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WO2011051401A1 - Sonde de mesure de stimulation in vivo - Google Patents

Sonde de mesure de stimulation in vivo Download PDF

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Publication number
WO2011051401A1
WO2011051401A1 PCT/EP2010/066392 EP2010066392W WO2011051401A1 WO 2011051401 A1 WO2011051401 A1 WO 2011051401A1 EP 2010066392 W EP2010066392 W EP 2010066392W WO 2011051401 A1 WO2011051401 A1 WO 2011051401A1
Authority
WO
WIPO (PCT)
Prior art keywords
probe
measuring
needle
measuring probe
electrical
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/EP2010/066392
Other languages
German (de)
English (en)
Inventor
Heinz Beck
Stefan Remy
Roland Krüppel
Manfred Lacher
Marion Bär
Sam Schmitz
Bernd Scheiding
Peter Holik
Michael Koch
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
FORSCHUNGSZENTRUM CAESAR
Rheinische Friedrich Wilhelms Universitaet Bonn
Life and Brain GmbH
Original Assignee
FORSCHUNGSZENTRUM CAESAR
Rheinische Friedrich Wilhelms Universitaet Bonn
Life and Brain GmbH
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 FORSCHUNGSZENTRUM CAESAR, Rheinische Friedrich Wilhelms Universitaet Bonn, Life and Brain GmbH filed Critical FORSCHUNGSZENTRUM CAESAR
Publication of WO2011051401A1 publication Critical patent/WO2011051401A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61B5/316—Modalities, i.e. specific diagnostic methods
    • A61B5/388—Nerve conduction study, e.g. detecting action potential of peripheral nerves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0601—Apparatus for use inside the body
    • 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
    • A61B5/4029—Detecting, measuring or recording for evaluating the nervous system for evaluating the peripheral nervous systems
    • A61B5/4041—Evaluating nerves condition
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/6848—Needles
    • A61B5/6849—Needles in combination with a needle set
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/0622—Optical stimulation for exciting neural tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00636—Sensing and controlling the application of energy
    • A61B2018/00773—Sensed parameters
    • A61B2018/00839—Bioelectrical parameters, e.g. ECG, EEG
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2503/00—Evaluating a particular growth phase or type of persons or animals
    • A61B2503/40—Animals
    • 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
    • A61B5/4058—Detecting, measuring or recording for evaluating the nervous system for evaluating the central nervous system
    • A61B5/4064—Evaluating the brain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0601—Apparatus for use inside the body
    • A61N2005/0612—Apparatus for use inside the body using probes penetrating tissue; interstitial probes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/063—Radiation therapy using light comprising light transmitting means, e.g. optical fibres
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/065—Light sources therefor
    • A61N2005/0651—Diodes

