HK1226682A1 - Medical device comprising an electrode and a light source - Google Patents

Description

Medical device comprising an electrode and a light source

Technical Field

The present invention relates to a first device comprising a medical microelectrode and a microluminate source for deployment in soft tissue, a second device formed in tissue from said first device, a method for producing the first device and the use of said device. Furthermore, the invention relates to a bundle and an array comprising two or more first devices of the invention and a corresponding bundle and array of second devices placed in soft tissue.

Background

Devices for implantation into soft tissue, including electrodes, light sources and combinations thereof in tissues of the Central Nervous System (CNS), have a wide range of applications. In principle, brain nuclei (brain nuclei) may be recorded by or stimulated by such devices, and their function monitored. Of particular interest are multichannel devices for brain nuclear stimulation. With a multi-channel device, groups of cores or even individual cores may be handled separately. This allows the user to select those nuclei whose stimulation produces a therapeutic effect. Selective stimulation should produce better results than non-selective stimulation. Stimulation of the brain or spinal cord may be particularly valuable in cases where the brain nuclei are degenerated or damaged. The multichannel design may provide an efficient measure of the effect of systemic or local drug delivery or gene transfer to neurons in the brain and spinal cord. Monitoring brain activity via implanted devices may be used to control local or systemic drug delivery or to control electrical stimulation of brain nuclei. By infecting neurons with a gene vector that causes the neurons to exhibit radiation-sensitive, in particular visible light-sensitive, ion channels, it is possible to stimulate or inhibit the neurons by radiation (in particular visible light). This is known as optogenetic technology. By combining the electrode means, the radiation or visible light emitting means and the radiation or visible light detecting means it is possible to record the neuronal activity caused by the radiation, in particular visible light.

This type of implantable device should affect the adjacent tissue as little as possible. Since the brain, spinal cord and peripheral nerves exhibit considerable movement caused by body movement, heartbeat and respiration, it is important that the implantable device be able to follow the movement of this tissue and be displaced as little as possible relative to the target tissue.

US 2011-0046148 a1 discloses a hybrid opto-electrical neural interface. The interface may comprise an array comprising a plurality of micro-optodes which combine optical and optionally electrical stimulation.

US 2013-0253261 a1 discloses a method for treating a specific nervous system disease by sensing bioelectric signals from a patient with the disease using an implantable electrode in combination with optical stimulation of cells transduced by a genetic factor of a viral vector

US 2013-0237906A discloses a liquid crystal polymer-based electrode-optode neural interface comprising integrated electrodes and optodes.

Object of the Invention

The main object of the present invention is to provide a device for insertion into soft tissue comprising a microelectrode and a microlouver, in particular a device that is smartly adaptable to movements in the surrounding tissue.

It is another object of the present invention to provide a device of the above type capable of stimulating a single nerve cell or group of nerve cells when inserted into soft tissue;

it is a further object of the present invention to provide a device of the above type capable of recording both optical and electrical signals originating from nerve cells when inserted into soft tissue;

it is an additional object of the invention to provide a bundle and an array of such devices;

it is yet another object of the present invention to provide a method for producing the insertable apparatus of the present invention.

Other objects of the present invention will become apparent from the following summary of the invention, the preferred embodiments illustrated in the drawings and from the appended claims.

Disclosure of Invention

In the present application, "insoluble in water" means insoluble in aqueous body fluids, i.e. interstitial or extracellular fluids but may also be serum. "flexible" means the degree of flexibility to allow displacement of a portion of the device by movement of tissue adjacent to the portion. The displacement of a part of the device does not necessarily include the displacement of the entire device. "electrically isolated" means electrically isolated at the voltage/current used in treating human neuronal tissue. By "oblong" is meant a structure having a length greater than five times or more, specifically ten times or more, its diameter. "swellable" refers to capable of forming a transparent gel that is accompanied by volume expansion (e.g., 1.1 or 1.2 times) upon contact with aqueous body fluids. "porous" means the permeability of aqueous body fluids and biomolecules dissolved therein.

According to the present invention, there is disclosed a medical device for insertion into soft tissue having an anterior or distal end and a posterior or proximal end, comprising:

-a microelectrode;

-a micro light source capable of emitting light in a distal direction;

-a stiffening element comprising one of:

a) a material soluble or degradable in an aqueous body fluid in an amount sufficient to rupture a stiffening element in contact with the aqueous body fluid;

b) a material that is swellable in aqueous body fluids to form a transparent gel;

-a coating of a flexible non-conductive polymer material on the stiffening element preventing or at least retarding contact between the electrode and the soft tissue when the stiffening element is ruptured or expanded, the coating having a distal opening allowing light emitted from the light source to exit the device when said rupturing or expanding.

-a base placed at the proximal end of the device.

It is preferred that the substrate is a non-conductive material or is composed of 80% or 90% or more of such material. It is preferred that the base is substantially circular, such as in the form of an oblate cylinder. The substrate is preferably rigid.

It is preferred that the electrodes, light source and/or coating of flexible material is firmly attached to the substrate and extends in the distal direction from the distal face of the substrate. It is preferred that the electrodes and light source extend from the distal end face a smaller distance than the flexible coating.

Any miniature light source may be used, but the use of LEDs or miniature lasers is preferred. In the present invention, a "light source" comprises an optical fiber that receives light at one end thereof from a source, which may or may not be included by the device, and emits the received light at the other distal end thereof. The light emitted from the light source is preferably visible light, in particular monochromatic light, such as red light, but may also be infrared light.

The microelectrodes of the present invention comprise or consist of metals, alloys or conductive polymers or carbon. Preferred metals include aluminum, silver, gold, iridium, platinum, and alloys thereof. The microelectrodes may be in the form of rods or layers formed straight or curved on the optical fiber or on the face of the polymer coating facing the hardened layer. The microelectrode is preferably electrically insulating, except for a portion extending from its distal end in the proximal direction. The electrical insulation is provided by a layer of lacquer or polymer on the electrodes.

For devices inserted into soft tissue, a substantially rotationally symmetrical form, in particular a substantially cylindrical form, is preferred with respect to the central longitudinal axis. The flexible, non-conductive polymer coating and the stiffening element are also preferably of a substantially rotationally symmetrical form, in particular of a cylindrical form. The distal end of the electrode and/or the optical fiber is preferably withdrawn from the distal opening in a proximal direction. The electrode is also preferably electrically insulated except for a portion at or extending in a proximal direction from its distal tip or end.

According to a first preferred aspect of the invention, the electrodes are electrically shielded by an electrically conductive layer, which is held at ground potential or animal ground potential (animal ground potential), which is integrated into the flexible polymer coating or is attached to one side of the flexible polymer coating and covered by an electrically insulating layer.

According to a second preferred aspect of the invention, the stiffening element comprises or consists of a carbohydrate and/or a proteinaceous material and/or a mixture thereof. Other polymer-forming biocompatible gels, such as polyethylene glycol (PEG) and polypropylene glycol (PPG), may also be used.

The device inserted into soft tissue is extendable in the longitudinal direction (proximal-distal) upon insertion into the soft tissue and dissolution, degradation or expansion of its stiffening element, in particular a portion of its polymer coating. To be extensible, the flexible polymer coating need not be an elastically flexible material. It is preferred that the non-elastic or only slightly elastic polymer coating is rendered extensible by providing it or at least a portion thereof in a bellows-like configuration. Thus, according to a third preferred aspect of the invention, the flexible polymer coating of the device for insertion into soft tissue is bellows-shaped and the stiffening element reflects this shape.

According to a fourth preferred aspect of the invention, the device for insertion into soft tissue comprises a microprocessor control unit. The microcontroller may control the electrode voltage; an electrode potential comprising its variation with time; one or more of the light emissions over time. The microprocessor unit may be capable of detecting voltage phenomena originating from tissue structures, in particular neurons. In addition, the microprocessor unit may control a radiation sensor, in particular a sensor for visible and/or near infrared light. The radiation sensor is preferably mounted on the substrate. It may detect light reflected from tissue structures, such as neurons, and/or fluorescence emitted from such structures.

According to a fifth preferred aspect of the invention, the stiffening element comprises two or more cylindrical sections of different compositions placed adjacent to each other in the longitudinal (distal-proximal) direction. At least one segment thereof may comprise a pharmacologically active agent, in particular an agent affecting neurons or glial cells, e.g. dopamine, dopamine agonists, dopamine antagonists, serotonin, 5-hydroxytryptamine antagonists. In another preferred embodiment, the pharmacologically active agent is a formulation having anti-inflammatory properties. In yet another preferred embodiment, the pharmacologically active agent is selected from neurotropic factors (particularly BDNF and NGF). Pharmacologically active agents also include genes.

