TWI287088B - Multichannel microelectrode probe and fabricating method thereof - Google Patents

Abstract

A multichannel microelectrode probe is provided, and is suitable for biological electrical signal detection. The multichannel microelectrode probe includes a substrate, a first isolation layer, microelectrode pads, micro-conductive wires, transmission pads, a second isolation layer, microelectrodes and bonding pads. The first isolation is located on the substrate. The microelectrode pads, the micro-conductive wires and the transmission pads are located on the first isolation layer, wherein each microelectrode pad is connected with the transmission pad by the micro-conductive wire. The second isolation covers the microelectrode pads, the micro-conductive wires and the transmission pads, wherein the second isolation layer has first openings exposing the microelectrode pads, and second openings exposing transmission pads. The microelectrodes and bonding pads are respectively located in the first openings and the second openings.

Description

1287088 14922twf.doc/g IX. Invention Description:

BACKGROUND OF THE INVENTION 1. Field of the Invention This invention relates to a probe for detecting bioelectrical signals and a method for manufacturing the same, and more particularly to a multichannel microelectrode probe and a method of fabricating the same. [Prior Art] The brain is one of the most important organs of the organism, which is responsible for directing, controlling, and coordinating the operation of various parts of the body. The brain contains millions of complex, interconnected neurons that can process complex sensory signals when a site is stimulated. In the brain, the Thalamus can be regarded as a transmission station (Rday), which transmits the sensory signal from the Periphery to the relevant area of the Cerebral Cortex, making it a higher order. Perception (percepti〇n). On the other hand, in living organisms, different nervous systems, such as the peripheral nervous system and the central nervous system, have different purposes, and therefore, the area in which the 彳 s is transmitted to the brain is also different. Therefore, one of the new tools for biological in vivo detail research in recent years has been carried out using multi-channel microelectrode probes. Since such a probe has a plurality of microelectrodes, the spatial arrangement of the microelectrodes can be used to record signals transmitted from different nerve tissues such as the peripheral nervous system and the central nervous system to different regions of the brain. In addition, such microelectrode probes can also be applied to cardiac signal extraction (Cardiac myocytes) for electrical signal extraction or drug screening. However, it is worth noting that the use of multi-channel microelectrode probes to detect the electrical signal changes in biological tissues is accurate or not, and is based on the micro-! 287〇88 14922twf.doc/gr electrode on the probe. Organize mosquito swabs to be extremely close. For example, if the density of the microelectrodes is too thin, when the beans enter the * bioelectrical signal, such as entering the hypothalamus of the brain, the neural signal detection of the specific brain region can be missed, resulting in the detection result. Distortion In addition, if the microelectrode arrangement density is too high, although the accuracy of the detection result can be improved', it may take more time and cost to perform the processing of 0. In addition, today's multi-channel microelectrode The process of the probe also faces some problems. For example, although such probes can be achieved by integration of MEMS semiconductor technology, the conventional process steps mainly utilize the chemical or wet-type side technology to unload the processed probe from the Shixi wafer. = Down, but due to the cumbersome process steps, it has not been able to effectively improve the production capacity. SUMMARY OF THE INVENTION In view of the above, it is an object of the present invention to provide a method of manufacturing a multi-channel microelectrode probe to increase productivity. A further object of the present invention is to provide a multi-channel microelectrode probe for use in the detection of multi-channel bioelectrical signals in vivo (/«F?VO) or in vitro (/w tissue/cells, These tests, for example, neuronal activity signals, and can ensure the accuracy of the detection results. ° The present invention provides a method of manufacturing a multi-channel microelectrode probe suitable for bioelectrical signal detection, which is first Providing a substrate, wherein the substrate has a bioelectric signal detection area and a rear end signal transfer area. Then, a first insulating layer is formed on the substrate. Then, a number is formed on the first layer of the 12 1287088 14922 twf.doc/g edge layer a microelectrode pad, a plurality of microwires and a plurality of transmission pads, wherein the microelectrode pads are located in the bioelectric signal detection area, and the transmission pads are located in the rear end signal transfer area, and the respective microelectrode contacts are corresponding a microwire is connected to a corresponding one of the transfer pads. Thereafter, a second insulating layer is formed on the substrate, covering the microelectrode pad, the microwire and the transfer pad, wherein the second insulating layer is in the bioelectrical signal The measuring area has a plurality of first electrode pads' and has a plurality of first and second output transmission pads in the rear end signal transfer region. Then, a plurality of microelectrodes and numbers are formed in the first openings and the middle (four) A wire bonding point, and each microelectrode is electrically connected with each microelectrode pad, and each wire bonding point is electrically connected with each transmission pad. The laser cutting process is most performed, and the bioelectric signal detection area and the back end 4 The membrane layer in the transition zone is made into a probe pattern. The present invention provides a multi-channel microelectrode probe whose proper gas signal detection is based on the substrate, the first insulating layer, The microelectrode, the microwire, the transmission pad, the second insulating layer, the microelectrode and the snoring line are formed, wherein the substrate has a bioelectric signal detection zone and a rear end signal transmission zone. In addition, the first insulation layer The microelectrode pad is disposed on the first insulating layer of the bioelectric signal detecting area. In addition, the micro wire is disposed on the first insulating layer. In addition, the transmission & Letter_connection area - insulation In the above, each of the microelectrode tethers is connected to the corresponding transfer pad by the corresponding microwire. Further, the second insulating layer covers the microelectrode pad, the microwire and the transmission pad, wherein the second layer is a layer, and there are several An opening exposes the microelectrode pad, and a plurality of second electrodes expose the transfer pad. In addition, a plurality of microelectrodes and wire bonding points are respectively disposed in & 7 1287088 14922twf.doc/g opening and opening And each of the microelectrodes is electrically connected to each of the microelectrodes, and each of the wire bonding points is electrically connected to each of the transmission pads. According to the present invention, the multi-pass electrode probe or the "manufacturing method, the above phase" The spacing of the adjacent two microelectrodes (pi just d is calculated by the cross correlation of equation (1). The correlation coefficient calculated by (Cong^^(4)(4) is not less than ^·95' and the individual difference is evaluated by student's paired /-test. Finally, P is used. Value determines whether it has reached statistically <0.05), , and (1) X"

