EP4260055A1 - Biopuce ferroélectrique - Google Patents

Biopuce ferroélectrique

Info

Publication number
EP4260055A1
EP4260055A1 EP21839004.5A EP21839004A EP4260055A1 EP 4260055 A1 EP4260055 A1 EP 4260055A1 EP 21839004 A EP21839004 A EP 21839004A EP 4260055 A1 EP4260055 A1 EP 4260055A1
Authority
EP
European Patent Office
Prior art keywords
biochip
layer
biological material
ferroelectric
coupling
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.)
Pending
Application number
EP21839004.5A
Other languages
German (de)
English (en)
Inventor
Maximilian Becker
Claus Burkhardt
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.)
NMI Naturwissenschaftliches und Medizinisches Institut
Original Assignee
NMI Naturwissenschaftliches und Medizinisches Institut
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 NMI Naturwissenschaftliches und Medizinisches Institut filed Critical NMI Naturwissenschaftliches und Medizinisches Institut
Publication of EP4260055A1 publication Critical patent/EP4260055A1/fr
Pending legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • A61B5/25—Bioelectric electrodes therefor
    • A61B5/263—Bioelectric electrodes therefor characterised by the electrode materials
    • 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
    • A61B5/25—Bioelectric electrodes therefor
    • A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
    • A61B5/28—Bioelectric electrodes therefor specially adapted for particular uses for electrocardiography [ECG]
    • A61B5/283—Invasive
    • A61B5/287—Holders for multiple electrodes, e.g. electrode catheters for electrophysiological study [EPS]
    • 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
    • A61B5/25—Bioelectric electrodes therefor
    • A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
    • A61B5/28—Bioelectric electrodes therefor specially adapted for particular uses for electrocardiography [ECG]
    • A61B5/283—Invasive
    • A61B5/29—Invasive for permanent or long-term implantation
    • 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
    • A61B5/25—Bioelectric electrodes therefor
    • A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
    • A61B5/291—Bioelectric electrodes therefor specially adapted for particular uses for electroencephalography [EEG]
    • A61B5/293—Invasive
    • 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
    • A61B2562/04—Arrangements of multiple sensors of the same type
    • A61B2562/046—Arrangements of multiple sensors of the same type in a matrix array
    • 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
    • A61B2562/12—Manufacturing methods specially adapted for producing sensors for in-vivo measurements
    • A61B2562/125—Manufacturing methods specially adapted for producing sensors for in-vivo measurements characterised by the manufacture of electrodes
    • 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
    • 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
    • A61N1/0534—Electrodes for deep brain stimulation
    • 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
    • A61N1/0543—Retinal electrodes
    • 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
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36057—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for stimulating afferent nerves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36067—Movement disorders, e.g. tremor or Parkinson disease
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/403—Cells and electrode assemblies
    • G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
    • G01N27/4145—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS specially adapted for biomolecules, e.g. gate electrode with immobilised receptors