According to a sixth preferred aspect of the invention, the stiffening element comprises two sections of different compositions placed adjacent to each other in the radial direction. At least one segment thereof preferably comprises a pharmacologically active agent, in particular a neuron affecting agent, such as dopamine, dopamine agonists, dopamine antagonists, serotonin, 5-hydroxytryptamine antagonists, neurotropic factors such as BDNF, NGF, and genes.

According to a seventh preferred aspect of the present invention, a device for insertion into soft tissue comprises a reservoir filled with a solution (in particular an aqueous solution) of a pharmacologically active agent. The reservoir is placed at the proximal section of the device, in particular at or near its proximal end. The dissolution or degradation of the stiffening element allows the reservoir to communicate with the soft tissue into which the device has been inserted. The communication is provided by a body fluid filled column defined by a flexible polymer coating through which a solution of the pharmacological agent can be pushed by applying pressure to the reservoir or through which the pharmacological agent can diffuse to exit the column at the open distal end thereof.

According to an eighth preferred aspect, the device for insertion into soft tissue comprises at its rear end means for wireless communication with an external control unit and/or non-wireless means for electrical and/or optical communication with such a unit, such as one or more electrically insulated electrical conductors and/or one or more optical fibres.

According to another preferred embodiment, the device of the invention comprises a radiation sensor, in particular a sensor sensitive to visible and/or near infrared light. The sensor is preferably mounted on a substrate.

According to yet another preferred aspect of the present invention, the distal opening is selected from an axial distal opening and a radial distal opening. In a first original device of the invention and a corresponding device of the invention, the distal opening is covered with a translucent sheet of polymer material, which is preferably as flexible as or more flexible than the polymer coating. Illumination of the soft tissue adjacent the radially distal opening may occur directly by a beam emitted from the radiation source or indirectly by such a beam being reflected one or more times from the inner wall surface of the device before exiting the interior void M via the radial opening. In order to enhance the strength of the portion of the beam that escapes through the radial distal opening, a section of the inner face of the wall may be made more reflective, for example by using a suitable high reflectivity polymer material and/or applying a high reflectivity polymer coating on the inner face of the wall. The high reflectivity polymer coating may include high reflectivity microscopic inorganic or organic particles, such as TiO₂Or platinum particles in the micron range.

The device for therapeutic and/or diagnostic use of the invention can be used for one or more of the following: a) emitting light into surrounding soft tissue; b) detecting light emitted from surrounding soft tissue; c) electrical stimulation of surrounding tissue structures; d) electrical signals emitted from surrounding soft tissue are detected.

The device for therapeutic and/or diagnostic use of the present invention placed in soft tissue has an anterior (distal) end and a posterior (proximal) end and comprises:

-a microelectrode;

-a micro light source capable of emitting light in a distal direction;

-a substantially cylindrical coating of a flexible non-conductive polymer material comprising a distal opening allowing light emitted from the light source to exit the device, said coating delimiting a substantially cylindrical space filled with an aqueous body fluid and/or a translucent gel;

-a base placed at the distal end of the device.

Upon insertion into soft tissue, the device for insertion into soft tissue of the present invention is transformed into a device for therapeutic and/or diagnostic use by dissolving, degrading or expanding its sclerosing element. In addition to replacing the stiffening element by aqueous body fluid and/or translucent gel (which makes the device flexible and able to adapt to the movements of the adjacent tissues, and an optional cap of body fluid soluble material placed over the distal face of the device for insertion into soft tissues), the device for therapeutic and/or diagnostic use of the present invention shares most or all of the features of the previous example, and therefore its design and structure is identified.

According to the invention, use of the device for therapy and/or diagnosis is also disclosed, to provide light and/or electrical stimulation to soft tissue structures (such as neurons), to record electrical signals emanating from such structures, to damage such structures, to combine drug delivery, to record nerve cell signals and nerve cell stimulation.

According to the present invention, there is further disclosed a method of placing a device of the present invention for therapeutic and/or diagnostic use relative to a selected structure in tissue, comprising:

-inserting the device for insertion into soft tissue of the invention with its distal end foremost so that it occupies a first position;

-maintaining the device in the first position until the stiffening element has been dissolved, degraded or swollen to form a transparent gel;

-causing a light source to emit light in the direction of the selected tissue structure;

-monitoring the position of the selected tissue structure by detecting light reflected from the structure;

-displacing the device relative to the selected tissue structure such that it adopts the second position.

The present invention will now be explained in more detail by referring to a number of preferred embodiments shown in a sketch, which is merely intended to illustrate the principles of the invention. The figures are not to scale. The radial dimensions are greatly exaggerated.

Drawings

All figures show embodiments of the invention. In some of them, the combination of light sources and electrodes of the invention is shown only schematically to illustrate its deployment in a pre-stage device, original device or device of the invention. It should be understood that each of the embodiments of the combination of electrodes and light sources shown in fig. 1 h-1 s' and fig. 15, 16 is made up of all embodiments of the pre-stage device, original device or device of the present invention.

Fig. 1a to 1g show in a more general way the distal part of a pre-stage device, a former device or a device of the invention. Specifically, shown in the following figures:

FIG. 1a is a longitudinal section (corresponding to section B-B in FIG. 1e), the prestage of the apparatus of the invention;

FIG. 1b is a same view of a distal portion of the prestage of FIG. 1 a;

FIG. 1c is the same view as FIG. 1a, showing the distal portion of the original device of the present invention, manufactured from the prestage of FIGS. 1a, 1 b;

FIG. 1d is the same view as FIG. 1a, showing the distal portion of the original device of FIG. 1c as it is inserted into the soft tissue and the stiffening elements thereof partially dissolved;

FIGS. 1e, 1f in the same view as FIG. 1a, the distal part of the first embodiment of the device of the invention (FIG. 1e) and the main part of the device formed by contact with aqueous body fluids from the original device of FIGS. 1c,1d (FIG. 1 f);

FIG. 1g radial section A-A (FIG. 1b) of the original apparatus of FIG. 1 c;

fig. 1h the distal part of the prestage of the second embodiment of the original device of the invention in longitudinal axial section B-B;

fig. 1i the prestage of fig. 1h in a radial section a-a;

fig. 1l' the distal part of the first embodiment of the original device of the invention, manufactured from the previous stage of fig. 1h,1i, in an axial section corresponding to section B-B in fig. 1 i;

figure 1m 'the original apparatus of figure 1l' in a radial section a x-a;

1l,1m distal portion of a first embodiment of the device of the invention formed by contact with aqueous body fluid from the original device of FIGS. 1l ',1m' and in the same view;

fig. 1l is a variant of the original apparatus of fig. 1l ',1m ' and in the same view as fig. 1l ';

fig. 1j shows in axial section B-B (fig. 1i) the distal part of the prestage of the second embodiment of the original apparatus of the invention;

fig. 1k the prestage of fig. 1j in a radial section a x-a;

fig. 1n' in longitudinal axial section B x B (fig. 1i), from fig. 1j,1k in radial plane a "-a", the distal portion of the second embodiment of the original device of the invention, made with its rounded tip portion, is removed;

fig. 1o' original device of fig. 1n in radial section a-a;

FIG. 1n is an axial cross-section of the distal portion of a second embodiment of the device of the present invention formed from the original device of FIGS. 1n ',1o' upon insertion into soft tissue;

fig. 1o the device of fig. 1n' in a radial cross-section a x-a;

figure 1n is a variant of the original device of figures 4n ',4o' in the same view as figure 1 n;

figure 1p' distal part of a third embodiment of the original device of the invention in axial section B x-B (figure 1 i);

figure 1q 'original apparatus of figure 1p' in radial section a-a;

FIG. 1p in an axial section corresponding to that of FIG. 1i, a distal portion of a third embodiment of the device of the present invention formed from the original device of FIGS. 1p ',1q' upon contact with aqueous body fluid;

figure 1q the embodiment of figure 1p in a radial section a-a;

FIG. 1r' is a distal portion of a fourth embodiment of the original apparatus of the present invention in axial cross-section;

figure 1s 'original apparatus of figure 1r' in radial section a-a;

