Abstract:
A flexible microelectrode for detecting neural signals and a method of fabricating the same are disclosed. The method comprises steps: growing a graphene electrode layer on a temporary substrate; growing a flexible substrate on the graphene electrode layer and patterning the flexible substrate; removing the temporary substrate but preserving the graphene electrode layer and the flexible substrate to form an electrode body; and using an insulating layer to wrap the electrode body but exposing a bio-electrode end to contact a living body and detect the signals thereof. The graphene electrode layer features high electric conductivity, high biocompatibility and low noise. The flexible substrate is bendable. Thus is improved the adherence of the skin tissue to the bio-electrode end and decreased the likelihood of skin inflammation.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to a flexible electrode, particularly to a flexible microelectrode for detecting neural signals and a method of fabricating the same. 
       BACKGROUND OF THE INVENTION 
       [0002]    The brain and the nervous system are neural networks formed of numerous cross-linked neurons. It is very important to understand the operation of the nervous system for diagnosis, therapy and prosthesis design of neural diseases. Probes can easily pierce the skin and detect electrophysiological signals in vivo, so they can also function as a medium between analog physiological signals and digital signals. 
         [0003]    The abovementioned probe is an electrode of a biomicroelectromechanical system, which should be able to conduct very weak nerve current. Therefore, the electrode must have high electric conductivity. Further, the electrode should have high biocompatibility so that cells can adhere thereto and survive thereon. The heartbeat and breathing of an animal or a human being will cause the cells or tissue on the body surface thereof to pulsate. When a probe is directly applied to the body surface, the pulsation will cause tiny friction between the probe and the cells. The tiny friction may accelerate skin inflammation. Therefore, flexibility is necessary for an electrophysiological electrode. 
         [0004]    A prior art disclosed an electrode having a carbon nanotube interface, wherein the surface of the carbon nanotubes has abundant carboxyl groups to effectively reduce impedance between the electrode and the tissue fluid, whereby is achieved better measurement quality. A U.S. patent of publication No. 20100268055, a “Self-Anchoring MEMS Intrafascicular Neural Electrode”, disclosed a method for using the same to detect, record, and stimulate the activity of the nervous system and the peripheral nerve tracts. However, the conductivity of the electrode disclosed in the prior art still generates much noise. Therefore, the prior art cannot provide required sensitivity for neural signal detection. Further, the biocompatibility and flexibility of the prior art should be improved. 
       SUMMARY OF THE INVENTION 
       [0005]    The primary objective of the present invention is to provide an electrode structure having high biocompatibility, flexibility and electric conductivity. 
         [0006]    To achieve the abovementioned objective, the present invention proposes a method of fabricating a flexible microelectrode for detecting neural signals, which comprises steps: 
         [0007]    S 1 : growing a graphene electrode layer on a temporary substrate; 
         [0008]    S 2 : growing a flexible substrate on one surface of the graphene electrode layer, which is far away from the temporary substrate; 
         [0009]    S 3 : removing the temporary substrate and preserving the graphene electrode layer and the flexible substrate to form an electrode body, wherein the electrode body has a bio-electrode end and an interface-connection end; and 
         [0010]    S 4 : using an insulating layer to wrap the electrode body but expose the bio-electrode end. 
         [0011]    The flexible microelectrode fabricated according to the abovementioned method comprises an electrode body and an insulating layer. The electrode body includes a flexible substrate and a graphene electrode layer. The electrode body has a bio-electrode end and an interface-connection end. The insulating layer warps the graphene electrode layer but reveal the bio-electrode end. 