Definitions

  • the invention relates to a biochip with at least one coupling arrangement for electrical stimulation of biological material or for electrical measurements on the biological material.
  • Patent EP 1 478 737 B1 discloses a biochip which is set up for the capacitive stimulation and/or detection of biological tissue. In order to improve the coupling efficiency of the purely capacitive coupling provided in this biochip, it is proposed to use a dielectric with the highest possible relative permittivity e r , namely TiO 2 .
  • FeFET ferroelectric field effect transistor
  • MAAs microelectrode arrays
  • the stimulation efficiency determines the minimum area of each electrode for which effective electrical stimulation of the biological material, which may contain nerve cells, is practically possible.
  • One object of the present invention can therefore be seen as providing a biochip with improved stimulation efficiency, with which, for example, microelectrode arrays or electrically active implants with a high density of electrodes can be implemented, electrochemical degradation processes on the electrodes also being suppressed should be.
  • a biochip with at least one coupling arrangement for electrically stimulating biological material or for electrically measuring the biological material having: a carrier structure on and/or in the at least one coupling arrangement is arranged; and a layer, one layer surface of which is arranged on the coupling arrangement and the opposite layer surface of which forms a coupling surface for electrical stimulation of the biological material and/or for electrical measurements on the biological material; which is characterized in that the layer has ferroelectric properties.
  • the layer of such a biochip has a non-linear and/or hysteretic relationship between an electric field E within the layer and an electric displacement density D, which is caused by the presence of a ferroelectric polarization is caused within the layer.
  • ferroelectric behavior This non-linear and hysteretic behavior of this connection DE is also referred to as ferroelectric behavior.
  • materials with ferroelectric properties also include antiferroelectric materials, ferrielectric materials, multiferroic materials or relaxor ferroelectric materials.
  • the layer can therefore have ferroelectric, antiferroelectric, ferrielectric and/or relaxor ferroelectric materials or also be formed from one of these materials.
  • the layer with the ferroelectric properties makes an additional contribution to the electrical stimulation of the biological material, which results from the ferroelectric polarization in the layer.
  • This additional contribution occurs in addition to a contribution caused by the known purely capacitive stimulation. In many cases, the additional contribution can even be higher than the contribution of the purely capacitive coupling.
  • the layer can have, for example, hafnium oxide (HfO 2 ) with ferroelectric properties or be formed therefrom.
  • hafnium oxide HfO 2
  • ferroelectric hafnium oxide is compatible with known semiconductor processes, such as CMOS technology, so that simple production of the biochip is possible.
  • a further improvement in the properties of the biochip and/or a simplification of the manufacturing process can be achieved by doping hafnium oxide, for example if the hafnium oxide having ferroelectric properties is doped with silicon.
  • the hafnium oxide can also be doped with one of the following materials: aluminum (Al), germanium (Ge), yttrium (Y), gadolinium (Gd), lanthanum (La) or strontium (Sr).
  • the hafnium oxide having ferroelectric properties can also be doped with zirconium (Zr).
  • Zr zirconium
  • the layer comprises or is formed from a material of the class Hf 1.x ZrxO 2 .
  • the material is preferably Hf 0 5 Zro. 5 0 2 .
  • This material has a high remanent polarization P r compared to other dopings with zirconium, as a result of which the additional contribution to electrical stimulation of biological material described above is particularly pronounced.
  • the layer has zirconium oxide (ZrO 2 ) with ferroelectric properties or is formed from such.
  • the layer has aluminum scandium nitride with ferroelectric properties or is formed from aluminum scandium nitride.
  • Aluminum scandium nitride is to be understood as class A .xSCxN materials. On the one hand, this class of materials is compatible with common manufacturing processes that are also used to produce CMOS circuits, and on the other hand it has a particularly high remanent polarization of over 100 pC/cm 2 .
  • the layer has a ferroelectric perovskite and/or ferroelectric polymer or is formed from such.
  • the layer has multiferroic properties. So the layer can be a multiferroic Have material or be formed from such.
  • the multiferroic material can be bismuth ferrite (BiFeO 3 ), for example.