FIG. 1r is an axial cross-section of a distal portion of a fourth embodiment of the device of the present invention formed from the original device of FIG. 1r' upon contact with aqueous body fluid;

fig. 1s the device of fig. 1r in a radial cross-section a x-a;

FIG. 2 is a fifth embodiment of the original apparatus of the present invention in axial cross-section;

FIG. 3 is a sixth embodiment of the original apparatus of the present invention in axial cross-section;

FIG. 4 is a distal terminal portion of a seventh embodiment of the original apparatus of the present invention in axial cross-section;

FIG. 5 is a distal portion of an eighth embodiment of the original apparatus of the present invention in axial cross-section;

FIG. 6 is a distal portion of a ninth embodiment of the original apparatus of the present invention in axial cross-section;

fig. 7 a distal part of a tenth embodiment of the original device of the present invention comprising a medicament delivery compartment in axial cross-section;

FIG. 8 shows, in axial section, a tenth embodiment of the apparatus of the invention, corresponding to the original apparatus of FIG. 7;

FIGS. 9 a-9 c bundles of 4 original devices of the invention in longitudinal section R-R (9a) and two radial sections O-O and P-P (9b,9 c);

fig. 10, 11 comprise an array of 6 bundles, each bundle comprising two original devices of the invention in longitudinal section (fig. 10) and a corresponding bundle in perspective view (fig. 11);

FIG. 12 includes an array of nine beams, each beam including five of the original devices of the present invention in an angular side view;

FIG. 13 is a distal portion of an eleventh embodiment of the original apparatus of the present invention in axial cross-section;

FIG. 14a shows an eleventh embodiment of the original apparatus of the invention in axial cross-section;

FIG. 14b shows, in the same view, a twelfth embodiment of the device of the invention, corresponding to the original device of FIG. 14 a;

FIG. 15 is a thirteenth embodiment of the original apparatus of the present invention in axial cross-section;

FIG. 16 is a fourteenth embodiment of the original apparatus of the invention in axial cross-section, including, in addition to the features of the thirteenth embodiment, a radiation sensing device;

FIG. 17 in an axial section A-A (FIG. 29) is a fifteenth embodiment of the original apparatus of the present invention, including an axial distal opening and three transverse distal openings;

FIG. 18 is an axial cross-section A-A (FIG. 30) of the device of the present invention formed from the original device of FIG. 17 when implanted in soft tissue;

FIG. 19 in an axial cross-section corresponding to that of FIG. 17, a sixteenth embodiment of the original apparatus of the invention, including three lateral distal openings;

FIG. 20 is an axial cross-section, corresponding to the cross-section of the embodiment of FIG. 18, of the device of the present invention formed from the original device of FIG. 19 when implanted in soft tissue;

FIG. 21 in an axial cross-section corresponding to that of the embodiment of FIG. 17, a seventeenth embodiment of the original apparatus of the invention, comprising a light sensor;

FIG. 22 is an axial cross-section, corresponding to the cross-section of the embodiment of FIG. 18, of the device of the present invention formed from the original device of FIG. 21 when implanted in soft tissue;

FIG. 23 in an axial cross-section corresponding to that of the embodiment of FIG. 17, an eighteenth embodiment of the original apparatus of the invention, comprising a light-reflective inner wall section and a body fluid-permeable wall section;

FIG. 24 is an axial cross-section, corresponding to the cross-section of the embodiment of FIG. 18, of the device of the present invention formed from the original device of FIG. 23 when implanted in soft tissue;

FIG. 25 is a nineteenth embodiment of the original apparatus of the present invention in radial cross-section corresponding to that of the embodiment of FIG. 17, except that its transverse distal opening is covered by a translucent flexible polymer coating;

FIG. 26 in a corresponding radial cross-section, a device of the present invention formed from the original device of FIG. 25 when implanted in soft tissue;

FIG. 27 is a twentieth embodiment of the original apparatus of the invention in radial cross-section corresponding to the cross-section of the embodiment of FIG. 17, except that its transverse distal opening is covered by a flexible, translucent polymeric material sheet;

FIG. 28 in a corresponding radial cross-section, a device of the present invention formed from the original device of FIG. 27 when implanted in soft tissue;

FIG. 29 is the original apparatus of FIG. 17 in a radial section B-B;

FIG. 30 is the apparatus of FIG. 18 in corresponding radial cross-section;

fig. 31 bellows-type axial section of the flexible wall of the device of the invention consisting of a layer combination flexible coating/flexible electrode layer/flexible insulating layer.

Detailed Description

Example 1 general deployment of a combination of microelectrodes and optical fibres in the pre-stage apparatus, original apparatus and device of the present invention.

Fig. 1a, 1b show axial sections of the terminal portion and the main portion, including the terminal portion of the pre-stage device 1 "of the composition. The plurality of S-shaped portions extending from the terminal portion are extendable in the distal/proximal direction.

The terminal portion comprises a blunt distal tip 9. The combination of optical fiber and electrode 2 is schematically represented. The combination 2 is centrally located in the distal and main portions. The central axis B-B of the terminal part fig. 1f is rotationally symmetrical. The electrode and fiber combination 2 is surrounded by a stiffening element or layer 3, which is also rotationally symmetric at least in the straight distal terminal portion. The stiffening element 3 is a material that is soluble in aqueous body fluids including water or is degradable by liquids or water, and is preferably a biocompatible carbohydrate and/or protein material, such as glucose and albumin. Alternatively, the stiffening element 3 is a gel of a biocompatible material such as gel or hyaluronic acid or a mixture of gel or hyaluronic acid with carbohydrate and/or proteinaceous material, in contact with aqueous body fluids. In the gelled state, the gel material is translucent. A thin layer 4 of a flexible, electrically insulating material, such as parylene C, is placed on the stiffening element so as to completely surround it.

Fig. 1c shows the distal terminal portion of the original device 1' of the invention obtained by cutting the pre-stage device 1 "radially in the plane a-a. Reference numerals 2, 3, 4 identify the same features as in fig. 1a, 1 b. By cutting the prestage 1 ″, a round, flat end face 6, as shown in fig. 1g, is produced.

Fig. 1d shows the state of the original device 1' when soft tissue is inserted for a short period of time. The terminal portion of the stiffening element 3 has been dissolved or degraded or transformed into a translucent gel by contact with aqueous body fluids, said transformed portion being identified by 8.

In fig. 1e and 1f, the entire layer of the stiffening element 3 has been transformed. The reference numerals 2-4 and 8 retain their meanings explained above.

Example 2 Pre-stage apparatus, Primary apparatus and apparatus of the invention comprising a first combination of microelectrodes and optical fibers

Fig. 1h and 1i show the axial B-B and radial a-a cross-sections of the distal terminal part of the pre-stage device 40 "comprising a first combination of microelectrodes 22 and optical fibers 21. The optical fiber 21 and the electrode 22 are placed in parallel and attached to each other by a permanent adhesive bridge 25. The combination of the optical fibre 21 and the electrode 22 is surrounded by a layer or element 23 of hardened material. The optical fiber 21 has a polished flat distal end face 31 placed at approximately the same radial level as the distal end of the electrode 22.

The original device 40' shown in fig. 1l ',1m ' is formed by cutting out the preliminary device 40 "radially in a plane a ' -a ' at the distal end of the face 31, wherein the reference numerals of fig. 1h,1i retain their meaning.

Upon insertion of the original device 40' into the soft tissue with the proximal end most forward in the soft tissue, the stiffening element 23 is dissolved or degraded by contact with the aqueous body fluid 8 and replaced by it or converted into a translucent gel 28, fig. 1l,1 m. The end face 31 of the cutting fiber 21 and the prestage device 40 "distal to the distal end or tip of the electrode 22, the fiber 21 and the electrode 22 being placed to withdraw from the distal end face 26 of the stiffening element 23 and the distal circular rim 26 of the flexible polymer coating 24, respectively (fig. 1l), thus preventing or at least delaying contact of the electrode 22 and the fiber 21 of the device of the invention with the surrounding tissue.

In fig. 1l, a variant 40 'of the original device 40' is shown, the distal end face 26 of which is covered with a cap 27 of a water-soluble material, such as glucose or a mixture of glucose and lactose or a gel. The cap 27 functions to facilitate insertion of the original device into soft tissue and to retard contact of the electrode 22 with surrounding tissue.

