U.S. patent application number 14/439810 was filed with the patent office on 2015-10-15 for microelectrode array for an electrocorticogram.
This patent application is currently assigned to Leibniz-Institut fur Neurobiologie. The applicant listed for this patent is GOOGLE INC.. Invention is credited to Martin Deckert, Soren Hirsch, Michael Lippert, Frank Ohl, Bertram Schmidt.
Application Number | 20150289778 14/439810 |
Document ID | / |
Family ID | 49515358 |
Filed Date | 2015-10-15 |
United States Patent
Application |
20150289778 |
Kind Code |
A1 |
Ohl; Frank ; et al. |
October 15, 2015 |
MICROELECTRODE ARRAY FOR AN ELECTROCORTICOGRAM
Abstract
A first plurality of images of a scene may be captured. Each
image of the first plurality of images may be captured using a
different TET. Based at least on the first plurality of images, a
long TET, a short TET, and a TET sequence that includes the long
TET and the short TET may be determined. A second plurality of
images of the scene may be captured. The images in the second
plurality of images may be captured sequentially in an image
sequence using a sequence of TETs corresponding to the TET
sequence. Based on one or more images in the image sequence, an
output image may be constructed.
Inventors: |
Ohl; Frank; (Osterweddingen,
DE) ; Lippert; Michael; (Leipzig, DE) ;
Hirsch; Soren; (Wusterwitz, DE) ; Schmidt;
Bertram; (Villingen-Schwenningen, DE) ; Deckert;
Martin; (Magdeburg, DE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
GOOGLE INC. |
Mountain View |
CA |
US |
|
|
Assignee: |
Leibniz-Institut fur
Neurobiologie
Magdeburg
DE
Otto-Von-Guericke-Universitat
Magdeburg
DE
|
Family ID: |
49515358 |
Appl. No.: |
14/439810 |
Filed: |
October 29, 2013 |
PCT Filed: |
October 29, 2013 |
PCT NO: |
PCT/US2013/072638 |
371 Date: |
April 30, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
13713734 |
Dec 13, 2012 |
9087391 |
|
|
14439810 |
|
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Current U.S.
Class: |
600/301 ;
600/378; 600/476; 600/544 |
Current CPC
Class: |
H04N 5/2355 20130101;
A61B 5/0084 20130101; G06T 5/50 20130101; A61N 2005/0653 20130101;
A61N 5/0622 20130101; G06T 2207/20221 20130101; A61B 5/6868
20130101; A61B 5/0478 20130101; A61B 5/04001 20130101; A61N 1/0529
20130101; A61N 5/0601 20130101; H04N 5/35554 20130101; G06T
2207/10144 20130101; A61B 2562/028 20130101; A61N 2005/0652
20130101; A61B 5/6849 20130101; A61B 2562/0209 20130101; A61B 5/686
20130101; A61B 5/0484 20130101; A61B 5/01 20130101 |
International
Class: |
A61B 5/0478 20060101
A61B005/0478; A61N 5/06 20060101 A61N005/06; A61B 5/00 20060101
A61B005/00; A61N 1/05 20060101 A61N001/05; A61B 5/0484 20060101
A61B005/0484; A61B 5/01 20060101 A61B005/01 |
Claims
1. A microelectrode array comprising a multiplicity of electrodes
for electrically measuring brain waves and comprising an integrated
optical stimulation unit for stimulating brain regions with optical
signals, wherein the stimulation unit has one or a plurality of
electrical light sources.
2. The microelectrode array as claimed in claim 1, wherein the
microelectrode array has a filmlike, thin substrate, wherein the
electrodes are arranged in a manner distributed over the areal
extent of the substrate on the surface of the substrate or in the
substrate.
3. The microelectrode array as claimed in claim 1, wherein the
microelectrode array has a filmlike, thin substrate, wherein a
multiplicity of electrical light sources of the stimulation unit
are arranged in a manner distributed over the areal extent of the
substrate on the surface of the substrate or in the substrate.
4. The microelectrode array as claimed in claim 1, wherein the
electrical light source or the electrical light sources is/are
arranged according to a fixed, predefined scheme relative to the
electrodes and is/are distributed over the areal extent of the
substrate.
5. The microelectrode array as claimed in claim 1, wherein the
substrate comprises or consists of an at least partly transparent
film material.
6. The microelectrode array as claimed in claim 1, wherein
electrically conductive structures are formed on the surface of the
substrate or in the substrate, said electrically conductive
structures forming electrodes, electrical connection lines to the
electrodes and/or electrical connection lines to the electrical
light source or the electrical light sources.
7. The microelectrode array as claimed in claim 1, wherein the
microelectrode array has a sensor side, which is designed to be
brought into contact with the brain surface of a living being to be
examined, wherein one, a plurality or all of the electrical light
sources are arranged at a greater distance from the sensor side
than the electrodes.