  • the layer or thin layer has ferroelectric properties.
  • the ferroelectric properties can be verified by measurement.
  • the layer having ferroelectric properties is not made of barium titanate and/or the layer having ferroelectric properties is not made of PZT.
  • the ferroelectric property layer does not include barium titanate and/or the ferroelectric property layer does not include PZT.
  • the thickness of the layer can be greater than 200 nm and preferably in the range between 200 nm and 1500 nm, in particular between 500 nm and 1500 nm or between 200 nm and 800 nm .
  • the layer thickness can be selected to be relatively high in the biochip described here and good stimulation efficiency can nevertheless be achieved.
  • the high layer thickness ensures good electrical insulation between the biochip and the biological material, ie low leakage currents. Furthermore, a biochip with a comparatively large layer thickness is more stable over the long term.
  • the carrier structure has a substrate made of a semiconductor material or is formed from such a material, the biochip can be easily manufactured using manufacturing processes known from semiconductor technology. It can also be provided that the carrier structure has at least one of the following materials or is formed from it: polyimide, epoxy resin, parylene. These materials are biocompatible and therefore particularly suitable for producing the biochip. However, other biocompatible and/or dielectric materials can also be used.
  • the layer can form part of a ferroelectric field effect transistor (FeFET) of the biochip.
  • FeFET ferroelectric field effect transistor
  • the FeFET can form part of an input stage of a corresponding measuring circuit.
  • the FeFET belongs to an artificial neuron. This can, for example, be coupled to a biological neuron present in the biological material.
  • the procedure can be that the coupling surface has a gate electrode of the ferroelectric field effect transistor or forms one.
  • the layer can correspond to a ferroelectrically acting insulating layer of the FeFET.
  • a multi-layer construction of the gate area of the FeFET is also conceivable, with the gate area comprising the ferroelectric layer and a further layer, which can be an insulating layer.
  • the biochip can be designed in such a way that it has memresistive or memristive properties.
  • the layer can be formed in such a way that a ferroelectric tunnel contact is formed.
  • the biochip can be designed as a memristor be.
  • the memristive properties can occur in particular in that a so-called ferroelectric tunnel contact is formed.
  • Memristive properties can then occur due to the ferroelectric properties of the layer between the electrodes: for example, because a ferroelectric tunnel contact is formed.
  • the biochip can therefore be set up in such a way that a ferroelectric tunnel contact is formed.
  • a thickness of the layer with ferroelectric properties is, for example, less than or equal to 10 nm, in particular less than or equal to 7.5 nm, in particular less than or equal to 5 nm.
  • a biochip designed as a memristor can be used as an artificial synapse.
  • the biochip can be set up to be used as part of an arrangement which couples at least one artificial neural network to a biological neural network.
  • the biochip can be set up to couple an artificial neuron to a biological neuron.
  • the biochip can have a plurality of mutually separate coupling surfaces of different coupling arrangements of the biochip.
  • a coupling surface can be assigned to each coupling arrangement.
  • a multi-channel biochip can be provided in this way.
  • the coupling surfaces can be arranged, for example, along a line or in a grid.
  • Such a biochip can have several separate layers with ferroelectric properties.
  • a method for producing a biochip with at least one coupling arrangement for electrical stimulation of biological material or for electrical measurements on the biological material comprising: arranging a carrier structure on and/or in the coupling arrangement; and producing a layer in such a way that one layer surface is arranged on the coupling arrangement and the opposite layer surface forms a coupling surface for electrical stimulation of the biological material and/or for electrical measurements on the biological material, the method being characterized in that the layer is produced as a layer with ferroelectric properties.
  • a further embodiment comprises an electrically active implant with the biochip described here.
  • the implant can be, for example, a retina implant, a cochlear implant, an implant for deep brain stimulation and/or an implant for providing a brain-machine interface.
  • implants for stimulating nerve cells and/or for measurements on nerve cells can be provided, such implants having at least one biochip described here.