N Μ w=1 Λ __~F) _ - J)2 (1 ― - i)d (?二?7# where 'Xn[tm] is the nth measurement of the single point microelectrode repeated at a recording point The sampled signal value of the mth (fourth) point is recorded later; Yn[tm] is the sampling signal of the mth time point recorded after the nth measurement of the single point microelectrode is repeated at the position from the recording point d Value; variable n = i ~ Ν, Ν is the number of repeated measurements (Sweep); variable m = 1 ~ Μ, Μ is the number of data points sampled during the measurement. ', according to the oxygen preferred embodiment of the invention The multi-channel microelectrode probe or the manufacturing method thereof, the above-mentioned repeated measurement times Ν value is related to the cross-correlation of the formula (2) 8 1287088 14922twf.doc / g heart jin knows the phase _ number p 2 value is not less than (4), and use dent, s / ca Ping to estimate the individual differences of the experiment, and finally use P value to determine whether there is a statistically significant difference (household < 〇〇 5), formula (7)

Bu N

Ati

N rtj=l 一 1 Μ a =—Yau 2N ixu «2=(^+1) __ 1 Μ b^±-Ybu Μ±ί

Am[tm] and Bn2[tm] are the n2th system at the same recording point.

When the sampling surface is 2N = η2 = (Ν+ΐ)^2Ν· λ, λ ηι — 1 Ν Ν, change J points. , 遽m = 1~M 'M is the sample taken during the measurement. 3== The multi-channel microelectrode described in the example is recorded as the multi-channel microelectrode as described in the production example, for example It is titanium, turned or silver/silver chloride. In the above-mentioned first-insulating layer or second insulating layer by the method of bismuth metal wood: = 1287088 14922twf.doc / g gasification bismuth, bismuth oxynitride, non-conductive plastic or non-conductive according to the present invention In the manufacturing method described in the preferred embodiment, the substrate material is, for example, a stone, plastic or non-conductive polymer material. The laser cutting process of the multi-channel microelectrode probe described in the preferred embodiment of the present invention can be used, for example, the power of the pulse-type subgrid-type subgrain is 65 to 7 1 is L. 64 micron, pulse type sub = = the focal length of the beam is, for example, between 15 〇 and 16 〇, and the beam diameter is, for example, 2. To 3. The method of the multi-electrode microelectrode probe according to the preferred embodiment of the present invention, wherein the width of the probe pattern is, for example, gradually oriented toward one direction = the present embodiment. The k method of the multi-channel microelectrode probe, the above-mentioned attack method is a probe shape rear end signal transfer region, and the total thickness of one insulating layer, the first insulating layer and the substrate is cut. The multi-channel upper crucible according to the preferred embodiment of the present invention performs the pre-cutting process after the formation of the microelectrode and the bonding point, and after performing the lightning-cutting process, for example, Reactivity 14922 twf.doc/g A multi-channel microelectrode probe according to a preferred embodiment of the invention, which is applicable to biological in vivo coffee (4) and ex vivo tissue or fine = sample detection 'such as detection is large Electrical sputum or cardiac electrical signal detection in the rat biological nervous system. In accordance with a preferred embodiment of the present invention, the multi-channel microelectrode probe has a thickness that is greater than or equal to the depth of the first opening and the first opening. Since the fabrication of the multi-channel microelectrode probe of the present invention cuts the probe pattern by laser cutting, the process can be simplified, thereby improving the production yield. In addition/due to the multi-channel microelectrode probe of the present invention, The correlation coefficient a of the electrode d calculated by the cross-correlation calculation of the formula (1) is smaller than G.95 and conforms to the statistically significant difference (P&lt;G.G5), so the sputum channel organism is performed by the probe of the ^ month. Electrical (4) system, the results have higher reliability and accuracy. The above and other objects, features and advantages of the present invention will become more apparent.实施 [Embodiment] FIG. 1A to FIG. 1A are schematic perspective views showing a manufacturing process of a =channel micro-f pole probe according to a preferred embodiment of the present invention, and the multi-channel microelectrode needle picking system is suitable for bioelectrical signals. checking. Referring to FIG. 1A, a substrate 100 is provided, and the substrate 100 has a biogas detection region 102 and a rear end signal transition region 1-4. The material of the substrate 10 is, for example, germanium, glass, non-conductive plastic, non-conductive high molecular material 1287088 14922twf.doc/g or other suitable materials. Then, an insulating layer 1% was formed on the substrate 100. For example, it is a oxidized stone, a nitrogen oxide, or a non-conductive polymer or a complex non-V-electricity. In addition, the insulating layer 106 is formed into a woven or cell vapor deposition process or other suitable process. The chemistry is 1500 angstroms. The thickness of the formed signal is as above! r-conducting layer - wherein the conductive material is, for example, low::,,,, non-gold; heteropoly (4), if it has a high dopant concentration; :,. In addition, the formed or =: layer, the middle 'is a high degree of one = then 'please', please refer to FIG. 1B, the signal conducting layer (10) is specially patterned to form a plurality of microelectrodes on the edge layer 106. The defamation and several micro-systems are located in the bioelectricity mti〇8c°, where these microelectrode 塾_ regions 1〇4, and each microelectrode 塾 塾 藉 藉 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应 对应(^). 12 1287088 14922twf.doc/g It is worth mentioning that the correlation between the above-mentioned adjacent two microelectrode 塾3 spacing d is calculated by the cross-correlation calculation of equation (1)...the value is not small, paired , -test a oq take ^ to determine whether there is a statistically significant difference (p < ^ /7=1 -1 χ-η^Σχ eight "=1 -1 ^ = T7ly-

^/(1 /(N -1))^=1 {Xtm -X)2(\/(Ν - where xn[tm] is the number of times after repeating the ηth measurement with a single-point microelectrode at a recording point Recording the sampling signal value at the mth time point; Υηω is the sampling signal value of the mth time point recorded after the single-point microelectrode repeats the second measurement at the position of the recording point d; the variable η=1 Νν, ν is the number of repeated measurements (Sweep); the variable m = 1~Μ, Μ is the number of data points sampled during the measurement. In the preferred embodiment, 'the number of repeated measurements performed above (4) The correlation coefficient calculated by the cross-correlation calculation of equation (2) is not less than 0.95, and the Student's paired i-test is used to evaluate the experimental individuals. Finally, the P value is used to determine whether there is a statistically significant difference (household &lt; 〇' 〇5), Equation (7),. 13 1287088 14922twf.doc/g

