Abstract:
An apparatus for automatically testing CMOS magnetoresistive biochips is disclosed. The apparatus includes: means for directly or indirectly applying physical pressure to the fluid pumping chamber in a cartridge; a liquid injector for injecting liquid into the reaction chamber in the cartridge through an inlet or inlets in fluid connection to said reaction chamber; a CMOS magnetoresistive biochip located in the reaction chamber in the cartridge; means for applying a magnetic field to said CMOS magnetoresistive biochip in the cartridge; an electronic module for communicating with and supplying power as well as control signals to said biochip; a microprocessor to control and coordinate the aforementioned components; and a user interface for information processing. The apparatus provided by the present invention reduces the complexity of operation and enhances the detection sensitivity to a great extent.

Description:
FIELD OF THE INVENTION 
       [0001]    This invention relates to testing techniques for chemical and biological molecules, cells and microorganism. More particularly, the invention relates to a testing apparatus of biochips using Hall devices, giant magneto-resistive devices or magnetic tunnel junction arrays as magnetic sensors. 
       BACKGROUND OF THE INVENTION 
       [0002]    Magnetoresistive sensors have been widely used in applications such as magnetic hard disks and angular transducers in cars. In 1998, Baselt et al. described using functionalized magnetic particles as tags for detecting biological molecules hybridized to probe biomolecules attached to the surface of giant magneto-resistive (GMR) sensors. More details are described in U.S. Pat. No. 5,981,297, which is hereby incorporated by reference in its entirety. Biochips using magnetoresistive devices as sensors are based on detecting biologically functioned magnetic particles of micrometer or nanometer in diameter. The surface of the biochip is functionalized with antibodies or antigens (probe molecules) that recognize and conjugate specifically with the target molecules in the sample applied onto the surface of the biochip. Paramagnetic particles functionalized with the same type of antibodies or antigens as those on the surface of the biochips are then dropped onto the chip surface. Some of the paramagnetic particles conjugate with the target molecules which have hybridized with the probe molecules on the chip surface, forming a sandwich structure. After free magnetic particles are removed, a magnetic field is applied to the biochip to detect to existence of the paramagnetic particles. Target molecules are quantified by the amount of paramagnetic particles detected. 
         [0003]    In Addition to Magnetoresistive (GMR) devices, Magnetic Tunnel Junction (MTJ) devices can also be used as the sensing elements for detecting magnetic particles. Such a biochip is described by Xifu Jiang et al. (Korea) in SIPO China patent application Biosensors and Arrays of Sensor Units (Appl. No. 200310113330), which is hereby incorporated by reference in its entirety. Chao Chen et al. proposed the application of MTJ as the sensing element of biochips in SIPO Pat. No. ZL 0213936. X, which is hereby incorporated by reference in its entirety. In SIPO Pat. Appl. No. 200510005035.5, Lei Wang et al. suggested that Si 3 N 4  passivation layer could be replaced by plastic passivation layer. 
         [0004]    Researches in the past decade has shown that, as a new technology platform in the development of various bio-sensor chips, magnetoresistive biosensor is a very good candidate for high speed, high sensitivity and high throughput detection of biomolecules at a reasonable cost. At the 2006 Biosensor Congress in Toronto, researchers with Philips reported that there had been more than 30 groups worldwide developing magnetoresistive biosensors. 
         [0005]    Even though there are numerous publications on biochips using magnetoresistive sensors, what is still needed is a testing apparatus for biosensors and biochips using magnetoresistive or magnetic tunnel junction devices as the sensing element, particularly a testing apparatus for magnetoresistive biochips. 
       SUMMARY OF THE INVENTION 
       [0006]    Addressing the shortcomings in the prior art, the present invention provides a testing system for CMOS magnetoresistive biochips. The apparatus of the present invention offers high sensitivity and high speed with automated testing procedure. 
         [0007]    The CMOS magnetoresistive biochips referred here are defined as chips of CMOS circuit integrated with arrays of magnetic sensors, including but not limited to giant magnetoresistive (GMR) sensors, magnetic tunnel unction sensors, or Hall effect sensors. 
         [0008]    The present invention provides automatic testing apparatus for CMOS magnetoresistive biochips comprising means for directly or indirectly applying pressure to a reagent reservoir or a plurality of reservoirs in a cartridge with at least one reaction chamber where the CMOS magnetoresistive biochip is located. Under said pressure, the reagent in the reservoir or reservoirs flows into the reaction chamber via a micro-channel or a plurality of micro-channels. The apparatus further comprises a fluid injection system connected to the cartridge, injecting liquid into the reaction chamber via microfluidic channels. The apparatus further comprises means for applying a magnetic field, either positive or negative, with a required magnitude to the CMOS magnetoresistive biochips in said cartridge. The apparatus further comprises an electronic module to supply power and control signal to said CMOS magnetoresistive biochip in said cartridge, test the information stored in the sensing elements of the CMOS magnetoresistive biochip, and convert the tested analog signal to digital signal. The apparatus further comprises a microprocessor to control and coordinate the aforementioned components: said means for directly or indirectly applying pressure to the reagent reservoir in said cartridge, said liquid injection system connected to said cartridge used to inject liquid into said microfluidic channel or channels connected to said reaction chamber in said cartridge, said means for applying positive or negative magnetic field to said CMOS magnetoresistive biochip, said electronic module for supplying power and controlling signal to said CMOS magnetoresistive biochip in said cartridge, testing the information stored in the sensing elements of said CMOS magnetoresistive biochip, and converting the tested analog signal to digital signal; and to process information measured under different magnetic fields. The apparatus further comprises a user interface to receive and display information from said microprocessor. 
         [0009]    In one embodiment, the means in the above apparatus for applying pressure to the reagent reservoir comprises an electrical motor or electrical stepping motor. The linear actuator of said motor puts pressure on the wall of the reagent reservoir, pushing the reagent to flow into the reaction chamber via a micro-channel in fluid connection to the reservoir at one end and to the reaction chamber at the other end. The reagent flows out of the exit of the reaction chamber into a waste reservoir which has a pressure release hole to facilitate the fluid flow. 
         [0010]    In another embodiment, the means for applying pressure to the reagent reservoir comprises means to increase air pressure in the reagent reservoir. The air pressure causes the reagent to flow into the reaction chamber via a micro-channel in fluid connection to the reservoir. The reagent flows out of the exit of the reaction chamber into a waste reservoir which has a pressure release hole to facilitate the fluid flow. 
         [0011]    In yet another embodiment, the means for applying pressure to the reagent reservoir comprises means to create a vacuum at the exit end of the reaction chamber connected to the waste reservoir in the cartridge. The vacuum created at the exit of the reaction chamber causes the reagent to flow into the reaction chamber via a micro-channel in fluid connection to the reagent reservoir. The reagent flows out of the exit of the reaction chamber into a waste reservoir. 
         [0012]    In the automatic testing apparatus described above, one embodiment of the fluid injection system comprises a plurality of syringes delivering fluid into the reaction chamber via inlets in fluid connection with the reaction chamber through microfluidic channels. Controlled and coordinated by a microprocessor, electrical stepping motors powered by their drive circuits actuate the syringes. The injection needles of the syringes are driven by a stepping motor controlled by the microprocessor to achieve fluid-tight coupling with the inlets. The liquid injected by said syringes may contain sample, magnetic particles or buffer solutions. 
         [0013]    In the automatic testing apparatus described above, the direction of the magnetic field from the means for applying magnetic fields can be adjusted manually or automatically is according to the instructions of said microprocessor. 
