examples are not limiting to the scope of the invention. These embodiments present both the essential features of the invention and additional features related to the embodiments considered.

[0034] The invention will be better understood and other features, objectives and advantages thereof will become apparent from the following detailed description and with reference to the accompanying drawings given by way of non-limiting examples and in which:

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

[0036] The [Fig.2] already cited 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 array of gallium nitride-based micro-LEDs for a mouse.

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

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

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

[0041] Figure 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] Figure 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 S1, and the probe comprises at least a second structure S2 stacked on top of the first SI structure, the S2 structure presenting an architecture identical to the SI structure (substrate + elementary lasers).

[0043] Figure 9 illustrates the steps A1 to F1 of the process 100 according to the invention.

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

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

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

[0047] An embodiment of the MP medical probe according to the invention, adapted for the fabrication of a cochlear implant with a ribbon-shaped substrate and in-line transmitters, 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 side 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 activated. This stimulates the cochlear branch of cranial nerve VIII, into which opsins have been injected, thus generating an artificial sound perception.

[0049] However, the principle of stimulating a neuron or nerve with an optical device via opsin is applicable to any other optogenetic application, by modifying the device design. The invention is thus applicable to other types of optogenetic probes having different emitter arrangement geometries, for example, a planar array, a rod, a tube obtained from a planar array (thanks to the flexible substrate)... The probe according to the invention can be applied, for example, for integration into the visual cortex for restoring sight or into the motor cortex for compensating for motor disabilities.

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

[0051] Two-dimensional materials have a planar structure and are composed of one to several monolayers L, each monolayer comprising several 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 semiconductive, 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 consists of 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 it is non-toxic. It also exhibits good lattice matching 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 between 0.3 and 20 nm.

[0054] The MP probe also includes a plurality of vertical cavity surface-emitting (pVL) IILV semiconductor microlasers, referred to as elementary lasers, and conventionally called VCSELs for Vertical Cavity Surface Emitting Lasers. The pVL elementary lasers are arranged on the M2DS substrate and integrated into an insulating IL layer. The elementary lasers have a maximum dimension between 5 and 50 pm. The maximum dimension is understood to be the largest lateral dimension of the laser. Typically, the lasers have a thickness (height) on 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 disposed between a lower reflective layer BBR and an upper reflective layer TBR. It also comprises: - a lower semiconductor contact BSCC disposed between the lower reflective layer and the substrate and a lower metallic contact BMC, - an upper semiconductor contact TSCC disposed on the upper reflective layer TBR and an upper metallic contact TMC connected to the upper semiconductor contact.

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

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

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

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

[0060] For VCSEL type elementary 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 and control unit.

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

[0062] Despite the conductive nature of the substrate, lower metallic contacts and lower electrical traces 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 TMT track associated with the laser, which carries the control signal for the elementary laser.

[0064] According to the embodiment of [Fig. 5], the substrate is ribbon-shaped, on a portion of which lasers are arranged in a line. The lower metal contacts of the plurality of lasers are connected to a common lower CBMT electrical track for the elementary lasers in the line, intended to be connected to the electrical ground of the device. This reduces the number of electrical contacts by half. This geometry is well suited to a cochlear implant.

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

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

[0067] First, the small size of the elementary lasers and the highly directional nature of the emitted ELB light beam allow for a very dense arrangement of emitters on the 2D substrate material, with the limitation of being able to accommodate electrical wiring if necessary (typically the tracks are a few microns wide). For 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 target cells with very good spatial resolution.

[0068] Furthermore, VCSELs have a much better quantum efficiency than LEDs (more (of electrons transformed into photons), which induces a much lower Joule effect heat generation. This is very important for medical probes since the permissible heating of the device is very limited. Therefore, there is no need for an additional heat dissipation system, which also allows for denser 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 in a planar matrix array as illustrated [Fig. 6]. Preferably, the elementary lasers of a line Li (index i) of the matrix are connected to a shared lower electrical track associated with 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 AL active layer, an n-doped III-V Bragg reflector and a p-doped III-V contact.

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

[0073] According to a first embodiment of the probe according to the invention, the lower semiconductor contacts B SCC and upper semiconductor contacts TSCC of an elemental 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 with a wavelength in the blue to green range.