An Bt&gt; NN /7,=1 Α = 1 Μ = million ΣΧ m^\ 2N *1 kj ΣβΜ n2=(N+l) Β = 1 - &quot;λ/Σ^- w=l _,Σί =1 (In particular, eight 111 [111] and Bn2 [tm] are the measurements of the (1)th and the nth:th times with a single-point microelectrode at the same recording point, and the sampling of the (f)th time point is recorded. Signal value; repeated measurement times 2N, variable...=, variable n2 = (N+1)~2N; variable m = 1~M, M is the number of data points sampled during measurement. - About the above repeated measurement The number of times N and the difference between the adjacent two microelectrodes w are determined by the following fine electrical stimulation of the middle segment of the rat and the potential of the hypothalamic sensory region is measured as an example. First, please refer to FIG. 2A, compare, The average number of induced field potentials is measured and compared with the nr of the lake. The surface is designed to be 1 (VPL), with the middle segment of the rat tail and the sensory area of the ventricle. '发,位(EV_咖Ρ〇_). The increase in the number of times of the flat potential of the graph, the two highs are mutually _ number. The N" is getting higher and higher, and the more representative is in the same - record point Two waveforms obtained by entering two 〇 phase The average waveform. The long-term _ human evoked field potential measurement and the resulting equation (2), 1287088 14922twf.doc / g in determining the spacing d between the microelectrode pads l 〇 8a, After defining the microelectrode pad 108a, the microwire l8b and the transfer pad i〇8c, please refer to FIG. ic to form an insulating layer 110 on the substrate 100, covering the microelectrode pad 108a, the microwire 108b and the transfer pad i〇8c. Moreover, the insulating layer 11() has a plurality of openings 112a in the bioelectric signal detecting area 102 exposing the microelectrode pads 10a, and a plurality of openings I in the rear signal switching area 1? The conductive pad 110 is exposed to a material such as yttrium niobium nitride, yttrium oxynitride, a non-conductive plastic, a non-conductive polymer material or other suitable insulating material. In the example, the material of the insulating layer 110 must be non-toxic to biological tissues or cells. Further, the method for forming the ruthenium layer 110 is, for example, a chemical vapor deposition process suitable for biting the pot. Further, the thickness formed. For example, 3000 angstroms. In addition, '= mouth 112a and U2b The formation method is, for example, using a reactive ion (RIE) to etch a portion of the insulating layer 11 。. For the micro ray, please refer to FIG. 1D, and form a “wire line U4b” in the open heart and the coffee, respectively, wherein each microelectrode For example, the system: the = microelectrode pad electrical connection, the microelectrode U4a: electrical signal detection point. In addition, each wire point (10) is used as (four) ^ each transmission pad electrical connection, the wire point Beam. In addition, the micro-electric 'pole' 丨 ̄ ̄ electrical electrical signal and external line transfer bridge material or Α other, south or line point (10) material can be metal qi = medium metal material such as gold, &quot;, In the material example of the point (10), the microelectrode (10) and the wire-bonding material must be non-toxic. In addition, the method of forming the microelectrode 114a and the wire bonding point U4b is, for example, depositing a metal material in the openings 112a and 112b, respectively, and the thickness of the deposited metal-material is greater than or equal to the opening 112&amp;; with the depth of n2b. Further, &quot; In an embodiment, the area of the microelectrode 114a is, for example, 225//m2, i.e., 15/mxl5/m. Then, referring to FIG. 1E, a laser cutting process is performed to cut the film layer in the bioelectric heart detection area 102 and the rear end signal transfer area 1〇4, for example, φ, edge f U〇, 106 and The substrate 100 is made into a probe pattern. In particular, the entire multi-channel microelectrode probe can be removed from the substrate 100 by the laser cutting process described above, and the cut probe pattern includes the bioelectric signal detection area 102 and the back end signal transfer area. 1〇4, and the cut/jumancy includes the total thickness of the insulating layers 106, 110 and the substrate 10Q. Among them, the above laser cutting process can use a pulse type yag (Nd: YAG) laser knives, one-on-one oxidized carbon laser or other types of lasers. The power of this pulse-type subgrain is, for example, between 65 and 70 watts/pulse, the wavelength of the pulsed subgrain is, for example, h046 micrometers, and the focal length of the pulsed subgrain is, for example, between 150 and 160 millimeters, pulse The beam diameter of the type of subgrid is, for example, between 20 and 30 microns. Further, the cut probe pattern has a width which gradually decreases toward one direction, which is, for example, a needle tip shape or other shape. In particular, the length and shape of the probe pattern are not particularly limited, and the end depends on the area to be detected and its depth. For example, the VPL region of the hypothalamus of the rat is detected, and the length of the probe pattern is preferably selected to be 6 mm °. In addition, in a preferred embodiment, the laser cutting process is performed. 