CN112107307B - Preparation method and structure of high-flux implanted flexible nerve electrode - Google Patents

Preparation method and structure of high-flux implanted flexible nerve electrode Download PDF

Info

Publication number
CN112107307B
CN112107307B CN202010860818.6A CN202010860818A CN112107307B CN 112107307 B CN112107307 B CN 112107307B CN 202010860818 A CN202010860818 A CN 202010860818A CN 112107307 B CN112107307 B CN 112107307B
Authority
CN
China
Prior art keywords
electrode
metal wiring
wiring layer
preparing
area
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.)
Active
Application number
CN202010860818.6A
Other languages
Chinese (zh)
Other versions
CN112107307A (en
Inventor
陶虎
杨会然
周志涛
魏晓玲
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.)
Shanghai naohu Technology Co.,Ltd.
Original Assignee
Shanghai Institute of Microsystem and Information Technology of CAS
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 Shanghai Institute of Microsystem and Information Technology of CAS filed Critical Shanghai Institute of Microsystem and Information Technology of CAS
Priority to CN202010860818.6A priority Critical patent/CN112107307B/en
Publication of CN112107307A publication Critical patent/CN112107307A/en
Application granted granted Critical
Publication of CN112107307B publication Critical patent/CN112107307B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0209Special features of electrodes classified in A61B5/24, A61B5/25, A61B5/283, A61B5/291, A61B5/296, A61B5/053
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/12Manufacturing methods specially adapted for producing sensors for in-vivo measurements
    • A61B2562/125Manufacturing methods specially adapted for producing sensors for in-vivo measurements characterised by the manufacture of electrodes

Landscapes

  • Electrotherapy Devices (AREA)

Abstract

The preparation method and the structure of the high-flux implanted flexible nerve electrode disclosed by the embodiment of the application comprise the steps of preparing a substrate and a plurality of electrode block groups on the substrate, wherein each electrode block group comprises a first electrode area, a second electrode area and a third electrode area, each electrode area comprises a first preset number of electrodes, preparing first insulating layers on a plurality of areas to be prepared of the substrate, preparing a first metal wiring layer on the first electrode area, preparing a second insulating layer on the first metal wiring layer, preparing a second metal wiring layer on the second electrode area, preparing third insulating layers on the second insulating layers and the second metal wiring layers, preparing a third metal wiring layer on the third electrode area, preparing fourth insulating layers on the second insulating layers, the third insulating layers and the third metal wiring layers, stripping the substrate along a release surface to obtain a single nerve electrode unit, and connecting the single nerve electrode units with a second preset number with the circuit board to obtain the high-flux implanted flexible nerve electrode.