8. The microelectrode array as claimed in claim 1, wherein one, a
plurality or all of the electrical light sources is/are arranged as
SMD components, as dies or as thin-film elements on the substrate
or within the substrate.
9. The microelectrode array as claimed in claim 1, wherein one, a
plurality or all of the electrical light sources is/are embodied as
light emitting diodes, in particular as inorganic or organic light
emitting diodes (OLEDs).
10. The microelectrode array as claimed in claim 1, wherein the
microelectrode array has a sensor side which is designed to be
brought into contact with the brain surface of a living being to be
examined, wherein at least the sensor side of the microelectrode
array is electrically and biologically passivated.
11. The microelectrode array as claimed in claim 1, wherein one, a
plurality or all of the electrodes is/are integrated into the
material of the substrate and the substrate, on a sensor side
designed to be brought into contact with the brain surface of a
living being to be examined, has openings leading to the integrated
electrodes.
12. The microelectrode array as claimed in claim 1, wherein one, a
plurality or all of the electrodes is/are embodied as ECoG
electrodes.
13. The microelectrode array as claimed in claim 1, wherein the
microelectrode array has one or a plurality of stimulation
electrodes for stimulating brain regions with electrical
signals.
14. The microelectrode array as claimed in claim 13, wherein one or
a plurality of electrodes for electrically measuring brain waves
is/are simultaneously stimulation electrodes for stimulating brain
regions with electrical signals.
15. The microelectrode array as claimed in claim 1, wherein in each
case one or a plurality of further electrical and/or electronic
components, in particular sensor components, is/are arranged in
relative proximity to one, a plurality or all of the electrical
light sources.
16. The microelectrode array as claimed in claim 15, wherein in
each case one or a plurality of further electrical and/or
electronic sensor components, each of which outputs an electrical
sensor signal, is/are arranged in relative proximity to one, a
plurality or all of the electrical light sources in such a way that
at least one physical variable influenced by the electrical light
source or the electrical light sources is detectable by the
respective sensor component.
17. The microelectrode array as claimed in claim 16, wherein one, a
plurality or all of the electrical light sources have one or a
plurality of sensor components assigned to the respective light
source, each of which sensor components outputs an electrical
sensor signal which is assignable to the influenced physical
variable of a specific light source.
18. The microelectrode array as claimed in claim 16, wherein one, a
plurality or all of the sensor components is/are embodied as
temperature sensors.
19. The microelectrode array as claimed in claim 16, wherein one, a
plurality or all of the sensor components is/are embodied as
light-sensitive sensors.
20-31. (canceled)
32. A device comprising a microelectrode array as claimed in claim
1 and at least one electronic control device, wherein the
electronic control device is coupled to one, a plurality or all of
the electrical and/or electronic components of the microelectrode
array.
33-35. (canceled)
Description
[0001] The invention relates to a microelectrode array comprising a
multiplicity of electrodes for electrically measuring brain waves
as claimed in claim 1.
[0002] There are already approaches for miniaturizing electrodes
for measuring brain waves in particular in the form of so-called
microelectrode arrays. In this case, the term array denotes an
arrangement of a multiplicity of electrodes which can be arranged
regularly or irregularly, e.g. in a matrix arrangement. Such
electrodes or such microelectrode arrays can be used to record
electrical signals of the brain of a living being, measurements
being possible both on the brain surface and within the brain. In
particular, an electrocorticogram (ECoG), can be recorded using
such microelectrode arrays.
[0003] Moreover, there are developments in the field of so-called
"optogenetics", involving the use of light to stimulate neurons in
the brain, provided that they express specific light-sensitive
channel proteins. The light required for the stimulation is
typically radiated into the brain from outside through optical
fibers or light emitting diodes (LEDs) mounted on the skull.
[0004] A number of problems arise here, namely that the
implantation of the light source and of the microelectrode array
takes up a great deal of room spatially, the experimental objects
are linked to external technology by means of an optical waveguide
and the exact spatial alignment of the light source and the
individual electrodes with respect to one another is difficult. The
entire implantation process is relatively complicated owing to the
need for a plurality of steps and technologies.
[0005] The invention is based on the object of simplifying
this.
[0006] The object is achieved as claimed in claim 1 by means of a
microelectrode array comprising a multiplicity of electrodes for
electrically measuring brain waves and comprising an integrated
optical stimulation unit for stimulating brain regions with optical
signals, wherein the stimulation unit has one or a plurality of
electrical light sources. One advantage of the invention is that
the electrical light source or the electrical light sources is/are
integrated into the microelectrode array and therefore need not be
positioned and implanted as separate parts. The electrical
contacting is also simplified since common lines, e.g. in the form
of a ribbon cable, can be used. A further advantage of the
invention is that the electrical light source or the electrical
light sources is/are spatially fixed and exactly positioned in
relation to the electrodes, wherein the exact positioning is
already predefined by the production of the microelectrode array.
