Patent Document

FIELD OF THE INVENTION 
     The present invention relates to a 3D microelectrode structure, particularly to a 3D microelectrode structure for physiological signal measurement. The present invention also relates to a method for assembling a 3D microelectrode structure, particularly to a method for assembling a 3D microelectrode structure, which can align accurately and assemble easily. 
     BACKGROUND OF THE INVENTION 
     Since a planar multi-electrode array was proposed to study the transmission mechanism of neural signals in 1972, microelectrode arrays have been extensively used in the biomedical engineering. Taking the signal measurement of the nervous system for an example, the brain and a neural network is a complicated network consisting of many neurons interconnecting each other. Understanding the operation of the neural network is very important to diagnose and treat neural diseases, and even fabricate neural prostheses. A probe can easily insert into the tissue to research the variations of the electrophysiological signals in vivo. 
     The early study of neural signal transmission is mainly implemented by a single electrode probe, such as a metal probe or a glass micropipette. However, such an electrode probe is bulky and likely to be interfered. Further, the single electrode probe can only record a single or few nerve cells at the same time. Recently, the MEMS (Micro-Electro-Mechanical System) or semiconductor manufacturing process has implemented a microelectrode array containing multiple micron-scale probes, whereby a higher number of nerve cells can be measured. The photolithography technology of the semiconductor manufacturing process can precisely define the positions of electrodes. Further, the abovementioned processes can easily integrate the circuits. However, the above-mentioned processes usually fabricate the microelectrodes into a planar microelectrode array, which has limited application in the 3D biological tissues. 
     There are mainly three conventional methods to fabricate 3D microelectrode arrays. One method uses photolithography and etching technologies to directly fabricate a microelectrode array on a silicon wafer. For example, R. A. Normann et al. disclosed “A Silicon-Based, Three-Dimensional Neural Interface: Manufacturing Processes for an Intracortical Electrode Array” in IEEE Transactions on Biomedical Engineering, vol. 38, pp. 758-768, 1991. Such a device is also called the “Utah Array”. However, the thickness of the wafer limits the length of the probes to adjust freely. Further, each probe has only an electrode, which limits the recording density. Besides, the biocompatibility of silicon is not as good as other material (e.g. polymer, ceramic, and glass). 
     A second method uses a self-assembly technology to form a 3D microelectrode array. For example, Shoji Takeuchi et al. disclosed “3D Flexible Multichannel Neural Probe Array” in Journal of Micromechanics and Microengineering, vol. 14, pp. 104-107, 2004, wherein a magnetic material is coated on planar polymer arrays, and then the flexible polymer probes are assembled with the magnetic force to form a 3D array structure. However, the structural strength of such a mircoprobe is hard to control. Further, the magnetic material may have adverse effect to the organism. 
     A third method assembles 2D planar microprobe arrays into a 3D microprobe array. For example, the research team led by Wise of Michigan University discloses “A High-Yield Microassembly Structure for Three-Dimensional Microelectrode Arrays” in IEEE Transactions on Biomedical Engineering, vol. 47, pp. 281-289, 2000, wherein planar microelectrode arrays are separated by spacers and inserted into slots of a silicon platform to form a 3D structure. However, such a device is complicated, and the orthogonality thereof is hard to control. 
     The conventional methods that assemble planar microelectrode arrays into a 3D microelectrode array have the advantages of increasing electrode design flexibility, promoting efficiency of recording electroneurographic signals, and implementing space analysis. However, the conventional methods for assembling 3D microelectrode arrays have the disadvantages of inconvenient assembly. Further, the conventional 3D microelectrode arrays still have room to improve in biocompatibility. 
     SUMMARY OF THE INVENTION 
     One objective of the present invention is to provide a method for assembling a 3D microelectrode structure, whereby the 3D microelectrode array and the carrier chip have better electric connection, and whereby the 3D microelectrode structure is easy to assemble and has accurate alignment. 