Description

Preparation method and structure of high-flux implanted flexible nerve electrode
Technical Field
The invention relates to the field of preparation of nerve electrodes, in particular to a preparation method and a structure of a high-flux implanted flexible nerve electrode.
Background
In human brain and animal brain, perception of external information and related motion control are coordinated and controlled by different neuron sets, the distribution of the neurons in different brain areas has certain limitation on acquisition and decoding of neural signals, and higher requirements are provided for simultaneously recording a large number of single neuron signals with high space-time fidelity and performance of signal acquisition equipment.
In the field of experimental neuroscience, the advantages and the disadvantages of a large number of neurons are respectively revealed while great progress is made by recording the neurons by an optical method or an electrical method. In the optical recording method, 10000 or more live neurons can be recorded simultaneously using a fluorescent protein contrast agent,such as the coded calcium ion protein or the pressure sensitive protein, but in clinical use, the fluorescent protein has low signal penetration depth and potential safety problems in expression mode. In the electrical recording method, brain electrodes based on brain-computer interface technology are mainly used as recording tools, wherein the utah electrode has wide clinical application and can record more neuron signals in different brain areas, but the utah electrode has low electrode density and is usually arranged in a block of 4 x 4mm2Only 100-channel electrodes can be prepared on the silicon substrate, thus making it difficult to extend the electrodes to higher-channel electrode recording.
In addition, implanted nerve probes are widely used in single neuron signal recording and sub-millisecond high resolution recording, but the collected single neuron signals are degraded with time due to uncertainty of peripheral chronic tissue reaction and neuron contact of an implanted part. In addition, considering the limitation of the size of the implanted nerve probe and the damage caused by the tissue of the implanted part, the number of channels recorded by the implanted nerve electrode needs to be limited to be below 100, which is far from meeting the signal acquisition requirements for a large number of different functional neurons.
Disclosure of Invention
The embodiment of the application provides a preparation method and a structure of a high-flux implanted flexible neural electrode, which can improve the number of channels of the implanted flexible neural electrode to record a large number of neuron activity signals in a single brain area or record activity signals of neurons with different functions across the brain area, reduce the damage of the high-flux implanted flexible neural electrode to the cerebral cortex and facilitate later-stage more complex brain activity analysis and diagnosis.
The embodiment of the application provides a preparation method of a high-flux implanted flexible neural electrode, which comprises the following steps:
preparing a substrate; the substrate has a release surface;
preparing a plurality of electrode zone groups on the release surface of the substrate; each electrode area group in the plurality of electrode area groups comprises a first electrode area, a second electrode area and a third electrode area, each electrode area in the first electrode area, the second electrode area and the third electrode area comprises a first preset number of electrodes, and the electrode areas are distributed at intervals so that the substrate is divided into a plurality of areas to be prepared;
preparing a first insulating layer on a plurality of regions to be prepared; the thickness of the first insulating layer is greater than that of each electrode region;
preparing a first metal wiring layer on a first electrode area of the electrode area group, and preparing a second insulating layer on the first metal wiring layer; the area of the second insulating layer is larger than that of the first metal wiring layer;
preparing a second metal wiring layer on a second electrode area of the electrode area group, and preparing a third insulating layer on the second insulating layer and the second metal wiring layer; the thickness of the second metal wiring layer is larger than that of the first metal wiring layer;
preparing a third metal wiring layer on a third electrode area of the electrode area group, and preparing a fourth insulating layer on the second insulating layer, the third insulating layer and the third metal wiring layer; the thickness of the third metal wiring layer is larger than that of the second metal wiring layer;
stripping the substrate along the release surface to obtain a single nerve electrode unit;
and connecting the single nerve electrode units with a second preset number with the circuit board to obtain the high-flux implanted flexible nerve electrode.
Further, preparing a first metal wiring layer on a first electrode region of the electrode region group, including:
photoetching a first electrode area of the electrode area group by using a stepping photoetching machine, and preparing a first metal wiring layer on the upper surface of the first electrode area by using a metal evaporation and stripping process; the wiring width of the first metal wiring layer is within a first preset range.
Further, preparing a second metal wiring layer on a second electrode region of the electrode region group, including:
photoetching a second electrode area of the electrode area group by using a stepping photoetching machine, and preparing a second metal wiring layer on the upper surface of the second electrode area by using metal evaporation and stripping processes; the wiring width of the second metal wiring layer is within a first preset range.
Further, preparing a third metal wiring layer on a third electrode region of the electrode region group, including:
photoetching a third electrode area of the electrode area group by using a stepping photoetching machine, and preparing a third metal wiring layer on the upper surface of the third electrode area by using a metal evaporation and stripping process; the wiring width of the third metal wiring layer is within a first preset range.
Furthermore, the number of channels of a single nerve electrode unit is 2160;
the number of channels of the high-flux implanted flexible nerve electrode is 10800.
Furthermore, the setting interval of the number of the electrode zone groups in the plurality of electrode zone groups is [10, 15 ];
the setting interval of the second preset number is [4, 6 ].
Further, preparing a plurality of electrode zone groups on the release side of the substrate, comprising:
12 electrode block groups are prepared on the release surface of the substrate, each of the 12 electrode block groups comprises a first electrode zone, a second electrode zone and a third electrode zone, and each of the first electrode zone, the second electrode zone and the third electrode zone comprises 60 electrodes.
Further, connecting a second preset number of single neural electrode units with the circuit board to obtain the high-flux implantable flexible neural electrode, comprising:
and connecting the 5 single nerve electrode units with a circuit board to obtain the high-flux implanted flexible nerve electrode.
Further, the manufacturing method further includes a step of manufacturing a substrate;
the step of preparing the substrate comprises:
obtaining a substrate;
preparing a sacrificial layer on the upper surface of the base to obtain a substrate; the upper surface of the sacrificial layer is a release surface.
Accordingly, the embodiment of the present application also provides a structure of a high-throughput implantable flexible neural electrode, which includes:
a plurality of single neural electrode units; each of the plurality of single nerve electrode units comprises a plurality of electrode zone groups;
each electrode area group in the plurality of electrode area groups comprises a first electrode area, a second electrode area, a third electrode area and a plurality of first insulating layers; the first electrode region, the second electrode region, the third electrode region and the plurality of first insulating layers are on the same plane, and the electrode regions in the first electrode region, the second electrode region and the third electrode region are distributed at intervals with the first insulating layers in the plurality of first insulating layers;
a first metal wiring layer on the first electrode region;
a second insulating layer on the first metal wiring layer; the area of the second insulating layer is larger than that of the first metal wiring layer;
a second metal wiring layer on the second electrode region; the thickness of the second metal wiring layer is larger than that of the first metal wiring layer;
a third insulating layer on the second insulating layer and the second metal wiring layer;
a third metal wiring layer on the third electrode region; the thickness of the third metal wiring layer is larger than that of the second metal wiring layer;
a fourth insulating layer on the second insulating layer, the third insulating layer, and the third metal wiring layer;