         [0014]    In the automatic testing apparatus described above, said CMOS magnetoresistive biochip contains CMOS circuit and magnetic tunnel junction arrays, or CMOS circuit and giant magneto-resistive devices, or CMOS circuit and Hall magneto-resistance devices. 
         [0015]    The present invention provides another automatic testing apparatus for CMOS magnetoresistive biochips comprising means for directly or indirectly applying pressure to a reagent reservoir or a plurality of reservoirs in a cartridge with at least one reaction chamber where the CMOS magnetoresistive biochip is located. Under said pressure, the reagent in the reservoir or reservoirs flows into the reaction chamber via a micro-channel or a plurality of micro-channels. The apparatus further comprises means for applying a magnetic field, either positive or negative, with a required magnitude to the CMOS magnetoresistive biochips in said cartridge. The apparatus further comprises an electronic module to supply power and control signal to said CMOS magnetoresistive biochip in said cartridge, test the information stored in the sensing elements of the CMOS magnetoresistive biochip, and convert the tested analog signal to digital signal. The apparatus further comprises a microprocessor to control and coordinate the aforementioned components: said means for directly or indirectly applying pressure to the reagent reservoir in said cartridge, said means for applying positive or negative magnetic field to said CMOS magnetoresistive biochip, said electronic module for supplying power and controlling signal to said CMOS magnetoresistive biochip in said cartridge, testing the information stored in the sensing elements of said CMOS magnetoresistive biochip, and converting the tested analog signal to digital signal; and to process information measured under different magnetic fields. The apparatus further comprises a user interface to receive and display information from said microprocessor. 
         [0016]    In one embodiment, the means in the above apparatus for applying pressure to a reagent reservoir comprises an electrical motor or electrical stepping motor. The linear actuator of said motor puts pressure on the wall of the reagent reservoir, pushing the reagent to flow into the reaction chamber via a micro-channel in fluid connection to the reservoir at one end and to the reaction chamber at the other end. The reagent flows out of the exit of the reaction chamber into a waste reservoir which has a pressure release hole to facilitate the fluid flow. 
         [0017]    In another embodiment, the means for applying pressure to a reagent reservoir comprises means to increase air pressure in the reagent reservoir. The air pressure causes the reagent to flow into the reaction chamber via a micro-channel. The reagent flows out of the exit of the reaction chamber into a waste reservoir which has a pressure release hole to facilitate the fluid flow. 
         [0018]    In yet another embodiment, the means for applying pressure to a reagent reservoir comprises means to create a vacuum at exit end of the reaction chamber connected to the waste reservoir in the cartridge. The vacuum created at the exit of the reaction chamber causes the reagent to flow into the reaction chamber via a micro-channel in fluid connection to the reagent reservoir. The reagent flows out of the exit of the reaction chamber into a waste reservoir. 
         [0019]    In the automatic testing apparatus described above, the direction of the magnetic field from the means for applying magnetic fields can be adjusted manually or automatically is according to the instructions of said microprocessor. The CMOS magnetoresistive biochip contains CMOS circuit and magnetic tunnel junction arrays, or CMOS circuit and giant magneto-resistive devices, or CMOS circuit and Hall magneto-resistance devices. 
         [0020]    The present invention provides yet another automatic testing apparatus for CMOS magnetoresistive biochips, comprising a fluid injection system connected to the cartridge, injecting liquid into the reaction chamber via microfluidic channels. In one embodiment, the fluid injection system comprises a plurality of syringes delivering fluid into the reaction chamber via inlets in fluid connection with the reaction chamber through microfluidic channels. Controlled and coordinated by a microprocessor, electrical stepping motors powered by their drive circuits actuate the syringes. The injection needles of the syringes are driven by a stepping motor controlled by the microprocessor to achieve fluid-tight coupling with the inlets. The liquid injected by said syringes may contain sample, magnetic particles or buffer solutions. The apparatus further comprises means for applying a magnetic field, either positive or negative, with a required magnitude to the CMOS magnetoresistive biochips in said cartridge. The apparatus further comprises an electronic module to supply power and control signal to said CMOS magnetoresistive biochip in said cartridge, test the information stored in the sensing elements of the CMOS magnetoresistive biochip, and convert the tested analog signal to digital signal. The apparatus further comprises a microprocessor to control and coordinate the aforementioned components: said liquid injection system connected to said cartridge used to inject liquid into said microfluidic channel or channels connected to said reaction chamber in said cartridge, said means for applying positive or negative magnetic field to said CMOS magnetoresistive biochip, said electronic module for supplying power and controlling signal to said CMOS magnetoresistive biochip in said cartridge, testing the information stored in the sensing elements of said CMOS magnetoresistive biochip, and converting the tested analog signal to digital signal; and to process information measured under different magnetic fields. The apparatus further comprises a user interface to receive and display information from said microprocessor. 
         [0021]    The present invention provides yet another automatic testing apparatus for CMOS magnetoresistive biochips, comprising means for applying a magnetic field, either positive or negative, with a required magnitude to the CMOS magnetoresistive biochips in said cartridge. The apparatus further comprises an electronic module to supply power and control signal to said CMOS magnetoresistive biochip in said cartridge, test the information stored in the sensing elements of the CMOS magnetoresistive biochip, and convert the tested analog signal to digital signal. The apparatus further comprises a microprocessor to control and coordinate the aforementioned components: said means for applying positive or negative magnetic field to said CMOS magnetoresistive biochip, said electronic module for supplying power and controlling signal to said CMOS magnetoresistive biochip in said cartridge, testing the information stored in the sensing elements of said CMOS magnetoresistive biochip, and converting the tested analog signal to digital signal; and to process information measured under different magnetic fields. The apparatus further comprises a user interface to receive and display information from said microprocessor. 
       ADVANTAGES OF THE INVENTION 
       [0022]    The present invention provides automatic testing apparatus for biochips using magnetoresistive sensors. Said apparatus reduce the complexity of operation and the consumption of reagents and offers high detection speed with good repeatability by using automatic liquid injectors with the microfluidic cartridge. The combination of CMOS magnetoresistive biochips and microfluidic systems enhances the detection sensitivity to a great extent. The actuation of the reagent reservoir on the cartridge by the means for applying pressure in said testing apparatus forms a highly efficient microfluidic pump and reduces the cost of the cartridge effectively. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0023]      FIG. 1   a  is the front view of the cartridge of magnetoresistive sensor biochips in the first embodiment. 
           [0024]      FIG. 1   b  is the left view of  FIG. 1   a.    
           [0025]      FIG. 2  is a block diagram of the testing apparatus for magnetoresistive sensor biochips in the second embodiment. 
           [0026]      FIG. 3   a  is a front view of the cartridge of magnetoresistive sensor biochips in the third embodiment. 
           [0027]      FIG. 3   b  is the left view of  FIG. 3   a.    
           [0028]      FIG. 4  shows the testing apparatus for magnetoresistive sensor biochips in the fourth embodiment. 
           [0029]      FIG. 5   a  shows a front view of the cartridge of magnetoresistive sensor biochips in the fifth embodiment. 
           [0030]      FIG. 5   b  is the left view of  FIG. 5   a.    
           [0031]      FIG. 6  shows the testing apparatus for magnetoresistive sensor biochips in the sixth embodiment. 
           [0032]      FIG. 7  shows the testing apparatus for magnetoresistive sensor biochips in the seventh embodiment. 
           [0033]      FIG. 8  shows the testing apparatus for magnetoresistive sensor biochips in the eighth embodiment. 
           [0034]      FIG. 9  shows the testing apparatus for magnetoresistive sensor biochips in the ninth embodiment. 
       