  • an in vitro arrangement with a biochip described here and an electrolyte receptacle i.e. an arrangement for receiving an electrolyte
  • the electrolyte receptacle for arranging the electrolyte on at least one coupling surface of the biochip for electrical stimulation of the biological material and/or for electrical measurement of the biological material.
  • An in vitro arrangement can hereby be provided which has at least one biological neuron and at least one artificial neuron.
  • the biological neuron can be formed, for example, by a nerve cell of the biological material located in the electrolyte.
  • the artificial neuron can comprise an FeFET, which can be part of the biochip and can be implemented as described above.
  • the implant or the in-vitro arrangement can have a semiconductor chip separate from the biochip, a connection of the semiconductor chip being electrically connected via a conductor track to an electrode layer adjoining the layer surface, and the conductor track and the biochip being arranged on a common substrate .
  • FIG. 1 shows a schematic representation of an arrangement with a biochip
  • FIG. 2 shows the basic structure of the biochip from FIG. 1;
  • FIG. 3 shows a stimulation device of the biochip from FIG. 1;
  • FIG. 4 shows how the stimulation device from FIG. 3 works
  • FIG. 5 shows a graphic representation of the time profile of a possible voltage signal U(t) for the stimulation device from FIG. 3;
  • FIG. 7 shows a representation similar to FIG. 6, but for the case of an antiferroelectric layer
  • FIG. 8 shows a measuring device of the biochip from FIG. 1;
  • FIG. 9 shows a further measuring device of the biochip from FIG. 1;
  • FIG. 10 a biochip arrangement with a measuring device.
  • the arrangement 11 shows an arrangement 11 with a biochip 13.
  • the arrangement has only one biochip 13.
  • FIG. it is also possible to provide several biochips, preferably arranged next to one another in a grid, on or in the arrangement 11 .
  • the arrangement 11 has a plurality of coupling surfaces 15 .
  • at least one of these coupling surfaces 15 can be set up for the electrical stimulation of biological material, in particular a nerve cell located therein.
  • at least one of these coupling surfaces 15 for electrical measurements on the biological material, in particular on a nerve cell located therein.
  • the biochip 13 can therefore have a plurality of coupling surfaces 15 , with each coupling surface 15 being assigned to exactly one coupling arrangement 21 of the biochip 13 .
  • the coupling surfaces 15 and/or the coupling arrangements 21 can be arranged along a line or, as shown in FIG. 1, in a grid.
  • the arrangement 11 can, for example, be an electrically active implant such as a neuroprosthesis.
  • the arrangement can be a cochlear or retina implant.
  • the arrangement 11 can be an implant for deep brain stimulation for the treatment of neurological symptoms such as Parkinson's disease.
  • neuroprostheses 11 it can be provided that all coupling surfaces 15 of the at least one biochip 13 are set up for stimulating nerve cells.
  • the arrangement can be an in vitro arrangement comprising a microelectrode array (MEA) whose microelectrodes correspond to the coupling surfaces 15 .
  • MEA microelectrode array
  • Such an in-vitro arrangement can have at least one biological neuron, which is formed by a nerve cell located in the biological tissue, and/or at least one artificial neuron, which belongs to the biochip 13.
  • the biological material can be in an electrolyte, which can be brought into contact with the biochip 13, in particular its coupling surfaces 15, via a suitable electrolyte receptacle of the arrangement 11, such as an electrolyte container 16, for example.
  • Known arrangements 11 have electrically conductive (metallic) electrodes.
  • Such electrodes enable a high charge transfer per unit area (stimulation efficiency) of electrical charge between the biological material and the biochip 11.
  • the high stimulation efficiency allows the area of the individual electrodes to be kept small, which in turn allows a high area density of electrodes.
  • a threshold value required for the successful stimulation of nerve cells is the the charge density to be transmitted by the nerve tissue depends on the size of the electrodes or the coupling surfaces 15 .
  • a disadvantage of conductive electrodes is that irreversible electrochemical processes in the form of a Faraday current can occur at the electrode/electrolyte interface, which can lead to degradation of the electrode or to cell damage in the biological material.
  • the Faraday currents at the electrodes can be avoided, at least to a large extent, if a biochip with purely capacitive coupling is used.
  • Such a biochip usually has conductive areas (for example p-doped areas in silicon) which are covered with a dielectric layer which suppresses the Faraday currents.