Therefore, the microelectrode array according to the invention is
significantly more application-friendly than known devices. The
invention makes it possible for cortical neurons to be optically
stimulated spatially precisely and in a structured fashion with the
aid of one or a plurality of integrated electrical light sources
and at the same time for the thereby triggered and spontaneous
brain waves to be derived electrophysiologically through the
microstructured electrodes.
[0007] A further advantage is that there is the possibility of
stimulating brain regions with different spatial patterns, for
example in order to measure and stimulate topographical relations
in the brain, e.g. for tonotopy, somatotopy, retinotopy.
[0008] In accordance with one advantageous development of the
invention, the microelectrode array has a filmlike, thin substrate.
The substrate can be a flexible substrate, in particular. Suitable
materials for producing the substrate are e.g. films composed of
polyimide, parylene, polydimethylsiloxane (PDMS) or polyurethane.
It is advantageous, in particular, to use an optically sufficiently
transparent material, e.g. a film material, for the substrate, such
that the light emitted by the electrical light sources can
penetrate through the substrate. The substrate can be constructed
from the same or different materials in particular in a
multilayered fashion, e.g. in the manner of a sandwich
structure.
[0009] In accordance with one advantageous development of the
invention, the electrodes are arranged in a manner distributed over
the areal extent of the substrate on the surface of the substrate
or in the substrate. The electrodes can be embodied e.g. as
electrically conductive coating, e.g. as metal coating, on the
surface of the substrate or as metal layer in the substrate. In
accordance with one advantageous development of the invention, a
multiplicity of electrical light sources of the stimulation unit
are arranged in a manner distributed over the areal extent of the
substrate on the surface of the substrate or in the substrate.
[0010] The electrical light sources can be embodied in particular
as light emitting diodes, wherein inorganic light emitting diodes
or organic light emitting diodes (OLEDs) can be employed, including
in combination with one another. Furthermore, the electrical light
source or the electrical light sources can be integrated into the
construction of the microelectrode array as phosphorescent organic
light emitting diodes (PHOLEDs) or can be used in combination with
the abovementioned light sources. The improved efficiency of the
PHOLEDs in comparison with other light sources is advantageous
since, for the same light intensity, a reduced evolution of heat is
induced and the risk of tissue damage or damage to brain regions as
a result of heating is reduced.
[0011] In accordance with one advantageous development of the
invention, it is provided that the electrical light source or the
electrical light sources is/are arranged according to a fixed,
predefined scheme relative to the electrodes and is/are distributed
over the areal extent of the substrate. A fixedly predefined
assignment between the electrodes and the electrical light sources
is predefined as a result, such that the stimulation--recorded via
the electrodes--of the neurons by means of the electrical light
sources can be unambiguously assigned in individual stimulation
signals, such that an unambiguous correlation can be
determined.
[0012] In accordance with one advantageous development of the
invention, electrically conductive structures are formed on the
surface of the substrate or in the substrate, said electrically
conductive structures forming the electrodes, electrical connection
lines to the electrodes and/or electrical connection lines to the
electrical light source or the electrical light sources. This has
the advantage that the electrically conductive structures, e.g. in
the form of one or a plurality of metal layers, can be directly
embedded in the substrate or can be applied thereto, e.g. can be
applied by vapor deposition.
[0013] The electrically conductive structures can be provided e.g.
in the form of one or a plurality of metallization planes in the
substrate. The metallization plane or the metallization planes
forming the electrodes and/or connection lines can be used directly
for the power supply of the light sources. An additional, if
appropriate thicker and/or structured metal layer can also be
provided for the purpose of power supply in the microelectrode
array.
[0014] In accordance with one advantageous development of the
invention, the microelectrode array has a sensor side, which is
designed to be brought into contact with the brain surface of a
living being to be examined. In this case, one, a plurality or all
of the electrical light sources can advantageously be arranged at a
greater distance from the sensor side than the electrodes. This
enables the light sources to be accommodated expediently. In
particular, it is possible to arrange one, a plurality or all of
the electrical light sources on that surface of the substrate which
faces away from the sensor side. Furthermore, the advantageous
arrangement of the electrical light source or of the electrical
light sources at a relative distance from the sensor side makes it
possible to reduce the heat input into the stimulated brain
regions, in order to prevent tissue damage.
[0015] The electrical light sources can be arranged in particular
as SMD components, as dies or as thin-film elements on the
substrate or within the substrate.
[0016] In accordance with one advantageous development of the
invention, at least the sensor side of the microelectrode array is
electrically and biologically passivated. Undesirable reciprocal
effects with the brain tissue are avoided as a result. The
passivation can be embodied e.g. as insulation layer.
[0017] In accordance with one advantageous development of the
invention, the electrodes are integrated into the material of the
substrate, e.g. embedded therein. The substrate then has, on a
sensor side designed to be brought into contact with the brain
surface of a living being to be examined, openings leading to the
electrodes. As a result, the electrical contact to the electrodes
can be produced even with electrodes integrated into the material
of the substrate. The integration of the electrodes into the
substrate has the advantage that they are arranged in a
space-saving fashion therein and are better protected against
damage.