     To achieve the abovementioned objective, the present invention proposes a method for assembling a 3D microelectrode structure, which comprises the steps of: fabricating 2D microelectrode arrays, wherein each 2D microelectrode array has a base, a plurality of probes connected to the base and a plurality of alignment members connected to the base, and wherein the probe has at least one electrode electrically connected to the alignment member via a corresponding wire; stacking the 2D microelectrode arrays into a 3D microelectrode array and aligning the alignment members of the 2D microelectrode arrays to the predetermined positions; assembling the 3D microelectrode array to a carrier chip to form a 3D microelectrode structure with each alignment member electrically connected to the corresponding electric-connection pad of the carrier chip. 
     Another objective of the present invention is to provide a 3D microelectrode structure, which is fabricated according to the abovementioned method, and which can simultaneously measure many physiological signals, and which has the advantages of high measurement density, high insertion capability, great insertion depths, flexible probe/electrode arrangement, and high biocompatibility. 
     Below, the embodiments will be described in detail in cooperation with the drawings to demonstrate the technical contents of the present invention. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The embodiments of the present invention will be described in detail in cooperation with the following drawings. 
         FIG. 1  is a flowchart of a method for assembling a 3D microelectrode structure according to the present invention; 
         FIG. 2  is a perspective view of the appearance of a 2D microelectrode array according to one embodiment of the present invention; 
         FIGS. 3A-3D  are diagrams schematically showing the process of fabricating a 2D microelectrode array according to one embodiment of the present invention; 
         FIGS. 4A to 4E  are diagrams schematically showing the procedures of Step b according to one embodiment of the present invention; 
         FIG. 5A  is a perspective view of the appearance of a carrier chip according to one embodiment of the present invention; 
         FIG. 5B  is a diagram schematically showing the procedures of Step c according to the present invention; and 
         FIG. 5C  is a perspective view of the appearance of a 3D microelectrode structure according to the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     Refer to  FIG. 1  for a flowchart of a method for assembling a 3D microelectrode structure according to the present invention. The method for assembling a 3D microelectrode structure of the present invention comprises the steps of:
     a. fabricating 2D microelectrode arrays;   b. stacking and neatly arranging the 2D microelectrode arrays at predetermined positions to form a 3D microelectrode array;   c. assembling the 3D microelectrode array to a carrier chip to form a 3D microelectrode structure.   

     Below, the steps are described in detail. 
     In Step a, a 2D microelectrode array  10  is fabricated. Refer to  FIG. 2  for an embodiment of a 2D microelectrode array  10  according to the present invention. The 2D microelectrode array  10  comprises a base  11 , a plurality of probes  12  connected to the base  11 , a plurality of alignment members  13  connected to the base  11 , and a plurality of positioning members  14  connected to the base  11 . The probes  12  and the alignment members  13  are respectively located at different sides of the base  11 . Each alignment member  13  has an exposed electric-connection member  130 . Each probe  12  has at least one electrode  120 . The electrodes  120  are respectively electrically connected to the corresponding electric-connection member  130  via wires  15 . The wires  15  are electrically insulated to each other. The wires  15  are wrapped inside the probes  12  and the base  11  lest the wires  15  electrical short to the body fluid. In this embodiment, the alignment members  13  and the positioning members  14  are located at the same side of the base  11 . 
     Considering the biocompatibility with organisms, the 2D microelectrode array  10 , especially the base  11  and probe  12 , are made of a high biocompatibility material, such as a glass, PDMS (Polydimethylsiloxane), PI (polyimide), or a thick SU-8 photoresist. Considering the influence of material strength on the insertion depth, the 2D microelectrode array  10  is made of a glass and fabricated with a glass reflow technology in one embodiment. However, the present invention is not limited by this embodiment. As the glass reflow technology is a prior art, it will not repeat herein. For the details of the glass reflow technology, please refer to an U.S. Pat. No. 7,259,080 “Glass-type Planar Substrate, Use Thereof, and Method for the Production Thereof”, and an U.S. Pat. No. 6,951,119 “Method for producing micromechanical and micro-optic components consisting of glass-type materials”. 