    
    
     REFERENCE OF THE NUMERICAL LABELS IN THE DRAWINGS AND DESCRIPTION 
       [0035]      1  A cartridge, which comprises either all or some of the following features: 
         [0000]    
       
         
               
               
               
               
             
           
               
                   
               
             
             
               
                 111 
                 The substrate, 
                   
                   
               
               
                 121 
                 The cartridge layer with 
                 122 
                 Microfluidic channels 
               
               
                   
                 microchannels, 
                   
                   
               
               
                 131 
                 The reaction chamber, 
                 132 
                 The biochip 
               
               
                 141 
                 The reagent reservoir, 
                 142 
                 The liquid reservoir 
               
               
                 151 
                 The pump chamber, 
                 152 
                 The pressure chamber, 
               
               
                 153 
                 Inlets and outlets of liquid or air 
                   
                   
               
               
                 161 
                 The waste reservoir, 
                 161{acute over ( )} 
                 Waste outlets 
               
               
                 171 
                 The opening of the reagent 
                   
                   
               
               
                   
                 reservoir, 
                   
                   
               
               
                 171{acute over ( )} 
                 The sealing cap of the 
                   
                   
               
               
                   
                 reagent reservoir 
                   
                   
               
               
                 181 
                 Fluid inlets 
                   
                   
               
               
                 191 
                 Electrical conductive lines 
               
               
                   
               
             
          
         
       
     
         [0036]      2  Means for applying pressure, which comprises either all or some of the following features:
     21  Control circuits of the stepping motor,     22  The stepping motor,     23  The driving rod,     24  Coupling pipes,     25  The apparatus for generating and regulating pressured liquid or air   
 
         [0042]      3  A liquid injection system comprises:
     311 ,  312  Injectors     321 ,  322 ,  323  The electrical stepping motor     33  Control circuit of the stepping motor,     34  Injection needle   
 
         [0047]      4  Means for generating a magnetic field comprises
     41  Electromagnets,     42  The power circuit for the electromagnets,     43  A device for adjusting the direction of the magnetic field     5  Electronic module for controlling and reading information from said biochip     6  A microprocessor     7  A user interface   
 
       DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
       [0054]    The cartridge described in the present invention serves as a carrier for magnetoresistive sensor biochips to facilitate their connection and interaction with the testing apparatus in the present invention. The microfluidic channels in said cartridge make the biochemical reaction easier on biochips, enhancing its detection sensitivity. The concrete structure and function of said cartridge have been described in detail in SIPO China patent application No. 200710175624.7 on Oct. 9, 2007, which is hereby incorporated by reference in its entirety. 
       Embodiment 1 
     Cartridge of Magnetoresistive Sensor Biochips 
       [0055]    Refer to  FIGS. 1   a  and  1   b . Substrate  111  of cartridge  1  can be made of glass, ceramics, single crystal silicon with an layer of silicon dioxide on the surface, or polymer. Orifice  171  of reagent reservoir  141  on substrate  111  serves as inlet of reagents. Orifice  171  can be sealed fluid-tight by cap  171 ′. In contact with substrate  111  is the channel and chamber layer  121  of the cartridge, wherein a plurality of channels and chambers are formed. There are at least one reaction chamber  131 , one reagent reservoir  141 , one pump chamber  151 , one waste reservoir  161  and more than one fluid inlet  181  in connection with microfluidic channels  122 . Inlets  181  are for the injection of reaction reagent, buffer solution or rinsing buffer into reaction chamber  131 . Pump chamber  151  is capped with a layer of flexible material which can bend under pressure, hence pumping the reagent in reservoir  141  into reaction chamber  131 . Changing the direction of the applied pressure changes the direction of fluid flow in reaction chamber  131 . Such an oscillation movement of reagent improves the efficiency of the biochemical reaction of molecules in the reagent with the molecules on the surface of biochip  132  located in reaction chamber  131 . Waste reservoir  161  consists of a plurality of concentric circular micro-channels and orifice  161 ′ as the waste outlet. When reagent is moved back and forth through reaction chamber  131 , the structure of waste reservoir  161  reduces the chance of cross contamination of the reagent in reaction with the waste already in waste reservoir  161 . Biochip  132 , using Hall effect, giant magnetoresistive or magnetic tunnel junction devices as sensors, is placed in reaction chamber  131 , wherein the CMOS circuit on biochip  132  is connected with the testing apparatus outside cartridge  1  through a plurality of conducting lines  191  on the cartridge  1 . 
       Embodiment 2 
       [0056]    The testing apparatus for magnetoresistive sensor biochips shown in  FIG. 2  includes:  2 , means for applying pressure, which comprises a control circuitry  21  for electrical motor or electrical stepping motor  22  and driving rod  23 , wherein the output signal of circuit  21  is controlled by microprocessor  6 . By applying pressure either to pump chamber  151 , which is in fluid connection with reagent reservoir  141  in cartridge  1 , or directly to reagent reservoir  141 , driving rod  23  pushes fluid into reaction chamber  131  in said cartridge  1 . 
         [0057]    Besides an electrical motor or electrical stepping motor, other linear actuating devices such as piezoelectric devices can serve as  2 , the means for applying pressure to either pump chamber  151  or reagent reservoir  141 . 
         [0058]    The testing apparatus shown in  FIG. 2  further includes fluid injection system  3 , which comprises the first injector  311  and the second injector  312 ; the first stepping electrical motor  321 , the second stepping electrical motor  322 , the third stepping electrical motor  323 ; the control circuits for the stepping motors  33 ; and injection needle  34 . The driving rod of the first electrical stepping motor  321  actuates the first injector  311 ; the driving rod of the second electrical stepping motor  322  actuates the second injector  312 . Injection needles  34 , which are connected with liquid injectors  311  and  312 , are driven by the third electrical stepping motor  323  to form fluid-tight connection with fluid inlets  181  in cartridge  1 . The output of control circuits  33  is regulated by microprocessor  6 . Driven by electrical stepping motors  321  and  322 , the first injector  311  and second injector  312  inject fluid, either successively or simultaneously, into reaction chamber  131  via an inlet or inlets  181  connected to reaction chamber  131  through microfluidic channels  122 . Said liquid stream can also drive the fluid in microfluidic channels  122  into the waste reservoir  161  through the reaction chamber  131  in said cartridge  1  to drain the waste through liquid outlet  161 ′. The liquid stream ejected by fluid injection system  3  contains biomolecules, magnetic particles or buffer solution. 
         [0059]    The testing apparatus shown in  FIG. 2  further includes  4 , the means for generating a magnetic field, which comprises electromagnet  41  in series connection with power circuit  42 . The operation of power circuit  42  is controlled by microprocessor  6 . Power circuit  42  provides either a positive or negative current with particular amplitude to the electromagnet. Accordingly, the electromagnet applies either a positive or negative magnetic field on to the CMOS magnetoresistive biochip  132  under test. 
         [0060]    There can be two directions for the magnetic field applied by electromagnet  41 , either parallel or perpendicular to the surface of CMOS magnetoresistive biochip  132 . With proper signal processing scheme, field in either direction can magnetize the magnetic particles to stimulate magnetoresistive sensor biochip and test the existence of magnetic particles. In the present invention, the field direction is perpendicular to the surface of the CMOS magnetoresistive biochip. Device  43  is used to tune the direction of electromagnet  41  to ensure that the magnetic field is perpendicular to magnetoresistive sensor biochip  132 . According to the response of magnetoresistive sensor biochips  132  to the magnetic field applied by electromagnet  41 , microprocessor  6  can calculate the direction of magnetic field, and then instructs device  43  to adjust electromagnet  41  accordingly. 
         [0061]    Electronic module  5 , which is used for controlling and reading information from the biochip  132 , is connected with biochip  132  via conductive lines  191  on substrate  111  on cartridge  1 . The function of electronic module  5  is to supply power and control signals for magnetoresistive sensor biochip  132  in said cartridge  1 , test the information stored in each magnetoresistive sensor elements in biochip  132 , and perform analog-to-digital conversion of the results; 
         [0062]    Microprocessor  6  controls and coordinates the operation of the means for applying pressure  2 , fluid injection system  3 , means for applying magnetic field  4  and electronic module  5 . Additionally, microprocessor  6  is also used to processes information and test results, such as performing the necessary calculation to remove background noise and extract out the user data. 
         [0063]    User interface  7  is connected to microprocessor  6  to receive users&#39; instruction and display the test condition and results. 
         [0064]    Procedures of said apparatus are shown below: 
         [0000]    Step 1: Turn ON the power supply of the test apparatus;
 