a circuit board; the circuit board is connected with a plurality of single nerve electrode units.
Further, the structure comprises 5 single nerve electrode units;
each of the 5 single nerve electrode units comprises 12 electrode groups;
the number of channels of a single nerve electrode unit is 2160;
the number of channels of the high-flux implanted flexible nerve electrode is 10800.
The embodiment of the application has the following beneficial effects:
the preparation method and the structure of the high-flux implanted flexible nerve electrode disclosed by the embodiment of the application specifically comprise the steps of preparing a substrate, wherein the substrate is provided with a release surface, preparing a plurality of electrode block groups on the release surface of the substrate, each electrode block group in the plurality of electrode block groups comprises a first electrode area, a second electrode area and a third electrode area, each electrode area in the first electrode area, the second electrode area and the third electrode area comprises a first preset number of electrodes, each electrode area is distributed at intervals so that the substrate is divided into a plurality of areas to be prepared, preparing a first insulating layer on the plurality of areas to be prepared, the thickness of the first insulating layer is larger than that of each electrode area, preparing a first metal wiring layer on the first electrode area of the electrode block groups, and preparing a second insulating layer on the first metal wiring layer, the area of the second insulating layer is larger than that of the first metal wiring layer, and finally, preparing a second metal wiring layer on a second electrode area of the electrode area group, preparing a third insulating layer on the second insulating layer and the second metal wiring layer, wherein the thickness of the second metal wiring layer is greater than that of the first metal wiring layer, preparing a third metal wiring layer on the third electrode area of the electrode area group, preparing a fourth insulating layer on the second insulating layer, the third insulating layer and the third metal wiring layer, wherein the thickness of the third metal wiring layer is greater than that of the second metal wiring layer, stripping the substrate along the release surface to obtain single nerve electrode units, and connecting a second preset number of single nerve electrode units with the circuit board to obtain the high-flux implantable flexible nerve electrode. Based on the embodiment of the application, the channel number of the implanted flexible nerve electrode can be increased by setting the values of the number of the shank, the first preset number and the second preset number so as to record a large number of neuron activity signals in a single brain region or record activity signals of different functional neurons across the brain region, and the damage of the high-flux implanted flexible nerve electrode to the cerebral cortex can be reduced, so that the later-stage more complex brain activity analysis and diagnosis are facilitated.
Drawings
In order to more clearly illustrate the technical solutions and advantages of the embodiments of the present application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative efforts.
Fig. 1 is a schematic flow chart of a method for manufacturing a high-throughput implantable flexible neural electrode according to an embodiment of the present application;
FIG. 2 is a process flow chart of a method for manufacturing a high-throughput implantable flexible neural electrode according to an embodiment of the present application;
FIG. 3 is a schematic plan view of the structure of a high-throughput implantable flexible neural electrode provided in an embodiment of the present application;
FIG. 4 is a schematic plan view of a single nerve electrode unit provided by an embodiment of the present application;
fig. 5 is a schematic structural diagram of a single neural electrode unit according to an embodiment of the present disclosure.
Detailed Description
To make the objects, technical solutions and advantages of the present application more clear, embodiments of the present application will be described in further detail below with reference to the accompanying drawings. It should be apparent that the described embodiment is only one embodiment of the present application and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.
An "embodiment" as referred to herein relates to a particular feature, structure, or characteristic that may be included in at least one implementation of the present application. In the description of the embodiments of the present application, it should be understood that the terms "upper" and "lower" etc. indicate orientations or positional relationships based on those shown in the drawings, and are only for convenience in describing the present application and simplifying the description, but do not indicate or imply that the referred device/system or element must have a specific orientation, be constructed in a specific orientation, and be operated, and thus should not be construed as limiting the present application. The terms "first", "second", "third" and "fourth" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or an implicit indication of the number of technical features indicated. Thus, features defined as "first", "second", "third" and "fourth" may explicitly or implicitly include one or more of the features. Moreover, the terms "first," "second," "third," and "fourth," etc. are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the data so used is interchangeable under appropriate circumstances such that the embodiments of the application described herein are capable of operation in other sequences than described or illustrated herein. Furthermore, the terms "comprises" and "comprising," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, structure, article, or apparatus that comprises a list of steps or elements is not necessarily limited to those steps or elements expressly listed, but may include other steps or elements not expressly listed or inherent to such process, method, structure, article, or apparatus.
A specific embodiment of a method for manufacturing a high-throughput implantable flexible neural electrode according to the present application is described below, fig. 1 is a schematic flow chart of a method for manufacturing a high-throughput implantable flexible neural electrode according to the present application, and fig. 2 is a process flow chart of a method for manufacturing a high-throughput implantable flexible neural electrode according to the present application, where the present specification provides the method steps as shown in the embodiment or the flow chart, but more or fewer steps may be included based on conventional or non-inventive labor. The order of steps recited in the embodiments is only one of many possible orders of execution and does not represent the only order of execution, and in actual execution, the steps may be performed sequentially or in parallel as in the embodiments or methods shown in the figures (e.g., in the context of parallel processors or multi-threaded processing). Specifically, as shown in fig. 1 and 2, the method includes:
s101: preparing a substrate; the substrate has a release surface.
In an alternative embodiment, the step of preparing the substrate may include obtaining a base, specifically, the base may be a 4-inch silicon wafer, and growing a sacrificial layer on an upper surface of the base by photolithography, metal evaporation and lift-off processes to obtain the substrate, wherein the upper surface of the sacrificial layer is a release surface. As shown in fig. 2 a-b, which illustrate the structure of the substrate and the sacrificial layer, the substrate is located below the overall structure, and the sacrificial layer is located above the overall structure.
S103: preparing a plurality of electrode zone groups on the release surface of the substrate; each electrode area group in the plurality of electrode area groups comprises a first electrode area, a second electrode area and a third electrode area, each electrode area in the first electrode area, the second electrode area and the third electrode area comprises a first preset number of electrodes, and the electrode areas are distributed at intervals so that the substrate is divided into a plurality of areas to be prepared.
In the embodiment of the present application, after the substrate is prepared, a plurality of electrode regions may be prepared on the release surface of the substrate, that is, metal electrodes are grown on the upper surface of the substrate, so as to obtain a plurality of handle shanks. It should be noted that each of the plurality of electrode regions includes a first electrode region, a second electrode region, and a third electrode region, so that a three-layer metal wiring structure can be obtained in a subsequent preparation process, wherein each of the first electrode region, the second electrode region, and the third electrode region includes a first predetermined number of electrodes, and each of the electrode regions is distributed at intervals so that the substrate is divided into a plurality of regions to be prepared. As shown in fig. 2c, which illustrates a schematic structure diagram of one electrode region group on the substrate, in the diagram, three regions of the protrusion on the sacrificial layer are three electrode regions included in one electrode region group, and for convenience of subsequent description, it is assumed that the first electrode region, the second electrode region, and the third electrode region are sequentially arranged from left to right.