Definitions

  • the invention relates to an in vivo usable stimulation probe which preferably stimulates nerve cells with light in vivo and electrically measures the response of the stimulated nerve cell.
  • an electrode was described for optogenetic applications in which an electrode tip was generated by which both light can be applied and electrical signals can be measured
  • This application consists of a tapered optical fiber with a small aperture at the tip caused by gold plating, through which aperture illumination can be made in the near-field region, the measurement of electrical signals by gold plating i) not the measurement of single cell signals of multiple nerve cells in the exposed area, ii) not the measurement of signals in vivo, and iii) not the telemetric measurement of signals in vertebrates.
  • the invention provides a measuring probe, in particular a stimulation measuring probe, and a method for the targeted optical in vivo stimulation of at least one nerve cell, preferably several nerve cells.
  • the nerve cell pulses of the optically stimulated nerve cells can be measured electrically.
  • the measuring probe preferably has at least one (measuring) needle which is suitable for being introduced in vivo into a brain of a vertebrate or mammal.
  • the measuring needle has at least one electrical sensor or measuring contact, which serves for contacting with the nerve cell to be measured.
  • the measuring probe preferably has at least one light source with whose emitted light the at least one nerve cell can be optically stimulated.
  • the light source is not limited to a specific wavelength. Preferably, however, light from the visible range is used or from the area adjacent to the visible light. According to another preferred embodiment, the light may be monochromatic or approximately monochromatic.
  • the at least one sensor or measuring contact is preferably attached to the (pointed) or distal end of the measuring needle in order to bring the sensor or measuring contact directly into contact with the at least one nerve cell and to derive the electrical impulses of the nerve cell (s).
  • the at least one light source may also be attached directly to the electrical sensor on the needle tip.
  • the measuring probe may alternatively or additionally comprise optical means for directing the light emitted by a light source remote from the at least one measuring contact to the nerve cell.
  • optical fibers may be used alone or in combination with lenses for light conduction.
  • the measuring probe according to the invention is preferably designed so that the emitted light can substantially illuminate and thus optically stimulate the nerve cell to be derived from the electrical contact, and / or optically stimulate at least one nerve cell adjacent to the nerve cell, which can be derived with the electrical contact.
  • the probe also preferably has at least one of the following
  • Components comprising: a signal preamplifier for amplifying the electrical nerve cell signals detected by the electrical sensor, a microactuator for moving the measuring needle relative to the nerve cell, an electrical circuit for preprocessing the amplified electrical signals, and an electrical circuit for selectively controlling the light source.
  • the microactuator is used for positioning or fine positioning of the measuring needle within the brain.
  • a microactuator according to the invention can be, for example, as a microelectromotor, a piezomotor, a pneumatic / hydraulic drive or an actuator based on shape memory metals, wherein a transmission is preferably provided for transmitting an actuator movement to the needle, preferably a planetary gear.
  • the microactuator preferably allows a (translational) movement of the measuring needle relative to the brain of preferably up to 5 mm, wherein the relative movement preferably has an accuracy of about 5 ⁇ .
  • An electrical circuit provided on the measuring probe preferably has a device for preprocessing.
  • the analog nerve cell signals derived with the measuring transducers are already preprocessed within the measuring probe with an analog-to-digital converter (ADC).
  • ADC analog-to-digital converter
  • pre-amplifier can be arranged on the probe.
  • the measuring probe according to the invention has at least one, preferably a plurality of electrical sensors at the front end of the measuring needle. For digital processing, it may also be advantageous if the probe has 2 n sensors, where n can be any integer between 1 and 16.
  • the measuring probe according to the invention is preferably adapted in its dimensions to the object to be measured.
  • the measuring needle is preferably at least 2 mm long, and preferably at least 4 to 5 mm long.
  • the diameter of the measuring needle is preferably between 100 ⁇ and 400 ⁇ , preferably at about 250 ⁇ . If a light source is mounted remotely from the measuring needle on the measuring sensor and the light emitted by the light source is passed to the sensors, the diameter of the optical waveguide should also be made thin, preferably about 60 ⁇ to 300 ⁇ be, for example, 110 ⁇ .
