Abstract:
A microarray biochip workstation allowing positioning of chips, immobilization of molecules, mixing of sample solution, molecular interactions and washing and processing qualitative and quantitative analyses consists of a positioning device for holding a biochip, a mixing device for acting on the sample solution applied on the biochip, a pumping device for removing the sample solution from the biochip surface that does not react, and a reading device for detecting reaction results of the biochip. The workstation thus constructed provides an integrated and effective work interface.

Description:
FIELD OF THE INVENTION  
         [0001]    The present invention relates to an array biochip workstation and particularly to a workstation that allows positioning of chips, immobilization of molecules, mixing of sample solution, molecular interactions and washing and processes qualitative and quantitative analyses of testing.  
         BACKGROUND OF THE INVENTION  
         [0002]    Biochips are high-tech biological elements designed based on principles of molecular biology, protein chemistry, analytic chemistry and optoelectronics and bioformation, and are manufactured by employing Micro Electro Mechanical System, precision manufacturing and other automatic processes. Their applications cover life science basic research, biomedical diagnosis, new drug discovery, and food safety, and the likes.  
           [0003]    The techniques being used include immobilizing biological probes (mainly originating from nucleic acid, protein, carbonhydrate, cells, tissues or the likes) on a substrate, then biological sample solution (such as blood, urine, body fluid, or saliva) containing a target to be tested is mixed on the chip. As the target and the corresponding biological probes have specificity, molecular interactions such as binding reaction or enzyme-catalytic reaction may occur, and resulting in alteration of signals (including optical, piezoelectric, electrochemical, energy signals), or labelling methods such as colormetric, fluorimetric, chemiluminescent or radiative detection may be employed to do image analyses and quantitate optical or radiative intensity of the probe-target complexes to obtain the information of the tested sample.  
           [0004]    Many conventional methods for processing biochips such as immobilizing biological probes, mixing sample solution, molecular interaction, and washing and separation are done manually without continuity. They are mostly time-consuming and tedious. The steps used generally include immobilizing biological probes, applying biological sample solution, holding biochips still for molecular interactions for a selected time period, then washing manually and consecutively for a number of times, or utilizing a shaking device to perform mixing operation and manually replacing buffer solution a number of times for washing and separation. The discontinuous operating steps and various devices being used tend to incur problems such as (1) manual control tends to incur time variances, (2) washing by shaking does not have consistent force and tends to damage binding, (3) array spot on the array biochip cannot be anchored and separated properly and may result in solution pollution with each other, (4) washing and removing of solution are not done thoroughly or completely and tend to have residual fluid remained, and (5) scanning is not done timely to detect reaction signals on the array biochip. As a result, errors could incur in signal detection or image analysis.  
         SUMMARY OF THE INVENTION  
         [0005]    Therefore the primary object of the invention is to resolve aforesaid disadvantages. The invention provides a complete workstation to reduce the errors mentioned above, and to combine functions of positioning for the array spots of the biochip, mixing, interaction, washing and separation, and scanning and reading in the same device body to facilitate integrated operation and utilization for users.  
           [0006]    In order to achieve the foregoing objects, the array biochip workstation of the invention consists of a positioning device for holding a biochip, a mixing device for acting on sample solution applied on the biochip, a pumping device for removing the sample solution from the biochip surface that do not react, and a reading device for detecting reaction results of the biochip. The array biochip that has biological probes immobilized thereon is placed in the positioning device, or the chip is placed in the positioning device and biological probes are immobilized thereon, then add sample solution, then dispose the mixing device over corresponding to array spots on the chip to do mixing, then wash and remove the sample solution that does not react through the pumping device, thereafter employ the reading device to process image analysis and comparison of the reaction results of array spots on the array biochip. The biochip workstation of the invention thus constructed can provide complete operations and reduce experimental errors.  
           [0007]    The foregoing, as well as additional objects, features and advantages of the invention will be more readily apparent from the following detailed description, which proceeds with reference to the accompanying drawings. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0008]    [0008]FIG. 1 is a perspective view of the invention.  
