Method for assembling a 3-dimensional microelectrode structure

The present invention discloses a method for assembling a 3D microelectrode structure. Firstly, 2D microelectrode arrays are stacked to form a 3D microelectrode array via an auxiliary tool. Then, the 3D microelectrode array is assembled to a carrier chip to form a 3D microelectrode structure. The present invention uses an identical auxiliary tool to assemble various types of 2D microelectrode arrays having different shapes of probes to the same carrier chip. Therefore, the method of the present invention increases the design flexibility of probes. The present invention also discloses a 3D microelectrode structure, which is fabricated according to the method of the present invention and used to perform 3D measurement of biological tissues.

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.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Refer toFIG. 1for 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 array10is fabricated. Refer toFIG. 2for an embodiment of a 2D microelectrode array10according to the present invention. The 2D microelectrode array10comprises a base11, a plurality of probes12connected to the base11, a plurality of alignment members13connected to the base11, and a plurality of positioning members14connected to the base11. The probes12and the alignment members13are respectively located at different sides of the base11. Each alignment member13has an exposed electric-connection member130. Each probe12has at least one electrode120. The electrodes120are respectively electrically connected to the corresponding electric-connection member130via wires15. The wires15are electrically insulated to each other. The wires15are wrapped inside the probes12and the base11lest the wires15electrical short to the body fluid. In this embodiment, the alignment members13and the positioning members14are located at the same side of the base11.

Considering the biocompatibility with organisms, the 2D microelectrode array10, especially the base11and probe12, 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 array10is 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 toFIGS. 3A-3Dfor diagrams schematically showing the process of fabricating a 2D microelectrode array10according to the present invention. As shown inFIG. 3A, a master mold200is formed on a silicon wafer100firstly; then, molten glass is cast into the master mold200via a glass reflow technology; then, the undesired portions are removed via lapping; thus is formed the rough structure of the base11plus the probes12. Next, as shown inFIG. 3B, a metal film300and an insulating film400are deposited to define the electrodes120, the wires15and the electric-connection members130of the 2D microelectrode array10. The insulating film400is made of an insulating material, such as silicon dioxide, silicon nitride, or Parylene. Next, as shown inFIG. 3C, the undesired silicon structure is removed by etching, and the thickness of the silicon structure of the alignment members13is defined at the same time. Next, as shown inFIG. 3D, an adhesive layer500is deposited on the predetermined position. The adhesive layer500may be made of Parylene-C. Thus is completed the 2D microelectrode array10. Refer toFIG. 2again. In the abovementioned embodiment, the metal film300is located on the probe12and is exposed from the insulating silicon dioxide film400to be defined the electrode120; the metal film300, which is exposed from the alignment member13, is defined to be the electric-connection member130.

It should be understood that the process of fabricating a 2D probe12array described in the abovementioned embodiments is only an exemplification of the present invention. In practical applications, the electrode120, wire15, and electric-connection member130may be made of different material according to the characteristics and requirements, such as the electrode120can 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 base11, probes12, alignment members13and positioning members14mentioned in the embodiments may be fabricated into independent parts or a one-piece component.

In Step b, the 2D microelectrode arrays10are stacked and neatly arranged to form a 3D microelectrode array30. Refer toFIGS. 4A-4Efor diagrams schematically showing the procedures of Step b according to one embodiment of the present invention. In this embodiment, an auxiliary tool20is used to arrange the alignment members13of the 2D microelectrode arrays10neatly at the predetermined positions, whereby the 2D microelectrode arrays10are stacked to form a 3D microelectrode array30.

As shown inFIGS. 4A and 4B, the auxiliary tool20has a plurality of slots21arranged in parallel. The slots21accommodate the alignment members13and the positioning members14, enable the 2D microelectrode arrays10to slide along the direction parallel to the slots21, and align the corresponding 2D microelectrode arrays10. The width of each slot21and the spacing between two adjacent slots21are not strictly limited. However, considering the positioning effect, the width of each slot21is preferred to be slightly greater than the width of the alignment member13. In one embodiment, the sections of the slots21are patterned on a wafer, and the sections are etched to form the auxiliary tool20.