  • the light can be emitted by any suitable light source. Due to the preferred small dimensions, however, it is preferred to use as the light source a photodiode or an LED, which preferably emits light in the wavelength range between 300 nm and 650 nm.
  • the measuring probe according to the invention is preferably intended for small vertebrates or mammals, wherein the vertebrate is preferably a mouse, rat, guinea pig or cat.
  • the dimensions and weight of the probe are designed to allow for in vivo introduction into a mouse, rat, guinea pig or cat brain, and the probe is small enough from mice, rats, guinea pigs, or both Cat to be born.
  • the probe can weigh between 0.5 g and 10 g.
  • the length of the probe is preferably 10-30 mm.
  • the diameter of the measuring probe is preferably between 4-10 mm.
  • the invention also relates to a system for optogenetic in vivo examination of nerve cells, which, in addition to the measuring probe according to the invention, also has a processing station which is separate from the measuring probe and preferably external (stationary).
  • the processing station serves to process the signals measured and preferably preprocessed by the measuring probe and / or to control the measuring probe.
  • the measuring probe In order for the measuring probe to be able to communicate with the processing station, the measuring probe preferably has a transmitter or transceiver in order to transmit the signals from the measuring probe, preferably digitally and preferably wirelessly, to the processing station.
  • a communication between the probe and the processing station can be unidirectional or bidirectional.
  • wireless communication for example, light, ultrasound and / or a radio frequency can be used as the carrier medium.
  • the system according to the invention may additionally have a measuring probe additional module which is designed separately from the measuring probe, but is electrically connected to the measuring probe and can be carried by the living vertebrate as a "backpack" on its back.
  • This additional module can have at least one of the following components: an electrical energy source for the electrical power supply of the measuring probe, a microcontroller for (pre-) processing of the signals emitted by the measuring probe, a storage medium for (intermediate) storage of the signals emitted by the measuring probe.
  • the processing station communicates with the probe via the probe add-on module, i. the wireless communication takes place between the processing station and the probe add-on module (backpack).
  • the invention also includes individual features in the figures, even though they are shown there in connection with other features and / or are not mentioned above or below.
  • the invention also includes embodiments with any combination of features mentioned or shown above or below various embodiments.
  • Fig. La is a perspective view of a component of an inventive
  • Fig. Lb is an enlarged view of the needle tip of the Invention according
  • FIG. 2 schematically shows preferred electronic components or functions of a system according to the invention with a measuring probe, a backpack and a processing station for a telemetric measurement;
  • traversing units shows a perspective view of a measuring probe according to the invention attached to a skull of a vertebrate animal;
  • Fig. 5 is an illustration of individual components of the inventive
  • an electrical in vivo measurement is combined with an optogenetic stimulation.
  • Optogenetic approaches allow the manipulation of the activities of specified subsets of neurons in an in vivo system.
  • the use of the in vivo optogenetic measuring probe can be used to study the function or the behavior of neurons in the case of pathological behavior such as epileptic seizures.
  • the measuring probe according to the invention is designed as a novel lightweight in-vivo measuring probe with which an electrically measuring nerve flows in response to a specific light stimulation can be performed in freely movable vertebrates (mice).
  • a plurality of electronic components are combined to form a measuring probe according to the invention, wherein the measuring probe itself is fastened on the upper side of the skull and the vertebrate is only slightly limited in its movement.
  • FIG. 1 shows a main component of a measuring probe 42 according to the invention with a measuring needle 10 embodied as a microneedle, which is introduced into a brain of a vertebrate for measuring the nerve cell currents.
  • a measuring needle 10 embodied as a microneedle
  • 16 measuring contacts are shown.
  • the measuring needle 10 At the proximal end of the measuring probe or the measuring needle 10 are bonding pads for contacting electronic circuit elements 30 and a light source in the form of a photodiode 20, which are arranged on a circuit board.