17 1287088 14922twf.doc/ g Do not perform the pre-cutting process to pre-draw the outline of the pattern to be cut so that the subsequent laser cutting process can be made easier. Wherein, the pre-cutting process is, for example, performing a reactive ion etching process. Since the manufacturing method of the multi-channel microelectrode probe of the present invention cuts the probe pattern by the laser cutting process, the process can be simplified, thereby improving the production of the second generation, which is compared with the conventional dry or wet engraving process. Define the plate needle pattern. This laser cutting process does not require the use of chemicals. Moreover, the photoresist layer needs to be formed so that the lithography process is not required and, therefore, the process cost can be saved and the throughput can be improved. Cloth Spear The following describes the probe structure obtained by the above manufacturing method. 3C ^ Same time reference: 1Ε and Μ to Figure 3C, where Figure 3Α to Figure 由 1 from Figure 1E of W, IWI, and 1 job, the d-face of the profile is not considered. The multi-channel microelectrode probe of the present invention is composed of a base insulating layer 106, a microelectrode pad 1〇8a, a microwire 1 〇2, an insulating, a microelectrode 114a and a wire bonding point 114b, and is specially configured as a wheel pad 108c, /, The substrate 100 has a signal detection area 1〇2盥104', and its material such as cut, glass, and transmission area=_ are other suitable materials. Further, = on the substrate 100, the material thereof is, for example, an oxide stone, a non-conductive plastic material, a non-conductive polymer material, or an emulsified stone material. In the embodiment, the insulating material or the cell as the insulating layer 10 ς ^ is non-toxic. The material must be on the insulating layer 106 of the micro-electrode pad system 102 of the biological group, 1 material, f material electric rolling k detection area, eight material shell, for example, non-gold 1287088 14922twf.d〇c/g tr hard, Metal or other suitable conductive material. In the embodiment, the conductive material is, for example, graphite having a low resistance; in another embodiment, the heteropoly crystal dream is, for example, a polycrystalline fine having a high f concentration. In particular, the spacing between the microelectrode tests is greater than the cross-correlation of equation (1) = the correlation coefficient of the difference is not less than G95 and reaches a statistically significant difference, (P &lt; 0. (6). In a preferred embodiment, the value of the correlation coefficient p2 obtained by calculating the number of times of multi-measurement N in equation (1) is not less than 〇95 and reaches a statistically significant difference (7) < (10) 5). The explanation of this section has been described in the above, and will not be repeated here. Further, the microwires 8 8b are disposed on the insulating layer 1 〇 6 and are made of, for example, a non-metallic conductive material, a doped crystal 11, a metal or other suitable material. In the embodiment, the non-metallic conductive material is, for example, a stone having a low resistance; in another embodiment, the doped polysilicon is, for example, a polycrystalline second having a high dopant concentration. In addition, the transfer pad grade is disposed on the signal transfer region 1〇4, the germanium edge layer 106, and the material thereof is, for example, a non-metal conductive material, a doped polysilicon, a metal, or other suitable conductive material. In one embodiment, the non-metallic conductive material is, for example, graphite having a low resistance; in another embodiment, the doped polysilicon is, for example, a polycrystalline germanium having a high dopant concentration. Moreover, each of the above-described microelectrode pads is connected to the corresponding transfer port 8c by the corresponding microwire leg. Further, the insulating layer 110 covers the microelectrode pad 108a, the microwires 1〇8b, and the transfer pad 108c. Wherein, the insulating layer 110 has a plurality of openings 112a exposing the microelectrode pad l〇8a, and a plurality of openings n2b exposing the transfer pad 19 «