Step 2: Inject samples and functionalized magnetic particles into reagent reservoir  141 , and put the cartridge into the testing apparatus in the present invention;
 
Step 3: Input testing conditions and requirements through user interface  7 ;
 
Step 4: Under the instruction of microprocessor  6 , the means for applying pressure  2  applies pressure to pump chamber  151  to inject the mixed liquid stream in reagent reservoir  141  into reaction chamber  131  via micro-channel  122 , wherein the bio molecules in the liquid hybridize with biological probes on biochip  132 ;
 
Step 5: Controlled by microprocessor  6 , fluid injection system  3  injects rinsing buffer into reaction chamber  131  to remove the molecules and magnetic particles which are non-specifically bound on the surface of biochip  132 .
 
Step 6: Controlled by microprocessor  6 , power circuit  42  for electromagnet  41  applies a magnetic field to magnetoresistive sensor biochip  132 .
 
Step 7: Controlled by microprocessor  6 , electronic module  5  read the information of magnetoresistive sensor devices.
 
Step 8: Microprocessor  6  processes the tested results under different magnetic fields to get the results.
 
Step 9: User interface  7  displays the results.
 
       Embodiment 3 
     Fabrication and Materials of the Cartridge for Magnetoresistive Sensor Biochips 
       [0065]      FIGS. 3   a  and  3   b  show said cartridge, wherein substrate  111  can be made of glass, ceramics, single crystal silicon with an layer of silicon dioxide on the surface or polymer. Orifice  171  of reagent reservoir  141  on substrate  111  serves as inlet of reagents. Orifice  171  can be sealed fluid-tight by cap  171 ′. In contact with substrate  111  is the channel and chamber layer  121  of the cartridge, wherein a plurality of channels and chambers are formed. Channel and chamber layer  121  can be made of flexible material such as silastic by molding, or plastic materials such as polymethylmethacrylate (PMMA), polycarbonate (PC), polypropylene (PP), nylon, polytetrafluoroethene, and polyether-ether-ketone. Microfluidic channels  122  and reagent reservoir  141  are fabricated by molding, while flexible material such as PDMS should be used as the cap of pump chamber  151 . There are at least one reaction chamber  131 , one reagent reservoir  141 , one pump chamber  151 , one waste reservoir  161  and more than one fluid inlet  181  in connection with microfluidic channels  122 . Inlets  181  are for the injection of reaction reagent, buffer solution or rinsing buffer into reaction chamber  131 . Pressure chamber  152  lies above pump chamber  151 . Orifice  153  is used to connect pressure chamber  152  with an equipment which can create either a negative or positive pressure in chamber  152  with liquid or gas. Pump chamber  151  is capped with a layer of flexible material which can bend under pressure, pumping the reagent in reservoir  141  into reaction chamber  131 . Changing the direction of the applied pressure in chamber  152  changes the direction of fluid flow in reaction chamber  131 . Such an oscillation movement of reagent improves the efficiency of the biochemical reaction of molecules in the reagent with the molecules on the surface of biochip  132  located in reaction chamber  131 . Waste reservoir  161  consists of a plurality of concentric circular micro-channels and orifice  161 ′ as the waste outlet. When reagent is moved back and forth through reaction chamber  131 , the structure of waste reservoir  161  reduces the chance of cross contamination of the reagent in reaction with the waste already in waste reservoir  161 . Biochip  132 , using Hall effect, giant magnetoresistive or magnetic tunnel junction devices as sensors, is placed in reaction chamber  131 , wherein the CMOS circuit on biochip  132  is connected with the testing apparatus outside cartridge  1  through a plurality of conducting lines  191  on the cartridge  1 . Layer  121  can be made of flexible material such as polydimethylsiloxane (PDMS) or rubber, or the same material as that of  111 , but flexible material should be used as the capping layer of pump chamber  151 . 
       Embodiment 4 
       [0066]    The test apparatus for magnetoresistive sensor biochips in  FIG. 4  includes means for applying pressure  2 , which comprises the means for creating a vacuum and/or pressure  25  and coupling pipe  24 . Coupling pipe  24  connects with the means for creating a vacuum and/or pressure  25  at one end, and orifice  153  of pressure chamber  152  at the other end. Since pump chamber  151  is capped by a layer of flexible material, the increase or decrease of pressure in pressure chamber  152  by the means for creating a vacuum and/or pressure  25  will drive pump chamber  151  to contract or expand and push the liquid in reagent reservoir  141  through reaction chamber  131 . 
         [0067]    The testing apparatus shown in  FIG. 4  further includes fluid injection system  3  which comprises: the first injector  311  and the second injector  312 ; the first stepping electrical motor  321 , the second stepping electrical motor  322 , the third stepping electrical motor  323 ; the control circuits for the first and second stepping motors  33 ; injection needle  34 . The driving rod of the first electrical stepping motor  321  actuates the first injector  311 ; the driving rod of the second electrical stepping motor  322  actuates the second injector  312 . Injection needles  34 , which are connected with liquid injectors  311  and  312 , are driven by the third electrical stepping motor  323  to form fluid-tight connection with fluid inlet  181  in cartridge  1 . The output of control circuits  33  is regulated by microprocessor  6 . 
         [0068]    Driven by electrical stepping motors  321  and  322 , the first injector  311  and second injector  312  inject fluid, either successively or simultaneously, into reaction chamber  131  via an inlet or inlets  181  connected to reaction chamber  131  through microfluidic channels  122 . Said liquid stream can also drive the fluid in microfluidic channels  122  into the waste reservoir  161  through the reaction chamber  131  in said cartridge  1  to drain the waste through liquid outlet  161 ′. The liquid stream ejected by fluid injection system  3  contains biomolecules, magnetic particles or buffer solution. 
