WO2013149707A1 - Dispositif pour la stimulation et/ou la détection d'activités cellulaires dans un environnement biologique de cellules - Google Patents

Dispositif pour la stimulation et/ou la détection d'activités cellulaires dans un environnement biologique de cellules Download PDF

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Publication number
WO2013149707A1
WO2013149707A1 PCT/EP2013/000885 EP2013000885W WO2013149707A1 WO 2013149707 A1 WO2013149707 A1 WO 2013149707A1 EP 2013000885 W EP2013000885 W EP 2013000885W WO 2013149707 A1 WO2013149707 A1 WO 2013149707A1
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WO
WIPO (PCT)
Prior art keywords
hollow channel
implant body
channel
light
optical
Prior art date
Application number
PCT/EP2013/000885
Other languages
German (de)
English (en)
Inventor
Thomas Stieglitz
Young-Hyon Jin
Original Assignee
Albert-Ludwigs-Universität Freiburg
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Albert-Ludwigs-Universität Freiburg filed Critical Albert-Ludwigs-Universität Freiburg
Publication of WO2013149707A1 publication Critical patent/WO2013149707A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/40—Detecting, measuring or recording for evaluating the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0551—Spinal or peripheral nerve electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/06—Arrangements of multiple sensors of different types
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1473—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0526—Head electrodes
    • A61N1/0529—Electrodes for brain stimulation