1287088 14922twf.doc/g = In addition, the material of the insulating layer 110 is, for example, an oxidized bismuth oxide, a non-conductive plastic, a non-conductive polymer material, and a suitable insulation (4). In the case of - (4) ^ sub-materials or other known examples, the loose button v as the insulating layer 110 must be non-toxic to biological tissues or cells. In addition, the microelectrode 114a and the wire bonding point 114b are respectively disposed in the opening 112b. Among them, 'the respective microelectrode core system and each mineral electrode 塾: the sex electrode 114a is used as a bioelectric signal detection of the probe", ,. In addition, each of the transmission contact windows 114b is electrically connected to each of the transmission pads 108c. This wiring point 114b serves as a bridge between the bioelectric money and the external line. In addition, the material of the microelectrode 114a or the wire bonding point may be a metal material or other suitable material, wherein the metal material is, for example, gold flip or silver/silver chloride. In one embodiment, the material as the microelectrode 11 and the wire bonding point 114b must be non-toxic to biological tissues or cells. Further, in another embodiment, the thickness of the microelectrodes 114 &amp; and the wire bonding point U4b is greater than or equal to the depth of the openings 112a and 112b. It is worth mentioning that the multi-channel microelectrode probe of the present invention is suitable for biological (in vivo) (j&gt;7 Wvo) and ex vivo (/« tissue or cell sample detection, which is, for example, electrical of rat biological nervous system. Signals, for example, detection of activity signals of the neurons in the rat brain, or detection of cardiac electrical signals. That is, according to the detection of tissue or cell samples in biological organisms (/„Wvo), according to animal experiment management The law anesthetizes the animal, and the probe of the present invention is introduced into the animal for multi-channel bioelectrical signal measurement without pain, so that a better reliability result can be obtained. In addition, in the above embodiment In the above, although only four micro 20 l287 〇 88 14922 twf.doc / g electrode of the wire _ text, the number of micro-electrodes, the arrangement between the scale and the probe can be different according to the needs of the user. The change may be as follows: as shown in FIG. 4A, there are 16 microelectrodes 114 probes, probes, microelectrodes, and individual wire-bonding points (10), which are connected to each other by micro-wires. Probe station : An enlarged view of the system shown in Figure 4B dagger &amp; 200 or the.