Example 3 Pre-stage apparatus, Primary apparatus and apparatus of the invention comprising a second combination of microelectrodes and optical fibers

Fig. 1j and 1k show cross-sections of axial and radial B-B and a-a of the distal terminal portion of a pre-stage device 50 "comprising a second combination of microelectrodes 22 and optical fibers 21 surrounded by a layer or element 23 of hardened material. The electrode 22 has a polished flat distal end face 31 and is surrounded by an electrically conductive layer 22 forming an electrode. The distal end of the electrode layer 22 and the distal end face 31 of the optical fiber 21 are placed at the same radial level.

The original devices 50' shown in fig. 1l ',1m ' are formed by cutting the pre-stage devices 50 "radially in the plane a x-a x at the distal end of the face 31, in which the reference numerals of fig. 1h,1h retain their meaning.

Upon insertion of the original device 50' into the soft tissue with its proximal end up to the foremost point in the soft tissue, the stiffening element 23 is dissolved or degraded by contact with the aqueous body fluid 8 and replaced by it or converted into a translucent gel 28, fig. 1l,1 m. The end face 31 of the optical fibre and the pre-stage device distal to the tip of the electrode are cut away, the end face 31 being positioned to be withdrawn from the distal face 26 of the stiffening element 23 and the distal circular rim 26 of the flexible polymer coating 24 (fig. 1l), thereby preventing or at least delaying contact of the electrode 22 and optical fibre 21 with the surrounding tissue.

In fig. 1n ', a variant 50' of the original device 50' is shown, the distal end face 26 of which is covered with a cap 27 of a water-soluble material (such as glucose). The cap 27 functions to facilitate insertion into soft tissue.

Example 4 Pre-stage apparatus, Primary apparatus and apparatus of the invention comprising a third combination of microelectrodes and optical fibers

Fig. 1p ',1q' show the axial B-B and radial a-a cross-sections of the distal terminal part of the original device 60 "of the invention comprising a third combination of microelectrodes 22 and optical fibers 21. The optical fiber 21 and the electrode 22 are placed in parallel and attached to each other by a permanent adhesive bridge 25. The combination of the optical fibre 21 and the electrode 22 is surrounded by a layer or element 23 of hardened material, which is in turn surrounded by a coating 24 of a flexible polymer material such as parylene C. The optical fiber 21 has a polished flat distal face 31 placed at substantially the same radial level as the distal end of the electrode 22. Except for the distal portion, the electrode 22 is electrically insulated by a lacquer coating 29. The original equipment 60' has been produced from corresponding pre-stage equipment (not shown) in the manner described in examples 2 and 3.

Upon insertion of the original device 60' into soft tissue with its proximal end up to the foremost point in the soft tissue, the hardened element 23 is dissolved or degraded by contact with the aqueous body fluid 8 and replaced by it or converted into a translucent gel 28 to form a third embodiment 60 of the device of the present invention, fig. 1p,1 q.

Example 5 Pre-stage apparatus, Primary apparatus and apparatus of the invention comprising a fourth combination of microelectrodes and optical fibers

Fig. 1r ',1s ' show axial and radial a-a cross sections of the distal terminal part of a primary device 70' of the invention comprising a fourth combination of microelectrodes 22 and optical fibers 21. The combination of microelectrodes 22 and optical fiber 21 is surrounded by a layer or element 23 of hardened material. The optical fiber 21 has a polished flat distal end face 31. It is surrounded by a conductive layer 22 forming an electrode. The electrode layer 22 is covered with an insulating varnish 32 except for a portion 33 extending proximally from the distal end thereof. A lacquer 32 is placed between the electrode layer 22 and the stiffening element 23. The distal end of the electrode layer 22 and the distal end face 24 of the optical fiber 21 are placed at the same radial level.

Upon insertion of the original device 70' into soft tissue with its proximal end up to the foremost point in the soft tissue, the hardened element 23 is dissolved or degraded by contact with the aqueous body fluid 8 and replaced by it or converted to a translucent gel 28. Thus, a corresponding device 70 of the present invention is formed, fig. 1r,1 s.

EXAMPLE 6 fifth embodiment of the original apparatus of the present invention

The original device 201' of fig. 2 is substantially rotationally symmetric about a central longitudinal axis D-D. In addition to the optical fiber and electrode combination 202, the original device 201' also includes a stiffening member 203 of a water-soluble or degradable material and a coating 204 of a flexible, water-insoluble polymeric material on the stiffening member 203. The original device 201' is provided with a circular cover 207 on its front end. The purpose of the cap 207 is to minimize tissue damage caused by insertion of the original device 201' into soft tissue. The cap 207 is of a material that is readily soluble in body fluids (that is, dissolves in a few minutes) but is different from the water soluble material of the stiffening element 203. The electrodes and the optical fibers are electrically and optically connected to a control unit 230, respectively, placed at the proximal end of the original device 201'. The control unit is of the same type as the controller unit of the example described below.

Example 7 sixth embodiment of the original apparatus of the present invention

The original device 301' of fig. 3 is substantially rotationally symmetric about a central longitudinal axis E-E. In addition to the optical fiber and electrode combination 302, the original device 301' also includes a stiffening element 303 and a coating 304 of a flexible, water-insoluble polymer material on the stiffening element 303. The original device 301' is provided with a circular cap 307 on its front end. The purpose of the cap 307 is to minimize tissue damage caused by the insertion of the original device 301' into soft tissue. The material of the cap 307 is the same as the material of the stiffening element 303. The electrodes and the optical fibers are electrically and optically connected to a control unit 330, respectively, placed at the proximal end of the original device 301'. The control unit 330 can be of various types and for various purposes, such as for controlling the current and voltage fed to the electrodes and/or for recording and/or sending electrical signals received from the electrodes and/or for emitting radiation into the optical fiber or receiving radiation emitted from the tissue through the optical fiber and detecting it.

EXAMPLE 8 seventh embodiment of the original apparatus of the present invention

A seventh embodiment 401' of the original apparatus of the present invention shown in fig. 4 shows only the distal terminal portion. The original device 401' is rotationally symmetric about a central longitudinal axis J-J and comprises an optical fibre 421, a conductive coating 422 forming an electrode on the optical fibre 421, a stiffening layer or element 423 on the electrode 422, and a second coating 424 of a flexible, water-insoluble polymer material on the stiffening element 423. The distal terminal section of the electrode layer 422 has a brush 422 of tiny metal fibers extending radially from the layer 422 in order to provide a large electrode tip surface. Except for the brush segments 422, the electrodes 422 are insulated by a lacquer (not shown). The optical fiber has a distal terminal flat 431 that is placed in the same radial plane as the distal rim of the flexible polymer coating 424.

EXAMPLE 9 eighth embodiment of the original apparatus of the present invention

An eighth embodiment 501' of the original apparatus of the present invention shown in fig. 5 shows only the distal terminal portion. The original device 501' is rotationally symmetric about a central longitudinal axis K-K and comprises an optical fibre 521, a conductive coating 522 forming an electrode on the optical fibre 521, a hardened layer or element 523 on the electrode 522, and a coating 524 of a flexible water-insoluble polymer material on the hardened element 523. The conductive layer 533 is provided on the flexible polymer coating 524 and covered with a coating 524 'of the same material as the flexible polymer coating 524 so as to be completely surrounded by the insulating coating 524,524'. The conductor layer 533 is held at ground potential to shield the electrode 522. The optical fiber 521 has a distal terminal flat surface 531 that lies in the same radial plane as the distal rim of the flexible polymer coating 524.

EXAMPLE 9 ninth embodiment of the original apparatus of the present invention

The original apparatus 601 'of fig. 6 of the present invention in cylindrical form (central axis M-M) is similar to the original apparatus of fig. 1c except that the water-soluble stiffening element is comprised of two sections, namely a front (distal) section 603 and a proximal section 603' extending back from the distal end of the front section 603. The elements 602, 604, 606 correspond functionally to elements 2, 4 and 6 of the embodiment of fig. 1 c. By providing two or more water-soluble hardening element sections in combination with each other in a radial plane, it is possible to make the change of its dissolution profile more than the possible dissolution profile of the hardening element of one cross-sectional section.