Definitions

  • the invention relates to a device for stimulating and / or detecting cell activities within a biological cell environment, preferably in the form of nerve cells, with a biocompatible implant body that is temporarily or chronically implantable in the cell environment and comprises at least one hollow channel which has both medium and proximal ends. or directly connected to a fluid pump or connectable as well as an electrical contact with the
  • the device serves primarily to investigate the cell activity in the intact living organism, wherein in addition to the surgical intervention no further manipulation of the
  • neuronal target tissue is made.
  • Neurosciences gain insight into the activity of biological cells, in particular nerve or brain cells.
  • such devices are used in the field of diagnosis of neurological diseases and for auditory neuromonitoring.
  • cell-specific signals are applied to a cell or a cell network to be examined, whereby stimulation effects within the cell or the cell network can be caused.
  • bio-signals emitted by a cell or a cell network it is possible to metrologically record bio-signals emitted by a cell or a cell network.
  • optical signals as well as the application and detection of chemical substances which are present in liquid-dissolved form are used for stimulation as well as for detecting cell-specific activities within a biological cell environment.
  • US 2004/0224002 A1 discloses a neuronal device for modulating neuronal activities, with which a cell or a cell composite can be locally acted upon by a liquid containing at least one bioactive substance.
  • the device provides a housing aperture in the region of which a cell to be examined or a cell assembly to be examined is positioned. Adjacent to the aperture, on the housing side, is a fluid reservoir from which, with the aid of a flow regulator integrated within the housing, a predetermined amount of bioactive agent can be applied to the cell or the cell assembly.
  • chemical substances such as. Anti-inflammatory drugs, neurotransmitter-containing solutions, etc. locally and dosed to individual cells or cell networks. In the same way it is possible to extract cell liquids locally, for example.
  • the device provides a housing aperture in the region of which a cell to be examined or a cell assembly to be examined is positioned. Adjacent to the aperture, on the housing side, is a fluid reservoir from which, with the aid of a flow regulator integrated within the housing,
  • the device For promoting and extracting solutions or fluids, the device provides electrical contract surfaces.
  • Measuring body on whose surface a plurality of individual
  • Contact electrode surfaces are arranged distributed over the inside of the measuring body extending electrical connection lines are connected to a signal generator and - detector and in each case be brought into contact with cells or cell areas in order to cause electrical cell stimulation and tap cells own bioelectric signals.
  • the implantable neuronal interface described in document US 2011/0112591 A1 provides both electrical contact surfaces along an elongate biocompatible measuring body an optical waveguide which has a light exit opening in the region of the electrode surfaces distributed on the measuring body. With such a combination of optical fibers and measuring electrodes, it is possible to detect both the bioelectrical responsiveness of cells to optical stimulation events and the optical responsiveness of cells to electrical stimulation events.
  • Such temporary or chronically implantable probes that have a combined electrical and optical
  • Transport 1 (2), pages 139-158, shows an implantable measuring device for receiving and delivering both bioelectrical signals and bioactive substances in liquid form.
  • the substrate body is a shaft-shaped, formed of biocompatible polyimide implant body 1, at the top in the distal region a plurality of individual electrode surfaces 2 is attached, the intracorporeal in
  • Each individual electrode surface 2 is over one within the
  • Implant body extending, electrical connection line with an electrical Signalgenerator- and evaluation unit (not shown).
  • an optical waveguide 3 is applied to the upper side of the shaft-shaped implant body 1, which is optically separated from the shaft-shaped implant body 1 by means of an opaque layer.
  • the optical waveguide 3 has a frontal Lichtein- and -auskoppel structure 4, which is located in close proximity to the electrode surfaces 2, whereby it is possible bioelectrical cell signals, which are caused by light-induced cell stimulation, directly, d. H. in close proximity to the optical stimulation with the help of
  • a hollow channel is incorporated within the shaft-shaped implant body 1, which has a channel opening 5, which opens at the surface of the shaft-shaped implant body 1 in the immediate vicinity of the electrode surfaces 2.
  • the hollow channel is connected via a fluid adapter to a fluid reservoir, from which fluid can be delivered through the hollow channel by means of a fluid pump.
  • Fluid pump is connected or connectable and provides an opening on the distal side, in such a way that in addition to the application or recording of a liquid substance through the hollow channel, it should also be possible to make through it optical and electrical cell stimulation or detection of bio-optical and bioelectric signals, the required design effort over known solutions simplified, reduced and regarding the
  • Cell activities within a biological cell environment is developed such that on or in the hollow channel, a means is attached, can be coupled via the light into the hollow channel and / or auskoppelbar from the hollow channel.
  • a means is attached, can be coupled via the light into the hollow channel and / or auskoppelbar from the hollow channel.
  • an electrically conductive means is provided, on which an electrical signal can be applied and / or tapped off.
  • the invention is based on the idea that the hollow channel whose previous
  • Liquid transport is limited, additionally as a photoconductive channel, d. H. as a light guide, as well as a signal transmitting electrical signals can be used.
  • the combined use of the hollow channel both as a fluid transport channel and as an optical waveguide and as an electrical signal conductor is the highest
  • the optical means via the light in the hollow channel can be coupled and ultimately auskoppelbar from this, as formed along the hollow channel coupling window, which consists of a
  • the coupling window can be formed separately from a light source and a light detector and be part of the light source and light detector.
  • Hollow channels for example, to be attached to the proximal end region, in order to avoid light losses due to the coupling event unavoidably occurring at the coupling window.
  • crystal clear liquids are used, in which the chemical stimulation of the respective cells or Cell-containing chemical or medical active ingredients completely dissolved. Furthermore, it is necessary for a possible loss-free light pipe along the hollow channel of a suitable adjustment of the optical refractive index of the hollow channel inner wall with respect to the optical refractive index of the liquid flowing through the hollow channel. To light losses through along the
  • Hollow channel inner wall is totally reflected.
