Patent Description:
The field of technologies for optical interfaces with the central nervous system has seen significant developments in the last <NUM> years, creating a need for implantable devices which are able to control and monitor the cellular activity in three dimensions and at a high spatial-temporal resolution. This has increased the need for new methods for manufacturing non-planar surfaces to be developed, in order to integrate elements for applying and monitoring the nerve activity along and around the implantation axis. In such a scenario, a micro-structuring approach (also known as "micro-patterning") which may be applied directly to highly curved surfaces or to multiple sides of a three-dimensional probe would be highly desirable, because it could pave the way for the production of implantable optoelectronic devices that have complex interaction geometries with the tissue around the implantation axis.

In this respect, tapered optical fibers (TF) have recently emerged as a promising platform for forming optical and electrical neural interfaces, with optical channels provided by the guided modes, and the possibility for the tapered surface that provides a non-planar surface ready for structuring to be coated with metal. The metal coating in fact aims to provide a reflective coating in order to obtain a waveguide confined by metal, while the structuring thereof may make it possible to use mode division multiplexing to obtain a selective distribution of light and the formation of electrical contacts. The TF are characterized by a tapered section extending over a length of > <NUM>, with an initial diameter between <NUM> and <NUM> and a diameter at the tip of < <NUM> (cf. the schematic view in <FIG>), and the mode division multiplexing properties thereof allow for light to be distributed in a manner resolved along the axis of the device and/or for light to be collected with depth resolution. However, forming electronic circuits and electric devices on the tapered section of the fiber is a challenge, since: (i) the tapered surface is non-planar, (ii) the radius of curvature thereof is small and reduces along the axis of the waveguide (<FIG>), and (iii) the fiber has to be structured over its <NUM>° of symmetry. The methods for structuring the surface of the TF are limited to a few geometries and only allow for the formation of a single site for recording the electrical signal in order to monitor the electrical activity of the cells in the vicinity of the implant. These approaches include the use of focused ion beam (FIB) abrasion (milling) [<NUM>, <NUM>, <NUM>], laser ablation [<NUM>, <NUM>], and focused ion beam local deposition (FIBID) [<NUM>, <NUM>]. The latter makes it possible to locally deposit platinum on a metal layer and obtain an extracellular site for recording the electrical signal, but requires work to be carried out on a system that already has an electrical connection [<NUM>]. Moreover, the formation of two or more electrodes is restricted by the fact that each electrode would require an additional metal layer, which would generate capacitive coupling effects that would prevent the device from functioning correctly. A structuring approach that would make it virtually possible to form any bespoke geometry and multiple recording sites over <NUM>° of the tapered surface would significantly increase the set of characteristics that may be integrated into the tapered section.

In view of this need, the invention relates to a method for manufacturing an electromagnetic waveguide from a tapered optical fiber, comprising the following steps:.

The method according to the invention achieves the following advantages:.

Further features and advantages of the method according to the invention will be presented in the following detailed description, which refers to the accompanying drawings, provided solely by way of non-limiting example, in which:.

A method for producing an optoelectronic device based on tapered optical fibers, in particular an optoelectronic neural interface, will now be described. A device of this kind is described, for example, in <CIT> and <CIT>, from the same applicant.

An example of this device is shown in <FIG>, and essentially comprises two parts: a micro-structured implantable probe, which is denoted by reference sign <NUM> and comprises electrodes <NUM> for electrically recording the neural activity and optical windows <NUM> for allowing light to be emitted and collected in the cerebral tissue with depth resolution, and a printed circuit interface <NUM> which is used as an interface between the non-planar electronics on the probe <NUM> and a planar printed circuit board <NUM>.

The probe <NUM> is substantially an electromagnetic waveguide comprising a tapered optical fiber. <FIG> shows the tapering at the tip of the waveguide/optical fiber, which tapering is denoted by <NUM>.

The fiber (and therefore the optical windows <NUM>) receive and transmit light from/to external systems via a ferrule connection <NUM>, while the signal collected by the electrodes <NUM> is sent to an external amplifier via a connector <NUM> on the planar board <NUM>. Alternatively (as will be described below), the printed circuit interface <NUM> may be configured to send the signal collected by the electrodes <NUM> to an external amplifier via a connector integrated on the printed circuit interface <NUM>, without the need for a planar board <NUM>.

The optical windows <NUM> are used to distribute and/or collect light onto/from the tissue, while the electrodes <NUM> are used to detect nearby electric fields that are linked to cellular activity. Both of these are manufactured along and around the tapered section <NUM> using a multi-stage method shown in <FIG>, which allows them to be produced despite the small and non-constant radius of curvature r(y), which may fall below <NUM>.