Example 10 tenth embodiment of original apparatus of the present invention

A tenth embodiment of the original device 701' (axial section N-N) of the invention of fig. 7 comprises a front portion of the original electrode functionally corresponding to the embodiment of fig. 1c, elements 702, 703, 704 corresponding to elements 2, 3 and 4, respectively. The water-soluble material of the stiffening element 703 does not extend along the entire original device 701' but rather extends back from its distal end over only a portion thereof. At the rear end of the stiffening element 703, a protruding reservoir 715 of polymer material is incorporated through which the combination 702 of optical fibre and electrode extends centrally. The rear end of a container 715 of a polymer material such as parylene or silicone rubber is bonded to a rigid polymer tube 717, and the optical fiber and electrode combination 702 extends further through the rigid polymer tube 717. The stiff tube 717 is dimensioned such that a tubular void 718 is formed between it and the container 715. The container 715 is filled with a porous, water-insoluble material 716, for example, silica. Pharmacologically active agents such as dopamine are absorbed by the porous material 716. The space between the optical fiber and electrode combination 702 and the flexible coating 704 of water-insoluble polymeric material becomes filled with body fluid by dissolving the water-soluble hardener 703 by aqueous body fluid entering through the distal terminal opening 719. Through this process, the original device of fig. 7 is converted into the device 701 of fig. 8. By providing a controlled forward flow F in the void 718 of the tube 717, the absorbed dopamine on the porous material 716 is dissolved and diffused into the void 708 and passes from the void 708 through the distal terminal opening 719 into the adjoining tissue to exert its influence on the biological structure (such as a neuron), whose electrical activity can be monitored by the electrodes and can be irradiated by radiation guided through the optical fibers of the optical fiber and electrode combination 702.

Example 11 bundle of original devices of the invention

In a bundle 800' of 4 original devices 801a ' to 801d ' of fig. 9a (section R-R), 9b (section O-O) and 9c (section P-P), the original devices are placed in parallel and mounted in through holes of a cylindrical substrate 820. Each of the original devices 801a ',801b',801c ',801d' includes a central combination of optical fibers and electrodes 802a,802b,802c,802d, a water-soluble stiffening element or layer 803a,803b,803c,803d on each combination of optical fibers and electrodes 802a,802b,802c,802d, and a water-insoluble polymer coating 804a,804b,804c,804d on the corresponding stiffening element 803a,803b,803c,803 d. The original devices 801a ',801b',801c ',801d' are arranged symmetrically about the central beam axis Q-Q. The proximal sections 810a,810c of the optical fibers and electrical conductors of the bundle are connected to a control unit (not shown).

Each of the various original devices of the present invention described in the foregoing embodiments may be bundled to form a bundle of original devices of the present invention. The bundle of original devices of the invention may comprise two or more different original devices of the invention. By inserting the bundle of the original device of the invention into the soft tissue, the corresponding bundle of the device of the invention is formed via dissolution or degradation of the water-soluble or degradable stiffening element.

To facilitate insertion into soft tissue, the bundle of the primary device of the present invention may be integrated into a housing (not shown) of water-soluble material. The housing has a blunt front end shape and is preferably rotationally symmetric about a beam axis Q-Q and extends to the base 820.

EXAMPLE 12 first embodiment of the Beam array of the original apparatus of the invention

The array 950 of the invention shown in fig. 10 (section V-V) comprises 6 bundles 901'a,902' a,903'a,904' a,905'a,906' a of the original device of the invention. Each bundle includes a pair of original devices. Each of the bundles 900a ',900b',900c ',900d',900e ',900f' is mounted in a bundling stand (fig. 11) at its rear end. The holder 911a of bundle 900a' only is specifically identified in fig. 10 as a bundled holder 911 that is mounted by gluing onto an oblong, generally rectangular flat base 910 having a pointed front end 909. The substrate 910 is preferably a biocompatible polymeric material such as polypropylene, polyacrylate, or polycarbonate. The holder 911a is mounted symmetrically about the long base axis U-U, so that the three bundles 900a ',900b',900c 'of the original device are mounted at the left hand long side 970 of the base 910, and the other three bundles 900d',900e ',900f' are mounted at the right hand long side 971 in the following manner: so that the front end portions of the original device bundles 900a ',900b',900c ',900d',900e ',900f' extend on the respective sides in the obliquely forward direction. Near the rear end of the substrate 910, electrical and electrically identifiable optical conductors connecting the electrodes and optical fibers of the left 900a ',900b',900c 'and right 900d',900e ',900f' bundles are combined in flexible polymer tubes 907, 908. To facilitate insertion into soft tissue, the array of raw beams may be integrated into a housing (not shown) of water-soluble material.

After insertion into soft tissue, the array 950 of bundles 900a ',900b',900c ',900d',900e ',900f' of the primary device of the present invention is converted into a corresponding array of bundles of the device of the present invention (not shown) by dissolution, degradation, or expansion of their stiffening elements

Example 13 second embodiment of an array of beams h of a master device of the invention

The array 1001 of fig. 12 comprises a thin round flat support of polyurethane 1002 from which nine bundles of original devices 1003,1004,1005,1006,1007, etc. of the present invention extend perpendicularly to one face (top face) so as to be placed parallel with respect to each other. Each bundle comprised 5 original devices of the present invention. The original equipment of bundles 1003,1004,1005,1006,1007, etc. penetrate the support 1002 and extend a short distance from the other (bottom) side thereof. They are bundled in a flexible tube 1008 and optically and electrically connected to a control unit 1009. The control unit 1009 allows one to activate the selected fibers and electrodes of the selected bundle, and even the selected fibers and electrodes of one bundle, and to receive the light and electrical signals emitted from the soft tissue to be transmitted to the control unit. The control unit 1009 also allows one to send different types of radiation through the optical fibers of the selected bundle. In this way, various excitation and radiation patterns can be achieved, as well as electrical signals and radiation patterns emanating from the soft tissue to be received and detected.

EXAMPLE 14 eleventh embodiment of the original apparatus of the present invention

An axial cross-section F ' -F ' of the distal terminal portion of a tenth embodiment 1201' of the original device of the present invention is shown in fig. 13. Reference numeral 1202 identifies a combination of optical fibers and electrodes that are retracted in the proximal direction a distance h from the distal end face 1206 of a corresponding geometry of the bellows-shaped stiffening element 1203 on which a correspondingly shaped flexible polymer coating 1204 is placed. The corresponding device of the present invention is formed by the dissolution of the water-soluble stiffening element 1203 by tissue fluid contacting the stiffening element 1203 at its flat distal end face 1206. In this way, the coating 1204 of the device of the invention is formed to be extensible in the proximal/distal direction and thus designed to accommodate movement of different portions of tissue into which the device is inserted and to anchor in the tissue.

EXAMPLE 15 twelfth embodiment of original apparatus of the present invention

An eleventh embodiment of the rotational symmetry (central axis F-F) of the master device 1301' of the invention, shown in fig. 14a, comprises an LED 1309 as a light source and a cylindrical layer 1302 of gold or platinum on the inner face of the cylindrical flexible polymer coating 1302. A cap 1307 of water-soluble material is attached to the distal face of the coating 1304, the proximal face of which is attached to the circular base 1330. The coating 1304/gold layer 1308, cap 1307 and substrate 1330 define a cylindrical space occupied by the stiffening element 1303 of a water-soluble mixture of glucose and albumin or a gel selected from natural gels and gels cross-linked by heat or chemistry. The LEDs 1309 and the electrode layer 1302 are electrically connected to a control unit (not shown) by a plurality of leads 1331.

Upon insertion of the primary device 1301' into the soft tissue ST, the stiffening element contacts and dissolves the aqueous soft tissue fluid STF at its distal face. Thus, the device 1301 of the invention is formed, fig. 14 b. Over time, the solution of glucose and albumin in the voids previously occupied by the stiffening element 1303 is replaced by the pure soft tissue fluid STF, or if the stiffening element is swellable, like a gel, the voids are filled with a translucent gel. By energizing the LED, a neuron placed distally of the device 1301 is illuminated. By detecting fluorescent light emitted from the neuron 1320, the position relative to the device 1301 can be determined, allowing the device to be displaced in a desired direction relative to the neuron to optimize the arrangement for optical and/or electrical interaction with the neuron 1320.