In the embodiment of the application, the number of the electrode zone groups in the plurality of electrode zone groups is set to be [10, 15], so that the number of the recorded electroencephalogram signals can be increased, and meanwhile, the number of the probes can be reduced to reduce the contact area between the nerve electrodes and the cerebral cortex, and the damage to a human body is reduced. Furthermore, the first preset number can be adjusted correspondingly based on the number of the electrode area groups in the plurality of electrode area groups.
S105: preparing a first insulating layer on a plurality of regions to be prepared; the first insulating layer has a thickness greater than a thickness of each electrode region.
In the embodiment of the application, after a plurality of electrode area groups are prepared on the release surface of the substrate, each electrode area is distributed at intervals so that the substrate is divided into a plurality of areas to be prepared, and then a first insulating layer is prepared on the plurality of areas to be prepared, namely, a flexible insulating layer is prepared on the release surface corresponding to the plurality of areas to be prepared in the substrate. As fig. 2d illustrates a schematic structural view of the first insulating layer prepared on the plurality of regions to be prepared, it can be clearly determined based on fig. 2d that the thickness of the first insulating layer is greater than that of each electrode region.
S107: preparing a first metal wiring layer on a first electrode area of the electrode area group, and preparing a second insulating layer on the first metal wiring layer; the area of the second insulating layer is larger than that of the first metal wiring layer.
In the embodiment of the application, after the first insulating layers are prepared on the plurality of regions to be prepared, the first electrode region of the electrode region group is subjected to photoetching by using a stepper, and the first metal wiring layer is prepared on the upper surface of the first electrode region by using a metal evaporation and stripping process, so that the first metal wiring layer is connected with the first electrode region. That is, a stepper is used to pattern the upper surface of the first electrode region, and a metal evaporation and stripping process is used to prepare a first metal wiring layer in the pattern, which can be prepared by introducing from the edge of the first electrode region, so that a partial region of the first metal wiring layer does not cover the first electrode region. In the process of preparing the first metal wiring layer on the first electrode region, a photoresist of model UV135G-0.9 or UV135G-0.5 may be used. Here, the wiring width of the first metal wiring layer is within a first preset range, specifically, the first preset range may be [0.35 μm, 0.50 μm ], and fig. 2e illustrates a schematic structural diagram of the first metal wiring layer prepared on the first electrode region of any one group of electrode regions of the electrode region group. Furthermore, a second insulating layer is prepared on the upper surface of the first metal wiring layer, and the material of the second insulating layer may be SU8 or polyimide, as shown in fig. 2f, which illustrates the schematic structure of the second insulating layer prepared on the first metal wiring layer.
S109: preparing a second metal wiring layer on a second electrode area of the electrode area group, and preparing a third insulating layer on the second insulating layer and the second metal wiring layer; the thickness of the second metal wiring layer is greater than that of the first metal wiring layer.
In the embodiment of the application, the second metal wiring layer is prepared on the second electrode area of the electrode area group in the same way as the first metal wiring layer is prepared on the first electrode area of the electrode area group, and the second electrode area of the electrode area group is subjected to photoetching by using a stepping photoetching machine, so that the second metal wiring layer is prepared on the upper surface of the second electrode area and is connected with the second electrode area. That is, a stepper is used to pattern the upper surface of the second electrode region, and a metal evaporation and stripping process is used to prepare a second metal wiring layer in the pattern, which can be introduced from the edge of the second electrode region so that a partial region of the second metal wiring layer does not cover the second electrode region. The direction of introducing and preparing the second metal wiring layer may be the same as the direction of introducing and preparing the first metal wiring layer described above, or may be different from the direction of introducing and preparing the first metal wiring layer described above. In the process of preparing the second metal wiring layer on the second electrode region, a photoresist of model UV135G-0.9 or UV135G-0.5 may be used. Here, the wiring width of the second metal wiring layer is also within the first predetermined range, and likewise, the first predetermined range may be [0.35 μm, 0.50 μm ], as shown in fig. 2g, which illustrates a schematic structural view of the second metal wiring layer prepared on the second electrode region of any one set of electrode regions of the electrode region group. Furthermore, a third insulating layer is prepared on the upper surface of the second insulating layer and the upper surface of the second metal wiring layer, and fig. 2h illustrates a schematic structural diagram of the third insulating layer prepared on the second insulating layer and the second metal wiring layer.
S111: preparing a third metal wiring layer on a third electrode area of the electrode area group, and preparing a fourth insulating layer on the second insulating layer, the third insulating layer and the third metal wiring layer; the thickness of the third metal wiring layer is greater than that of the second metal wiring layer.
In the embodiment of the application, the method for preparing the third metal wiring layer on the third electrode area of the electrode area group is the same as the method for preparing the first metal wiring layer on the first electrode area of the electrode area group, and the third electrode area of the electrode area group is subjected to photoetching by using a stepping photoetching machine, so that the third metal wiring layer is prepared on the upper surface of the third electrode area, and the third metal wiring layer is connected with the third electrode area. That is, a stepper is used to pattern the upper surface of the third electrode region, and a metal evaporation and stripping process is used to prepare a third metal wiring layer in the pattern, which can be introduced from the edge of the third electrode region so that a partial region of the third metal wiring layer does not cover the third electrode region. The direction of introducing and preparing the third metal wiring layer may be the same as the direction of introducing and preparing the first metal wiring layer and the direction of introducing and preparing the second metal wiring layer described above, may be the same as the direction of introducing and preparing the first metal wiring layer described above and the direction of introducing and preparing the second metal wiring layer described above, and may be the same as the direction of introducing and preparing the first metal wiring layer described above and the direction of introducing and preparing the second metal wiring layer described above. In the process of preparing the third metal wiring layer on the third electrode region, a photoresist of model UV135G-0.9 or UV135G-0.5 may be used. Here, the wiring width of the third metal wiring layer is also within the first predetermined range, and likewise, the first predetermined range may be [0.35 μm, 0.50 μm ], as illustrated in fig. 2i, a schematic view of the structure of the third metal wiring layer prepared on the third electrode region of any one set of electrode regions of the electrode region group. Furthermore, a fourth insulating layer is formed on the upper surface of the second insulating layer, the upper surface of the third insulating layer, and the upper surface of the third metal wiring layer, and fig. 2j illustrates a schematic structural diagram of the fourth insulating layer formed on the second insulating layer, the third insulating layer, and the third metal wiring layer.
S113: and peeling the substrate along the release surface to obtain the single nerve electrode unit.
In the embodiment of the present application, based on the connection between the upper surface of the substrate and the lower surface of the sacrificial layer, and the upper surface of the sacrificial layer is a release surface, after the fourth insulating layer of the encapsulation layer is prepared on the second insulating layer, the third insulating layer, and the third metal wiring layer, the substrate is peeled off along the upper surface of the sacrificial layer, that is, the release surface, so that the single neural electrode unit can be obtained. Fig. 2k illustrates a schematic structure diagram of a single nerve electrode unit.