     Refer to  FIGS. 3A-3D  for diagrams schematically showing the process of fabricating a 2D microelectrode array  10  according to the present invention. As shown in  FIG. 3A , a master mold  200  is formed on a silicon wafer  100  firstly; then, molten glass is cast into the master mold  200  via a glass reflow technology; then, the undesired portions are removed via lapping; thus is formed the rough structure of the base  11  plus the probes  12 . Next, as shown in  FIG. 3B , a metal film  300  and an insulating film  400  are deposited to define the electrodes  120 , the wires  15  and the electric-connection members  130  of the 2D microelectrode array  10 . The insulating film  400  is made of an insulating material, such as silicon dioxide, silicon nitride, or Parylene. Next, as shown in  FIG. 3C , the undesired silicon structure is removed by etching, and the thickness of the silicon structure of the alignment members  13  is defined at the same time. Next, as shown in  FIG. 3D , an adhesive layer  500  is deposited on the predetermined position. The adhesive layer  500  may be made of Parylene-C. Thus is completed the 2D microelectrode array  10 . Refer to  FIG. 2  again. In the abovementioned embodiment, the metal film  300  is located on the probe  12  and is exposed from the insulating silicon dioxide film  400  to be defined the electrode  120 ; the metal film  300 , which is exposed from the alignment member  13 , is defined to be the electric-connection member  130 . 
     It should be understood that the process of fabricating a 2D probe  12  array described in the abovementioned embodiments is only an exemplification of the present invention. In practical applications, the electrode  120 , wire  15 , and electric-connection member  130  may be made of different material according to the characteristics and requirements, such as the electrode  120  can be selected from a group consisting of CNT (Carbon Nano-Tubes), iridium oxide, platinum, gold, titanium, platinum black, or an electric-conduction polymer PEDOT (polyethylenedioxythiophene). Further, the base  11 , probes  12 , alignment members  13  and positioning members  14  mentioned in the embodiments may be fabricated into independent parts or a one-piece component. 
     In Step b, the 2D microelectrode arrays  10  are stacked and neatly arranged to form a 3D microelectrode array  30 . Refer to  FIGS. 4A-4E  for diagrams schematically showing the procedures of Step b according to one embodiment of the present invention. In this embodiment, an auxiliary tool  20  is used to arrange the alignment members  13  of the 2D microelectrode arrays  10  neatly at the predetermined positions, whereby the 2D microelectrode arrays  10  are stacked to form a 3D microelectrode array  30 . 
     As shown in  FIGS. 4A and 4B , the auxiliary tool  20  has a plurality of slots  21  arranged in parallel. The slots  21  accommodate the alignment members  13  and the positioning members  14 , enable the 2D microelectrode arrays  10  to slide along the direction parallel to the slots  21 , and align the corresponding 2D microelectrode arrays  10 . The width of each slot  21  and the spacing between two adjacent slots  21  are not strictly limited. However, considering the positioning effect, the width of each slot  21  is preferred to be slightly greater than the width of the alignment member  13 . In one embodiment, the sections of the slots  21  are patterned on a wafer, and the sections are etched to form the auxiliary tool  20 . 
     As shown in  FIGS. 4C and 4D , a plurality of 2D microelectrode arrays  10  located at the alignment positions of the auxiliary tool  20  is stuck to form a 3D microelectrode array  30  via adhesive layers  22 . As shown in  FIG. 4E , the alignment members  13  are thus arranged to have a predetermined shape. During the assembling, the positioning and securing effect is enhanced via heating and applying pressure to the 3D microelectrode array  30  along the direction to the slots  21  (indicated by the arrow in  FIG. 4D ). In one embodiment, Parylene-C is uniformly coated on the contact faces of the bases  11  of the 2D microelectrode arrays  10 , and then the 2D microelectrode arrays  10  are pressured and heated to a temperature of 260° C. for 2 hours, whereby forms the 3D microelectrode array  30 . As shown in  FIG. 4E , the alignment members  13  of different 2D microelectrode arrays  10  are alternately arranged lest interference occurs. However, it should be understood that the present invention does not strictly limit the arrangement of the alignment members  13  of the established 3D microelectrode array  30 . 