EXAMPLE 16 thirteenth embodiment of the original apparatus of the present invention

A twelfth embodiment 1401 'of the original device of the invention, shown in fig. 15, corresponds to the eleventh embodiment 1301' of fig. 14a, except that the electrodes are insulated (except for their distal terminal portions) by a shielding metal layer 1405 placed on the outer face of the flexible polymer coating 1404. On its outer face, the shield layer 1405 is covered by a coating 1406 of the same material as the coating 1404 so as to be completely insulated. Layer 1404 of shield electrode 1402 is held at ground potential to protect electrode 1402 from external electric fields. The electrode 1302 is insulated on its interior surface (except for a small portion at 1410 extending from its distal end) by a lacquer 1408. To avoid or at least delay contact with soft tissue, the electrodes 1402 are retracted a distance h in the distal direction from the stiffening element 1403 and the distal end face 1411 of the flexible polymer coating 1404. The electrode layer 1402 and the shield layer 1405 and the flexible polymer layers 1404, 1406 are attached to a substrate 1430 and electrically connected to a plurality of leads 1431 through the substrate 1430. The elements identified by reference numerals 1407 and 1409 correspond to the elements 1307 and 1309, respectively, of the embodiment of fig. 14 a.

EXAMPLE 17 coating of Water-soluble Material on Metal or Polymer elements

The grease and oil were removed from the combination by dipping it in diethyl ether for 10 seconds, removing it and drying. A sugar coating of approximately 30 μm thickness was applied to the combination in the following manner. Sucrose (100g) was dissolved in 50ml water. The solution was boiled for about 5 minutes until it appeared pure. The solution was allowed to cool to 80 ℃. The combination, held at its rear end by a pair of stainless steel tongs, was completely immersed in the solution. It was removed from the solution by taking it vertically at a speed of 6 mm/s. The sucrose-covered combination was dried overnight to form a dry sucrose coating of approximately 40 μm thickness on the body. The coating thickness can be selected by varying the withdrawal speed and/or multiple impregnations. The reduced speed presents a thinner coating.

EXAMPLE 18A prestage device of the invention was made by coating parylene C on the dry sucrose element of example 14

A coating of parylene C of approximately 4 μm thickness was applied by a prior art vacuum coating process (http:// www.scscookson.com/parylene/properties. cfm, in which dichloroparaxylene dimer was evaporated and subsequently pyrolysed to paraxylene), which was introduced into a deposition chamber maintained approximately at room temperature under high vacuum and precipitated there on the sucrose-coated component of example 17. The double-coated device thus obtained corresponds to the prestage device of the invention.

EXAMPLE 19 original apparatus of the present invention was manufactured from the front-end apparatus of example 18

The pre-stage apparatus of example 18 had its front end dipped foremost into molten high melting paraffin wax (melting point about 40 ℃) in a short, 3mm diameter polypropylene cylinder. After cooling to room temperature, the paraffin block containing the prestage equipment was placed on a polypropylene holder and cut with a blade in the radial direction in order to segment its tip. After removing most of the paraffin by melting the paraffin block and retrieving the original equipment thus formed, the original equipment was rinsed several times with pentane and dried. Prior to cutting, the insulated electrode body recorded an impedance of >10 megaohms, which was measured by dipping the electrode body into salt. After cutting the tip and dipping the original device into salt for 2-3 hours, the impedance recorded was <50 kilo ohms. Alternatively, the pre-stage device of example 15 was trimmed under a microscope and the portions of the parylene C coating near the front end were removed by scratching the coating with a micro-file made by coating a thin iron wire (0.1mm diameter) with titanium oxide powder (approximately 10 μm particles) by means of cyanoacrylate prepolymer dissolved in diethyl ether into which the wire was dipped immediately prior to powder application.

The dimensions of the original equipment may vary within wide limits: sizes up to 100 μm or more are useful. Preferred diameters are from 5 μm to 30 μm. The length of the original device may be adapted to its desired position after insertion.

EXAMPLE 20 fourteenth embodiment of the original apparatus of the present invention

The fourteenth embodiment 1501 'of the basic device of the invention shown in fig. 16 differs from the thirteenth embodiment 1401' in that in addition to the light source 1509 mounted on the base 1530, it comprises a light sensor 1532, in particular a sensor for fluorescence, which is also mounted on the base 1530. The radiation sensor 1532 is electrically connected by a flexible, electrically conductive wire 1533 to a recording unit (not shown) that includes a microprocessor, memory, and a data output device, such as a printer. The other features 15XX of the original device 1501 'correspond to the corresponding features 14XX of the original device 1401' of the thirteenth embodiment.

EXAMPLE 21A fifteenth embodiment of an inventive proto-device and a corresponding device of the invention formed from the proto-device when implanted in soft tissue

A fifteenth embodiment 1601' of the original apparatus of the present invention, shown in fig. 17, 29, comprises a stiffening element 1603, which is degradable or soluble in aqueous body fluids. The stiffening member 1603 is mounted on a rigid cylindrical substrate 1613 of polymeric material, such as highly cross-linked polyurethane. An LED light source 1609 is mounted on the distal face of the substrate 1613 and is energized by means of an insulated flexible conductor 1614 connected to a power source. The stiffening member 1603 is substantially cylindrical in shape, rotationally symmetric about its longitudinal axis F-F. The stiffening element 1613 and the substrate 1603 have approximately the same diameter. The stiffening element 1603 is covered by a continuous layer of electrically insulating flexible polymer 1608, electrically conductive flexible electrode layer 1604, and flexible coating layer 1602. The flexible electrode layer 1604 has been attached to the insulating polymer layer 1608 and to a narrow distal region of the stiffening element 1603 not covered by the insulating polymer layer 1608 by a suitable method, such as metal ion sputtering. Highly conductive metals like gold and copper are preferred for this purpose. Polymer layers 1608 and 1602 have been attached by dipping the original equipment to be formed into a solution of the corresponding polymer in a low polarity organic solvent in which the stiffening element 1603 material is insoluble. The distal end face 1611 of the stiffening element is then covered with a circular cap 1610, the material of which is readily soluble in aqueous body fluids. A cap 1610 is provided to facilitate insertion of the device into soft tissue. To avoid or at least make contact with the surrounding soft tissue more difficult when implanting the electrode, electrode layer 1604 is slightly retracted from the distal rim of the flexible polymer coating as shown by "h" in fig. 17. The distal terminal portion of the electrode layer 1604 is not covered by the insulating inner flexible polymer layer 1608 to provide electrical contact with body fluids. In addition to the distal axial opening 1615, three circular distal radial openings 1605,1606,1607 are provided, centered in the same radial plane B-B. The radial openings are arranged to allow light to be emitted in a radial direction to affect or cause an appearance of the adjacent soft tissue structure. To enhance the radial escape of light, the inner face of the electrically insulating polymer layer 1608 may be provided with a reflective coating, such as a thin coating of silver or platinum, or by using a polymer for the layer 1608 that has good visible light reflectivity properties. A wide beam of visible light emitted by the light source 1609 is directed into the distal direction; a portion of which impinges on the inner face of the insulating polymer layer of the reflective coating on that layer. From there it is reflected, partly in the direction of the distal transverse opening 1605,1606,1607, through which it escapes. Non-insulated annular portions of the electrode layer 1604 are placed in the lateral openings, only one of these portions 1604 being indicated in fig. 17 and 18. These two types of blank electrode faces may be used in combination. Alternatively, if only one of them is desired to be used, the others may be deactivated by applying a layer of electrically insulating material (not shown in the figures) thereon.

Upon insertion into soft tissue, the original device 1601' is transformed into the device 1601 of the present invention shown in fig. 18, 30 by dissolving or degrading its hardened elements. "M" indicates the inner space of the device 1601 filled with body fluid when the stiffening element 1603 is completely dissolved.

Fig. 31 shows a cross section 1601 of a physically modified wall of an apparatus 1601 of the present invention. The modification includes providing the wall with a shape in the form of a serpentine or bellows. Wall section 1601 includes a flexible polymer coating 1604, an electrode layer 1602, and an internal insulating polymer layer 1608. By such a modification, the inventive device comprising or consisting of a non-elastic wall material may become extensible in the axial direction.

EXAMPLE 21A sixteenth embodiment of an inventive proto-device and a corresponding device of the invention formed from the proto-device when implanted in soft tissue

The original apparatus 1701' of the present invention shown in fig. 19 is shown in an axial view corresponding to that of fig. 17, except that the cap 1610 has been replaced by a portion of its flexible polymeric coating 1704 as compared to the original apparatus of fig. 17. Upon implantation into soft tissue, the stiffening element 1703 is dissolved or degraded and replaced by aqueous body fluid. Thus, a corresponding apparatus 1701 of the present invention is formed as shown in fig. 20. Reference numeral 17XX in fig. 19 and 20, which is not specifically indicated, refers to an element 16XX of the corresponding type shown in fig. 17 and 18.