S115: and connecting the single nerve electrode units with a second preset number with the circuit board to obtain the high-flux implanted flexible nerve electrode.
In the embodiment of the present application, after obtaining a single neural electrode unit, multiple single neural electrode units may be obtained through the same preparation method, and a plurality of single neural electrode units with higher preparation quality are selected, where the setting interval of the second preset number may be [4, 6 ]. And the plurality of single nerve electrode units are connected with the circuit board by connecting modes such as bonding, welding and the like, and are led out by utilizing a metal lead to obtain the high-flux implanted flexible nerve electrode for acquiring and recording signals.
In the embodiment of the application, the number of the electrode zone groups, namely the number of the shank, the number of the electrodes contained in each electrode zone, namely the first preset number, and the number of the single nerve electrode units, namely the second preset number can be set, so that the damage of the high-flux implanted flexible nerve electrode to the cerebral cortex can be reduced while the number of channels of the implanted flexible nerve electrode is increased. In an alternative embodiment, the number of channels of the single neural electrode unit is 2160 and the number of channels of the high-throughput implantable flexible neural electrode is 10800 by setting the values of the number of shanks, the first preset number and the second preset number.
The number of channels of a single neural electrode unit is 2160, and the number of channels of the high-flux implantable flexible neural electrode is 10800 by setting the values of the number of shanks, the first preset number and the second preset number.
Example 1
Assuming that 12 electrode groups, namely the number of shanks is 12, are prepared on the release surface of the substrate, each of the 12 electrode groups includes a first electrode region, a second electrode region and a third electrode region, each of the first electrode region, the second electrode region and the third electrode region includes 60 electrodes, namely the first preset number is 60, so that each shank includes 3 × 60 — 180 metal detection points, and each shank is a three-layer metal wiring structure, the number of channels of a single nerve electrode unit is 180 × 12 — 2160, and if 5 single nerve electrode units are selected to be connected with the circuit board, namely the second preset number is 5, the number of channels of the high-flux implantable flexible nerve electrode is 2160 × 5 — 10800.
Example 2
Assuming that 10 electrode groups, namely the number of shanks is 10, are prepared on the release surface of the substrate, each of the 10 electrode groups includes a first electrode region, a second electrode region and a third electrode region, each of the first electrode region, the second electrode region and the third electrode region includes 72 electrodes, namely the first preset number is 72, so that each shank includes 3 × 72 to 216 metal detection points, and each shank is a three-layer metal wiring structure, the number of channels of a single nerve electrode unit is 216 × 10 to 2160, and if 5 single nerve electrode units are selected to be connected with the circuit board, namely the second preset number is 5, the number of channels of the high-flux implantable flexible nerve electrode is 2160 × 5 to 10800.
Example 3
Assuming that 15 electrode groups, namely the number of shanks is 15, are prepared on the release surface of the substrate, each of the 15 electrode groups includes a first electrode region, a second electrode region and a third electrode region, each of the first electrode region, the second electrode region and the third electrode region includes 48 electrodes, namely the first preset number is 48, so that each shank includes 3 × 48 to 144 metal detection points, and each shank is a three-layer metal wiring structure, the number of channels of a single nerve electrode unit is 144 × 15 to 2160, and if 5 single nerve electrode units are selected to be connected with the circuit board, namely the second preset number is 5, the number of channels of the high-flux implantable flexible nerve electrode is 2160 × 5 to 10800.
The number of channels of a single neural electrode unit is 1800, and the number of channels of the high-flux implantable flexible neural electrode is 10800 by setting the values of the number of shanks, the first preset number and the second preset number.
Example 1
Assuming that 12 electrode groups, namely the number of shanks is 12, are prepared on the release surface of the substrate, each of the 12 electrode groups includes a first electrode region, a second electrode region and a third electrode region, each of the first electrode region, the second electrode region and the third electrode region includes 50 electrodes, namely the first preset number is 50, so that each shank includes 3 × 50 to 150 metal detection points, and each shank is a three-layer metal wiring structure, the number of channels of a single nerve electrode unit is 150 × 12 to 1800, and if 6 single nerve electrode units are selected to be connected with the circuit board, namely the second preset number is 6, the number of channels of the high-flux implantable flexible nerve electrode is 1800 × 6 to 10800.
Example 2
Assuming that 10 electrode blocks, namely the number of shanks is 10, are prepared on the release surface of the substrate, each of the 10 electrode blocks includes a first electrode region, a second electrode region and a third electrode region, each of the first electrode region, the second electrode region and the third electrode region includes 60 electrodes, namely the first preset number is 60, so that each shank includes 3 × 60 — 180 metal detection points, and each shank is a three-layer metal wiring structure, the number of channels of a single nerve electrode unit is 180 × 10 — 1800, and if 6 single nerve electrode units are selected to be connected with the circuit board, namely the second preset number is 5, the number of channels of the high-flux implantable flexible nerve electrode is 1800 × 6 — 10800.
Example 3
Assuming that 15 electrode blocks, namely the number of shanks is 15, are prepared on the release surface of the substrate, each of the 15 electrode blocks contains a first electrode region, a second electrode region and a third electrode region, each of the first electrode region, the second electrode region and the third electrode region contains 40 electrodes, namely the first preset number is 40, so that each shank contains 3 × 40 to 120 metal detection points, and each shank is a three-layer metal wiring structure, the number of channels of a single nerve electrode unit is 120 × 15 to 1800, and if 6 single nerve electrode units are selected to be connected with the circuit board, namely the second preset number is 5, the number of channels of the high-flux implantable flexible nerve electrode is 1800 × 6 to 10800.
The number of channels of a single neural electrode unit is 1800, and the number of channels of the high-flux implantable flexible neural electrode is 10800 by setting the values of the number of shanks, the first preset number and the second preset number.
Example 1
Assuming that 12 electrode groups, namely the number of shanks is 12, are prepared on the release surface of the substrate, each of the 12 electrode groups contains a first electrode region, a second electrode region and a third electrode region, each of the first electrode region, the second electrode region and the third electrode region contains 75 electrodes, namely the first preset number is 75, so that each shank contains 3 × 75 to 225 metal detection points, and each shank is a three-layer metal wiring structure, the number of channels of a single nerve electrode unit is 225 × 12 to 2700, and if 4 single nerve electrode units are selected to be connected with the circuit board, namely the second preset number is 4, the number of channels of the high-flux implantable flexible nerve electrode is 2700 × 4 to 10800.
Example 2
Assuming that 10 electrode blocks, namely the number of shanks is 10, are prepared on the release surface of the substrate, each of the 10 electrode blocks includes a first electrode region, a second electrode region and a third electrode region, each of the first electrode region, the second electrode region and the third electrode region includes 90 electrodes, namely the first preset number is 90, so that each shank includes 3 × 90-270 metal detection points, and each shank is a three-layer metal wiring structure, the number of channels of a single nerve electrode unit is 270 × 10-2700, and if 4 single nerve electrode units are selected to be connected with the circuit board, namely the second preset number is 4, the number of channels of the high-flux implantable flexible nerve electrode is 2700 × 4-10800.
Example 3