  • the refractive index of the hollow channel inner wall smaller than the refractive index of the liquid flowing along the hollow channel. Since the liquids used have optical properties of water whose optical refractive index has the dimensionless size of 1.33, the optical refractive index is the
  • the implant body comprises, on or in the at least one
  • Hollow channel an electrically conductive means on which an electrical signal can be applied or tapped from this.
  • the attachment of the electrically conductive means on or in the implant body takes place in a manner such that the electrically conductive means is an integral part of the implant body.
  • the electrically conductive means is embodied as at least one pin-shaped or needle-shaped electrode body, which is preferably introduced in a proximal-side region of the hollow channel and with one outside the hollow channel, preferably separately from the implant body
  • electrical signals along the hollow channel for targeted cell stimulation lead to can, in a simplest embodiment, the use of an electrically conductive liquid, in the form of an electrolyte liquid which flows through the hollow channel or at least fills the hollow channel.
  • an electrically conductive liquid in the form of an electrolyte liquid which flows through the hollow channel or at least fills the hollow channel.
  • the pin-shaped or needle-shaped electrode made of metal or a metal / metal salt combination (electrode of the second kind, eg Ag / AgCl), which is flowed over by the electrically conductive liquid along the hollow channel, the electrical signals applied to the electrode be transmitted to the electrically conductive liquid for further transmission.
  • the liquid serves as a guide medium for the electrical stimulation signals.
  • electrically conductive electrode surfaces which locally bound the hollow channel are also suitable.
  • the hollow channel at least locally enclosing, electrically conductive
  • Hollow channel inner wall surfaces have the advantage that electrical signals can be transmitted to or from the electrolyte flowing through the hollow channel without permanently impairing the flow behavior.
  • Hollow channel inner wall extending, electrically conductive structures.
  • Such an electrical conductor structure can be realized, for example, by direct deposition of electrically conductive material on the hollow channel inner wall, in the form of an elongated conductor track structure.
  • Hollow channel inner wall along the hollow channel extending conductor track structure is connected to the proximal end to the hollow channel with an externally provided signal generator or detector.
  • the electrical interconnect structure opens at the distal end to the hollow channel, preferably forming an electrode surface that is freely accessible to the cell or the cell assembly. In this case, it is not necessary for bioelectric signal transport to pass an electrically conductive liquid through the hollow channel.
  • Conductor structures may be appropriate.
  • Information transmission techniques through at least a single hollow channel within the implant body allows a maximum of system integrity for the simultaneous transmission of optical, electrical and chemical material biosignals.
  • Implant body has additional electrical conductor structures which extend separately and along the hollow channel within the implant body, in the distal region of the implant body in the form of freely accessible electrode surfaces terminate and the proximal side to the implant body by means of suitable connection structures with an electrical signal generator or detector are connected.
  • the electrode surfaces arranged on the distal region of the implant body are mounted as close as possible to the hollow channel opening in order to be able to pick up bioelectrical signals in the immediate vicinity of the cell region, which has been stimulated by means of optical, electrical and / or materially chemical stimuli.
  • the biocompatible implant body preferably consists of a biocompatible polymer, for example parylene C, polyimide or polydimethylsiloxane, and is furthermore designed to be transparent for diagnostic X-radiation, IR radiation or visible light, so as not to present any disturbing artifacts Generate images that can be obtained from tissue or cell areas using standard diagnostic methods.
  • a biocompatible polymer for example parylene C, polyimide or polydimethylsiloxane
  • the novel implant body is preferably suitable as temporary or chronic, d. H. permanently implantable neuronal prosthesis and is able to gently allow investigations on the central and peripheral nervous system for purposes of neuronal stimulation applications. With the help of the novel implant body, it is not only possible bioelectric
  • Neurotransmitter substances are made, which are delivered from the side of individual cells or cell clusters by optical and / or electrical stimulation of the cells or cell clusters. Furthermore, it is possible to detect optical biosignals emitted by the cells by artificial stimulation as a result of bioelectrical or materially chemical excitation as a function of the local electrical potential prevailing at the location of the cell.
  • FIG. 1a, b representations of an implant body with a hollow channel, which is designed both for a liquid transport, for optical waveguide and for the transmission of electrical signals,
  • FIG. 3a, b showing an implant body formed in accordance with the solution
  • FIG. 4 longitudinal sectional view through an implant body with optical
  • FIG. 5a, b, c schematic representation of an implant body with several
  • FIG. 6 is a schematic representation of the distal end region of a
  • Implant body with a variety of additional freely accessible
  • FIG. 1a shows a biocompatible polymeric material
  • Implant body 1 which encloses a hollow channel 6, the hollow channel opening 5 ends the end face at the distal end of the implant body.
  • the hollow channel 6 is formed in a straight line in the illustrated embodiment and has a linear channel axis A, the one by the channel opening 5 delimiting
  • the hollow channel 6 is connected via a suitably formed fluid adapter 7 with a fluid pump 8, which is able to deliver a stored within a fluid reservoir 9 fluid along the hollow channel 6 metered.
  • the fluid pump 8 is followed by an analysis unit 10, with which it is possible to chemical substances within the fluid flow to
  • the fluid pump 8 is able to reverse the conveying direction.
  • an electrical means is provided in the proximal region of the hollow channel 6, which is preferably designed in the form of a pin or needle-shaped electrode 16, which projects locally into the hollow channel 6.
  • the electrode 16 is in suitably connected to a signal generator as well as signal detector 17 which generates electrical signals and detects bioelectric signals.
  • an electrolyte fluid stored in the fluid reservoir 9 is metered by means of the fluid pump 8.
  • Hollow channel opening 5 adjacent cell area slides, leading to cell stimulation.
  • an optical means 11 is mounted in the proximal region of the implant body 1, via the light L of a light source 12 attached externally to the implant body 1 along the otherwise rectilinearly formed hollow channel 6
  • the refractive index of the hollow channel inner wall is dimensioned smaller than the refractive index of the through the hollow channel. 6