EXAMPLE 22A seventeenth embodiment of a proto-device of the invention and a corresponding device of the invention formed from the proto-device when implanted in soft tissue

The original device 1801' of the present invention shown in fig. 21 is shown in an axial view corresponding to that of fig. 17, except that an optical sensor 1815 mounted on the distal face of a base 1813 is provided, in comparison with the original device of fig. 17. The sensor 1815 is sensitive to visible light. It is particularly suitable for monitoring fluorescent radiation of a certain wavelength and is therefore chosen from many commercially available light sensors. It is electrically coupled to a recording unit (not shown) by insulated flexible leads 1816. The recording unit may convert the electrical signals from the sensors into digital data and store the data in a memory. The recording unit is also capable of coordinating the tissue irradiation of the light source 1809, recording data from the sensors 1815, and control of the electrodes 1802. Reference numeral 18XX in fig. 21, which is not specifically indicated, refers to a corresponding type of element 16XX shown in fig. 17 and 18. Upon implantation in soft tissue, the original device 1801' is converted to a device 1801 of the present invention by dissolving or degrading its stiffening element 1803, as shown in fig. 22.

EXAMPLE 23 eighteenth embodiment of an inventive proto-device and a corresponding device of the invention formed from the proto-device when implanted into soft tissue

The original device 1901' of the present invention shown in fig. 23 is shown in an axial view corresponding to the original device of fig. 17, differing from the original device of fig. 17 in a reflective inner wall portion 1919 provided with micro-openings and a distal wall portion 1918. The micro-openings are provided by laser techniques; their function is to provide access for body fluids to the stiffening element 1903 to allow or facilitate its dissolution and the transfer of its components outside the interior M of the device. The diameter of the micro-openings is of the order of 50 μm or less, more preferably from 5 μm to 30 μm. Reference numeral 19XX in fig. 21, which is not specifically indicated, refers to a corresponding type of element 16XX shown in fig. 17 and 18. Upon implantation in soft tissue, the original device 1901' is converted to a device 1901 of the present invention by dissolving or degrading its stiffening element 1903, as shown in fig. 24.

EXAMPLE 24A primary device of the present invention shown in FIG. 17 and a first variation of a corresponding device of the present invention shown in FIG. 18 formed from the primary device upon implantation into soft tissue

The original apparatus 2001' of the present invention shown in fig. 25 is shown only in a cross-sectional radial view, which corresponds to the radial view of fig. 29 (section B-B) of the original apparatus of fig. 17. Section B-B cuts through the center of circular window 2005,2006,2007, which is covered by portions of flexible polymer coating 2004. Coating 2004 is a translucent polymeric material.

Upon implantation in soft tissue, the original device 2001' is transformed into the device 2001 of the present invention by dissolving or degrading its stiffening element 2003, as shown in FIG. 26. The void filled with body fluid is designated as M. Reference numeral 20XX in fig. 24, which is not specifically indicated, refers to a corresponding type of element 16XX shown in fig. 17.

Example 25A second variation of the inventive protodevice shown in FIG. 17 and a corresponding inventive device shown in FIG. 18 formed from the protodevice when implanted in soft tissue

The original device 2101' of the present invention shown in fig. 27 is shown only in a cross-sectional radial view, which corresponds to the radial view of fig. 29 (section B-B) of the original device of fig. 17. Section B-B cuts through the center of circular window 2105,2106,2107, which is covered by individual pieces of translucent flexible polymeric material 2115,2116,2117.

Upon implantation in soft tissue, the original device 2101' is transformed into the device 2001 of the present invention by dissolving or degrading its stiffening element 2103, as shown in fig. 28. The void filled with body fluid is designated as M. Reference numeral 20XX in fig. 27, 28, which is not specifically indicated, refers to a corresponding type of element 20XX shown in fig. 17.

Material

And an electrode. The electrodes are preferably noble metals or noble metal alloys or include noble metals such as gold, silver, platinum, iridium, but other biologically acceptable metals such as stainless steel and tantalum, as well as gold-plated copper, may also be used. Aluminum is the preferred metal for coating optical glass fibers. Instead of a metal or metal alloy, the electrode conductor may consist of or comprise a conductive polymer, such as PEDOT. The conductive state of carbon may also be used. The portion of the electrode conductor that is not electrically insulated from tissue fluid upon removal of the first coating may advantageously be provided with surface enlarging elements or structures, such as roughened surfaces, banks of electrically conductive nanowires (e.g., carbon nanowires), or be porous. This type of surface enlarging structure will reduce the resistance of the electrical conductor. The electrical connection of the conductor and the control unit may be provided by a wire or similar coupling between the rear end of the electrical conductor and the control unit or by the conductor itself, the rear part of which serves as the electrical coupling means. In such a case, the rear section must be electrically insulated.

And hardening the element coating. The combination of the electrode and the light source of the invention is embedded/coated with one or more biocompatible first coating materials, which may be water-soluble, swellable, and/or degradable. If embedded in two or more such materials, they differ in their dissolution rate. Preferred first coating materials are water soluble carbohydrates and proteins and mixtures thereof. However, it is also possible to use polymeric materials which are not water-soluble but which are swellable in water and/or degradable in body fluids. Suitable hardened element coating materials whose dissolution time can be controlled are obtained by: repeatedly boiling and cooling an aqueous solution of a sugar or a mixture of sugars selected from sucrose, lactose, mannose, maltose and an organic acid selected from citric acid, malic acid, phosphoric acid, tartaric acid. By selecting a specific combination of sugar and organic acid it is possible to obtain materials with different dissolution times. Gel may also be used as the first coating material. It is well known that different types of gels or gel-based materials have different dissolution rates. If the first coating of water soluble or swellable material comprises two or more segments placed along the oblong combination of optical fiber/light source and electrode. Selection of a suitable combination of gels provides a distal first coating segment with less dissolution time and a proximal first coating segment with a longer dissolution time. It is also possible to use a sugar-based first coating material for the distal first coating section and a gel-based first coating material for the proximal first coating section or vice versa, and to use a gel for the distal first coating section and gum arabic for the first coating proximal section. Selection of further useful combinations of first coating materials, such as various types of natural gums, is readily accomplished by one skilled in the art. Alternatively, a first coating material having a significantly longer dissolution time, such as a modified collagen, cellulose derivative, modified starch, or other biocompatible material (such as polyglycolic acid), may also be used.

Optionally, the pre-stage device, the original device, the bundle of original devices and the array of original devices, as well as the polymer insulating coating of the bundle of the present invention or another coating of water-soluble material on the first coating, may be completely or partially covered by a biocompatible lubricant to reduce friction during insertion into tissue. Useful lubricants include glycerin, glycerol, stearate, glycerol distearate, palmityl alcohol, stearyl alcohol. A thin coating of lubricant may be applied by spraying, for example, with a solution of the agent in ethanol or ethyl acetate.

A flexible polymer coating. In principle, all types of polymer materials that are suitable for electrical insulation can be used. However, the small structure of the pre-stage device of the present invention to be produced by polymer coating limits the method of application and the number of useful polymers. While monomer deposition from the vapor phase is preferred, such as for providing parylene coatings, it is also useful to dip a pre-stage device coated with a water-soluble/expandable/degradable stiffening element material into a polymer or prepolymer solution, withdraw it from the solution, and evaporate the solvent, optionally allowing the prepolymer to settle. The impregnation method should be by means of a polymeric solvent which does not interact with the water-soluble/swellable/degradable material, in particular a non-polar solvent such as an alkane, or an alkene or cycloalkane or a non-polar aromatic solvent or a mixture thereof, in particular pentane or hexane, but may also be diethyl ether or dichloromethane. Suitable polymers include biocompatible types of polyurethanes, polyurethaneureas, and polyimides. Other useful polymers include various types of silicon. Further useful polymers include polyethylene terephthalate. The flexible polymeric coating of the present invention moves with the surrounding tissue and does not restrict the movement of the tissue. The thickness of the flexible coating is from a few μm up to 20 μm or 50 μm or more.