[0074] According to a second embodiment of the probe according to the invention, the lower semiconductor contacts B SCC and upper semiconductor contacts TSCC 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 with 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 in the manufacturing process of elementary lasers on a 2D material substrate, which is graphene, differ for the two families of IILV semiconductor laser components. As a result, the GaAs-based pVL lasers are indeed arranged on the graphene substrate, but the latter includes 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 embodiment illustrated in [Fig. 8], the 2D material substrate and the elementary lasers are considered to form a first structure SI, and the probe MP comprises at least a second structure S2 stacked on top of the first structure SI, the structure S2 having an architecture identical to the structure SI (substrate + elementary lasers). The entire S1+S2 assembly is then encapsulated. Preferably, elementary lasers of both structures are arranged such that pVL2 elementary lasers of the second structure do not obscure a beam emitted ELB1 by pVL1 elementary lasers of the first structure, as illustrated in part A of [Fig. 8] (top view of the probe). Part B illustrates a side view along 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 allows for a probe that can be located near the cells of interest and emit one color or another. Such a probe, in combination with cells incorporating an excitatory opsin (for example, at XI) and an inhibitory opsin (for example, at X2), allows the cell channels to be excited and inhibited on command by switching the associated emitters of the dual-level probe on and off.

[0079] According to one embodiment of the dual-level probe of [Fig.8], one of the two structures consists of elementary lasers comprising at least one layer of gallium nitride (GaN-based component family) and the other structure consists of elementary lasers comprising at least one layer of gallium arsenide (GaAs-based component family).

[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 layers in AlGaN and GaN, and the active layer AL comprises InGaN quantum wells separated by gallium nitride barriers.

[0082] Typically, the lower BSCC semiconductor contact in gallium nitride exhibits 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 realization of such an emitter on graphene, the lattice matching between GaN and graphene favors such a structure.

[0084] In a conventional manner, when the lower semiconductor contact is along the

[1000] axis and all the materials in the stack forming the VCSEL are GaN-based, 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 selected 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

[100] axis structure of GaN is the most suitable for GaN growth 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 of 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 quantum multiwells 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 elemental lasers made of GaN (at least the lower semiconductor contact) on a 2D graphene-type substrate. Graphene has the advantage of having a mature manufacturing process and being non-toxic. It also has the advantage of having a lattice structure matched to that of GaN.

[0090] The process 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 a first initial substrate IS1 comprising a semiconductor substrate SS, such as silicon, an insulating layer called the substrate ILS, typically dielectric, a metallic layer ML, for example copper or nickel, and a graphene layer GS deposited on the metallic layer. Graphene is not soluble in these metals. Typically, the graphene layer is grown on the metallic layer by a chemical vapor deposition (CVD) technique using CH4-H2.

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

[0093] In 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, the etching stops at a 2D material layer of atomic thickness, and the integrity of the graphene layer must be preserved. Dry etching of the ionic type (or RIE for "Reactive Ion Etching"), for example, based on chlorine, cannot be used, as it is necessarily partly mechanical and could damage the graphene. Only wet etching is usable for this step. Preferably, according to one embodiment, buffered hydrofluoric acid (HF) etching such as BOE for "Buffered Oxide Etching" is used because graphene resists this type of etching.

[0094] In a step Dl, 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 an El step, a stack of semiconductor materials is created by epitaxy, typically by MOCVD (for "MetalOrganic Chemical Vapor Deposition") or GSMBE (for "Gas Source Molecular Beam Epitaxy") in the first Opl openings. The Emp stack comprises a bottom semiconductor contact BSCC made of gallium nitride (or a GaN-based ternary) epitaxially grown on the graphene layer, a bottom reflective layer BBR, an active layer AL, a top reflective layer TBR, and a top semiconductor contact TSCC made of gallium nitride (or a GaN-based ternary).

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

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

[0097] Thus, in areas where the graphene is exposed, VCSELs are grown, all isolated from each other, with a common ground. Thanks to this technology, called SAG (for Selective Area Growth), the semiconductor grows on the graphene and nowhere else, which makes it possible to define the geometry of the laser without chlorinated etching (just the etching of the dielectric layer and the contact to allow light to exit).

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

[0099] In step Gl, 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 before, namely to avoid degrading the graphene layer.