Assuming that 15 electrode blocks, namely the number of shanks is 15, are prepared on the release surface of the substrate, each of the 15 electrode blocks contains a first electrode region, a second electrode region and a third electrode region, each of the first electrode region, the second electrode region and the third electrode region contains 60 electrodes, namely the first preset number is 60, so that each shank contains 3 × 60 — 180 metal detection points, and each shank is a three-layer metal wiring structure, the number of channels of a single nerve electrode unit is 180 × 15 — 2700, and if 4 single nerve electrode units are selected to be connected with the circuit board, namely the second preset number is 4, the number of channels of the high-flux implantable flexible nerve electrode is 2700 × 4 — 10800.
In the embodiment of the present application, the number of channels of a single neural electrode unit and the number of channels of the high-flux implantable flexible neural electrode may also be increased by setting the values of the number of shanks, the first preset number, and the second preset number, which are not described herein again.
By adopting the preparation method of the high-flux implanted flexible neural electrode provided by the embodiment of the application, the channel number of the implanted flexible neural electrode can be increased by setting the values of the number of the shanks, the first preset number and the second preset number so as to record a large number of neuron activity signals in a single brain area or record activity signals of neurons with different functions spanning the brain area, and the damage of the high-flux implanted flexible neural electrode to the cerebral cortex can be reduced, thereby facilitating the later-stage more complex analysis and diagnosis of the brain activity.
Fig. 3 is a schematic plan view of the structure of the high-throughput implantable flexible neural electrode provided in the embodiment of the present application, and the diagram includes 5 single neural electrode units, a first region of the 5 single neural electrode units, that is, a solid frame, is a connection region connected to a circuit board, and a second region, that is, a frame selecting frame, is an implanted electrode region.
Fig. 4 is a schematic plan view of a single nerve electrode unit provided in an embodiment of the present application, which includes a connection area connected to a circuit board, i.e., a partial area located above the overall plane of the single nerve electrode unit, a metal wiring layer, i.e., a partial area located in the middle of the overall plane of the single nerve electrode unit, and an implantation area, i.e., a partial area located below the overall plane of the single nerve electrode unit, wherein the metal wiring layer has a three-layer structure, the implantation area includes 12 electrode area groups, and each of a first electrode area, a second electrode area, and a third electrode area in each electrode area includes 60 electrodes.
Fig. 5 is a schematic structural diagram of a single neural electrode unit according to an embodiment of the present disclosure. As shown in fig. 5, the structure includes:
accordingly, the embodiment of the present application also provides a structure of a high-throughput implantable flexible neural electrode, which includes:
a plurality of single neural electrode units; each of the plurality of single nerve electrode units comprises a plurality of electrode zone groups;
each electrode area group in the plurality of electrode area groups comprises a first electrode area, a second electrode area, a third electrode area and a plurality of first insulating layers; the first electrode region, the second electrode region, the third electrode region and the plurality of first insulating layers are on the same plane, and the electrode regions in the first electrode region, the second electrode region and the third electrode region are distributed at intervals with the first insulating layers in the plurality of first insulating layers;
a first metal wiring layer on the first electrode region;
a second insulating layer on the first metal wiring layer; the area of the second insulating layer is larger than that of the first metal wiring layer;
a second metal wiring layer on the second electrode region; the thickness of the second metal wiring layer is larger than that of the first metal wiring layer;
a third insulating layer on the second insulating layer and the second metal wiring layer;
a third metal wiring layer on the third electrode region; the thickness of the third metal wiring layer is larger than that of the second metal wiring layer;
a fourth insulating layer on the second insulating layer, the third insulating layer, and the third metal wiring layer;
a circuit board; the circuit board is connected with a plurality of single nerve electrode units.
In the embodiment of the present application, the structure may specifically include 5 single neural electrode units;
each of the 5 single nerve electrode units comprises 12 electrode groups;
the number of channels of a single nerve electrode unit is 2160;
the number of channels of the high-flux implanted flexible nerve electrode is 10800.
The structure and method embodiments in the embodiments of the present application are based on the same application concept.
As can be seen from the above embodiments of the method or structure for manufacturing a high-throughput implantable flexible neural electrode provided in this application, the method for manufacturing this application specifically includes preparing a substrate, the substrate having a release surface, preparing a plurality of electrode block groups on the release surface of the substrate, wherein each of the plurality of electrode block groups includes a first electrode region, a second electrode region, and a third electrode region, each of the first electrode region, the second electrode region, and the third electrode region includes a first predetermined number of electrodes, each of the electrode regions is distributed at intervals so that the substrate is divided into a plurality of regions to be manufactured, preparing a first insulating layer on the plurality of regions to be manufactured, the first insulating layer having a thickness greater than that of each of the electrode regions, preparing a first metal wiring layer on the first electrode region of the electrode block groups, and preparing a second insulating layer on the first metal wiring layer, the second insulating layer having an area greater than that of the first metal wiring layer, and finally, preparing a second metal wiring layer on a second electrode area of the electrode area group, preparing a third insulating layer on the second insulating layer and the second metal wiring layer, wherein the thickness of the second metal wiring layer is greater than that of the first metal wiring layer, preparing a third metal wiring layer on the third electrode area of the electrode area group, preparing a fourth insulating layer on the second insulating layer, the third insulating layer and the third metal wiring layer, wherein the thickness of the third metal wiring layer is greater than that of the second metal wiring layer, stripping the substrate along the release surface to obtain single nerve electrode units, and connecting a second preset number of single nerve electrode units with the circuit board to obtain the high-flux implantable flexible nerve electrode. Based on the embodiment of the application, the channel number of the implanted flexible nerve electrode can be increased by setting the values of the number of the shank, the first preset number and the second preset number so as to record a large number of neuron activity signals in a single brain region or record activity signals of different functional neurons across the brain region, and the damage of the high-flux implanted flexible nerve electrode to the cerebral cortex can be reduced, so that the later-stage more complex brain activity analysis and diagnosis are facilitated.
It should be noted that: the foregoing sequence of the embodiments of the present application is for description only and does not represent the superiority and inferiority of the embodiments, and the specific embodiments are described in the specification, and other embodiments are also within the scope of the appended claims. In some cases, the actions or steps recited in the claims can be performed in the order of execution in different embodiments and achieve desirable results. In addition, the processes depicted in the accompanying figures do not necessarily require the particular order shown or connected to enable the desired results to be achieved, and in some embodiments, multitasking and parallel processing may also be possible or may be advantageous.
All the embodiments in the present specification are described in a progressive manner, and the same and similar parts among the embodiments may be referred to each other, and each embodiment is described with emphasis on differences from other embodiments. In particular, for the structural embodiment, since it is based on the method embodiment, the description is simple, and the relevant points can be referred to the partial description of the method embodiment.
While the foregoing is directed to the preferred embodiment of the present invention, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention.