         [0012]    The graphene electrode layer is a 2D graphite structure having very high electric conductivity. Further, graphene has biocompatibility much superior to that of ordinary metallic electrodes. Besides, the flexible substrate enables the electrode to bend, and the insulating layer protects the electrode from external interference. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0013]      FIGS. 1A-1F  are sectional views schematically showing steps of fabricating a flexible microelectrode for detecting neural signals according to one embodiment of the present invention; 
           [0014]      FIGS. 2A-2C  are perspective views schematically showing steps of fabricating a flexible microelectrode for detecting neural signals according to one embodiment of the present invention; 
           [0015]      FIG. 3A  is a photograph showing the state that neural cells adhere to glass; 
           [0016]      FIG. 3B  is a photograph showing the state that neural cells adhere to graphene; 
           [0017]      FIG. 3C  is a photograph showing the state that neural cells adhere to graphene fabricated by a steam plasma method according to one embodiment of the present invention; and 
           [0018]      FIG. 4  shows the signals and SNR obtained via a flexible microelectrode fabricated according to one embodiment of the present invention. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0019]    The technical contents of the present invention are described in detail in cooperation with the drawings below. 
         [0020]    Refer to  FIGS. 1A-1F  sectional views schematically showing steps of fabricating a flexible microelectrode for detecting neural signals according to one embodiment of the present invention. 
         [0021]    In Step S 1 , a graphene electrode layer  20  is grown on a temporary substrate  10 , as shown in  FIG. 1A . The graphene electrode layer  20  is grown on the temporary substrate  10  with a CVD (Chemical Vapor Deposition) method. In details, the temporary substrate  10  is made of copper; the temporary substrate  10  is annealed in a tube furnace filled with a gas mixture of hydrogen and argon to remove the organic substances and oxides thereon; then the tube furnace is filled with methane and maintained at a temperature of 1000° C. to form the graphene electrode layer  20  on the temporary substrate  10 . 
         [0022]    In order to provide the succeeding steps with a more stable environment, the present invention further comprises Step Al. 
         [0023]    In Step A 1 , a transfer-printing substrate  30  is grown on one surface of the temporary substrate  10 , which is far away from the graphene electrode layer  20 , as shown in  FIG. 1B . In one embodiment, the transfer-printing substrate  30  is made of PDMS (Polydimethylsiloxane). In one embodiment, the transfer-printing substrate  30  is grown on the surface of the temporary substrate  10  with a spin-coating method. 
         [0024]    In Step S 2 , a flexible substrate  40  is grown on one surface of the graphene electrode layer  20 , which is far away from the temporary substrate  10 , as shown in  FIG. 1C  and  FIG. 2A . In one embodiment, the flexible substrate  40  is formed with a spin-coating method. In one embodiment, the flexible substrate  40  is made of an epoxy-based negative photoresist, such as SU- 8 . SU- 8  can be fabricated into a thick flexible layer. Therefore, SU- 8  can be fabricated into a flexible substrate  40  having high insulativity and flexibility. Next, use a patterning process to form a first end  41  and a second end  42  opposite to the first end  41  on the flexible substrate  40 . The first end  41  gradually contracts toward a direction far away from the second end  42 . The second end  42  gradually expands toward a direction far away from the first end  41 . In one embodiment, the first end  41  is fabricated to have a needle-like shape, and the second end  42  is fabricated to have a plate-like shape. However, the first end  41  and second end  42  of the flexible substrate  40  may be fabricated to have other shapes according to practical requirement. 
         [0025]    In Step A 2 , the transfer-printing substrate  30  is removed after the flexible substrate  40  is completed, as shown in  FIG. 1D . 
         [0026]    In Step S 3 , the temporary substrate  10  is removed with oxide of iron ion, as shown in  FIG. 1E . Next, the flexible substrate  40  is applied as a mask to perform a patterning process on the graphene electrode layer  20  to fabricate the graphene electrode layer  20  to have a shape corresponding to the shape of the flexible substrate  20 , as shown in  FIG. 2B . Thus is formed an electrode body  60  containing the graphene electrode layer  20  and the flexible substrate  40 . The electrode body  60  has a bio-electrode end  61 , an interface-connection end  62  and a middle region  63  between the bio-electrode end  61  and the interface-connection end  62 . The bio-electrode end  61  gradually contracts toward a direction far away from the interface-connection end  62 . The interface-connection end  62  gradually expands toward a direction far away from the bio-electrode end  61 . Similar to the first end  41 , the bio-electrode end  61  is fabricated to have a needle-like shape. Similar to the second end  42 , the interface-connection end  62  is fabricated to have a plate-like shape. In the abovementioned steps, the flexible substrate  40  and the graphene electrode layer  20  are patterned in sequence. However, the abovementioned steps are only to exemplify the present invention. The present invention is not limited by the abovementioned steps. In a practical process, the flexible substrate  40  and the graphene electrode layer  20  may be patterned at the same time. The bio-electrode end  61  will contact an animal or a human being (not shown in the drawings) to detect signals. The interface-connection end  62  transmits the signals to a test device (not shown in the drawings). 
