Patent Publication Number: US-9429538-B2

Title: Method and apparatus for biochemical sensor array with integrated charge based readout circuitry

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. application Ser. No. 12/850,551, filed Aug. 4, 2010, now U.S. Pat. No. 8,591,723, which claims the benefit and priority to U.S. Provisional Application No. 61/231,277, entitled “METHOD AND APPARATUS FOR BIOCHEMICAL SENSOR ARRAY WITH INTEGRATED CHARGE BASED READOUT CIRCUITRY,” filed Aug. 4, 2009, and assigned to the assignee hereof and hereby expressly incorporated by reference herein. 
    
    
     BACKGROUND 
     1. Field 
     The present invention relates generally to the fields of biochemical molecule sensing method and apparatus, and more particularly to the fields of Micro-Electro-Mechanical System (MEMS) biochemical molecule sensing system implemented by Complimentary Metal-Oxide Silicon (CMOS) technology. 
     2. Description of the Related Art 
     Conventional biochemical molecules (e.g., DNAs, proteins, bacteria, enzymes, viruses, etc.) sensing techniques commonly involve electrochemical sensing and optical sensing. However, electrochemical sensing is generally slow and has poor resolutions, while optical sensing is generally expensive and impractical because it requires elaborate imaging setups. 
     Attempts have been made in the past to employ electrical sensors to detect or sense biochemical molecules. Potentially, electrical sensing may be faster and cheaper than the electrochemical sensing and optical sensing because it does not require any chemical reaction to take place or any elaborate imaging setups. Nevertheless, electrical sensing has limited sensitivity and limited spatial resolution because the size of each electrical sensor is typically larger than 200×200 μm 2 . 
     Thus, there is a need for a low cost biochemical sensing system that can provide high speed and high resolution molecule sensing. 
     SUMMARY 
     One aspect of the present invention is to provide a low cost, high speed and high resolution biochemical sensor, which may include one sensor cell and an integrated readout module. Another aspect of the present invention is to provide a low cost, high speed and high resolution biochemical sensing system, which may include a sensor array and an integrated readout module. Yet another aspect of the present invention is to provide a method for using the biochemical sensor to achieve low noise real time on-chip sensing. 
     In an embodiment of the present invention, a MEMS biochemical sensor may include a cell configured to be coupled to a probe molecule, the cell configured to retain a pre-sensing charge before the probe molecule is exposed to the target molecule and to retain a sensing charge after the probe molecule is exposed to the target molecule, and a readout module coupled to the cell and configured to generate a measurement signal based on the pre-sensing charge and the sensing charge. 
     In another embodiment of the present invention, a MEMS biochemical sensing system may include a plurality of cells, each of the plurality of cells configured to be coupled to one of a plurality of probe molecules, each of the plurality of cells configured to retain a pre-sensing charge before the plurality of probe molecules are exposed to the plurality of target molecules, and configured to retain a sensing charge after the plurality of probe molecules are exposed to the plurality of target molecules, and a readout module selectively coupled to the plurality of cells and configured to generate a plurality of measurement signals, each of the plurality of measurement signals based on the respective pre-sensing charge and the respective sensing charge of one of the plurality of cells. 