Claims (11)

1. A preparation method of a high-flux implantable flexible neural electrode is characterized by comprising the following steps:
preparing a substrate; the substrate has a release face;
preparing a plurality of electrode zone groups on the release side of the substrate; each electrode area group in the plurality of electrode area groups comprises a first electrode area, a second electrode area and a third electrode area, each electrode area in the first electrode area, the second electrode area and the third electrode area comprises a first preset number of electrodes, and the electrode areas are distributed at intervals so that the substrate is divided into a plurality of areas to be prepared;
preparing a first insulating layer on the plurality of regions to be prepared; the thickness of the first insulating layer is greater than that of each electrode region;
preparing a first metal wiring layer on a first electrode area of the electrode area group, and preparing a second insulating layer on the first metal wiring layer; the area of the second insulating layer is larger than that of the first metal wiring layer;
preparing a second metal wiring layer on a second electrode region of the electrode region group, and preparing a third insulating layer on the second insulating layer and the second metal wiring layer; the thickness of the second metal wiring layer is larger than that of the first metal wiring layer;
preparing a third metal wiring layer on a third electrode region of the electrode region group, and preparing a fourth insulating layer on the second insulating layer, the third insulating layer and the third metal wiring layer; the thickness of the third metal wiring layer is larger than that of the second metal wiring layer;
peeling the substrate along the release surface to obtain a single nerve electrode unit;
and connecting a second preset number of single nerve electrode units with the circuit board to obtain the high-flux implanted flexible nerve electrode.
2. The method of claim 1, wherein the preparing a first metal wiring layer on a first electrode region of the electrode region group comprises:
photoetching a first electrode area of the electrode area group by using a stepping photoetching machine, and preparing a first metal wiring layer on the upper surface of the first electrode area by using metal evaporation and stripping processes; the wiring width of the first metal wiring layer is within a first preset range.
3. The method of claim 2, wherein the step of forming a second metal wiring layer on a second electrode region of the electrode region group comprises:
photoetching a second electrode area of the electrode area group by using a stepping photoetching machine, and preparing a second metal wiring layer on the upper surface of the second electrode area by using metal evaporation and stripping processes; the wiring width of the second metal wiring layer is within a first preset range.
4. The method of claim 1, wherein the step of forming a third metal wiring layer on a third electrode region of the electrode region group comprises:
photoetching a third electrode area of the electrode area group by using a stepping photoetching machine, and preparing a third metal wiring layer on the upper surface of the third electrode area by using a metal evaporation and stripping process; the wiring width of the third metal wiring layer is within a first preset range.
5. The method of claim 1, wherein the number of channels of the single neural electrode unit is 2160;
the number of channels of the high-flux implanted flexible nerve electrode is 10800.
6. The production method according to claim 5, wherein the number of electrode zone groups in the plurality of electrode zone groups is set to [10, 15 ];
the setting interval of the second preset number is [4, 6 ].
7. The method of claim 6, wherein the preparing a plurality of electrode zone groups on the release surface of the substrate comprises:
preparing 12 electrode area groups on the release surface of the substrate, wherein each electrode area group of the 12 electrode area groups comprises a first electrode area, a second electrode area and a third electrode area, and each electrode area of the first electrode area, the second electrode area and the third electrode area comprises 60 electrodes.
8. The preparation method according to claim 6, wherein the step of connecting a second preset number of single nerve electrode units with a circuit board to obtain the high-flux implantable flexible nerve electrode comprises:
and connecting 5 single nerve electrode units with the circuit board to obtain the high-flux implanted flexible nerve electrode.
9. The production method according to claim 1, further comprising a step of producing the substrate;
the step of preparing the substrate comprises:
obtaining a substrate;
preparing a sacrificial layer on the upper surface of the base to obtain the substrate; the upper surface of the sacrificial layer is the release surface.
10. A structure of a high-flux implantable flexible neural electrode, comprising:
a plurality of single neural electrode units; each of the plurality of single nerve electrode units comprises a plurality of electrode zone groups;
each electrode area group in the plurality of electrode area groups comprises a first electrode area, a second electrode area, a third electrode area and a plurality of first insulating layers; the first electrode region, the second electrode region, the third electrode region and the plurality of first insulating layers are on the same plane, and electrode regions in the first electrode region, the second electrode region and the third electrode region are distributed at intervals with first insulating layers in the plurality of first insulating layers;
a first metal wiring layer on the first electrode region;
a second insulating layer on the first metal wiring layer; the area of the second insulating layer is larger than that of the first metal wiring layer;
a second metal wiring layer on the second electrode region; the thickness of the second metal wiring layer is larger than that of the first metal wiring layer;
a third insulating layer on the second insulating layer and the second metal wiring layer;
a third metal wiring layer on the third electrode region; the thickness of the third metal wiring layer is larger than that of the second metal wiring layer;
a fourth insulating layer on the second insulating layer, the third insulating layer, and the third metal wiring layer;
a circuit board; the circuit board is connected with the plurality of single nerve electrode units.
11. The structure of claim 10, wherein the structure comprises 5 single nerve electrode units;
each of the 5 single neural electrode units comprises 12 electrode zone groups;
the number of channels of the single nerve electrode unit is 2160;
the number of channels of the high-flux implanted flexible nerve electrode is 10800.
CN202010860818.6A 2020-08-24 2020-08-24 Preparation method and structure of high-flux implanted flexible nerve electrode Active CN112107307B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010860818.6A CN112107307B (en) 2020-08-24 2020-08-24 Preparation method and structure of high-flux implanted flexible nerve electrode