The results of the probes are described below. Please refer to ,5, which is the _ suppressor electrode does not repeat the measurement - the number of Sweep's repeated measurement times n and the signal to noise ratio SN system. Where '· indicates Cemerf〇rNe= by the University of Michigan

Probe designed by Commumcatum Technology (CNCT); ▲ indicates the needle of this month, ▼ indicates the flip/he microelectrode (Micr〇eiectr〇 (je); no glass microelectrode (Micropipette). In addition, the experiment is the amount In addition, the unit of the SNR of the Y-axis is 1〇1〇g(cjs2/c7N2). As can be seen from Fig. 5, on average, when the number of repeated measurements is increased, the SNR is also synchronized. However, when n is greater than 6〇, the increasing trend of SNr for N is gradually slowed down. It is particularly worth mentioning that the probe of the present invention performs better than the probe designed by the University of Michigan. Referring to FIG. 6A to FIG. 6C, FIG. 6A shows a profile of the probe of the present invention entering the hypothalamus; FIG. 6B shows a probe using a probe having 16 microelectrodes and a microelectrode pitch of 50/m. The field potential map obtained at different depths of the view hill of Fig. 6A; Fig. 6C shows the current source density (Currents Density) analysis chart converted by 21 1287088 14922 twf.doc/i using the result obtained in Fig. 6B. The present invention has at least the following advantages: 1. Due to the multi-pass of the present invention The manufacturing method of the micro-electrode probe is simplified by the laser, and thus, 2: due to the channel microelectrode probe of the present invention, the correlation coefficient Ρι value calculated by the cross-correlation calculation of the formula (1) between the microelectrodes is not less than • .95 and reached a statistically significant difference I (household &lt; 0.05), so the detection results performed by the probe of the present invention can have higher reliability. 3. In addition, due to the present invention The channel microelectrode probe can be applied to the bio-electrical signal detection in vivo (shu (4) or away (4), thus increasing the convenience and accuracy of the detection. Although the invention has been disclosed as the above, it is not used In the present invention, any person skilled in the art can make some changes and refinements when the money is within the spirit of the present invention. Therefore, the protection % of the present invention is subject to the definition of the patent application scope attached thereto. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1A to FIG. 1E are perspective views showing a manufacturing process of a multi-pass k-electrode probe according to a preferred embodiment of the present invention. FIG. 2A is an electrical stimulation of a rat tail at a frequency of 1 Hz.视丘体感二品VPL) The evoked field potential (Ey〇ked 祝 p 以 以 ( ( ( 以 以 以 以 以 以 以 以 以 以 诱发 诱发 诱发 诱发 诱发 诱发 诱发 诱发 诱发 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。