     In yet another embodiment of the present invention, a method for sensing a biochemical molecule may include the steps of coupling a probe molecule to a MEMS biochemical sensor, pre-charging the probe molecule to a bias voltage level, exposing the probe molecule to the biochemical molecule, and detecting, using the MEMS biochemical sensor, a target charge of the biochemical molecule. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Other systems, methods, features, and advantages of the present invention will be or will become apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features, and advantages be included within this description, be within the scope of the present invention, and be protected by the accompanying claims. Component parts shown in the drawings are not necessarily to scale, and may be exaggerated to better illustrate the important features of the present invention. In the drawings, like reference numerals designate like parts throughout the different views, wherein: 
         FIG. 1  shows a schematic view of a biochemical system according to an embodiment of the present invention; 
         FIG. 2  shows a top view of a sensor array system according to an embodiment of the present invention; 
         FIGS. 3A-3C  show the cross-sectional side views of the sensor array formed on the silicon substrate according to an embodiment of the present invention; 
         FIG. 4A  shows the cross-sectional side view of four sensor cells coupling to four probe molecules according to an embodiment of the present invention; 
         FIG. 4B  shows the cross-sectional side view of four sensor cells coupling to four probing molecules after the probing molecules are exposed to several target molecules; 
         FIG. 5  shows a schematic view of a sensor cell coupled to the readout module according to an embodiment of the present invention; 
         FIG. 6  shows a schematic view of a row of sensor cells coupled to the readout module according to an embodiment of the present invention; 
         FIG. 7  shows a schematic view of several rows of sensor cells coupled to the readout module according to an embodiment of the present invention; 
         FIG. 8  shows a schematic view of the readout module according to an embodiment of the present invention; 
         FIG. 9A  shows a top view of the sensor array being coupled to the probe molecules and exposed to the target molecules according to an embodiment of the present invention; 
         FIG. 9B  shows a front view of a computer screen displaying the output of the MEMS biochemical sensor; and 
         FIG. 10  shows a flow chart of a method for sensing a biochemical molecule by using the MEMS biochemical sensor according to an embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION 
     Apparatus, systems, and methods that implement the embodiment of the various features of the present invention will now be described with reference to the drawings. The drawings and the associated descriptions are provided to illustrate some embodiments of the present invention and not to limit the scope of the present invention. Throughout the drawings, reference numbers are re-used to indicate correspondence between reference elements. In addition, the first digit of each reference number indicates the figure in which the element first appears. 
       FIG. 1  shows a schematic view of a biochemical sensing system (BCSS)  100  according to an embodiment of the present invention. The BCSS  100  may include a sensor array  110 , a control module (e.g., a control circuitry)  121 , a row select module (e.g., a row select circuitry)  122 , a column select module (e.g., a column select circuitry)  123 , a biasing module (e.g., a biasing circuitry)  131 , a readout module (e.g., a readout circuitry)  140 , and an amplifying module (e.g., an amplifying circuitry)  132 . The BCSS  100  may be a single chip system such that all the components of the BCSS  100  may be formed on a single substrate. Alternatively, the BCSS  100  may be a multi-chip system such that the BCSS  100  is subdivided and formed on multiple substrates. 
     Generally, the BCSS  100  may be divided into three subsystems. The first subsystem is the sensor array system (sensor array)  110 , which is responsible for sensing or detecting the charges carried by the target biochemical molecules (not shown). The sensor array  110  may contain one or more sensor cells  111 , which may be arranged to form several columns and rows. For example, the sensor array  110  may have 16 sensor cells  111 , which are arranged to form 4 columns and 4 rows. Each sensor cell  111  may have a first (top) layer  113  and a second (bottom) layer  112 . The first layer  113  is responsible for coupling to a probe molecule (not shown) and the second layer  112  is responsible for retaining or sustaining a charge induced by the charge carried by the probe molecule. The sensor cell  111  may also include a sense amplifier (not shown) for converting and amplifying the induced charge to a sensed voltage or a sensed current. 
     The second subsystem is the logic control system  120 , which may include the control module  121 , the row select module  122 , and the column select module  123 . Generally, the logic control system  120  is responsible for controlling the overall operation of the BCSS  100 . The logic control system  120  may receive, process, and execute a Read Command. In one instance, the logic control module  120  may initiate a readout operation, select and set a readout mode, and adjust the bias voltages. For example, the control module  121  may be coupled to the biasing module  131  and the readout module  140 , so that it may adjust the bias voltage outputs of the biasing module  131  via digital signal  163  and control the timing and readout mode of the readout module  140  via digital signal  168 . 