The beam of the primary electrode. The original devices of the invention can be bound in different ways, for example by integrating their rear end portions into a substrate of polymer or other material, or by gluing their rear end portions with glue. The bundle may be temporary, such as to hold the device in a fixed relationship prior to or during insertion into soft tissue, or permanent. The bundle of original devices comprises a bundling means placed in a proximal direction from the distal ends of two or more devices comprised by said bundle and aligned parallel or substantially parallel. The bundled device is preferably permanent, i.e., not dissolved or degraded by bodily fluids, but may also be temporary, i.e., dissolved or degraded when the bundle is deployed into soft tissue. Preferred permanent bundling means are adhesives, in particular cold-setting polymeric adhesives, such as polyurethanes or polyacrylates. The polymeric adhesive is one that is not dissolvable or degradable by body fluids (unless a very long period of time in excess of 1 or five years has elapsed), the adhesive being applied to the aligned original device at the proximal portion of the original device.

Water soluble or degradable adhesives of corresponding nature allow the original device to separate quickly or slowly upon insertion. The expandable, but water insoluble, adhesive allows the original device inserted into the soft tissue and the device of the present invention formed therefrom to be displaced in a limited manner, while the insoluble and non-expandable adhesives limit their movement to bending and, if designed to be extensible, to changes in length.

The individual original devices of the bundle may differ in length. For example, the central original device of the beam may be longer than its surrounding devices to provide a central beam spot.

Upon insertion into soft tissue, the original device of the bundle is transformed into the device of the invention, and the bundle of the original device is thereby transformed into the bundle of the device of the invention.

In this application, the array of protodevices or beam of protodevices forms a protodevice pattern comprising a plurality of protodevices and/or beams of protodevices disposed on or attached to at least one side of a non-conductive support. Thin supports formed from suitable polymers (such as polypropylene, polyacrylate, polycarbonate and parylene C) comprising substantially only two faces are preferred. The support may be flat but may also be curved. The master and/or the bundle of master may be mounted on one or both surfaces of the support. The master and the bundle of master attached to the support may protrude from the support at an angle, in particular at an angle of from about 15 ° to about 75 °, and even up to about 90 °, which is the angle comprised by the apparatus or the bundle of apparatuses and its protrusion on the mounting surface of the support and/or at an angle of from about 15 ° to about 75 ° comprised by the master or the bundle of masters along the long axis and the central long axis of the support. The support may comprise a porous or semi-permeable to body fluids, i.e. permeable to at least water and inorganic salts.

Upon insertion into soft tissue and contact with aqueous body fluids in the tissue, the original device, the bundle of original devices and the array of original devices or the plurality of bundles of original devices are transformed into the corresponding device, bundle of devices and array of devices of the present invention.

The supports of the arrays of the invention may also be of a material that is soluble or degradable in soft tissue. Useful materials include the water soluble/swellable/degradable first coating materials identified above as useful.

The array support may if desired be provided with a control unit, such as a control unit comprising or consisting of an electronic chip in electrical contact with the electrical conductors of the individual devices. The control unit may comprise or be in electrical contact with a unit for electrical tissue stimulation and/or a signal amplifier for recording electrical neural signals. The array support may also be provided with a radiation control unit comprising radiation emitting means such as one or more LEDs optically coupled to the optical fibres of the array. Furthermore, the array support may also be provided with light sensors.

Claims (36)

1. A medical device for insertion into soft tissue having an anterior (distal) end and a posterior (proximal) end, comprising:

-a microelectrode;

-a micro light source;

-a stiffening element comprising one of:

a) a material soluble or degradable in an aqueous body fluid in an amount sufficient to cause dissolution or disruption of the stiffening element in contact with the aqueous body fluid;

b) a material that is swellable in aqueous body fluids to form a transparent gel;

a coating of a flexible non-conductive polymer material on the stiffening element preventing or at least delaying contact between the electrode and soft tissue upon rupture or swelling of the stiffening element, the coating having a distal opening allowing light emitted from a light source to exit the device upon said rupture or dissolution or swelling,

-a substrate placed at the rear end of the device.

2. The apparatus of claim 1, wherein the light source is a member of the group consisting of an LED, a micro-laser, an optical fiber that receives light from a source not included in the apparatus.

3. The device of claim 1 or 2, wherein the microelectrode comprises a metal or metal alloy or a conductive polymer.

4. The device of any of claims 2 or 3, wherein the microelectrodes comprise a rod or layer on the optical fiber or a layer on the polymer coating facing the stiffening element.

5. The apparatus of any one of claims 1-4, wherein the polymer coating is substantially cylindrical in shape.

6. The device of any of claims 1-5, wherein the electrode is electrically insulated except for a portion extending from its distal end in a proximal direction.

7. The apparatus of any of claims 1-6, wherein the electrode is electrically shielded by a conductive layer on an outer face of the polymer coating held at ground potential.

8. The device according to any of claims 1-7, wherein the stiffening element comprises or consists of a carbohydrate and/or protein material.

9. The device of any one of claims 1-8, comprising a portion that is extendable in a longitudinal (proximal-distal) direction upon dissolution, degradation, or expansion of the stiffening element.

10. The apparatus of claim 9, wherein said extendable portion comprises a portion of said polymer coating.

11. The apparatus of claim 10, wherein the portion is bellows-shaped.

12. The apparatus of any of claims 1-11, comprising a microprocessor control unit.

13. The apparatus of any of claims 1-12, wherein the flexible, non-conductive coating is substantially cylindrical in shape.

14. The device of any of claims 1-13, wherein a distal end of the electrode is withdrawn in a proximal direction from the distal opening.

15. The apparatus of any of claims 1-14, wherein a distal end of the optical fiber is retracted from the distal opening in a proximal direction.

16. The device according to any of the claims 1 to 15, wherein the stiffening element is substantially rotationally symmetric, in particular substantially cylindrical in shape, and comprises two or more cylindrical sections of different compositions placed adjacent to each other in a distal-proximal direction.

17. The apparatus of claim 16, wherein at least one segment comprises a pharmacologically active agent.

18. The apparatus of claim, wherein the stiffening element comprises two sections of different compositions placed adjacent to each other in a radial direction.

19. The apparatus of claim 17, wherein the at least one segment comprises a pharmacologically active agent.

20. The device of any one of claims 1 to 19, comprising a reservoir filled with a solution of the pharmacologically active agent.

21. An apparatus according to any of claims 1-20, comprising means at its rear end for wireless communication with an external control unit.

22. The device of any of claims 1-21, wherein the electrode, the light source, and/or the flexible coating are securely attached to the substrate.

23. A therapeutic and/or diagnostic medical device formed in tissue upon insertion of the device of any one of claims 1-22 and upon dissolution, degradation or expansion of the stiffening element, the device being capable of performing one or more of the following: a) emitting light into surrounding soft tissue; b) detecting light emitted from surrounding soft tissue; c) electrically stimulating the surrounding tissue structure; d) electrical signals emitted from surrounding soft tissue are detected.

24. Use of a device according to claim 23 for providing optical and/or electrical stimulation to a structure of soft tissue such as a neuron, recording electrical signals emanating from such a structure, damaging such a structure, combined drug delivery, recording nerve cell signals and nerve cell stimulation.

25. A method of deploying the device of any one of claims 1-22 into soft tissue relative to a selected structure, comprising:

-inserting the device into soft tissue such that it occupies a first position;

-maintaining the device in the first position until the stiffening element has been dissolved, degraded or swollen to form a transparent gel;

-causing a light source to emit light in the direction of the selected tissue structure;

-monitoring the position of the selected tissue structure by detecting light reflected from the selected tissue structure;

-deploying the device relative to the selected tissue structure.

26. The apparatus of any one of claims 1-22, comprising a radiation sensor.

27. The apparatus of claim 26, wherein the radiation sensor is sensitive to visible and/or near infrared light.

28. The apparatus of claim 26 or 27, wherein the radiation sensor is mounted at the substrate.

29. The apparatus of any of claims 13-22 and 26-28, wherein the distal opening is selected from an axial distal opening and a radial distal opening.

30. The apparatus of claim 29, comprising one distal axial opening and one or more distal radial openings.

31. The apparatus of claim 31, wherein the radiation sensor is mounted at a substrate.

32. The apparatus of any of claims 29-31, wherein the distal opening is covered by a sheet of translucent near-infrared material.

33. The apparatus of claim 32, wherein the sheet of translucent material is as flexible or more flexible than the polymer coating.

34. The apparatus of any of claims 29-33, comprising a high reflectivity inner wall surface disposed distal to the light source.

35. The device of any one of claims 29-24, comprising a distal wall segment comprising micro-passage openings.

36. The device according to claim 35, wherein the diameter of the body of the micro-passage opening is from 5 μ ι η to 50 μ ι η, in particular from 3 μ ι η to 30 μ ι η.