[0018] In accordance with one advantageous development of the
invention, one, a plurality or all of the electrodes is/are
embodied as ECoG electrodes.
[0019] In accordance with one advantageous development of the
invention, the microelectrode array has one or a plurality of
stimulation electrodes for stimulating brain regions with
electrical signals. This has the advantage that a stimulation is
additionally possible by means of electrical signals that are
transferred to brain regions directly galvanically. The
microelectrode array can thus also carry out combined stimulations
with optical and electrical signals. The application possibilities
for the microelectrode array are extended as a result.
[0020] In accordance with one advantageous development of the
invention, one or a plurality of electrodes for electrically
measuring brain waves is/are simultaneously stimulation electrodes
for stimulating brain regions with electrical signals. In this
case, one advantage is that the microelectrode array can be
embodied with a multiplicity of electrodes and the latter are
optionally used as measuring electrodes or as stimulation
electrodes. In accordance with one advantageous development of the
invention, electrodes are used at times for electrically measuring
brain waves and at times as stimulation electrodes for stimulating
brain regions with electrical signals. The function of the
respective electrode can be correspondingly controlled by means of
control electronics.
[0021] In accordance with one advantageous development of the
invention, in each case one or a plurality of further electrical
and/or electronic components, in particular sensor components,
is/are arranged in relative proximity to one, a plurality or all of
the electrical light sources. This has the advantage that, by means
of the further electrical and/or electronic component(s), depending
on the embodiment thereof, further possibilities for influencing
the tissue or brain regions are possible or, if sensor components
are involved, further data can be acquired. In this regard, a
further electrical and/or electronic component or a group of such
components can be assigned in each case to an electrical light
source and be arranged in proximity thereto, e.g. alongside the
light source or in a manner distributed around the light
source.
[0022] In accordance with one advantageous development of the
invention, in each case one or a plurality of further electrical
and/or electronic sensor components, each of which outputs an
electrical sensor signal, is/are arranged in relative proximity to
one, a plurality or all of the electrical light sources in such a
way that at least one physical variables influenced by the
electrical light source or the electrical light sources are
detectable by the respective sensor component. This has the
advantage that such sensor components can monitor physical
variables influenced by the light sources such as e.g. the light
which is emitted by the respective light source and which can be
detected directly on site, if appropriate taking account of
reflection and/or absorption properties of the brain tissue. Other
physical variables influenced by the electrical light sources such
as e.g. the local temperature, can also be detected. The data
detected by the sensor components can be displayed on a display
unit, for example, and thus be monitored visually. Automatic
monitoring for compliance with permissible limit values can also be
carried out, e.g. in such a way that, in the event of specific
limit values being exceeded or undershot, an indication signal to
the user is generated automatically. Moreover, it is advantageously
possible to use the detected sensor signals in turn for influencing
the light sources or the light emitted thereby, such that the light
sources can be controlled depending on the sensor signals. It is
also possible to realize a complete regulating circuit for
regulating the electrical light sources depending on sensor signals
of the electrical and/or electronic sensor components. In this
case, the light sources can be controlled and/or regulated e.g. by
variation of electrical parameters such as current and/or voltage.
The electrical parameters can also be influenced by means of pulsed
signals, the duty ratio of which is varied.
[0023] In accordance with one advantageous development of the
invention, one, a plurality or all of the electrical light sources
have one or a plurality of sensor components assigned to the
respective light source, each of which sensor components outputs an
electrical sensor signal which is assignable to the influenced
physical variable of a specific light source. Such a possibility of
assigning the physical variable influenced by the light source to
the light source makes it possible to carry out an independent,
differentiated control and/or regulation of the respective
individual light source in a targeted manner, which is advantageous
particularly in the case of a large number of electrical light
sources.
[0024] In accordance with one advantageous development of the
invention, one, a plurality or all of the sensor components is/are
embodied as temperature sensors. This has the advantage that the
local temperature in the tissue or in brain regions can be
measured. In particular, it is possible to carry out a measurement
of the temperature increase brought about by the light source or
the light sources in the tissue or in the brain regions. In
conjunction with the abovementioned control and/or regulation of
the light source, it can be ensured that the temperature increase
caused by the light sources is kept within limits such that damage
to the tissue is avoided. The temperature increase can thus be
restricted to permissible limit values by means of regulation
technology.
[0025] Heating of stimulation electrodes, e.g. caused by the light
sources, can also be detected by means of such temperature
sensors.
[0026] Such temperature sensors can be embodied as meanders, for
example, and the temperature dependence of the electrical
resistance of the metallization can be utilized as measurement
principle. The temperature sensors can be produced from platinum,
for example, wherein the electrodes of the microelectrode array can
also be produced from platinum. Other embodiments of temperature
sensors are also usable.