     In another instance, the logic control system  120  may select one or more sensor cells  111  from the sensor array  110  to be read by the readout module  140 . For example, the control module  121  may be coupled to the row select module  122  and the column select module  123 , which are ultimately coupled to the sensor array  110 . The control module  120  may select one or more rows of sensor cells  111  to be read by controlling the row select module  122  via a row select signal  161 . After receiving the row select signal  161 , the row select module  122  may couple one or more row nodes  164  to one or more read access nodes  170  such that the readout module  140  may read one or more rows of sensor cells  111 . The control module  120  may also select one or more columns of sensor cells  111  to be read by controlling the column select module  123  via a column select signal  162 . After receiving the column select signal  162 , the column select module  123  may couple one or more column nodes  165  to one or more read access nodes  170  such that the readout module  140  may read one or more columns of sensor cells  111 . Practically, the control module  121  may instantaneously select one sensor cell  111 , a row of sensor cells  111 , a column of sensor cells  111 , or an array of sensor cells  111 . 
     The third subsystem is the readout system  130 , which may include the biasing module  131 , the readout module  140 , and the amplifying module  132 . Unlike the control system  120 , which is mainly digital-based, the readout system  130  is mainly analog-based. For example, the biasing module  131  may be responsible for generating several analog bias voltages  166  for use in the readout operations. For another example, the amplifying module  132  may be implemented by an analog amplifier (not shown) to amplify a measurement signal  167  output by the readout module  140  such that an external device may properly receive the sensing results of the BCSS  100 . The readout module  140  may be coupled to one or more sensor cells  111  from the sensor array  110 , depending on the connection established by the row select module  122  and the column select module  123 . The readout module  140  may instantaneously sense, detect, or read the charge retained by one sensor cell  111 , a row of sensor cells  111 , a column of sensor cells  111 , or an array of sensor cells  111 . Alternatively, the readout module  140  may sense, detect, or read the charge retained by multiple sensor cells  111  selected from various rows and columns. After the readout operation, the readout module  140  may output the measurement signal  167 , which can be transmitted by a serial bus or a parallel bus. 
     As discussed earlier, the BCSS  100  may be a multi-chip system. For example, the sensor array system  110 , the logic control system  120 , and the readout system  130  may be implemented by three distinct chips. For another example, the sensor array system  110  and the logic control system  120  may be implemented by a first chip, which can be combined with a second chip that implements the readout system  130 . For yet another example, the sensor array system  110  and the readout system  130  may be implemented by a third chip, which can be combined with a fourth chip that implements the logic control system  120 . For still yet another example, the logic control system  120  and the readout system  130  may be implemented by a fifth chip, which can be combined with a sixth chip that implements the sensor array system  110 . 
       FIG. 2  shows a top view of a sensor array system  200  according to an embodiment of the present invention. The sensor array system  200  may include a sensor array  210  formed on top of a substrate  201 . The sensor array  210  may be similar to the sensor array  110  in  FIG. 1  such that it may have one or more sensor cells  211 , each of which may includes the first layer  213  and the second layer  212 . The first layer  213  may have a surface area  214 , which has a width  250  and a length  260 . According to an embodiment of the present invention, the first layer  213  may have a width  250  and a length  260 , both of which may range from about 1.5 um to about 25 um. As such, the surface area  214  of the first layer  213  may range from 2.25 um 2  to about 625 um 2 . Generally, the smaller the surface area  214 , the smaller the number of probe molecules (not shown) may be coupled to the first layer  213 . As the number of probe molecules per sensor cell  211  decreases, the sensing resolution of the sensor array system  200  increases. For example, the sensor cell  211  may have a resolution ranges from about 1 electron charge to about 5 electron charges. In any event, the sensor area  214  should be kept below about 10 mm 2  in order to achieve an efficient cost structure for mass producing the sensor array  210 . Depending on the fabrication process used, the number of sensor cells  211  in the sensor array system  200  may range from about 16,384 to about 4,552,931. As the number of sensor cells  211  increases, the spatial resolution of the sensor array system  200  increases. Hence, it is desirable that the sensor array  200  has as many sensor cells  211  as possible and that the surface area  214  of each sensor cell  211  be as small as possible. 