The method starts by mounting a tapered optical fiber <NUM> on a roto-translational handling apparatus RT which may be actuated to translationally move the optical fiber along at least one translation axis, preferably along three orthogonal axes x, y and z, and rotate the optical fiber <NUM> about a longitudinal axis thereof, which in the example coincides with the y-axis. The angle of rotation is denoted by θ (<FIG>). By means of the apparatus RT, the tapered fiber <NUM> is submerged in a negative photoresist droplet D supported by a substrate S. The tapered section <NUM> of the fiber is then subjected to a two-photon polymerization (2PP) process; one or more fs-pulsed (femtosecond-pulsed) focused beams FB are scanned on the tapered section <NUM> (by controlling the movement of the tapered section by means of the apparatus RT) in order to form a polymer mask <NUM>. The 2PP makes it possible to obtain a polymerization spot which has dimensions in the xy (dxy) plane and along the z (dz) direction below the diffraction limits, and therefore a smaller radius of curvature r(y) at the section in which the polymerization is carried out (i.e. dxy<<r(y) e dz<<r(y)). Quantitatively, for a given dxy and dz, the minimum value of r(y) that may accommodate the mask formed using the 2PP process may be evaluated by solving the following equation: <MAT>.

This condition, together with the possibility of roto-translating the fiber <NUM> and scanning more beams, makes it possible to address the non-planarity of the tapered surface <NUM> and ensures good adhesion of the polymer structure <NUM> after the photoresist has been developed (<FIG>).

The fiber is then placed in the chamber of a system for the directional evaporation of metals (for example an electron beam evaporator) and exposed to a plurality of different directional flows of metal (in the example, three flows DF), so as to cover the tapered section <NUM> with a first metal layer <NUM>, while leaving the lateral edge of the mask <NUM> uncovered (<FIG>). This is achieved by carrying out a plurality of different evaporations at different θ angles, for example three different, separate evaporations at angles θ<NUM> and θ<NUM> which are equal to approximately <NUM>°, but these values depend on the height and the shape of the structure(s) to be produced. The aspect ratio of the polymer mask <NUM> is generally greater than <NUM>, in order to reduce the quantity of material deposited on the lateral surfaces of the mask (for example, for a square pattern of <NUM> x <NUM>, the height may be ~<NUM>).

With regard to the shape of the polymer mask <NUM>, it is possible to produce square, rectangular or circular patterns, and, by properly controlling the laser focusing equipment, the shape may be freely defined while taking the limits of equation (<NUM>) into account.

Following the chemical removal of the photoresist mask <NUM>, one or more optical windows <NUM> are obtained on the tapered section <NUM> (<FIG>), which windows are formed through the first metal layer <NUM>.

A transparent and conformal insulating layer <NUM> is then deposited, by means of chemical vapor deposition (for example of parylene-c) or electron beam evaporation (for example of silicon dioxide), as shown schematically in <FIG>.

A second metal layer <NUM> is then deposited all around the fiber (<FIG>), which second layer is used as a substrate for the electrical tracks.

The device is re-inserted into the photoresist droplet D and the 2PP is used to define a new photoresist mask <NUM> on the tapered surface <NUM>, so as to define the geometry of one or more electrode contacts (<FIG>). The method makes it possible to obtain masks of which the dimensions may vary from a few microns to centimeters.

The fiber is subjected to another development step (<FIG>) and to subsequent wet etching in order to transfer the geometry of the photoresist to the metal layer <NUM> (<FIG>). The photoresist is chemically removed (<FIG>), thus revealing the metal paths formed by measurement pads 11a (the shape of which may be circular or round, with dimensions that vary from a few micrometers to a few millimeters), connection pads 11b (dimensions from a few tens of micrometers to a few mm) and electrical tracks 11c (representative lengths from a few mm to a few cm, with transverse dimensions typically between a few microns and approximately <NUM>). The measurement pads 11a define the points at which the signal is detected by direct exposure to the electrolyte, while the connection pads 11b are used, in combination with the printed circuit interface <NUM>, to interface the electrodes 11a, b, c with the planar printed circuit board <NUM>.

The system is then insulated using a second transparent, conformal layer <NUM> made of polymer or semiconductor material, which layer also acts as a sealing encapsulation for the device in order to allow it to function in ambient liquids.

By means of single-photon or two-photon laser ablation, or by means of focused ion beam (FIB) abrasion (<FIG>), a recess is <NUM> then formed in the second transparent layer <NUM> at the measurement pads 11a (<FIG>). Then, by means of focused ion beam deposition or electrochemical deposition, a third metal layer <NUM> is deposited only in the recess <NUM> (<FIG>), with the aim of regulating the final impedance of the electrode to values in the range from <NUM> MΩ a <NUM> MΩ.