         [0009]    [0009]FIG. 2 is an exploded view of the invention.  
         [0010]    [0010]FIG. 3 is a fragmentary exploded view of the invention.  
         [0011]    FIGS.  4 -A,  4 -B and  4 -C are schematic views of the invention in various operating conditions.  
         [0012]    FIGS.  5 -A,  5 -B and  5 -C are other schematic views of the invention in various operating conditions.  
         [0013]    FIGS.  6 -A and  6 -B are schematic views of another embodiment of the invention. 
     
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0014]    Referring to FIGS. 1, 2 and  3 , the array biochip workstation of the invention aims at holding a biochip  70 , and allowing biological probes  72  formed on array spots  71  of the biochip  70  to interact with sample solution  80 , and processing qualitative and quantitative testing analyses. The workstation consists of a positioning device  10  for holding the biochip  70 , a mixing device  20  for acting on sample solution  80  applied on the biochip  70 , a drawing device  30  for removing the sample solution  80  on the biochip  70  that does not react, and a reading device  40  for detecting reaction results of the biochip  70 . The biochip  70  that has biological probes  72  formed thereon is placed in the positioning device  10 , or the biochip  70  is placed in the positioning device  10 , then biological probes  72  are immobilized thereon, then sample solution  80  is added. The mixing device  20 , through a separation unit  15 , is used to process mixing on the corresponding array spots  71  of the biochip  70 . Then the drawing device  30  is employed to remove the sample solution  80  that does not react from the biochip  70  surface. Then a drying process is performed. And the reading device  40  is used to do image analysis and comparison of reaction results for the biochip  70 .  
         [0015]    The positioning device  10  includes a guiding trough  11  for anchoring the biochip  70 . The separation unit  15  is located on the guiding trough  11  for separating the array spots  71  of the biochip  70 . The guiding trough  11  has two sides forming respectively an anchoring member  12  with a compressing section  13 . The anchoring member  12  is harnessed by an elastic element  14 . The biochip  70  may be held in a chip cartridge  60  which has two sides may be slipped in and clamped by the compressing section  13 . The chip cartridge  60  has a test opening  61  whose periphery is coupled with a seeping guard  62  which may be compressed on the chip to form a common solution mixing zone for all array spots to prevent the sample solution  80  from flowing out.  
         [0016]    In addition, the separation unit  15  has a bottom section attaching to a first displacement mechanism  19  which may drive the separation unit  15  moving in parallel and up or down. The separation unit  15  further has a plurality of separation holes  16  corresponding to array spots  71  of the biochip  70 . The bottom section of the separation unit  15  further attaches to an anti-permeation pad  17  which has apertures  18  corresponding to the separation holes  16 . When the separation unit  15  is moved downwards, the anti-permeation pad  17  compresses the biochip  70  with the apertures  18  matching respectively the array spots  71  to form reaction zones. The anti-permeation pad  17  is made from a pliable material such as rubber.  
         [0017]    The mixing device  20  is located on the positioning device  10  and includes a mixing unit  22  passing through the separation unit  15  and corresponding to the array spots  71  for mixing the sample solution  80 , and a oscillation unit  21  which has piezoelectric ceramic material to generate oscillation to actuate the mixing unit  22 , thereby the biological probes  72  on the biochip  70  may be effectively enhanced to react with the sample solution  80 . Moreover, the mixing device  20  has a bottom end attaching to a second displacement mechanism  24  for moving the mixing device  20  downwards to perform mixing operation.  
         [0018]    The drawing device  30  includes a power unit  31  and a suction unit  32  fastening to the power unit  31  and being adjacent to the biochip  70 . The power unit  31  has at least one suction pipe  33  and one discharge pipe  37  extending therefrom. The suction pipe  33  has a free end connecting to a connection head  34  of the suction unit  32 . The suction unit  32  further has a suction needle  35  adjacent to the biochip  70 . The suction needle  35  has a head end  36  which forms an obtuse truncated angle. The head end  36  is spaced from the array spots  71  of the biochip  70  for a selected interval to prevent reaction results from damaging when drawing operation is performed. The mixing unit  22  has at least one anchoring hole  23  to receive the suction needle  35 .  