  • the stimulation efficiency of these biochips is relatively low and is determined in particular by the relative dielectric constant of the dielectric layer and its thickness. Attempts are therefore being made to use materials with the highest possible relative dielectric constant and to keep the thickness of the layer small.
  • a small layer thickness can lead to increased leakage currents, which counteracts the goal of reducing irreversible processes.
  • the biochip 13 has at least one layer 17 with ferroelectric properties, which is delimited by the coupling surface 15 .
  • the carrier structure 23 can consist of one layer. This layer can have, for example, conductive areas which consist of a semiconductor material which is p-doped or n-doped in order to achieve a desired electrical conductivity.
  • the carrier structure 23 can also have metallic conductor tracks which are arranged in or on the carrier structure 23 .
  • the support structure 23 consist of a flexible and biocompatible material such as polyimide.
  • the coupling surface 15 of the layer 17 delimits the biochip towards an area 25 in which the biological material is located.
  • the biological material can be in an electrolyte 24 .
  • the biochip 13 and the area 25 with the biological material are components of the biochip arrangement 11.
  • the biological material can have at least one nerve cell which can form a biological neuron.
  • the coupling surface 15 forms an electrode with a substantially smooth surface.
  • the coupling surface 15 is machined to have an increased surface area.
  • an actively effective surface can be enlarged in order to further increase the charge transfer.
  • the coupling surface 15 can be circular overall with a diameter of 5 ⁇ m to 200 ⁇ m, preferably 5 ⁇ m to 100 ⁇ m, in particular 30 ⁇ m.
  • the coupling surface 15 can also have another shape, for example a rectangle, square or other polygon shape (preferably with the same surface area as the circular coupling surface). If several coupling surfaces 15 are provided per biochip 13, they can have a minimum distance of 5 ⁇ m to 500 ⁇ m from one another.
  • the carrier structure 23 has two layers here, namely an electrically conductive electrode layer 27 directly adjoining the layer surface 19, which can be formed from metal or doped semiconductor material, and a substrate layer 29 adjoining the electrode layer 27.
  • the electrode layer 27 is therefore located between the layer 17 and the substrate layer 29.
  • the electrode layer 27 is arranged on the layer 17 so that it interacts with the material of the layer 17 having ferroelectric properties, in particular when a time-varying electrical voltage U(t) is applied to the electrode layer 27.
  • a suitable contact can be provided, as shown schematically in FIG. 3, via which a voltage source 31 can be connected to the electrode layer 27.
  • the biochip arrangement 11 a Have counter-electrode 33 with which the biological material and/or the electrolyte 24 can be contacted.
  • an electrical voltage U(t) is applied to the electrode layer 27 acting as an electrode and to the counter-electrode.
  • the electrolyte 24 is electrically insulated from the electrode layer 27, so that no direct current can flow, which leads to an electrochemical charge transport.
  • Material with ferroelectric properties is O (£), where s 0 denotes the permittivity of the vacuum.
  • Such voltage signals can be used, for example, for the electrical stimulation of electrogenic cells, but they can also be used to measure the nonlinear and hysteretic relationship D(E) of materials with ferroelectric properties.
  • FIG. 6 shows the typical course of the non-linear and hysteretic relationship D( ⁇ ) for a ferroelectric material.
  • the ferroelectric polarization can be reversed by applying a field strength E which is above the material-specific coercive field strength Ec. After switching off the electric field, the remanent FE remains)
  • Polarization P r P (0) obtained, which can assume the two states +P r and -P r depending on the history. Ferroelectric memories are based on these two stable states.
  • FIG. 7 shows the typical course of the nonlinear and hysteretic relationship D(E) for an antiferroelectric material.
  • the ferroelectric hysteresis occurs here only above a critical field strength EC r n D. After switching off the electric field, the electric polarization disappears again.
  • C s corresponds to the capacitance per unit area (measured e.g. in pF/cm 2 ) of a plate capacitor formed by the two layer surfaces 15, 19 and P r corresponds to the amount of remanent polarization of the ferroelectric material of layer 17.
  • the proportion 2P r of the transmitted charge density p stim that originates from the ferroelectric properties results from the fact that the voltage U(t) generated by the voltage source 31 causes a polarity reversal of the remanent polarization P r in the layer 17 .