     In Step c, the 3D microelectrode array  30  is assembled to a carrier chip  40  to form a 3D microelectrode structure  1 . Refer to  FIGS. 5A and 5B  respectively for a diagram schematically showing the appearance of the carrier chip  40  and a diagram schematically showing the procedure of Step c. The carrier chip  40  includes a plurality of electric-connection pads  41  and a plurality of slots  42 . The arranged pattern of the electric-connection pads  41  is corresponding to the alignment members  13  of the 3D microelectrode array  30 , whereby each exposed electric-connection member  130  of the alignment member  13  can electrically connect to the corresponding electric-connection pad  41 . The slots  42  accommodate the positioning members  14  to assist in aligning and securing the 3D microelectrode array  30  to the carrier chip  40 . As shown in  FIG. 5B , a conductive paste  43  is used as the adhesive and electric-conduction medium when the electric-connection pads  41  contact the electric-connection members  130 . In assembling, the positioning members  14  of the 3D microelectrode array  30  are inserted into the slots  42 , whereby the alignment members  13  can be aligned to contact the electric-connection pads  41 . The conductive paste  43  is heated and solidified to interconnect the electric-connection pads  41  and the electric-connection members  130 . The conductive paste  43  may be a silver paste. As shown in  FIG. 5C , the 3D microelectrode structure  1  is further integrated with a flexible substrate and an ASIC to perform nervous system measurement. 
     The alignment of the 2D microelectrode arrays  10  is implemented with the alignment members  13  of the base  11 . Different type 2D microelectrode arrays  10  may have different numbers and shapes of probes  12 . However, in the present invention, different type 2D microelectrode arrays  10  can be assembled into corresponding 3D microelectrode arrays  30  with the same auxiliary tool  20  or the same carrier chip  40 , as long as they have the same type of base  11 . Thus is increased the design flexibility and expanded the application of the probe  12 . For example, the combinations of the probes  12  having different lengths can be used to measure the physiological signals from different depths of an organism at the same time. Further, as the alignment member  13  has a greater bottom area, the electric-connection member  130  can easily conduct the electric-connection pad  41  in Step c. Thus, the disconnection caused by an alignment error will not occur. It should be understood that the electric-connection member  130  exposed from the alignment member  13  may be a portion of the alignment member  13  or the alignment member  13  itself in fact. In this specification, different terms do not necessarily indicate different entities but may be used to demonstrate different aspects of the same thing. 
     The present invention also proposes a 3D microelectrode structure  1 , which is assembled with the abovementioned method, comprises a carrier chip  40  and a 3D microelectrode array  30  electrically connected to the carrier chip  40 , wherein a plurality of 2D microelectrode arrays  10  is stacked to form the 3D microelectrode array  30 . The material and detailed structure of the 2D microelectrode array  10  is the same as that described above. The 2D microelectrode arrays  10  are stacked to make the bases  11  thereof contact each other and form the 3D microelectrode array  30 . In one embodiment, the probe  12  is made of a glass material and thus has high insertion ability and high biocompatibility. In the present invention, different type 2D microelectrode arrays  10  having different numbers and shapes of probes  12  may adopt the same type of base  11 . Therefore, the present invention can easily realize the 3D microelectrode arrays  30  having flexible arrangements and combinations of probes  12 , such as a 3D microelectrode arrays  30  having longer probes  12  for a greater insertion depth. In another embodiment, the probes  12  have several electrodes  120  to measure more nerve cells. 
     The signals of a nervous system are mainly transmitted by neurons. When a neuron is stimulated, special ion channels on the cell membrane is opened. Thus, ions, such as potassium ions and sodium ions, flow through cell membrane and result in potential change. When the potential is accumulated over a threshold, an action potential is generated and detected by the probe  12  in the form of voltage. The 3D microelectrode structure  1  of the present invention has succeeded in measuring and recording the action potential of crayfish nerve cord and rat cortices. The SNR (Signal-to-Noise Ratio) in measuring crayfishes is 32.6 dB, wherein the SNR is defined to be the ratio of the amplitude of the nerve impulse to the root-mean-square value of noise. 
     The embodiments described above are only to exemplify the present invention but not to limit the scope of the present invention. Any equivalent modification or variation according to the scope of the present invention is to be also included within the scope of the present invention.

Technology Category: 4