[0100] In step H1, a lower metallic contact (BMC) is deposited onto the graphene layer, thus connecting it to the lower semiconductor contact via the graphene conductive layer. An insulating layer (IL) is then deposited around the stacks. A top metallic contact (TMC) is also deposited, connected to the top semiconductor contact (TSCC), enabling emission from the top surface of the VCSEL. At this stage, the elementary lasers are complete. It is also at this stage that the lower CBMT track(s) and the top TMT track(s) for the connections are fabricated.

[0101] In a step II, the semiconductor substrate SS is removed using the substrate insulating layer ILS, preferably by mechanical cleavage. The presence of the substrate insulating layer ILS helps to decouple the graphene layer from the metallic layer ML.

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

[0103] The stacks and the associated first and second metallic contacts are configured to form vertical cavity surface emission (pVL) semiconductor microlasers embedded in the insulating layer, referred to as elementary lasers. The graphene layer forms a flexible substrate (GS), with the elementary lasers arranged on this flexible substrate.

[0104] The process 100 further comprising a step Kl of encapsulating the substrate and the elemental 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] Elementary lasers all have 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 of GaAs on a 2D graphene-type substrate. 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 certain steps that differ from process 100 because the 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 substrate ILS, a metallic layer ML (for example in copper or nickel) and a first graphene layer GL1 disposed on the metallic 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 to form a first mask Ml having first openings Opl. The first openings have a maximum dimension between 5 and 50 pm.

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

[0112] In a step D2, the first resin layer is removed, the graphene layer is etched, for example with chlorine RIE etching, and the metallic 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 Opl openings.

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

[0114] In a step E2, a stack of semiconductor materials is carried out by epitaxy, typically MOCVD or GSMBE, in the first Opl openings, comprising a lower semiconductor contact BSCC in gallium arsenide (or in a ternary material based on GaAs) epitaxially 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 process 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 is used to create stacks arranged on the gallium arsenide (GAS) substrate. Wet etching is employed here to avoid degrading the graphene remaining on either side of the stack.

[0117] In step H2, the lower metal contact BMC is deposited onto 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 and upper traces for the connectors are formed.

[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 metallic 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 provides the strength and flexibility of the graphene substrate and facilitates current injection. The stacks and the associated first and second metal contacts are configured to form vertical cavity surface-emitting (pVL) semiconductor microlasers embedded in the insulating layer, referred to as elementary lasers. The elementary lasers are arranged on the graphene substrate (GS), and here the graphene substrate includes housings in which the elementary lasers are arranged.

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

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

Claims

Demands

1. A medical probe (MP) for optogenetics comprising: - a flexible substrate of two-dimensional conductive material (2DCM), - a plurality of vertical cavity, surface-emitting (pVL) III-V semiconductor microlasers, referred to as elementary lasers, the elementary lasers being arranged on said substrate and integrated into an insulating layer (IL), the elementary lasers having a maximum dimension between 5 and 50 pm and comprising: • an active layer (AL) disposed between a lower reflective layer (BBR) and an upper reflective layer (TBR), • a lower semiconductor contact (BSCC) disposed between the lower reflective layer and the substrate and a lower metallic contact (BMC) disposed on the substrate and connected to said lower semiconductor contact (BSCC) via said substrate (2DCM), • an upper semiconductor contact (TSCC) disposed on the upper reflective layer (TBR),and an upper metallic contact (TMC) connected to said upper semiconductor contact, • the lower metallic 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. Medical probe (MP) according to claim 1 wherein the two-dimensional material is a dichalcogenide or a trichalcogenide configured to be conductive.

4. A medical probe according to any one of the preceding claims, wherein the substrate is ribbon-shaped, on a portion of which said elementary lasers of said plurality are arranged in a line, the lower metallic contacts of the elementary lasers being connected to a lower electrical track (CBMT) common to elementary laser audits of the line.

5. Medical probe according to any one of claims 1 to 3 wherein 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 any one of the preceding claims wherein the lower and upper semiconductor contacts of an elemental laser are made of gallium nitride (GaN) or of a ternary material comprising gallium nitride.

7. 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. 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 any one of claims 1 to 5 wherein the lower and upper semiconductor contacts of an elementary laser are made of gallium arsenide (GaAs) or of 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. Medical probe according to any one of the preceding claims wherein the active layer comprises quantum multiwells (MQW) or quantum dots (QD).