1287088 !4922twf.doc/g Detects the relationship between the _ position (#)/ and the correlation coefficient P. Electrode ==, the multi-channel micro-image of the other preferred embodiment of the present invention is an enlarged schematic view of a partial region 2A of Figure 4A. 7 accompanied by the micro-electrode of the lion (four) surface to perform the field-induced evoked field potential. Compare the relationship between different types of microelectrode recording induced field potential, % potential signal-to-noise ratio SNR and repeated measurement times]. ν Figure 6Α is a stained section of the probe of the present invention entering the hypothalamus. Fig. 6 is a field potential diagram obtained by detecting the different depths of the view hills of Fig. 6 using a microneedle with #16 microelectrodes and a microelectrode spacing of 刈 (4). Density = Γ 6 Β results obtained 'converted current source' [main component symbol description] 100 : substrate 102 : bioelectric signal detection area 104 : rear end signal transfer area 106 , 110 · • insulation layer 108 · • signal transmission Layer l 8a ··Microelectrode pad 108b ··Microwire 23 1287088 14922twf.doc/g 108c 112a 114a 114b 200 : :Transport pad, 112b: Opening: Microelectrode: marking point area label

twenty four

Claims (1)

1287088 14922iwf.doc/g (Nd: YAG) laser, a 3. For example, the patent scope of the first knife - the bismuth oxide electrode probe of the Μ to 70 manufacturing method 'where the pulse type yag two = electric tile / pulse.妁 妁 妁 介于 4 4 4 4 4 4 4 4 如 如 如 如 如 如 如 如 如 如 如 如 如 如 如 制造 制造 制造 制造 制造 制造 制造 制造 制造 制造 制造 制造 制造 制造 制造 制造 制造 制造 制造 制造·) Micron. The focal length system of the pulse-type subgrain shot, or the square of the multi-channel microelectrode probe described in item 2 of the /tt range is straight (four) is as in 7. As for the application A method for manufacturing a probe for a channel microelectrode according to item i, wherein a pitch (cord) between adjacent two electrodes is calculated by a cross-correlation of equation (1) The value is not less than 0.95, and the Student's paired &quot;test is used to evaluate the individual differences of the experiment'. Finally, the corpse value is used to determine whether there is a statistically significant difference CP &lt; 0.05), Equation (1) -1 Μ _ Y = -YYim Μ±ΐ 26 1287088 14922twf.doc/g , n a _ (1/(7V-(Xtm — X)(Y^ P\ factory - two &lt;m=l a ------V(1KN -1))^ 2=1 (Xtm ~ X)2 (1KN - 1))X^ (?/mp)2 Wherein, Xn[tm] is a sampling signal value of the mth time point recorded after repeating the nth measurement by the micro-electrode on a recording point, and Yn[tm] is at a position away from the recording point d The sampling signal value of the mth time point recorded after the ηth measurement is repeated by the single-point microelectrode; the variable η == 1~ν, ν is the number of repeated measurements (Sweep); the variable m = 1~Μ, Μ is the number of data points sampled during the measurement. 8. The method for manufacturing a multi-channel microelectrode probe according to claim 7, wherein the correlation coefficient ρ2 obtained by the cross-correlation calculation of the equation (2) is not less than 0.95. And use Student's paired r-test to assess the individual differences in the experiment, and finally determine whether there is a statistically significant difference by the corpse value 〇Ρ&lt;〇·05), (7) Bn N 2Nixu n2=(N+\) One 1 Α = —ΤΑίη Mti &quot; (上-一ν(ι"ι)) Σ二d—but (Ning-zhou 10,000) where 'Anl[tm] and Bn2[tm] are ηι times with single-point microelectrodes at the same recording point And the 112th measurement, and record the sampling value of the mth time point § § value; the number of repeated measurement is 2N, the variable ni = 1~N, the variable 27 1287088 14922twf.doc/g n2 - (N+ l) ~2N, variable m =; [~Μ, M is the number of points sampled during the measurement, 9 · The manufacturing method of the multi-channel microelectrode probe described in the scope of the patent scope, the towel needle The method of manufacturing the multi-channel microelectrode probe according to claim 9, wherein the cutting pattern is in the shape of a probe and includes the bioelectrical signal. The detection area and the back-end signal transition area include the second insulation layer, the total insulation degree of the first insulation layer and the base, and the multi-channel micro-electrode probe described in the first item: Before performing the laser cutting process, the needle further includes a contour for pre-cutting the pattern to be cut. The multi-channel described in Item 11 of the mouth Electrode probe engraving, process _) /, &quot; pre-cutting process includes - reactive ion button system = please use the material of the multi-pass pad including two non-metallic thunder, ° some micro-wire or these transmission 14 · For example, the scope of patent application is 13: the crystal or the metal. The non-metallic conductive material package = microelectrode probe 15. The manufacturing method as in the scope of the patent application, wherein the microelectrodes or secrets; =; pole probe metal