  • the light emitted by the photodiode 20 is passed through an optical waveguide 40 to the needle tip of the measuring needle and emitted in the vicinity of the electrical measuring contacts of the optical waveguide 40.
  • the measuring needle may preferably be produced by microtechnological / thin-film technology (MST, M (O) EMS).
  • the measuring needle is preferably embedded in a circuit board on which the electronic components for operating the measuring probe and the mechanical and optical actuators are bonded.
  • the measuring probe preferably has a housing in which an actuator (motor) and / or a preamplifier are arranged.
  • the housing of the measuring probe is fixedly attached to the skull of the test animal.
  • the measuring needle can be moved relative to the skull of the vertebrate, whereby an accurate and / or later positioning of the measuring contacts within the brain is possible.
  • an integrated signal preamplifier the electrical signals of the nerve cells derived from the measuring contacts can already be preprocessed within the measuring probe.
  • the measuring probe according to the invention is attached to the skull of the test animal, the dimensions and weight should be as low as possible.
  • further components for supplying energy to the measuring probe and / or for data transmission can likewise be carried by the vertebrate.
  • these further components are preferably carried in a probe addition module, preferably in the form of a "backpack", which is designed separately from the measuring probe, from the vertebrate.
  • the "backpack” contains at least one of the following components: battery, MikrokontroUer, analog-to-digital converter, memory and transmitter or transceiver.
  • the "backpack” is preferably connected via thin cables with the measuring probe according to the invention.
  • the "backpack” can also be implanted “encapsulated” under the skin.
  • FIG. 2 schematically shows the individual components of a system according to the invention with a measuring probe and a separate backpack, the measuring probe and / or the backpack preferably being carried by the vertebrate.
  • the system according to the invention preferably has an external processing station, which has a communication unit for communication with the measuring probe or the backpack.
  • the communication unit is in communication with a computer (personal computer, PC) on which software for data analysis (analysis software) and / or for control (control software) of the measuring probe is provided.
  • the probe according to the invention is attached to a "helmet", wherein essential components can not be attached directly to the probe according to the invention on the helmet, such as a motor and / or the probe with the board and the measuring needle and / or at least one preamplifier, optional with multiplexer.
  • a light source for example in the form of an LED, can either be mounted directly on the measuring probe board or on the helmet of the measuring probe.
  • unidirectional or bi-directional data exchange takes place between the "helmet" (and its components) and the backpack according to the invention, which is preferably carried by the living test animal, via at least one wire line.
  • the backpack preferably has an energy source and / or a processing device (for example in the form of a microcontroller) and / or a radio transmission device, preferably with an antenna.
  • a unidirectional or bidirectional data exchange preferably takes place wirelessly.
  • FIG. 4 shows a perspective view of a measuring probe according to the invention attached to a skull 100 of a vertebrate.
  • the housing of the measuring probe according to the invention is shown with an electric motor 50, which causes a translational movement of the measuring needle relative to the skull and thus allows a displacement of the measuring needle within the brain.
  • FIG. 5 shows individual components of a measuring probe according to the invention.
  • the housing 43 of the measuring probe is fastened via a base 45 to the head or head 100 of the vertebrate.
  • the motor is preferably releasably attached to the housing 43, for example by means of the retaining clip 44.
  • the motor 50 is connected to the circuit board 31 in such a way that the measuring needle 10 is displaceable relative to the housing 43 when the motor is actuated via an illustrated thread together with the circuit board 31. In other words, by the motor 50, the measuring needle 10 can be displaced relative to the housing in or within the brain of the experimental animal.
  • the invention also includes the exact or exact terms, features, numerical values or ranges, etc. when, above or below, these terms, features, numerical values or ranges are used in conjunction with terms such as, for example.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pathology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Surgery (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Medical Informatics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Physiology (AREA)
  • Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)