  • Refractive index which is smaller than the refractive index by the
  • Hollow channel 6 is flowing fluid flow.
  • the hollow channel inner wall with a suitably selected material coating 13, see cross-sectional view according to Figure 1 b.
  • the implant body 1 shown in a highly schematic manner in FIG. 1 a can thus transmit both optical, electrical and also chemical material signals through the hollow channel 6, both for the purposes of artificial stimulation of neuronal signals and for their detection and detection.
  • Figure 3 is a longitudinal sectional view through a preferred
  • Embodiment of an implant body 1 shown in which a possibility for coupling and decoupling optical signals in and out of the hollow channel 6 is realized in a simple manner.
  • the implant body 1 encloses along its entire axial extent a rectilinear hollow channel 6 which is closed in a fluid-tight manner on the proximal side by a light-transparent coupling window 14.
  • a light-conducting medium adjoins, preferably in the form of an optical fiber 18, which is capable of coupling light L of a light source 12 into the channel 6 through the coupling window 14.
  • a semitransparent mirror 19 along the optical axis of
  • Optical fiber 18 mounted opposite to the Lichteinkoppelraumiques propagating light signals L 'in the direction of a light detector 15 diverts.
  • intracorporeal placement of the implant body 1 is indirectly or directly distally brought to the opening 5 of the hollow channel 6 to the plant.
  • Stimulation of the cell environment with electrical, optical and / or material stimulus signals may u.U. bio-optical light signals L 'emitted by the cells, which are formed via the light-conducting hollow channel 6 of the solution
  • Implantat body l are passed to an extracorporeal detector unit 15.
  • a flange 21 is attached to the implant body 1 in the proximal region of the hollow channel 6, to which a fluid adapter 7 in the form of a hollow conduit 22 fluid-tight connects, which is connected at least to a fluid reservoir 9 via a fluid pump 8 .
  • the delivery volume of the fluid pump 8 can be controlled controlled.
  • the conveying direction of the fluid pump 8 can be predetermined, so that for purposes of analysis of cell fluid or similar intracorporeal fluids, the conveying direction of the fluid pump 8 is oriented proximally adjustable.
  • the electrical means for coupling and also discharging electrical signals in and out of the hollow channel 6 in the form of an electrode 16 is attached, which is connected to a signal generator and detector 17 for generating and detecting electrical signals.
  • a signal generator and detector 17 for generating and detecting electrical signals.
  • an electrically conductive liquid for example.
  • a biocompatible electrolyte fluid In the form of a biocompatible electrolyte fluid.
  • FIG. 4 shows a further variant for the coupling and uncoupling of light signals L, L 'into and out of the hollow channel 6 of the implant body 1.
  • the hollow channel 6 extends essentially straight through the implant body 1, but has a in the proximal region of the implant body 1 Channel bend by 90 °.
  • Hollow channel 6 serves a light transparent coupling window 14, which in the
  • the coupling window 14 is centrally mounted in the region of the rectilinear channel axis A in the curvature region, so that the light L of a provided outside the composite body 1 light source 12 can be coupled directly axially along the hollow channel 6.
  • a semitransparent mirror 19 is further introduced, is directed via the outgoing from the hollow channel 6 through the coupling window 14 light L 'on a light-detecting unit 15, the resulting from the hollow channel 6 from the side of a cell light signals L 'to detect.
  • the fluid adapter 7 preferably in the form of a hollow conduit 22, the components 16, 17, 8, 23, 9, 10 explained in Figure 4.
  • the electrode 16 it is also suitable for the electrode 16 to integrate within the implant body. In order to avoid that the electrode 16 affects the light path along the hollow channel 6 towards the coupling window 14, it is advisable to provide the electrode 16 in the exemplary embodiment according to FIG. 4 in the region of the downwardly curved hollow channel.
  • the hollow channel 6 may be innwandig locally coated with a metal layer as the electrode surface, neither the fluid flow nor the light signal propagation along the hollow channel. 6 impaired.
  • the inner surface in the hollow channel 6 mounted electrode surface to be electrically connected to a signal generator / detector.
  • the implant body 1 with a plurality of such hollow channels 6, as illustrated in the embodiment of FIG 5a.
  • three hollow channels 6 are located separately next to each other within an implant body 1, each of which is individual
  • Hollow channel 6 can be filled with different liquid.
  • each hollow channel 6 is connected on the proximal side via a separate fluid adapter each with a fluid pump 8, an analyzer 0 and a fluid reservoir.
  • the hollow channel 6 has a curved in its distal region Channel section 6 ', so that the channel opening 5 has an opening axis A', which forms an angle of 90 ° with the channel axis A of the remaining hollow channel 6.
  • the curvature region 6 ' it is advantageous in the curvature region 6 'to provide a sealing element 23 in the hollow channel 6 so that the light signals L, L' can follow the course of the curvature region 6 'without losses.
  • FIG. 5c Shown is the distal region of the implant body, which is to be placed intracorporally with respect to a cell environment to be examined. To form the part of the implant body 1, not shown, the measures illustrated in the preceding figures are suitable.
  • a distal extension 1 'of the implant body 1 open the openings 5 of four each separately within the implant body 1 extending hollow channels 6, the channel axes each orthogonal to the associated
  • Opening axes are oriented. It is obvious that such a design allows any number of hollow channels within an implant body.
  • Implant body 1 can be chosen arbitrarily, preferably array-shaped. Furthermore, the proposed solution also allows a two-dimensional arrangement (arrays) with openings perpendicular to this plane. A three-dimensional
  • electrode surfaces 2 for dispensing as well as receiving can be provided in the immediate vicinity of the hollow channel opening 5 on the implant body be attached to electrical signals.
  • Each individual electrode surface 2 is connected to an integrated within the implant body 1 extending electrical supply or
  • FIG. 6a shows electrode surfaces 2 attached laterally to the hollow channel opening 5
  • FIG. 3b shows directly around the
  • Hollow channel opening 5 attached electrode surfaces 2. Also, both are
  • Both bioelectrical signals for cell stimulation distributed as well as bioelectrical signals generated by the cells can be picked up by the electrode surfaces 2 arranged distally on the implant body 1 and removed correspondingly for further evaluation. Due to the spatially close arrangement of the electrode surfaces 2 relative to the hollow channel opening 5 can
  • high-precision cell examinations may be performed in which cell-specific response signals delivered by the cell in the form of bioelectric, bio-optical or biochemical signals in response to corresponding artificially applied stimulation events can be detected and examined.