[0027] The advantage of the integration of temperature sensors is
based on the temperature measurements simultaneously with the
stimulation of brain regions with optical signals in relative
proximity to the electrical light source or the electrical light
sources, in order to monitor and/or prevent the risk of tissue
damage or damage to brain regions as a result of impermissible
heating.
[0028] In accordance with one advantageous development of the
invention, one, a plurality or all of the sensor components is/are
embodied as light-sensitive sensors. In principle, all known types
of light-sensitive sensors can be used for this purpose, such as
e.g. light-sensitive resistors or photodiodes. Inorganic and/or
organic photodiodes are particularly advantageous since they are
readily integratable into the microelectrode array. The use of such
light-sensitive sensors as further sensor components of the
microelectrode array has the advantage that a simultaneous
measurement of the light intensity of the stimulating optical
signals becomes possible, which enables the correlation of the
light intensity applied for stimulating cortical neurons or the
brain regions with the neuronal activity recorded via the
electrodes. Corresponding computer-aided evaluation of the signals
of the electrodes and the signals of the light-sensitive sensors
makes it possible to determine corrected electrode signals from
which undesirable side effects such as e.g. shadings of light
sources or reflections of the emitted light have been eliminated.
At the same time, it is possible to determine the absorption and
the scattering of the stimulating optical signals by cortical
tissue. In conjunction with the abovementioned control and/or
regulation of the electrical light sources depending on the sensor
signals, it is also possible to carry out an automatic correcting
function of the light emission of the light sources to desired
light emission values by means of the sensor signals being checked
to ascertain whether the desired light emission values of the light
sources are achieved and, if this is not the case, a corrective
intervention being carried out by control and/or regulation of the
electrical light sources.
[0029] The above-mentioned control and/or regulation functions can
advantageously be realized by an electronic control unit which
carries out the control and/or regulation functions in terms of
hardware and/or by software control, e.g. using a microprocessor or
microcontroller.
[0030] In accordance with one advantageous development of the
invention, the further electrical and/or electronic components are
arranged according to a fixed, predefined scheme relative to the
light sources and are arranged in a manner distributed over the
areal extent of the substrate on the surface of the substrate or in
the substrate. This enables e.g. an area-covering sensor-based
detection of variables over the entire microelectrode array.
[0031] In accordance with one advantageous development of the
invention, electrically conductive structures are formed on the
surface of the substrate or in the substrate, said electrically
conductive structures forming electrical connection lines to the
further electrical and/or electronic component or to the further
electrical and/or electronic components. In this way, e.g. the
temperature sensors and/or the light-sensitive sensors can be
electrically contacted without external lines. The electrical
connection lines can be realized e.g. in the same way as in the
case of the electrical light sources.
[0032] Direct embedding of electrical connection lines in the
substrate can be carried out e.g. by deposition of metallic
materials e.g. by cathode sputtering. Such embedding of the
electrical connection lines on the substrate increases the degree
of integration and thus allows an extended functionality of the
microelectrode array, e.g. for temperature measurement and
measurement of the light intensity, without structural
enlargement.
[0033] The electrically conductive structures, embodied e.g. as
metallization planes, can thus be used e.g. directly for the power
supply of the temperature sensor or of the temperature sensors
and/or of the light-sensitive sensor or of the light-sensitive
sensors. It is advantageous here for the number of
function-integrating metallization planes not to be chosen to be
excessively large, e.g. for only one metallization plane to be
used. As a result, it is possible to improve the achievable
mechanical flexibility with low stiffness of the microelectrode
array, whereby an improved adaptability of the microelectrode array
to the topography of the brain surface is made possible at the same
time.
[0034] In accordance with one advantageous development of the
invention, one, a plurality or all of the further electrical and/or
electronic components are arranged as SMD components, as dies or as
thin-film elements on the substrate or within the substrate. This
has the advantage that the electrical and/or electronic components
are arranged in a space-saving fashion on or in the substrate and
can be better protected against damage. Bringing one, a plurality
or all of the electrical and/or electronic components, in
particular the sensor components such as the temperature sensors,
near to the sensor side in the substrate allows the detection of
physical variables, in particular a temperature measurement, which
has a high degree of correlation with actual physical variables of
stimulated brain region.
[0035] In accordance with one advantageous development of the
invention, the microelectrode array has a receiving apparatus for
wirelessly receiving electromagnetic waves emitted onto the
microelectrode array. The microelectrode array is wirelessly
suppliable with the electrical energy required for its operation
via the receiving apparatus and/or a rechargeable battery of the
microelectrode array is wirelessly chargeable via the receiving
apparatus. The receiving apparatus can be embodied e.g. as a coil
which is provided on the substrate or within the substrate and
which is formed e.g. from the material of the electrically
conductive structures from which the already mentioned electrical
connection lines to the light sources or the other electrical
and/or electronic components can be formed. This has the advantage
that there is no need for any cable connection for supplying the
microelectrode array with electrical energy. Instead, e.g. an
energy transmitting coil embedded into a flexible mat can be placed
externally onto the skin surface or the hair of a patient and the
microelectrode array can be wirelessly supplied with electrical
energy by said coil by means of a radio-frequency signal via the
receiving apparatus. A rechargeable battery possibly present in the
microelectrode array can also be charged thereby. By way of
example, provision can be made of a rechargeable battery of the
lithium polymer type in the form of a flat layer in the
microelectrode array.