         [0027]    In Step S 4 , an insulating layer  50  is applied to wrap the middle region  63  of the electrode body but expose the bio-electrode end  61 . The exposed bio-electrode end  61  will contact an animal or a human being and detect the signals thereof. In one embodiment, the insulating layer  50  is made of PDMS. The interface-connection end  62  may be exposed from or wrapped by the insulating layer  50  according to the test device to be connected with the interface-connection end  62 . 
         [0028]    Refer to  FIG. 3A  a photograph showing the state that neural cells adhere to glass. Generally speaking, cells can develop on and adhere to glass most optimally. The density of neural cells on glass reaches as high as 74.6 per square millimeter. However, the electric conductivity of glass is poor. Contrarily, the graphene has an electric conductivity of over 15,000 cm 2 v −1 s −1 . From  FIG. 3B , it is learned that the density of neural cells on graphene is about 61 per square millimeter. Nevertheless, the density of neural cells on an ordinary metal is only about 20 per square millimeter. Therefore, the graphene electrode layer  20  of the present invention outperforms ordinary metals in biocompatibility. In addition to general CVD methods, the graphene electrode layer  20  may be formed on the temporary substrate  10  with a steam plasma method to increase the electrochemical adhesion and biocompatibility of the graphene electrode layer  20 , whereby the density of neural cells on the graphene electrode layer  20  can reach as high as 77.4 per square millimeter, as shown in  FIG. 3 . In such a case, the level of biocompatibility of the graphene electrode layer  40  is identical to that of glass. 
         [0029]    Refer to  FIG. 4 . The signal obtained with the flexible microelectrode of the present invention has SNR (Signal to Noise Ratio) as high as 35.38 dB. Therefore, the present invention can achieve higher signal sensitivity and obtain better measurement results. 
         [0030]    The present invention also discloses a flexible microprobe for detecting neural signals, which comprises an electrode body  60  and an insulating layer  50 . The electrode body  60  includes a flexible substrate  40  and a graphene electrode layer  20  formed on the flexible substrate  40 . The electrode body  60  has a bio-electrode end  61  and an interface-connection end  62 . The flexible substrate  40  is made of a polymeric material SU- 8 . The shape of the graphene electrode layer  20  is corresponding to that of the flexible substrate  40 . The insulating layer  50  wraps the graphene electrode layer  20  but reveal the bio-electrode end  61 . In one embodiment, the interface-connection end  62  is also exposed from the insulating layer  50  for connecting with a test device. In one embodiment, the insulating layer  50  is made of PDMS. 
         [0031]    In conclusion, the graphene electrode layer  20  is a 2D graphite structure so it has very high electric conductivity. Further, graphene has biocompatibility much superior to that of ordinary metallic electrodes. Besides, the flexible substrate  40  enables the electrode to bend, and the insulating layer  50  protects the electrode from external interference lest tiny vibration cause friction and accelerate inflammation. Furthermore, the present invention also discloses a method of using a steam plasma method of fabricating the graphene electrode layer  20 , whereby to promote the biocompatibility of the graphene electrode layer  20 . Therefore, the microelectrode of the present invention features flexibility, high biocompatibility and high electric conductivity simultaneously. 
         [0032]    The present invention possesses utility, novelty and non-obviousness and meets the condition for a patent. Thus, the Inventors file the application for a patent. It is appreciated if the patent is approved fast. 
         [0033]    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.