  • the amplitude of the voltage signal U(t) can be selected such that the corresponding field strength E in the layer 17 is at least as great in absolute terms as the coercive field strength E c .
  • the layer 17 can consist of hafnium oxide (HfO 2 ) with ferroelectric properties or doped hafnium oxide with ferroelectric properties or at least contain the same.
  • the layer 17 can consist of zirconium-doped hafnium oxide (Hf 1.x Zr x O 2 ) or at least contain the same.
  • Hf 1.x Zr x O 2 zirconium-doped hafnium oxide
  • the layer 17 can also consist of aluminum scandium nitride (A.xSCxN) with ferroelectric properties or at least contain the same. This material is compatible with semiconductor manufacturing processes that are also used to make CMOS circuits. Because of its relatively high remanent polarization of over 100 nC/cm, transferrable charge densities of more than 200 p.C/cm result.
  • A.xSCxN aluminum scandium nitride
  • the material from which the layer 17 consists or which the layer 17 comprises can also be an antiferroelectric.
  • the material can be, for example, hafnium oxide (HfO 2 ) doped with silicon (Si).
  • Antiferroelectrics have a curve D(E') shown qualitatively in FIG.
  • the material which has the layer 17 or from which the layer 17 consists can also have multiferroic properties, ie it can be both ferroelectric and ferromagnetic.
  • this can be bismuth ferrite (BiFeO 3 ).
  • a thickness of the layer with ferroelectric properties is, for example, less than or equal to 100 nm, in particular less than or equal to 50 nm, in particular less than or equal to 20 nm, in particular less than or equal to 10 nm, in particular less than or equal to 7.5 nm, in particular less than or equal to 5 nm. in particular less than or equal to 4 nm, in particular less than or equal to 2.5 nm.
  • ferroelectric layer (17) can be arranged not only exclusively in a planar (2D) plate capacitor design, but also in other arrangements such as, for example, in a 3D capacitor structure such as a so-called deep trench capacitor or a deep trench capacitor.
  • FIG. 8 shows a section of a biochip 13 that is set up to carry out electrical measurements on the biological material located in the electrolyte 24 .
  • the carrier structure 23 has a substrate layer 29 made of semiconductor material.
  • a drain zone 35 and a source zone 37 are arranged in the substrate layer 29, preferably in a region which adjoins the layer 17.
  • FIG. The two zones 35, 37 are arranged on the layer 17 at a distance from one another.
  • the two zones 35 and 37 can be formed in that the semiconductor material there is oppositely doped with respect to a doping of the substrate layer 17 outside of the zones 35, 37.
  • the two zones 35, 37 can be n-doped and the rest of the substrate layer 29 can be p-doped (or vice versa).
  • the substrate layer 29, the drain region 35 and the layer 17 form a ferroelectric field effect transistor (FeFET).
  • the coupling surface 15 of the layer 17 corresponds to a gate contact of the FeFET 39 which is electrically connected to the electrolyte 24 .
  • the layer 17 forms an insulating layer of the FeFET 39, which is comparable to a gate oxide of a classic MOSFET.
  • the drain zone 35, the source zone 37 and the substrate layer 29 are electrically connected to corresponding terminals U D , U S and U B of the FeFET 39 which each have a drain contact, a source contact and a bulk contact of the FeFETs 39 form.
  • the electrolyte 24 can be brought to a reference potential, for example a ground potential GND, by means of a reference electrode. It can be provided here that the bulk connection U B of the FeFET is at the same electrical potential as the electrolyte 24 and/or that the reference electrode is integrated into the substrate layer 29.
  • the FeFET 39 can form part of an input stage of the biochip arrangement 11, which is designed for electrical measurements on biological material, in particular on nerve cells contained therein. Furthermore, the FeFET 39 can also be a part of an artificial neuron. A total of 11 examinations of nerve tissue can be carried out using the biochip arrangement.
  • the biochip arrangement 11 can be used for neuromorphic computing.
  • the biochip arrangement 11 can be a brain-machine interface (brain-machine interface), in particular a brain-computer interface (brain-computer interface).
  • a measuring device of the biochip 11 can also be constructed as shown in FIG. Unlike the measuring device shown in FIG. 7, the carrier structure 23 has an electrical connection arrangement (“metal stack” 41).
  • An insulating layer 47 is assigned to the drain zone 35 and the source zone 37, so that a MOSFET structure 42 comprising the two zones 35, 37 and the insulating layer 47 results.