Abstract

L'invention concerne une sonde de mesure et un système pour la stimulation optique ciblée in vivo de cellules nerveuses et pour la mesure électrique d'impulsions de cellules nerveuses. La sonde de mesure comprend au moins une aiguille de mesure à insertion in vivo motorisée et commandée automatiquement dans le cerveau d'un vertébré, au moins un capteur de mesure électrique étant monté sur l'aiguille pour l'établissement d'un contact avec au moins une cellule nerveuse du cerveau afin d'en mesurer l'activité. La sonde de mesure comprend également au moins une source lumineuse dont la lumière émise peut stimuler optiquement la cellule nerveuse.
PCT/EP2010/066392 2009-10-29 2010-10-28 Sonde de mesure de stimulation in vivo Ceased WO2011051401A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102009051276.4 2009-10-29
DE102009051276A DE102009051276A1 (de) 2009-10-29 2009-10-29 In-Vivo Stimulations-Messsonde

Publications (1)

Publication Number Publication Date
WO2011051401A1 true WO2011051401A1 (fr) 2011-05-05

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Application Number Title Priority Date Filing Date
PCT/EP2010/066392 Ceased WO2011051401A1 (fr) 2009-10-29 2010-10-28 Sonde de mesure de stimulation in vivo

Country Status (2)

Country Link
DE (1) DE102009051276A1 (fr)
WO (1) WO2011051401A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013093463A3 (fr) * 2011-12-20 2013-08-22 Mled Limited Dispositif médical intégré

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102012110358B4 (de) 2012-10-30 2016-04-07 Leibniz-Institut für Neurobiologie Magdeburg Mikroelektrodenarray

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002013906A1 (fr) * 2000-08-16 2002-02-21 Vanderbilt University Procédés et dispositifs de stimulation optique de tissus nerveux
US20040102828A1 (en) * 2002-11-27 2004-05-27 Lowry David Warren Methods and systems employing intracranial electrodes for neurostimulation and/or electroencephalography
WO2006055582A2 (fr) * 2004-11-15 2006-05-26 Christopher Decharms Applications utilisant de la lumiere pour stimuler un tissu nerveux
US20070060984A1 (en) * 2005-09-09 2007-03-15 Webb James S Apparatus and method for optical stimulation of nerves and other animal tissue
US20080077198A1 (en) * 2006-09-21 2008-03-27 Aculight Corporation Miniature apparatus and method for optical stimulation of nerves and other animal tissue
US20080171948A1 (en) * 2007-01-11 2008-07-17 Broder Sidney M Subdermal needles
WO2009067592A1 (fr) * 2007-11-20 2009-05-28 Neurometrix, Inc. Électrode à aiguille jetable avec identification, et interface de connecteur modifiable
US20090222067A1 (en) * 2008-03-03 2009-09-03 Richard Toselli Endoscopic delivery of red/nir light to the substantia nigra to treat parkinson's disease

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002013906A1 (fr) * 2000-08-16 2002-02-21 Vanderbilt University Procédés et dispositifs de stimulation optique de tissus nerveux
US20040102828A1 (en) * 2002-11-27 2004-05-27 Lowry David Warren Methods and systems employing intracranial electrodes for neurostimulation and/or electroencephalography
WO2006055582A2 (fr) * 2004-11-15 2006-05-26 Christopher Decharms Applications utilisant de la lumiere pour stimuler un tissu nerveux
US20070060984A1 (en) * 2005-09-09 2007-03-15 Webb James S Apparatus and method for optical stimulation of nerves and other animal tissue
US20080077198A1 (en) * 2006-09-21 2008-03-27 Aculight Corporation Miniature apparatus and method for optical stimulation of nerves and other animal tissue
US20080171948A1 (en) * 2007-01-11 2008-07-17 Broder Sidney M Subdermal needles
WO2009067592A1 (fr) * 2007-11-20 2009-05-28 Neurometrix, Inc. Électrode à aiguille jetable avec identification, et interface de connecteur modifiable
US20090222067A1 (en) * 2008-03-03 2009-09-03 Richard Toselli Endoscopic delivery of red/nir light to the substantia nigra to treat parkinson's disease

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
J. ZHANG ET AL: "Integrated device for optical stimulation and spatiotemporal electrical recording of neural acivity in light-sensitized brain tissue", JOURNAL OF NEURAL ENGINEERING, vol. 6, 055007, 6 May 2009 (2009-05-06) - 1 September 2009 (2009-09-01), pages 1 - 13, XP002614417 *
ZHANG ET AL., J. NEURAL ENG., vol. 6, no. 055007, 2009, pages 13

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013093463A3 (fr) * 2011-12-20 2013-08-22 Mled Limited Dispositif médical intégré
US10694953B2 (en) 2011-12-20 2020-06-30 Facebook Technologies, Llc Integrated medical device

Also Published As

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