Abstract:
The present invention provides a microarray bioprobe device integrated with a semiconductor amplifier module, which integrates micro array biological probes and thin film transistors on a flexible substrate by Micro-Electro-Mechanical System (MEMS) processes and semiconductor processes. A signal from the microarray bioprobe device is amplified through a near amplifier to increase signal-to-noise ratio and impendence matching. The micro array biological probes of the present invention are produced on the flexible substrate such that the micro array biological probes can be disposed to conform to the profile of a living body&#39;s portion and improving contact between the probes and living body&#39;s portion.

Description:
BACKGROUND OF THE INVENTION 
   1. Field of the Invention 
   The present invention relates to a microarray bioprobe device integrated with a semiconductor amplifier module, and more particularly, to a microarray bioprobe device integrated with a semiconductor amplifier module on a flexible substrate by Micro-Electro-Mechanical System (MEMS) processes and semiconductor processes. 
   2. Description of Related Art 
   Conventional micro array biological probes are produced on a hard silicon wafer substrate. The product is not only heavy and frangible but also high temperature processes needed. The manufacture cost is expensive. Moreover, the conventional micro array biological probes fail to be designed and disposed relying on the profile of a living body&#39;s portion, and adversely affecting contact between the biological probes and living body. Besides, after a signal detected from the conventional micro array biological probes, the signal is picked up to process signal-to-noise ratio and impedance matching. Additional devices for signal processing are required. Thus, the manufacture cost of the conventional micro array probes requires more, and the manufacturing complexity is high. Although the signal-to-noise ratio and impendence matching can be improved by integrating the conventional micro array biological probes and a transistor amplifier for signal processing together, both of them are produced on the hard silicon wafer substrate, and thus the product still fails to be designed and disposed relying on the profile of the living body&#39;s portion. 
   In case that the conventional micro array biological probe element is produced on a flexible substrate, it can be designed and disposed relying on the profile of the living body&#39;s portion to increase the contact effect between the biological probes and living body. However, in view of the current technology, the conventional micro array biological probes and the transistor amplifier can not be integrated together to obtain better results of signal processing for facilitating further analysis and determination. The reason is that high temperature is required in the manufacture process of the transistor amplifier, and the flexible substrate will be deformed at this high temperature. As such, it is difficult to produce the transistor amplifier on the flexible substrate. 
   For the current micro array biological probe technology, there is lack of a micro array biological probe element capable of mass-produced, cost effective, being designed and disposed relying on the profile of the living body&#39;s portion, and also improving the signal-to-noise ratio and impedance matching. 
   SUMMARY OF THE INVENTION 
   The objective of the present invention is to provide a microarray bioprobe device integrated with a semiconductor amplifier module, which integrates micro array biological probes and thin film transistors on a flexible substrate by Micro-Electro-Mechanical System (MEMS) processes and semiconductor processes to improve the contact between the probes and living body and also the signal-to-noise ratio. 
   To achieve the objective, a microarray bioprobe device integrated with a semiconductor amplifier module of the present invention includes a first flexible substrate, a plurality of biological probes, a second flexible substrate, and at least one transistor amplifier and a plurality of lead wires. The first flexible substrate has a plurality of first conducting wires formed therein, by which electrical transmission is generated between a first and second surfaces of the first flexible substrate. The plurality of biological probes is formed on the first surface of the first flexible substrate, and each of the biological probes respectively electrically connects with one of the conducting wires corresponding thereto. The second flexible substrate has a plurality of second conducting wires formed therein, and by which an electrical transmission is generated between an upper and lower surfaces of the second flexible substrate, and the lower surface of the second flexible substrate is electrically jointed to the second surface of the first flexible substrate. The at least one transistor amplifier and a plurality of lead wires are formed on the upper surface of the second flexible substrate, wherein each of the lead wires is respectively electrically connected with one of the second conducting wires corresponding thereto. Electrical signals are transmitted between the biological probes and the transistor amplifiers by the first conducting wires, the second conducting wires and the lead wires. 
   On the other hand, the biological probe has a tip end to facilitate thrusting into the living body to decrease the contact impedance. The present invention can vary the density, occupied area and sharpness of the tip ends of the probes to change the contact impedance so as to meet different needs. 
   The present invention can integrate the micro array biological probes and the semiconductor amplifier module together on the flexible substrate such that the product of the present invention can be designed for roll-to roll types to facilitate mass-produced. 

   
     BRIEF DESCRIPTION OF THE DRAWINGS 
       FIG. 1A  is a schematic cross-sectional view of a microarray bioprobe device of the present invention. 
       FIG. 1B  is a schematic bottom view of  FIG. 1A . 
       FIG. 2A  is a schematic cross-sectional view of the microarray bioprobe device according to another embodiment of the present invention. 
       FIG. 2B  is a schematic bottom view of  FIG. 2A . 