  • the insulating layer 47 can be arranged on the substrate layer 29 and/or consist of polysilicon.
  • the connection arrangement 41 is arranged between the insulating layer 47 and the ferroelectric layer 17 in such a way that it electrically connects them to one another.
  • six metal layers (“metal layers”) are provided in the semiconductor technology used.
  • the connecting arrangement 41 has six conductors 43 arranged in different metal layers, conductors of adjacent metal layers being connected to one another via plated-through holes (“vias” 45). Deviating from this, the number of metal layers can be varied as required.
  • FIG. 10 Another example of a measuring device is the arrangement 11 shown in FIG. 10, which is particularly suitable for carrying out in-vivo measurements. Similar to the measuring device from FIG. 9, the measuring device has a MOSFET. However, this belongs to a semiconductor chip 49 that is separate from the biochip 13 . A connection of the semiconductor chip 49 is electrically connected to the electrode layer 27 via a conductor track 43 . The connection can be a gate connection of the MOSFET.
  • the conductor track 43 is on the substrate 29 of the biochip 13 appropriate.
  • the substrate 29 may be formed from a biocompatible dielectric material such as a polyimide.
  • the conductor track 43 and the substrate 29 can form a flexible printed circuit board (“flex PCB”).
  • the conductor track 43 can consist of gold, for example, and/or be electrically insulated on a side facing away from the substrate 29, for example by means of a parylene layer.
  • the elements 43, 27 and 17 can be present multiple times and can be arranged next to one another, for example in a direction which runs at least essentially orthogonally to the plane of the drawing in FIG. This results in a multi-channel measurement arrangement with a number of coupling arrangements 21.
  • the arrangement 11 in FIG. 10 can also be set up for stimulating the biological material. At least part of the coupling surfaces and/or a circuit in the semiconductor chip 49 can be designed accordingly for this purpose. If different coupling surfaces on the respective layers 17 are used for the measurements and for the stimulation, the measurements and the stimulation can be carried out at different locations on a surface of the arrangement 11 or at different locations on the biological material. Simultaneous and spatially resolved measurement and stimulation is thus made possible.
  • the biochip is optionally set up for simultaneous measurement and stimulation.
  • the biochip can have a number of different coupling surfaces.
  • the biochip can have at least one coupling surface for measurement and at least one further coupling surface for simultaneous stimulation.
  • a biochip 13 uses the nonlinear and hysteretic curve D(F) of the electrical displacement density D in the layer with ferroelectric properties 17 as a function of the electric field E shown in FIGS to achieve charge transfer in the electrolyte 24 than would be possible with a purely capacitive stimulation. In this way, electrical stimulation of biological material can be achieved with a higher stimulation efficiency.
  • This in turn enables the construction of microelectrode arrays and electrically active implants with a high electrode density without electrochemical charge transport between the coupling surface 15 and the electrolyte 24 for the first time a measuring device with the MOSFET 42, or with the help of a passive measuring device.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pathology (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Medical Informatics (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Cardiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Physiology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne une biopuce (13) comprenant au moins un dispositif d'accouplement (21) pour la stimulation électrique d'une matière biologique (24) ou pour des mesures électriques réalisées sur la matière biologique (24), la biopuce (13) présentant : une structure de support (23) qui est disposé sur et/ou dans le dispositif d'accouplement (21) ; et une couche (17) dont une surface de couche (19) est disposée sur le dispositif d'accouplement (21) et dont la surface de couche opposée forme une surface d'accouplement (15) pour la stimulation de la matière biologique (24) et/ou pour la réalisation de mesures sur la matière biologique (24). En vue d'améliorer l'efficacité de la stimulation de la biopuce (13), la couche (17) selon l'invention présente des propriétés ferroélectriques.
EP21839004.5A 2020-12-09 2021-12-07 Biopuce ferroélectrique Pending EP4260055A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102020132756.0A DE102020132756B3 (de) 2020-12-09 2020-12-09 Ferroelektrischer Biochip
PCT/EP2021/084639 WO2022122756A1 (fr) 2020-12-09 2021-12-07 Biopuce ferroélectrique