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  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
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Abstract

L'invention concerne un dispositif pour la stimulation et/ou la détection d'activités cellulaires dans un environnement de cellules biologiques, comprenant un corps d'implant biocompatible, qui peut être implanté temporairement ou de façon chronique dans l'environnement de cellules, et qui comprend au moins un canal creux qui est relié ou peut être relié indirectement ou directement sur le côté proximal à une pompe à fluide et qui présente une ouverture sur le côté distal. L'invention est caractérisée en ce que, sur ou dans le canal creux, est agencé un moyen optique au moyen duquel de la lumière peut être couplée dans le canal creux et/ou être découplée de ce canal, et en ce que, sur ou dans le canal creux, est disposé un moyen conducteur de l'électricité au niveau duquel il est possible d'appliquer et/ou de recevoir un signal électrique.
PCT/EP2013/000885 2012-04-04 2013-03-22 Dispositif pour la stimulation et/ou la détection d'activités cellulaires dans un environnement biologique de cellules WO2013149707A1 (fr)

Applications Claiming Priority (2)

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DE102012006953A DE102012006953A1 (de) 2012-04-04 2012-04-04 Vorrichtung zur Stimulierung und/oder Detektion von Zellaktivitäten innerhalb einer Zellenumgebung
DE102012006953.7 2012-04-04

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US20060217781A1 (en) * 2005-03-24 2006-09-28 John Michael S Systems and Methods for Treating Disorders of the Central Nervous System by Modulation of Brain Networks
US20120016261A1 (en) * 2009-03-20 2012-01-19 Nat. Univ. Corp. Toyohashi Univ. Of Technology Hollow microtube structure, production method thereof and biopsy device

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