[0036] In accordance with one advantageous development of the
invention, the microelectrode array has a wirelessly operating
signal transfer device designed for wirelessly transferring
signals, in particular in the form of data, from the microelectrode
array to a signal receiving device and/or for wirelessly
transferring signals, in particular in the form of data, from a
signal transmitting device to the microelectrode array. This has
the advantage that there is no need for any cable connections for
the signal transfer and/or the data transfer. The signal transfer
device can be designed e.g. according to one of the known
standards, e.g. as a Bluetooth signal transfer device. The use of
such cable-free connections allows the reduction of the risk of
inflammation after the microelectrode array has been implanted. The
advantage is based on the omission of cable feedthroughs, such as
e.g. ribbon cables, through the scalp. In particular, the risk of
infection can also be reduced as a result. The required electronic
components, e.g. amplifiers, impedance converters, filters,
multiplexers, analog/digital converters, energy stores, can be
wholly or partly combined e.g. in an application specific
integrated circuit (ASIC).
[0037] In accordance with one advantageous development of the
invention one, a plurality or all of the electrodes is/are
integrated in a respectively elevated column structure which spaces
apart the individual electrodes on the sensor side from the
substrate plane. This has the advantage that the electrodes on the
sensor side can project somewhat from the substrate and can thus be
led better or with greater sealing to positions to be sensed on the
brain surface. Furthermore, it is thereby possible to increase the
distance between the electrical light sources and the brain
surface, such that the heat input into the brain surface is
reduced. The microtechnological fabrication of the column
structures can implement e.g. lithographic masking and wet-chemical
patterning of a metallic hard mask, wherein the structure transfer
to the substrate is realized with the aid of a dry etching process,
for example. The use of a thicker substrate film and/or the
progressive deposition of a plurality of substrate thin-film layers
allows the production of column structures having varying
dimensions. Capillary blood vessels and biological structures on
the brain surface which impose limits on bringing planar
microelectrode arrays near to the brain surface can be overcome by
such elevated column structures. In this case, the flexible
substrate material allows local bypassing of biological structures.
The advantage of such electrode structures is accordingly based on
bringing the electrodes near to the brain surface without
penetrating the latter, and results in an improved spatial
resolution of derivation and stimulation. A further advantage is
that the three-dimensional column structures prevent implanted
microelectrode arrays from slipping.
[0038] In accordance with one advantageous development of the
invention, one, a plurality or all of the column structures is/are
produced from the substrate material. This allows an efficient
production process for the microelectrode array. Furthermore,
biological compatibility is still afforded since no further
materials are required.
[0039] In accordance with one advantageous development of the
invention, one, a plurality or all of the column structures
has/have a respectively circumferential sealing lip which laterally
delimits the active electrode area of the electrode integrated into
the column structure. In this case, the substrate can in turn have
on the sensor side openings which lead to the electrodes and which
expose the active electrode areas. The circumferential sealing lips
separate the electrode areas from the surrounding cerebrospinal
fluid, prevent compensation currents between the electrodes and
produce the direct contact with the brain surface. This ensures the
highest possible spatial resolution and best signal-to-noise ratios
of such non-penetrating microelectrode arrays.
[0040] In accordance with one advantageous development of the
invention, through openings are arranged in the substrate of the
microelectrode array, said through openings being suitable for
allowing the diffusion of pharmacological substances into the
tissue and/or for introducing one or a plurality of penetrating
depth electrodes into the tissue. The through openings are
advantageously arranged at positions at which the electrodes, the
electrical light sources or the other electrical and/or electronic
components of the microelectrode array are precisely not arranged.
In this regard, the through openings can be arranged e.g. in
proximity to the electrodes, the electrical light source or the
electrical light sources, the further electrical and/or electronic
component or components in the substrate. The through openings
allow e.g. pharmacological substances e.g. for optogenetic
applications to be introduced into the tissue. One or a plurality
of penetrating depth electrodes can also be introduced into the
cortical tissue. The application possibilities of the
microelectrode array are fundamentally extended as a result. At the
same time, the through openings bring about capillary effects that
advantageously influence the suction of the microelectrode array to
the brain surface and the displacement of surrounding cerebrospinal
fluid.
[0041] In accordance with one advantageous development of the
invention, a plurality or all of the through openings are arranged
in a manner distributed over the areal extent of the substrate
according to a fixed, predefined pattern.