       FIGS. 3A-3C  show the cross-sectional side views of the sensor array  210  formed on the silicon substrate  201  according to an embodiment of the present invention. Referring to  FIG. 3A , a well  302  may be developed in the middle of the silicon substrate  201 . Typically, the silicon substrate  201  may be formed with silicon based compound and the well  302  may be formed by doping the silicon substrate. The well  302  may delineate and shield the sensor array  210 . Within the well  302 , the second layers  212  may be deposited using conventional CMOS process. Because a variable amount of charges may be induced and retained in the second layers  212 , it is preferable that the second layers  212  to be formed by a conducting material. On top of the well  302  and the second layer  212  is an insulating layer  305 , which may be a field oxide deposited by conventional CMOS process. The insulating layer  305  may have several unmasked areas  303 , which may be etched away by applying a conventional lithographic process  301 . 
     As shown in  FIG. 3B , the unmasked areas  303  results in several openings  304  after the conventional lithographic process  301  is applied to the insulating layer  305 . In  FIG. 3C , the first layers  213  are deposited within the openings  304  by using a conventional CMOS process. To ensure proper coupling with the probe molecules, it is preferable that the first layers  213  be formed by gold or other materials that may establish good coupling with the probe molecules. Because the first layers  213  are separated from the second layers  212  by the thin insulating layers  306 , the second layers  212  may be dielectrically coupled to the first layers  213 . As such, when the first layers  213  are coupled to the charged probe molecules, the second layers  212  may retain the same amount of opposite charges. Although  FIGS. 3A-3C  show that the second layers  213  are floating for the sake of simplicity, there may be interconnecting wires (not shown) coupling the second layers  213  to the row select module  122 , the column select module  123 , and the readout module  140  as shown in  FIG. 1 . Accordingly, the charges retained in the second layers  212  may be sensed, read and processed by the readout module  140 . Moreover, each of the sensor cells  211  may be coupled to either a conventional voltage-mode input stage device (not shown) or a conventional charge-mode input stage device (not shown) before coupling to the interconnecting wires. 
     The discussion now turns to the coupling between the sensor cells and the probe molecules and the coupling between the probe molecules and the target biochemical molecules.  FIG. 4A  shows the cross-sectional side view of four sensor cells  420 ,  421 ,  422 , and  423  coupling to four probe molecules  401 ,  402 ,  403 ,  404  according to an embodiment of the present invention. Initially, the sensor array system  400  may be exposed to a solution containing the probe molecules  401 ,  402 ,  403 , and  404 . This process may be achieved by forming several micro-fluidic channels on top of the sensor array system  400 . As the solution circulates across the micro-fluidic channels, the probe molecules  401 ,  402 ,  403 , and  404  may be coupled to the first layers  440 ,  441 ,  442 , and  443 . According to an embodiment of the present invention, the probe molecule may be any biochemical molecule that is capable of coupling to the first layer of the sensor cell. For example, the probe molecule may be a DNA molecule and/or a protein molecule. 
     After the initial coupling, the control module  121  may instruct the biasing module  131  to perform a reset operation, which may pre-charge the probe molecules  401 ,  402 ,  403 , and  404  to a bias voltage level. This reset operation may serve two purposes. First, it may unify the amount of charges carried by the probe molecules  401 ,  402 ,  403 , and  404 . As a result, the reset operation may minimize the electrostatic noise introduced by these probe molecules and other correlated sources. Second, the pre-charged probe molecules  401 ,  402 ,  403 , and  404  may become more attracted to the target biochemical molecules (TBMs) because they are oppositely charged. After the reset operation, the readout module  140  may perform a pre-sensing read operation to ensure that the probe molecules  401 ,  402 ,  403 , and  404  are properly pre-charged. Alternatively, the control module  121  may skip the reset operation and instruct the readout module  140  to read or measure the pre-sensing charges retained by the second layers  430 ,  431 ,  432 , and  433 . These pre-sensing charges may be representative of the amount of charges carried by the probe molecules  401 ,  402 ,  403 , and  404 . 