         [0069]    The testing apparatus shown in  FIG. 4  further includes  4 , the means for generating a magnetic field, which comprises electromagnet  41  in series connection with power circuit  42 . The operation of power circuit  42  is controlled by microprocessor  6 . Power circuit  42  provides either a positive or negative current with a particular amplitude to the electromagnet. Accordingly, the electromagnet applies either a positive or negative magnetic field on to the CMOS magnetoresistive biochips  132  under test. 
         [0070]    There can be two directions for the magnetic field applied by electromagnet  41 , either parallel or perpendicular to the surface of CMOS magnetoresistive biochip  132 . With proper signal processing scheme, field in either direction can magnetize the magnetic particles to stimulate magnetoresistive sensor biochip and test the existence of magnetic particles. In the present invention, the field direction is perpendicular to the surface of the CMOS magnetoresistive biochip. Device  43  is used to tune the direction of electromagnet  41  to ensure that the magnetic field is perpendicular to magnetoresistive sensor biochip  132 . 
         [0071]    According to the response of magnetoresistive sensor biochips  132  to the magnetic field applied by electromagnet  41 , microprocessor  6  can calculate the direction of magnetic field, and then instructs device  43  to adjust electromagnet  41  accordingly. 
         [0072]    Electronic module  5 , which is used for controlling and reading information from the biochip  132 , is connected with biochip  132  via conductive lines  191  on substrate  111  on cartridge  1 . The function of electronic module  5  is supply power and control signals for magnetoresistive sensor biochips  132  in said cartridge  1 , test the information stored in each magnetoresistive sensor elements in biochip  132 , and perform analog-to-digital conversion of the results; 
         [0073]    Microprocessor  6  controls and coordinates the operation of the means for applying pressure  2 , fluid injection system  3 , means for generating a magnetic field  4  and electronic module  5 . Additionally, microprocessor  6  is also used to processes information and test results, such as performing the necessary calculation to remove background noise and extract out the user data. 
         [0074]    User interface  7  is connected to said microprocessor  6  to receive users&#39; instruction and display the test condition and results. 
       Embodiment 5 
     Fabrication of Cartridge  1  for Magnetoresistive Sensor Biochips 
       [0075]      FIGS. 5   a  and  5   b  show said cartridge  1 , wherein the substrate  111  can be made of glass, ceramics, single crystal silicon with an layer of silicon dioxide on the surface or polymer. Orifice  171  of reagent reservoir  141  on substrate  111  serves as inlet of reagents. Orifice  171  can be sealed fluid-tight by cap  171 . In contact with substrate  111  is the channel and chamber layer  121  of the cartridge, wherein a plurality of channels and chambers are formed. The material for layer  121  can be glass, ceramics or single crystal silicon with a layer of silicon dioxide on the surface, and the channels and chambers can be made by traditional wet etching or dry etching technologies. Layer  121  can also be made of plastic materials such as polymethylmethacrylate (PMMA), polycarbonate (PC), polypropylene (PP), nylon, polytetrafluoroethene, polyether-ether-ketone and silastic, and the channels and chambers can be formed by molding. The material of substrate  111  can be the same as or different from that of channel and chamber layer  121 . In layer  121  there are at least one reaction chamber  131 , one reagent reservoir  141 , one waste reservoir  161  and more than one liquid inlet  181 . Inlets  181  is used for injecting reagent, probe molecules, buffer solution or rinsing buffer into reaction chamber  131  via micro-channel  122 . Said liquid inlets  181  may be open before use, but sealed fluid-tight with injection needle  34  when it is used to inject liquid. Waste reservoir  161  consists of a plurality of concentric circular micro-channels and orifice  161 ′ as the waste outlet. When reagent is moved back and forth through reaction chamber  131 , the structure of waste reservoir  161  reduces the chance of cross contamination of the reagent in reaction with the waste already in waste reservoir  161 . Biochip  132  using Hall, giant magnetoresistive or magnetic tunnel junction sensor array are placed in the reaction chamber  131  and connected with the testing apparatus via a plurality of connective lines  191  on cartridge  1 . 
       Embodiment 6 
       [0076]    Shown in  FIG. 6 , the testing apparatus for magnetoresistive sensor biochips comprises means for applying pressure  2 , comprising the means for creating a vacuum and/or pressure  25  and coupling pipe  24 . Coupling pipe  24  is connected to the means for creating a vacuum and/or pressure  25  at one end, and orifice  161 ′ on waste reservoir  161  in cartridge  1  at the other end. The increase or decrease in pressure by the means for creating a vacuum and/or pressure  25  will move the fluid in microfluidic channels  122  through reaction chamber  131 . 
         [0077]    The testing apparatus for magnetoresistive sensor biochips shown in  FIG. 6  further comprises fluid injection system  3  which consists of the first injector  311  and the second injector  312 ; the first stepping electrical motor  321 , the second stepping electrical motor  322 , the third stepping electrical motor  323 ; the control circuit for the electrical stepping motors  33 ; and injection needles  34 . The driving rod of the first electrical stepping motor  321  actuates the first injector  311 ; the driving rod of the second electrical stepping motor  322  actuates the second injector  312 . Injection needles  34 , which are connected with liquid injectors  311  and  312 , are driven by the third electrical stepping motor  323  to form fluid-tight connection with fluid inlet  181  in cartridge  1 . The output of control circuits  33  is regulated by microprocessor  6 . Driven by electrical stepping motors  321  and  322 , the first injector  311  and second injector  312  inject fluid, either successively or simultaneously, into reaction chamber  131  via an inlet or inlets  181  connected to reaction chamber  131  through microfluidic channels  122 . Said liquid stream can also drive the fluid in microfluidic channels  122  into the waste reservoir  161  through the reaction chamber  131  in said cartridge  1  to drain the waste through liquid outlet  161 ′. The liquid stream ejected by fluid injection system  3  contains biomolecules, magnetic particles or buffer solution. 