[0042] In accordance with one advantageous development of the
invention, one or a plurality of depth electrodes or at least one
depth electrode array for simultaneously electrically measuring
brain waves of deeper brain regions and/or electrically and
optically stimulating deeper brain regions is/are inserted into the
through openings. A depth electrode array is understood to mean an
arrangement of depth electrodes which are arranged on a common
carrier at fixed positions with respect to one another. The
application possibilities of the microelectrode array are
fundamentally extended as a result. This has the advantage that the
signal space can be enlarged on account of the depth information
and it is possible to ascertain corresponding correlations in
derivation and stimulation.
[0043] The object mentioned in the introduction is furthermore
achieved by means of a device comprising a microelectrode array of
the type explained above and at least one electronic control
device, wherein the electronic control device is coupled to one, a
plurality or all of the electrical and/or electronic components of
the microelectrode array. In particular, the electronic control
device can be coupled to the electrodes of the microelectrode
array, the electrical light sources, further electrical and/or
electronic components and/or the depth electrodes. The electronic
control device can be wholly or partly integrated into the
microelectrode array. On account of the structural size of
present-day electronic control devices, it is advantageous to
realize at least part of the electronic control device separately
from the microelectrode array, e.g. in a separate control unit
which picks up and evaluates the signals output by the
microelectrode array and, if appropriate, outputs control signals
to the electrical light sources. The control of the electrodes
depending on sensor signals of the microelectrode array, e.g. in
the context of the regulating circuit mentioned, can be realized
locally on the microelectrode array by means of a part of the
electronic control device integrated there, or externally to the
microelectrode array in the separate control unit.
[0044] The electronic control device can be coupled to one, a
plurality or all of the electrical and/or electronic components of
the microelectrode array in a wired fashion and/or wirelessly.
Wireless coupling has the advantage that the microelectrode array
is handleable more easily after it has been implanted, and there is
a reduced burden on the patient.
[0045] In accordance with one advantageous development of the
invention, the electronic control device is coupled at least to
one, a plurality or all of the electrical light sources and is
designed for controlling the light emission from one, a plurality
or all of the coupled electrical light sources.
[0046] Furthermore, it can be provided that the electronic control
device is designed for controlling the light emission from one, a
plurality or all of the coupled electrical light sources depending
on electrical and/or electronic sensor components of the
microelectrode array, each of which an electrical sensor signal
depending on at least one physical variable which is influenced by
the electrical light source or the electrical light sources and
which is detected by the respective sensor component.
[0047] The microelectrode array and the device comprising a
microelectrode array can be used e.g. for mapping brain functions
and/or for analyzing epileptogenic zones. An application as the
human-machine interface (HMI) or brain-machine interface (BMI) is
also advantageous.
[0048] The invention is explained in greater detail below on the
basis of exemplary embodiments using drawings.
[0049] In the figures:
[0050] FIG. 1 shows a microelectrode array in an isometric
illustration, and
[0051] FIGS. 2, 3 and 5 show embodiments of a microelectrode array
in lateral sectional illustration, and
[0052] FIGS. 4 and 6 show the application of a microelectrode array
when recording an electrocorticogram.
[0053] In the figures, identical reference signs are used for
mutually corresponding elements.
[0054] FIG. 1 shows a microelectrode array 1, which can be embodied
e.g. as a thin-film array comprising a flexible, filmlike thin
substrate 4. A plurality of electrodes 2, each represented by
circles, and a plurality of electrical light sources 3 in the form
of light emitting diodes, each represented in the form of squares,
are arranged on or in the substrate 4. The electrodes 2 and the
light emitting diodes 3 are connected to a connection cable 9 via
electrical lines 5, of which only a few lines are illustrated by
way of example for reasons of clarity in FIG. 1. The connection
cable 9 can be embodied e.g. as a ribbon cable. Via the connection
cable 9, the electrical signals of the electrodes 2 are conducted
to an amplifier and a measuring system and the light emitting
diodes 3 are additionally supplied with power.
[0055] The microelectrode array 1 can have dimensions in the
millimeter or centimeter range with regard to width and length and
can be embodied in different shapes, which can also deviate from
the rectangular shape illustrated in FIG. 1.
[0056] FIG. 2 shows one embodiment of the microelectrode array 1 in
cross section. The thickness D of the substrate 4 is relatively
small in comparison with the width and length. The thickness D can
be in the micrometer range, in particular. The substrate 4 embodied
as a thin, flexible film e.g. composed of parylene, polyimide, PDMS
or polyurethane has metal structures 2, 8 introduced therein. The
metal structures 2 form the electrodes 2 in substrate regions
provided with openings 6. The openings 6 face a sensor side 16 of
the substrate 4, said sensor side being designed to be brought into
contact with the brain surface 11 of a living being to be examined.