Publications (1)

Publication Number Publication Date
EP4260055A1 true EP4260055A1 (fr) 2023-10-18

Family

ID=79269856

Family Applications (1)

Application Number Title Priority Date Filing Date
EP21839004.5A Pending EP4260055A1 (fr) 2020-12-09 2021-12-07 Biopuce ferroélectrique

Country Status (3)

Country Link
EP (1) EP4260055A1 (fr)
DE (1) DE102020132756B3 (fr)
WO (1) WO2022122756A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116459389A (zh) * 2023-05-04 2023-07-21 深圳先进技术研究院 一种仿生视觉修复材料、修复膜及其制备方法、修复器件

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4180126B2 (ja) * 1994-04-28 2008-11-12 古河機械金属株式会社 強誘電体と半導体からなる複合治療器
EP1085319B1 (fr) 1999-09-13 2005-06-01 Interuniversitair Micro-Elektronica Centrum Vzw Dispositif à base de matériaux organiques pour la détection d'un analyte dans un échantillon
FR2818287B1 (fr) 2000-12-14 2003-01-17 Commissariat Energie Atomique Support solide pour l'immobilisation d'oligonucleotides
DE10209075A1 (de) 2002-03-01 2003-09-18 Infineon Technologies Ag CMOS-Prozeß-kompatible Hoch-DK Oberflächenbeschichtung zur kapazitiven Detektion und Stimulation biologischer Gewebe
US7400021B2 (en) * 2002-06-15 2008-07-15 The University Of Houston System Thin film optical detectors for retinal implantation and methods for making and using same
DE10251243B3 (de) 2002-11-04 2004-06-09 Infineon Technologies Ag Biochip zur kapazitiven Stimulation und/oder Detektion biologischer Gewebe sowie ein Verfahren zu dessen Herstellung
DE10351201B3 (de) 2003-11-03 2005-07-14 Infineon Technologies Ag Sensorvorrichtung mit Waferbondverbindungsaufbau und Herstellungsverfahren derselben
EP3671199B1 (fr) * 2018-12-18 2022-05-25 Ecole Polytechnique Federale De Lausanne (Epfl) Capteur à semi-conducteur à capacité négative
DE102020126759B3 (de) * 2020-10-12 2022-02-24 NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen Stiftung bürgerlichen Rechts Piezoelektrisches Membran-Mikroelektroden Array

Also Published As

Publication number Publication date
DE102020132756B3 (de) 2022-03-24
WO2022122756A1 (fr) 2022-06-16

Similar Documents

Publication Publication Date Title
EP1448264B1 (fr) Implant retinien a agencement d'electrodes pour la stimulation electrique d'une matiere biologique
EP0951312B1 (fr) Systeme de micro-electrodes a commande optique pour stimuler des cellules, notamment un implant retinien
DE112012004348B4 (de) Verfahren zur herstellung eines multielektrodenarrays sowie eines multielektrodenarray-systems hoher dichte
EP1740935A1 (fr) Transistor a effet de champ pour mesures effectuees sur des bioconstituants
WO2022122756A1 (fr) Biopuce ferroélectrique
DE112012002136T5 (de) Halbleitervorrichtung
EP1057217A1 (fr) Circuit integre a elements capacitifs
EP3678735B1 (fr) Ensemble connecteur électrique implantable et ensemble électrode implantable
DE19724222A1 (de) DRAM und Verfahren zum Herstellen desselben
EP1722849A1 (fr) Electrode de stimulation
EP1946340B1 (fr) Composant électrique multicouche avec une forme d électrodes spéciale pour la réduction de la dispersion à la fabrication de la capacité
DE102018213735A1 (de) Bauelement und Verfahren zum Herstellen eines Bauelements
US20230302449A1 (en) Ferroelectric biochip
EP2054951A1 (fr) Composant piézoélectrique
WO2002017399A1 (fr) Dispositif a semi-conducteurs et son procede de production
EP3704440B1 (fr) Aide au réglage, assemblage de connecteurs sans fil et procédé de surveillance d'une position
EP1476223A1 (fr) Systeme de transistor a double porte pour recevoir des signaux electriques issus de cellules vivantes
EP2468354A2 (fr) Appareil implantable
DE102006049873A1 (de) Piezotransformator
DE102022116981A1 (de) Memristive struktur und memristive vorrichtung
DE102016013178A1 (de) Widerstandsbehaftete RAM-Zelle mit konzentriertem elektrischen Feld
DE102006043360A1 (de) Halbleitervorrichtung mit dreidimensionalem Aufbau und Verfahren zu ihrer Herstellung
EP3997450A1 (fr) Capteur de spectroscopie d'impédance pourvu d'un revêtement de glaçure d'étanchéité
WO2022200423A2 (fr) Composant électronique, agencement de composants, couche fonctionnelle pour former un composant électronique et procédé de fabrication d'un composant électronique
DE102019107600A1 (de) Antennenanordnung

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: UNKNOWN

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20230626

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)