         [0078]    The testing apparatus shown in  FIG. 6  further includes  4 , the means for generating a magnetic field, which comprises electromagnet  41  in series connection with power circuit  42 . The operation of power circuit  42  is controlled by microprocessor  6 . Power circuit  42  provides either a positive or negative current with a particular amplitude to the electromagnet. Accordingly, the electromagnet applies either a positive or negative magnetic field on to the CMOS magnetoresistive biochips  132  under test. 
         [0079]    There can be two directions for the magnetic field applied by electromagnet  41 , either parallel or perpendicular to the surface of CMOS magnetoresistive biochip  132 . With proper signal processing scheme, field in either direction can magnetize the magnetic particles to stimulate magnetoresistive sensor biochip and test the existence of magnetic particles. In the present invention, the field direction is perpendicular to the surface of the CMOS magnetoresistive biochip. Device  43  is used to tune the direction of electromagnet  41  to ensure that the magnetic field is perpendicular to magnetoresistive sensor biochip  132 . 
         [0080]    According to the response of magnetoresistive sensor biochips  132  to the magnetic field applied by electromagnet  41 , microprocessor  6  can calculate the direction of magnetic field, and then instructs device  43  to adjust electromagnet  41  accordingly. 
         [0081]    Electronic module  5 , which is used for controlling and reading information from the biochip  132 , is connected to biochip  132  via conductive lines  191  on substrate  111  on cartridge  1 . The function of electronic module  5  is supply power and control signals for magnetoresistive sensor biochip  132  in said cartridge  1 , test the information stored in each magnetoresistive sensor elements in biochip  132 , and perform analog-to-digital conversion of the results. 
         [0082]    Microprocessor  6  controls and coordinates the operation of the means for applying pressure  2 , fluid injection system  3 , means for generating a magnetic field  4  and electronic module  5 . Additionally, microprocessor  6  is also used to processes information and test results, such as performing the necessary calculation to remove background noise and extract out the user data. 
         [0083]    User interface  7  is connected to microprocessor  6  to receive users&#39; instruction and display the test condition and results. 
       Embodiment 7 
       [0084]    Shown in  FIG. 7  is a testing apparatus for magnetoresistive sensor biochips including means for applying pressure  2 , which comprises an electronic motor or electronic stepping motor  22 , and the control circuit of the electronic stepping motor  21 , the output of which are controlled by microprocessor  6 . In application, solution inlet  181  is sealed first, and then driving rod  23 , which is the actuation structure of said electrical motor or electrical stepping motor, put pressure on pump chamber  151  to inject liquid in reagent reservoir  141  into or through reaction chamber  131  in said cartridge  1 . 
         [0085]    The testing apparatus shown in  FIG. 7  further includes  4 , the means for generating a magnetic field, which comprises electromagnet  41  in series connection with power circuit  42 . The operation of power circuit  42  is controlled by microprocessor  6 . Power circuit  42  provides either a positive or negative current with particular amplitude to the electromagnet. Accordingly, the electromagnet applies either a positive or negative magnetic field on to the CMOS magnetoresistive biochip  132  in reaction chamber  131 . 
         [0086]    There can be two directions for the magnetic field applied by electromagnet  41 , either parallel or perpendicular to the surface of CMOS magnetoresistive biochip  132  in reaction chamber  131 . With proper signal processing scheme, field in either direction can magnetize the magnetic particles to stimulate magnetoresistive sensor biochip and test the existence of magnetic particles. In the present invention, the field direction is perpendicular to the surface of the CMOS magnetoresistive biochip. Device  43  is used to tune the direction of electromagnet  41  to ensure that the magnetic field is perpendicular to magnetoresistive sensor biochip  132  in reaction chamber  131 . 
         [0087]    According to the response of magnetoresistive sensor biochips  132  to the magnetic field applied by electromagnet  41 , microprocessor  6  can calculate the direction of magnetic field, and then instructs device  43  to adjust electromagnet  41  accordingly. 
         [0088]    Electronic module  5 , which is used for controlling and reading information from the biochip  132  in reaction chamber  131 , is connected with biochip  132  via conductive lines  191  on substrate  111  on cartridge  1 . The function of electronic module  5  is supply power and control signals for magnetoresistive sensor biochips  132 , test the information stored in each magnetoresistive sensor elements in biochip  132 , and perform analog-to-digital conversion of the results; 
         [0089]    Microprocessor  6  controls and coordinates the operation of the means for applying pressure  2 , means for generating a magnetic field  4  and electronic module  5 . Additionally, microprocessor  6  is also used to processes information and test results, such as performing the necessary calculation to remove background noise and extract out the user data. 
         [0090]    User interface  7  is connected to microprocessor  6  to receive users&#39; instruction and display the test condition and results. 
         [0091]    In comparison with embodiments 2, 4, and 6, this embodiment is not equipped with a microfluidic injection system. As a result, the many types of fluid can be injected by off-line peristaltic pumps or syringes. Fluid inlets  181  are sealed after sample addition, and then pressure is applied on pump chamber  151  by the test apparatus to start testing. 
       Embodiment 8 
       [0092]    Refer to  FIG. 8  for this embodiment. The testing apparatus for CMOS magnetoresistive biochips includes: 