Between steps (x) and (xi), i.e. before the second transparent layer <NUM> is formed, the fiber <NUM> is removed from the handling apparatus RT and mounted on the printed circuit interface <NUM> which is specifically designed to interface the electrodes 11a, b, c to the planar board <NUM> for connection to an external amplification system. <FIG> show two embodiments for the interface <NUM>, each of which comprises a first seat <NUM> which is configured to receive the electromagnetic waveguide <NUM>, and a second seat <NUM> which is aligned with the first seat <NUM> and configured to receive an optical cable <NUM> connected to the electromagnetic waveguide <NUM> (cf. also <FIG>). The interface <NUM> also comprises at least two conductive tracks <NUM>, each of which comprises a distal connection pad <NUM> which faces the first seat <NUM> and is configured to be welded to a relevant connection pad 11b of one of the electrodes <NUM> of the electromagnetic waveguide <NUM>, and a proximal connection pad <NUM> which is configured to be welded to a relevant contact of the planar board <NUM>. <FIG> shows an example (similar to that in <FIG>) where the distal connection pads <NUM> are formed on an upper face of the interface <NUM> (shown at the top in <FIG>), and the proximal connection pads <NUM> are formed on a lower face of the interface <NUM> (shown at the bottom in <FIG>). The conductive tracks <NUM> which connect the distal connection pads <NUM> to the proximal connection pads <NUM> are formed through the thickness of the interface <NUM>, as may be seen in <FIG>. <FIG> instead shows an example where the distal connection pads <NUM>, proximal connection pads <NUM> and conductive tracks <NUM> are formed on the same face of the interface <NUM>. As in the example in <FIG>, the printed circuit interface <NUM> is used to allow the electromagnetic waveguide <NUM> to be connected to a planar board <NUM>, which is in turn responsible for connection to external amplifiers. <FIG> shows an alternative example where the printed circuit interface, again denoted by reference sign <NUM>, acts as an independent interface with standard external systems, without the need for a planar board (the two images shown are views of the interface as seen from different directions). The example interface in <FIG> therefore has an integrated connector <NUM> for connection to external systems. In this case, the distal connection pads are directly connected to the connector <NUM>.

Preliminary results from the manufacturing method described above are shown in <FIG>. Frame A shows a microscope image which shows a detail on an electrode obtained using the described method, and a graph relating to the action potentials recorded in vivo, in the cerebral tissue of a mouse, from three different cells. Frame B shows microscope images (at different magnifications) which show multiple electrodes formed on the same tip, which electrodes are composed of measurement pads, conductive tracks and connection pads. Frame C is a microscope image which shows polymer structures formed all around the tapered section, in order to demonstrate the suitability of the described approach for being used over the entire tapered surface. Frame D shows a photograph of a printed circuit interface produced using polymer materials, with a tapered and structured fiber mounted thereon and connected to an optical cable. This configuration corresponds to that in <FIG>, and may be welded to a planar board in order to interface with conventional amplifiers.

<FIG> shows preliminary results relating to the crucial steps of the manufacturing method described above, i.e. the formation of the polymer masks and the transfer of their geometry onto the non-planar tapered surface. The three images at the top are microscope images which show a detail of the tip at the end of three different steps for forming a measurement pad, in particular:.

Claim 1:
A method for manufacturing a multifunctional electromagnetic waveguide (<NUM>) from a tapered optical fiber (<NUM>), comprising the following steps:
mounting the optical fiber (<NUM>) on a handling apparatus (RT) which may be actuated to translationally move the optical fiber (<NUM>) along at least one translation axis (x, y, z) and rotate the optical fiber (<NUM>) about a longitudinal axis (y) thereof,
submerging a tapered section (<NUM>) of the optical fiber (<NUM>) in a photoresist and subjecting the photoresist to two-photon polymerization to form a first mask (<NUM>) defining the shape of at least one optical window (<NUM>),
subjecting the masked tapered section (<NUM>) to a plurality of directional flows (DF) of metal material to form a first metal layer (<NUM>) around the tapered section (<NUM>), leaving at least one lateral edge of the first mask (<NUM>) uncovered,
removing the first mask (<NUM>) by chemical etching in such a way to uncover said at least one optical window (<NUM>),
depositing a transparent, conformal first layer (<NUM>) around the tapered section (<NUM>), said transparent, conformal first layer being made of insulating material,
depositing a second metal layer (<NUM>) around the insulating layer (<NUM>),
submerging the tapered section (<NUM>) in the photoresist and subjecting the photoresist to two-photon polymerization to form, at the tapered section (<NUM>), a second mask (<NUM>) defining the shape of at least one conductive track (<NUM>; 11a, 11b, 11c),
removing, by chemical etching, the second metal layer (<NUM>) where the second metal layer is not covered by the second mask (<NUM>), and
removing the second mask (<NUM>) by chemical etching in such a way to uncover said at least one conductive track.