       FIG. 3A  is a schematic cross-sectional view of a semiconductor amplifier module of the present invention. 
       FIG. 3B  is a schematic top view of  FIG. 3A . 
       FIG. 3C  is a schematic view of two inverting amplifier circuits formed of the semiconductor amplifier module of  FIG. 3A . 
       FIG. 4A  is a schematic cross-sectional view of an interface module provided with power, ground and input/output electrical connectors of the present invention. 
       FIG. 4B  is a schematic cross-sectional view of a semiconductor amplifier module and interface integrated module of the present invention. 
       FIG. 4C  is a schematic top view of  FIG. 4B . 
       FIG. 5  is a schematic cross-sectional view of the microarray bioprobe device integrated with the semiconductor amplifier module of the present invention. 
   

   DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
   The present invention employs the MEMS process and semiconductor process to integrate thin film transistor (TFT) amplifiers and micro array biological probes on the flexible substrate. It becomes possible to dispose the microarray bioprobe device in conformity with the profile of the living body&#39;s portion by forming the microarray bioprobe device on the flexible substrate. As such, the contact effect between the biological probes and living body becomes better. On the other hand, the TFT amplifier is also produced on the flexible substrate such that a signal detected from the biological probes can be amplified through a short path. The signal-to-noise ratio and impedance matching are improved, and the cost of manufacture is decreased. 
   The microarray bioprobe device integrated with the semiconductor amplifier of the present invention will be described in detail in the following according to preferred embodiments and accompanying drawing. 
     FIG. 5  is a schematic cross-sectional view of the microarray bioprobe device  30  integrated with the semiconductor amplifier module according to a preferred embodiment of the present invention. The microarray bioprobe device  30  integrated with the semiconductor amplifier module comprises: micro array biological probe element  10  and a semiconductor amplifier and interface integrated module  20   a .  FIG. 1A  is a schematic cross-sectional view of the micro array biological probe element  10 , and  FIG. 1B  is a schematic bottom view of  FIG. 1A . The micro array biological probe element  10  comprises: a first flexible substrate  100 , for example a flexible plastic substrate; a plurality of first conducting wires  130  passing through the first flexible substrate  100  to establish electrical connection between first and second surfaces of the first flexible substrate  100 , and the first conducting wires  130  can be formed of titanium or titanium nitride; a first conducting seeding layer  140  formed on an upper side of the first surface and a lower side of the second surface of the first flexible substrate  100  in electrical connection with the first conducting wires  130 , and the first conducting seeding layer  140  can be formed of copper, nickel or gold; a micro array biological probe module comprising a plurality of groups of array-typed biological probes  150  formed on the lower side of the first conducting seeding layer  140  of the first surface of the first flexible substrate  100 , and each of the biological probes  160  electrically connects with one of the first conducting wires  130  corresponding thereto; and a biological compatible conducting layer  170  covering the array biological probe module to be as an interface layer of the array-typed biological probes  150  for contacting the living body, and the biological compatible conducting layer  170  can be formed of titanium, titanium nitride or other biological compatible metals having high hardness with a thickness of 1 to 5 μm, generally a thickness of 2 μm. 
     FIG. 2A  is a schematic cross-sectional view of the microarray bioprobe device according to another preferred embodiment of the present invention. The only difference between this preferred embodiment and that of  FIG. 1A  is that each of biological probes  160   a  has a tip end for facilitating thrusting into the living body to decrease the contact impedance, and it is suitable for high-current signal input and output. 
   On the other hand, the present invention can change the density, occupied area and sharpness of the tip ends of the biological probes so as to change the impedance for meeting different needs. 