         [0093]    fluid injection system  3  which comprises: the first injector  311  and the second injector  312 ; the first stepping electrical motor  321 , the second stepping electrical motor  322 , the third stepping electrical motor  323 ; the control circuits for the stepping motors  33 ; injection needle  34 . The driving rod of the first electrical stepping motor  321  actuates the first injector  311 ; the driving rod of the second electrical stepping motor  322  actuates the second injector  312 . Injection needles  34 , which are connected with liquid injectors  311  and  312 , are driven by the third electrical stepping motor  323  to form fluid-tight connection with fluid inlet  181  in cartridge  1 . The output of control circuits  33  is regulated by microprocessor  6 . Driven by electrical stepping motors  321  and  322 , the first injector  311  and second injector  312  inject fluid, either successively or simultaneously, into reaction chamber  131  via an inlet or inlets  181  connected to reaction chamber  131  through microfluidic channels  122 . Said liquid stream can also drive the fluid in microfluidic channels  122  into the waste reservoir  161  through the reaction chamber  131  to drain the waste through liquid outlet  161 ′. The liquid stream ejected by fluid injection system  3  contains biomolecules, magnetic particles or buffer solution. 
         [0094]    The testing apparatus shown in  FIG. 8  further includes  4 , the means for generating a magnetic field, which comprises electromagnet  41  in series connection with power circuit  42 . The operation of power circuit  42  is controlled by microprocessor  6 . Power circuit  42  provides either a positive or negative current with a particular amplitude to the electromagnet. Accordingly, the electromagnet applies either a positive or negative magnetic field on to the CMOS magnetoresistive biochips  132  in reaction chamber  131 . 
         [0095]    There can, be two directions for the magnetic field applied by electromagnet  41 , either parallel or perpendicular to the surface of CMOS magnetoresistive biochip  132  in reaction chamber  131 . With proper signal processing scheme, field in either direction can magnetize the magnetic particles to stimulate magnetoresistive sensor biochip and test the existence of magnetic particles. In the present invention, the field direction is perpendicular to the surface of the CMOS magnetoresistive biochip. Device  43  is used to tune the direction of electromagnet  41  to ensure that the magnetic field is perpendicular to magnetoresistive sensor biochip  132 . 
         [0096]    According to the response of magnetoresistive sensor biochips  132  to the magnetic field applied by electromagnet  41 , microprocessor  6  can calculate the direction of magnetic field, and then instructs device  43  to adjust electromagnet  41  accordingly. 
         [0097]    Electronic module  5 , which is used for controlling and reading information from the biochip  132 , is connected with biochip  132  via conductive lines  191  on substrate  111  on cartridge  1 . The function of electronic module  5  is supply power and control signals for magnetoresistive sensor biochips  132  in said cartridge  1 , test the information stored in each magnetoresistive sensor elements in biochip  132 , and perform analog-to-digital conversion of the results; 
         [0098]    Microprocessor  6  controls and coordinates the operation of fluid injection system  3 , means for generating a magnetic field  4  and electronic module  5 . Additionally, microprocessor  6  is also used to processes information and test results, such as performing the necessary calculation to remove background noise and extract out the user data. 
         [0099]    User interface  7  is connected to said microprocessor  6  to receive users&#39; instruction and display the test condition and results. 
         [0100]    In comparison with embodiment 2, embodiment 8 does not have means for applying pressure to a pumping chamber on the cartridge; all fluid in microfluidic channels is driven by fluid injector  3 . 
       Embodiment 9 
       [0101]    A Testing Apparatus for Magnetoresistive Sensor Biochips is shown in  FIG. 9 , which mainly includes: 
         [0102]    means for generating a magnetic field  4  comprising electromagnet  41  and power circuit  42  for the electromagnet. Either a positive or negative current with required amplitude can be provided to the electromagnet, which accordingly applies either a positive or negative magnetic field to biochip  132  in cartridge  1 . Biochip  132  is placed in reaction chamber  131 . 
         [0103]    Electronic module  5 , which is used for controlling and reading information from the biochip  132 , is connected with biochip  132  via conductive lines  191  on substrate  111  on cartridge  1 . The function of electronic module  5  is to supply power and control signals for magnetoresistive sensor biochips  132  in said cartridge  1 , test the information stored in each magnetoresistive sensor elements in biochip  132 , and perform analog-to-digital conversion of the results; 
         [0104]    Microprocessor  6  controls and coordinates the operation of means for applying magnetic field  4  and electronic module  5 . Additionally, microprocessor  6  is also used to processes information and test results, such as performing the necessary calculation to remove background noise and extract out the user data. 
         [0105]    User interface  7  is connected to microprocessor  6  to receive users&#39; instruction and display the test condition and results. 
         [0106]    The structure of the cartridge used in this embodiment is detailed in the description of embodiment 1. Embodiment 9 is characterized by a simplified architecture for not having fluid injection system  3  and means for applying pressure  2 , which may be on a separate system dedicated to facilitate the biochemical reaction and hybridization process. 
         [0107]    The aforementioned embodiments show the details of the many aspects of the present invention. However, many modifications and variations of the embodiments can be made without departing from the spirit and scope of the present invention, as will be apparent to those skilled in the art. The specific embodiments described herein are offered by way of example only, and the invention is to be limited only by the terms of the appended claims, along with the full scope of equivalents to which such claims are entitled.