material. The material of a green dot includes a 丨6. The manufacturing method of the multi-channel microelectrode probe 28 1287088 14922twf.doc/g according to claim 15 of the patent application, wherein the gold 17 For example, the manufacturing method of the invention includes the method of manufacturing the first-insulated multi-channel microelectrode probe including yttrium oxide, cerium nitride, nitrogen q or The material of the insulating layer is a polymer material. Wei Miao, non-conductive _ or non-conductive 18 · The manufacturing method of the patent application range, wherein the multi-channel microelectrode probe glue or non-conductive polymer material Bell includes stone eve, glass, non-guide 9. The manufacturing method of the patented Weiyuan, wherein the multi-channel microelectrode probe described in the above section forms the microelectrodes and the :: line: opening and the second openings -: method 匕Included in the first -::r_ is greater than the second measurement, and is finer than the exhaust gas signal detection signal. The substrate has a bioelectric signal side region and a rear end: a first insulating layer disposed on the substrate; the first micro An electrode pad disposed on the insulating layer of the bioelectric signal side region; ^ a plurality of microwires disposed on the first insulating layer; and a plurality of transmissions arranged in the back signal routing region The first electrode, the upper electrode, wherein each of the microelectrode pads is connected to a transmission pad of 29 1287088 14922twf.doc/g by a corresponding one of the micro wires; a second insulating layer covering the micro An electrode pad, the micro-wires and the transfer pads, wherein the second insulating layer has a plurality of first openings exposing the micro-electrode pads, and a plurality of second openings exposing the transfer pads; and a plurality of micro-electrodes and Most of the line points are configured in the The first opening and the second openings are electrically connected to each of the microelectrode pads, and each of the wire bonding points is electrically connected to each of the transmission pads, wherein two adjacent ones of the microelectrodes are The correlation coefficient Pi calculated by the cross-correlation calculation of the formula (1) is not less than 0.95, and the individual differences of the experiment are evaluated by Student's paired /_test, and finally the corpse value is used to determine whether there is a statistically significant difference ( Corpse &lt;〇.〇5), Equation (1) _ 1 N __ 1 Λ / _ Y = — YYtm 30 1287088 14922twf.doc / g Measure times (Sweep); variables [is the number of data points sampled during the measurement. 21) The multi-channel microelectrode probe described in the second paragraph of the patent application scope wherein the number of times of the repeated measurement is determined by the cross-correlation calculation of the equation (2) is not less than 0.95, and is utilized. Studenfs paired itest α assesses the individual differences, and finally determines whether there is a statistically significant difference (P &lt; 〇.〇5). Formula (7) | ~ 1 μ Α = -7τΣΑ B: M\ 释 -1)) Σ II (I, where Anl[tm] and Bn2[tm] are the same as the single-point microelectrode at the same recording point. % second measurement, and record the sampling signal value at the (5th) time point; the number of repeated measurement is 2N, the variable n! = i~N, the variable n2 = _)~2N; the variable m = 丨~M, M The number of points sampled for measurement. The multi-channel microelectrode probe described in the patent scope 2G, wherein the multi-channel microelectrode probe is suitable for tissue or cell sample detection in a living body and in vitro (known FzWo). 23·Multi-channel microelectrode probe according to item 22 of the patent application scope. 12 1287088 14922twf.doc/g; gas;;:: channel microelectrode probe is suitable for rat biological nerve ECG_money=heart electrocardiogram signal Detection. The multi-channel microelectrode as described in item 2g of the range of needles includes two core microwires or (iv) W 士 掺杂, doped poly 11 or metal. The multi-channel microelectrode probe described in item 24, wherein the non-metallic conductive material comprises graphite. Needle, j: The multi-channel microelectrode probe described in item 20 of the jfefesl item 20. The material of the wire or the wire-bonding point includes a metal material. The multi-channel microelectrode probing material of item 26 of the needle 矽 1 includes titanium, gold, face or silver/silver chloride. The material of the multi-channel microelectrode probe V:/ba margin layer or the second insulation layer described in the twentieth range includes oxygen oxidizing material, material miscellaneous _ or electroconductive polymer needle, and the second GG Channel microelectrode probe c-package, glass, non-conductive plastic or non-conductive k-method of the multi-channel microelectrode probe described in item 2G, wherein the microelectrodes are related to the The depth of the opening and the second opening σ is greater than 32