         [0019]    The reading device  40  is for processing qualitative and quantitative scanning analyses for the array spots  71  on the biochip  70  that have gone through interaction, washing and drawing operations. It has an inlet  41  to receive the biochip  70 . The reading device  40  may be a optical transmittant or reflective scanner  42  depending on the nature of the substrate and film property of the biochip  70 .  
         [0020]    In addition, the positioning device  10 , the mixing device  20 , the drawing device  30  and the reading device  40  are mounted on a device body  50 . The device body  50  has at least one control panel  51  located on a surface thereof for controlling all other devices and at least one connection slot  52  for linking to a computer or other operation systems to process control and data analysis. The connection slot  52  may be a parallel transmission port or a series transmission port such as RS-232 or USB interface. Moreover, the device body  50  has at least one housing cavity  53  corresponding to two sides of the positioning device  10  for housing a container for holding reagents and the sample solution  80 .  
         [0021]    When in use, first adding biological probes  72  on the biochip  70  encased in the chip cartridge  60 , or inserting the chip  70  in the positioning device  10 , and sequentially adding the biological probes  72  and sample solution  80 . The process steps include:  
         [0022]    1. first, as shown in FIGS.  4 -A and  4 -B, insert the biochip  70  through the guiding trough  11  in the positioning device  10 ; two sides of the clip cartridge  60  are harnessed by the elastic elements  14  and compressed by the compression sections  13  at two sides of the anchoring member  12 ; the seeping guard  62  around the test opening  61  of the chip cartridge  60  compresses the chip to form a solution mixing zone for all array spots  71 ; then sample solution  80  may be added to process interaction with all array spots  71 ;  
         [0023]    2. then, as shown in FIGS.  4 -B and  4 -C, operate the control panel  51  to move the separation unit  15  downwards; the anti-permeation pad  17  is moved to depress the biochip  70 , and the apertures  18  of the anti-permeation pad  17  match every array spots  71  to form individual reaction zone; then add respectively different biological probe  72  and the sample solution  80  to each array spots  71 ;  
         [0024]    3. thereafter, as shown in FIGS.  5 -A,  5 -B and  5 -C, operate the control panel  51  to move the mixing device  20  and the suction unit  32  above the biochip  70  for a selected distance; connect the connection head  34  to the oscillation suction unit  32 ; activate the oscillation unit  21  and perform mixing operations through the mixing unit  22  to accelerate molecular interactions; after the mixing operations completed, operate the control panel  51  to activate the power unit  31  to remove at a selected suction speed the sample solution  80  does not react from the biochip surface; and  
         [0025]    4. finally, the surface of the biochip  70  is washed and sucked to dry, and the biochip  70  is removed from the guiding trough  11 , and inserted into the reading device  40  through the inlet  41 ; then optically reflective scanning or transmittant scanning may be performed on the array spots  71  of the biochip  70 ; through the connection slot  52  on the device body  50 , reading data may be transmitted to a computer or to further process qualitative and quantitative analyses for the reaction results.  
         [0026]    Refer to FIGS.  6 -A and  6 -B for another embodiment of the invention. In this embodiment, the anchoring hole  23 ′ is located on the rear side of the positioning device  10 , and the suction needle  35 ′ of the suction unit  32  is located in the anchoring hole  23 ′ to match operation of another type of biochip  70  which contains a microfluidic chip  73 . When to withdraw the sample solution  80  that does not react, the connection head  34  is coupled with the suction unit  32 ′ and the suction needle  35 ′ is horizontally inserted into the microfluidic chip  73  to perform suction operation. Thus form an array biochip workstation that can process a reactive chip and a microfluidic chip.