As shown inFIGS. 4C and 4D, a plurality of 2D microelectrode arrays10located at the alignment positions of the auxiliary tool20is stuck to form a 3D microelectrode array30via adhesive layers22. As shown inFIG. 4E, the alignment members13are 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 array30along the direction to the slots21(indicated by the arrow inFIG. 4D). In one embodiment, Parylene-C is uniformly coated on the contact faces of the bases11of the 2D microelectrode arrays10, and then the 2D microelectrode arrays10are pressured and heated to a temperature of 260° C. for 2 hours, whereby forms the 3D microelectrode array30. As shown inFIG. 4E, the alignment members13of different 2D microelectrode arrays10are alternately arranged lest interference occurs. However, it should be understood that the present invention does not strictly limit the arrangement of the alignment members13of the established 3D microelectrode array30.

In Step c, the 3D microelectrode array30is assembled to a carrier chip40to form a 3D microelectrode structure1. Refer toFIGS. 5A and 5Brespectively for a diagram schematically showing the appearance of the carrier chip40and a diagram schematically showing the procedure of Step c. The carrier chip40includes a plurality of electric-connection pads41and a plurality of slots42. The arranged pattern of the electric-connection pads41is corresponding to the alignment members13of the 3D microelectrode array30, whereby each exposed electric-connection member130of the alignment member13can electrically connect to the corresponding electric-connection pad41. The slots42accommodate the positioning members14to assist in aligning and securing the 3D microelectrode array30to the carrier chip40. As shown inFIG. 5B, a conductive paste43is used as the adhesive and electric-conduction medium when the electric-connection pads41contact the electric-connection members130. In assembling, the positioning members14of the 3D microelectrode array30are inserted into the slots42, whereby the alignment members13can be aligned to contact the electric-connection pads41. The conductive paste43is heated and solidified to interconnect the electric-connection pads41and the electric-connection members130. The conductive paste43may be a silver paste. As shown inFIG. 5C, the 3D microelectrode structure1is further integrated with a flexible substrate and an ASIC to perform nervous system measurement.

The alignment of the 2D microelectrode arrays10is implemented with the alignment members13of the base11. Different type 2D microelectrode arrays10may have different numbers and shapes of probes12. However, in the present invention, different type 2D microelectrode arrays10can be assembled into corresponding 3D microelectrode arrays30with the same auxiliary tool20or the same carrier chip40, as long as they have the same type of base11. Thus is increased the design flexibility and expanded the application of the probe12. For example, the combinations of the probes12having different lengths can be used to measure the physiological signals from different depths of an organism at the same time. Further, as the alignment member13has a greater bottom area, the electric-connection member130can easily conduct the electric-connection pad41in Step c. Thus, the disconnection caused by an alignment error will not occur. It should be understood that the electric-connection member130exposed from the alignment member13may be a portion of the alignment member13or the alignment member13itself 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 structure1, which is assembled with the abovementioned method, comprises a carrier chip40and a 3D microelectrode array30electrically connected to the carrier chip40, wherein a plurality of 2D microelectrode arrays10is stacked to form the 3D microelectrode array30. The material and detailed structure of the 2D microelectrode array10is the same as that described above. The 2D microelectrode arrays10are stacked to make the bases11thereof contact each other and form the 3D microelectrode array30. In one embodiment, the probe12is made of a glass material and thus has high insertion ability and high biocompatibility. In the present invention, different type 2D microelectrode arrays10having different numbers and shapes of probes12may adopt the same type of base11. Therefore, the present invention can easily realize the 3D microelectrode arrays30having flexible arrangements and combinations of probes12, such as a 3D microelectrode arrays30having longer probes12for a greater insertion depth. In another embodiment, the probes12have several electrodes120to 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 probe12in the form of voltage. The 3D microelectrode structure1of 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.