     FIG. 3A  is a schematic cross-sectional view of a semiconductor amplifier module  20  integrated with the microarray bioprobe device  30  of the present invention, and  FIG. 3B  is a schematic top view of  FIG. 3A . The semiconductor amplifier module  20  comprises: a second flexible substrate  200 , for example a flexible plastic substrate; a plurality of second conducting wires  220  passing through the second flexible substrate  200  to transmit signals between two surfaces thereof, and the second conducting wires  200  can be formed of titanium, titanium nitride or other metals with high hardness and high adhesiveness; a second conducting layer  230 , for example a copper layer is formed on the upper side of the second conducting wires  220  of the upper surface of the second flexible plastic substrate  200  and on the lower side of the second conducting wires  220  of the lower surface of the second flexible plastic substrate  200 ; a first dielectric layer  240 , such as a silicon dioxide (SiO 2 ) layer, a silicon nitride (Si 3 N 4 ) layer or other insulating layers, formed on the second conducting layer  230  of the upper surface of the second flexible substrate  200 ; a second dielectric layer  260 , for example a silicon dioxide (SiO 2 ) layer, formed on the upper side of the first dielectric layer  240 ; at least three first conductive type thin film transistors  250   a  with top gates (for example NMOS) and at least one second conductive type thin film transistor  250   b  with a top gate(for example PMOS) are formed on the upper side of the first dielectric layer  240 , and a portion of the second dielectric layer  260  is provided as gate oxide layers of the thin film transistors  250   a  and  250   b , and each of the first conductive type transistors  250   a  with the top gates comprises a gate  251   a , a pair of source/drain  252   a  and a first conductive type channel  253   a , and the second conductive type transistor  250   b  with the top gate comprises a gate  251   b , a pair of source/drain  252   b  and a second conductive type channel  253   b , and the aforesaid at least four thin film transistors constitute two groups of inverting amplifiers whose schematic circuits are shown in  FIG. 3C ; a plurality of lead wires  270  passing through the first dielectric layer  240  and second dielectric layer  260 , and each of the lead wires  270  electrically connects with one of the second conducting wires  220  corresponding thereto; a third dielectric layer  280 , for example a silicon nitride (Si 3 N 4 ) layer, a silicon dioxide (SiO 2 ) layer or other insulating layers, is formed on the first conductive type thin film transistors  250   a  with the top gates, the second conductive type thin film transistor  250   b  with the top gate and the lead wires  270 ; a plurality of third conducting wires  290   a  and a plurality of first pads  290   b  are formed in the via holes of the third dielectric layer  280  and on the surface thereof, and the conducting wires  290   a  electrically connect with the gates  251   a , sources/drains  252   a  of the first conductive type thin film transistors  250   a  with the top gates, source/drain  252   b  of the second conductive type thin film transistor  250   b  with the top gate, and the first pads  290   b  electrically connect with the lead wires  270 ; an insulating protecting layer  300  formed on the third conducting wire  290   a  and the first pad  290   b  so as to isolate humidity and protect the thin film transistors underneath, and the protecting layer  300  can be a silicon dioxide (SiO 2 ) layer, a silicon nitride (Si 3 N 4 ) layer or other insulating layers; a plurality of second pads  310  is respectively formed in through holes of the protecting layer  300  on the upper side of the third conducting wires  290   a ; a plurality of first conducting bumps  320  formed on the second pads  310 , and facilitating to establish electrical connection with the power, ground and input/output interface plate (electrical connectors such as BNC connectors are formed on a backside thereof). 
     FIG. 4A  is a schematic cross-sectional view of the interface plate  400  having the power, ground and input/output electrical connectors of the present invention, in which a plurality of second conducting bumps  410  are formed on a lower surface of the interface plate  400 , and each of the second conducting bumps  410  corresponds to one of the electrical connector  420 . The interface plate  400  is integrated with the semiconductor amplifier module  20  to form the semiconductor amplifier and interface integrating module  20   a , as shown in  FIG. 4B .  FIG. 4C  is a schematic top view of the semiconductor amplifier and interface integrating module  20   a . Referring to  FIG. 4B , the conducting bumps  320  of the semiconductor amplifier module  20  are aligned to and jointed to the conducting bumps  410  of the interface plate  400  to form the semiconductor amplifier and interface integrating module  20   a.    
   Referring to  FIG. 5  again, which is the schematic cross-sectional view of the microarray bioprobe device  30  integrated with the semiconductor amplifier module of the present invention, in which the semiconductor amplifier and interface integrating module  20   a  and the micro array biological probe element  10  are jointed together by back-to-back. For example, a layer of conducting glue  50 , like sliver glue or solder, is coated on the back of the semiconductor amplifier and interface integrating module  20   a , and likewise, a layer of conducting glue  50 , like sliver glue or solder, is coated on the back of the micro array biological probe element  10 . The semiconductor amplifier and interface integrating module  20   a  and the micro array biological probe element  10  are jointed together by back-to-back through both layers of the conducting glue  50  or solder to form the micro array biological probe element  30  integrated with the semiconductor amplifier module of the present invention. Moreover, because the silver glue can be soften and then separated from where it is coated after heating with the temperature lower than the glass transition temperature of the flexible substrate, it facilitates to replace the micro array biological probe element  10  by using the silver glue as the joint agent. The maintenance fee of the microarray bioprobe device  30  integrated with the semiconductor amplifier module of the present invention can be decreased. 
   On the other hand, the sliver glue can be replaced by a double-sided conducting film or a double-sided conducting tape to joint the semiconductor amplifier and interface integrating module  20   a  and the micro array biological probe element  10 . 
   The present invention integrates the micro array biological probe element and the semiconductor amplifier on the flexible substrate such that the product of the present invention can be designed for roll-to roll type, and facilitating mass-produced. 
   While the invention has been described by way of examples and in terms of preferred embodiments, it is to be understood that those who are familiar with the subject art can carry out various modifications and similar arrangements and procedures described in the present invention and also achieve the effect of the present invention. Hence, it is to be understood that the description of the present invention should be accorded with the broadest interpretation to those who are familiar with the subject art, and the invention is not limited thereto.