The metal structures 8 realize power supply lines of the light
emitting diodes 3 that are separate from the electrodes 2, i.e.
electrically isolated therefrom and are passivated with respect to
the biological tissue or cortex 11. The light emitting diodes 3 are
applied to the substrate 4 on that side of said substrate 4 which
faces away from the brain surface 11, or are integrated into the
substrate 4, e.g. in the manner of a sandwich structure. The light
emitting diodes 3 are electrically connected to the power supply
lines 8 either directly or by means of electrical connections 7,
e.g. in the form of bonds. The light emitting diodes 3 emit their
light 12 through the optically sufficiently transparent substrate 4
in the direction of the brain surface 11 and thereby stimulate the
nerve cells present therein. The nerve cells can be made sensitive
to light e.g. by means of channel rhodopsins. In this case, the
path of the light 12 can also be influenced by the metal structures
2, 8 or by additional elements such as refractive or reflective
optical elements, for example, which are present in the
microelectrode array 1.
[0057] FIG. 3 shows a further embodiment of a microelectrode array
in cross-sectional illustration. In accordance with FIG. 3, the
light emitting diodes 3 are embodied in the form of thin-film LEDs
integrated into the substrate 4, in particular as organic LEDs. In
this case, the substrate 4 can advantageously be produced as a
multilayer structure 15 composed of a plurality of layers. The
light emitting diodes 3 are then introduced directly into the
multilayer structure 15 of the substrate 4 in a microstructured
fashion. They are contacted by metal layers 13, 14 in the
multilayer structure 15 in order to ensure the power supply. The
electrodes 2 are in turn open toward the sensor side 16 via
openings 6. All other structures are electrically and biologically
passivated.
[0058] FIG. 4 shows an application of the microelectrode array 1
according to the invention when recording an electrocorticogram of
a human being. The microelectrode array 1 is connected via the
connection cable 9 to an electronic device 10, which comprises in
particular an amplifier for the electrode signals and a data
acquisition system. The recorded data can be displayed e.g. on a
screen.
[0059] FIG. 5 shows a further embodiment of a microelectrode array
in cross-sectional illustration. In accordance with FIG. 5, the
electrodes 2 are embedded in elevated column structures 22,
produced from the substrate material, for being brought near to the
brain surface 11 and are in turn opened toward the sensor side 16
by openings 6. Microstructured, circumferential sealing lips 23
laterally delimit the active electrode areas of the electrodes 2.
The light emitting diodes 3 are embodied in the form of thin-film
LEDs integrated into the substrate 4, in particular as
phosphorescent organic light emitting diodes, and are introduced
directly into the multilayer structure 15 of the substrate 4 in a
microstructured fashion. They are contacted by the metal structures
13, 14 in the multilayer structure 15 in order to ensure the power
supply, and emit their light 12 through the optically sufficiently
transparent substrate 4 in the direction of the brain surface 11.
The metal structures 13, 14, 19, 20, 21 realize electrical
connection lines that are separate from the electrodes 2, i.e.
electrically isolated therefrom, and are passivated with respect to
the biological tissue or cortex 11. In this case, the metal
structures 19 form the power supply line of the temperature sensors
17, embodied as meanders for example, and the metal structures 20,
21 form the electrical contacting of the photodiodes 18.
Temperatures sensors 17 and photodiodes 18 are embedded in the
substrate, e.g. in the manner of a sandwich structure, and are thus
electrically and biologically passivated. Through openings 24 are
arranged in the substrate 4, said through openings being suitable
for allowing the diffusion of pharmacological substances into the
tissue for e.g. optogenetic applications, and/or for introducing
penetrating depth electrodes 25 into the cortical tissue. The depth
electrodes 25 are integrated in a positionally fixed manner at a
defined distance in an adapted depth electrode array 26, wherein
the cable-based electrical connection lines 27, embodied e.g. as
ribbon cable, are led away on the side facing away from the sensor
side 16.
[0060] FIG. 5 shows alongside one another three of the
above-described arrangements in the substrate 4, which are
constructed identically and therefore, only one arrangement of
which has been completely provided with reference signs, for the
sake of better clarity.
[0061] FIG. 6 shows an application of the microelectrode array 1
according to the invention when recording an electrocorticogram of
a human being. In contrast to FIG. 4, the microelectrode array 1 is
wirelessly connected to an electronic control device 10, which
comprises in particular an amplifier for the electrode signals and
a data acquisition system. The microelectrode array 1, implanted
e.g. below the patient's scalp, has an energy receiving coil 60 and
an antenna 61 for bidirectional data transfer between the
microelectrode array 1 and the electronic control device 10. It is
also possible for the energy receiving coil 60 simultaneously to be
used as an antenna, such that no separate antenna 61 is
required.
[0062] For this purpose, the electronic control device 10 is
connected via a cable 9 to a satellite path 62, in which an energy
transmitting coil 63 and an antenna 64 are arranged. By means of
the energy transmitting coil 63, electrical energy is fed into the
energy receiving coil 60 by means of a radio-frequency signal, such
that the microelectrode array 1 is wirelessly supplied with the
electrical energy required for its operation. Bidirectional data
communication between the electronic control device 10 and the
microelectrode array 1 takes place via the antennas 61, 63.
* * * * *