12. Medical probe according to any one of the preceding claims wherein the two-dimensional material substrate and the elemental lasers form a first structure (SI), the probe comprising at least a second structure (S2) stacked on top of the first structure (SI), elemental lasers of both structures being arranged so that elemental lasers (pVL2) of the second structure do not obscure a beam emitted (ELB1) by elemental lasers (pVL1) of the first structure.

13. Medical probe according to the preceding claim wherein 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 wherein 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.

15. A 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 a substrate layer (ILS), a metallic layer (ML) and a graphene layer (GS) disposed on the metallic 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 (M1) having first openings (Opl), the first openings having a maximum dimension 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 performing by epitaxy, in said first openings (Opl),a stack of semiconductor materials, the stack comprising a lower semiconductor contact (BSCC) of gallium nitride epitaxially bonded to the graphene layer, a lower reflective layer (BBR), an active layer (AL), a upper reflective layer (TBR) and an upper semiconductor contact (TSCC) of gallium nitride, Fl depositing a second dielectric layer (DL2), structuring a second resin layer (RL2) 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 deposit a lower metal contact (BMC) on the graphene layer, deposit an insulating layer around the stacks and deposit a higher metal contact (TMC) connected with the upper semiconductor contact (TSCC), J1 remove the semiconductor substrate (SS) using the substrate insulating layer (ILS), J1 remove the metal layer (ML), the stacks and the first and second associated metal contacts being configured to form vertical cavity surface emission (pVL) semiconductor microlasers inserted into the insulating layer, called elemental lasers, the graphene layer forming a flexible substrate (GS), the elemental lasers being arranged on said flexible substrate, the process further comprising a step K1 of encapsulating the substrate and the elemental lasers with a biocompatible material.

16. A method according to the preceding claim wherein during step El the growth of the lower gallium nitride semiconductor contact by epitaxy on the graphene substrate occurs in a direction [1000],

17. A method according to any one of claims 15 or 16 wherein in step Cl the wet etching of the first dielectric layer up to the graphene layer is of the BOE type for "Buffered Oxide Etching".

18. A method (200) for manufacturing a medical probe for optogenetics comprising the steps of: A2 having a second initial substrate (IS2) comprising a gallium arsenide (GAS) substrate, an insulating substrate layer (ILS), a metallic layer (ML) and a first graphene layer (GL1) disposed on the metallic layer, B2 depositing on the second initial substrate a first dielectric layer (DL1) and a first resin layer (RL1), structuring the first resin layer to form a first mask (Ml) having first openings (Opl), the first openings having a maximum dimension between 5 and 50 pm, C2 etching the first dielectric layer down to the graphene layer, D2 removing the first resin layer, etching the graphene layer, etch the metallic layer and etch the insulating substrate layer, so as to expose the gallium arsenide substrate in the first openings, E2 to produce by epitaxy, in said first openings (Opl), a stack of semiconductor materials comprising a lower semiconductor contact (BSCC) of gallium arsenide epitaxially on the gallium arsenide substrate, a lower reflective layer (BBR), an active layer (AL), a upper reflective layer (TBR) and a upper semiconductor contact (TSCC) of gallium arsenide, F2 deposit a second dielectric layer (DL2) and a second resin layer (RL2), structure the second resin layer (RL2) to form a second mask (M2) with second openings (Op2) above each stack, etch the second dielectric layer, etch the upper semiconductor contact, and remove 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 metallic contact (BMC) on the remaining graphene layer on each side of the stacks, deposit an insulating layer around the stacks and deposit a higher metallic contact (TMC) in contact with the upper semiconductor contact (TSCC), 12. Remove the gallium arsenide (GAS) substrate using the substrate insulating layer (ILS), J2 remove the metallic layer (ML), and deposit 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 metallic contacts being configured to form vertical cavity surface-emitting (pVL) semiconductor microlasers embedded in the insulating layer, referred to as elementary lasers, the elementary lasers being arranged on said graphene substrate, the graphene substrate comprising housings in which the elementary lasers are arranged, the process further comprising a step K2 of encapsulating the substrate and elemental lasers with a biocompatible material.

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