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010860818.6A CN112107307B (en) 2020-08-24 2020-08-24 Preparation method and structure of high-flux implanted flexible nerve electrode

Publications (2)

Publication Number Publication Date
CN112107307A CN112107307A (en) 2020-12-22
CN112107307B true CN112107307B (en) 2021-05-25

Family

ID=73805112

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010860818.6A Active CN112107307B (en) 2020-08-24 2020-08-24 Preparation method and structure of high-flux implanted flexible nerve electrode

Country Status (1)

Country Link
CN (1) CN112107307B (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113729717A (en) * 2021-08-09 2021-12-03 江西脑虎科技有限公司 Preparation method and structure of flexible electrode probe
CN114356074B (en) * 2021-11-30 2024-04-23 上海交通大学 Animal brain-computer interface implementation method and system based on in-vivo fluorescence signals
CN114515154A (en) * 2022-02-15 2022-05-20 中国科学院上海微系统与信息技术研究所 Integrated brain electrode structure and preparation method thereof

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4953132B2 (en) * 2007-09-13 2012-06-13 日本電気株式会社 Semiconductor device
EP2087838A1 (en) * 2008-02-05 2009-08-12 Ikerlan, S. Coop. Metallization process to obtain a microelectrode on a photopatternable substrate and its biomedical application on an organ transplant monitoring device
US8261428B2 (en) * 2009-11-25 2012-09-11 National Tsing Hua University Method for assembling a 3-dimensional microelectrode structure
CN101973508B (en) * 2010-09-17 2012-09-05 上海交通大学 Flexible substrate MEMS technology-based electroencephalogram dry electrode array and preparation method thereof
US20170079568A1 (en) * 2015-09-17 2017-03-23 Greg GERHARDT Dual-Sided Biomorphic Bioflex Polymer-based Microelectrode Array and Fabrication Thereof
CN106073771B (en) * 2016-06-29 2019-10-18 中国科学院上海微系统与信息技术研究所 A kind of customizable various dimensions high density flexible brain electrode and preparation method thereof
CN109922714A (en) * 2016-11-07 2019-06-21 夏普株式会社 Apparatus for measuring biological data, the control method of apparatus for measuring biological data, control device and control program
CN107485386B (en) * 2017-09-21 2021-03-19 中国科学院电子学研究所 Intracranial cortical neural information detection electrode, electrode array and preparation method thereof
CN110935495B (en) * 2019-11-29 2021-02-23 中国科学院电子学研究所 GABA and electrophysiological micro-nano synchronous sensing detection chip and preparation method thereof

Also Published As

Publication number Publication date
CN112107307A (en) 2020-12-22

Similar Documents

Publication Publication Date Title
CN112107307B (en) Preparation method and structure of high-flux implanted flexible nerve electrode
Hoogerwerf et al. A three-dimensional microelectrode array for chronic neural recording
Kuperstein et al. A practical 24 channel microelectrode for neural recording in vivo
CN106073771B (en) A kind of customizable various dimensions high density flexible brain electrode and preparation method thereof
US8170638B2 (en) MEMS flexible substrate neural probe and method of fabricating same
US6024702A (en) Implantable electrode manufactured with flexible printed circuit
Drake et al. Performance of planar multisite microprobes in recording extracellular single-unit intracortical activity
DE60114031T2 (en) ELECTRODE ARRANGEMENT AND SENSOR CONNECTION SYSTEM FOR A NON-INVASIVE DEVICE FOR PLACING AND FIGUREING NERVES
Krüger et al. Simultaneous recording with 30 microelectrodes in monkey visual cortex
Fofonoff et al. Microelectrode array fabrication by electrical discharge machining and chemical etching
CA2426330A1 (en) Electrical sensing and/or signal application device
CN101194831A (en) Self-adhering electrodes and methods of making the same
CN112006685B (en) Flexible micro-nano electrode array for positioning cortex epileptic brain function and preparation method thereof
CN112244850B (en) Intracranial deep electrode recording device and preparation method and system thereof
Mendoza et al. Recording extracellular neural activity in the behaving monkey using a semichronic and high-density electrode system
Schander et al. A flexible 202-channel epidural ECoG array with PEDOT: PSS coated electrodes for chronic recording of the visual cortex
DE102009044029A1 (en) Electrode set for a patient monitoring device
EP2397071A1 (en) Neural probe with a modular microelectrode for stimulating neurons or recording neural activity
CN114469113A (en) Multi-channel flexible microneedle electrode and preparation method
CN110709692A (en) Apparatus and method for acquiring neural recordings
CN113181549A (en) Flexible micro-nano electrode array for positioning deep brain of epileptogenic focus and preparation method thereof
CN113545790B (en) Preparation method of magnetic compatible nerve probe
Hetke et al. Silicon microelectrodes for extracellular recording
EP2033575A1 (en) Method for continuously or step by step manufacturing or biomedical multiple electrodes for single use, and matrix electrode system consisting of same
Pickard et al. Flexible printed-circuit probe for electrophysiology

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
TR01 Transfer of patent right
TR01 Transfer of patent right

Effective date of registration: 20220304

Address after: 200001 Building 1, building 2 and building 3, No. 787, manufacturing Bureau Road, Huangpu District, Shanghai (centralized registration place)

Patentee after: Shanghai naohu Technology Co.,Ltd.

Address before: 200050 No. 865, Changning Road, Shanghai, Changning District

Patentee before: SHANGHAI INSTITUTE OF MICROSYSTEM AND INFORMATION TECHNOLOGY, CHINESE ACADEMY OF SCIENCES