     After the pre-sensing read operation, the sensor cells  420 ,  421 ,  422 , and  423 , along with the probe molecules  401 ,  402 ,  403 , and  404 , may be exposed to a solution containing the TBMs. Similar to the process of coupling the probe molecules to the sensor cells, this process may be achieved by forming several micro-fluidic channels on top of the sensor array system  400 . As the solution circulates across the micro-fluidic channels, the TBMs may be coupled to the probe molecules  401 ,  402 ,  403 , and  404 . Referring to  FIG. 4B , two TBMs  411  and  412  are coupled to the probe molecule  401 , one TBM  413  is coupled to the probe molecule  402 , no TMB is coupled to the probe molecule  403 , and three TBMs  414 ,  415 , and  416  are coupled to the probe molecule  404 . 
     When the probe molecules are coupled to the TBMs, the charges carried by the TBMs may be transferred to the probe molecules, thereby reinforcing or cancelling the initial charges carried by the probe molecules. For example, assuming that the probe molecule  401  carries 4 negative charges and the TBMs  411  and  412  each carries 1 positive charge, the coupled probe molecule  401  may carry only 2 negative charges. For another example, assuming that the probe molecule  402  carries 4 negative charges and the TBM  413  carries 1 negative charge, the coupled probe molecule  402  may carry 5 negative charges. For yet another example, assuming that the probe molecule  404  carries 4 negative charges and the TBMs  414 ,  415 , and  416  carry a total of 4 positive charges, the coupled probe molecule  404  may have 0 charges. 
     As the charges carried by the probe molecules  401 ,  402 , and  404  change, the second layers  430 ,  431 , and  433  may retain a new set of sensing charges. The sensing charges may directly reflect the electrostatic interaction between the probe molecules and the TBMs, and it may indirectly reflect the amount of target charges carried by the TBMs. Hence, after the sensor array  400  has been exposed to the TBM solution for a period of time, the control module  121  may instruct the readout module  140  to perform another read operation to sense, detect and measure the sensing charges. 
     Besides the correlated noise introduced by the probe molecules, there is uncorrelated noise introduced by the TBMs and the active circuitry surrounding the sensor array  400 . To minimize the uncorrelated noise, the readout module  140  may perform a multiple-read operation at a sampling frequency ranges from about 0.5 MHz to about 10 MHz for each sensor cell. The readout module  140  may then obtain a sensing charge reading by averaging these sample readings. Because the noise among multiple readings is likely to be uncorrelated, this sampling and averaging process may reduce the overall uncorrelated noise level. 
     The discussion now turns to the coupling between the sensor cell and the readout module  140 . Although  FIG. 1  shows that all the sensor cells  111  of the sensor array  110  share a single readout module  140 , the readout module  140  may be incorporated in the sensor array system such that each sensor cell may have its own readout module. For example,  FIG. 5  shows a schematic view of the sensor cell  510  coupled to the readout module  540  via a switch  520  according to an embodiment of the present invention. The purpose of the switch  520  is to allow selective coupling between the sensor cell  510  and the readout module  540 . When the switch  520  is turned on, the readout module  540  may access the charges retained by the sensor cell  510 , and when the switch  520  is turned off, the sensor cell  510  may be isolated from the readout module  540 . As such, the switch  520  may be implemented using a conventional CMOS pass gate or other similar electronic components having functionalities consistent with the purpose of the switch  520 . The advantages of this one-to-one configuration may include fast readout time and low parasitic noise because of the reduction of interconnecting wires. However, this one-to-one configuration may become more difficult to implement as the number of sensor cells increases. 
     For another example,  FIG. 6  shows a schematic view of a row of sensor cells  510 ,  520 , and  530  coupled to the readout module  540  via the switches  610 ,  620 , and  630  according to an embodiment of the present invention. In this row configuration, the row of sensor cells  510 ,  520 , and  530  may share one readout module  540 . Hence, only one sensor cell may be coupled to the readout module  540  at a single moment of time. As such, the column select module  123  in  FIG. 1  may selectively turn on one of the switches  610 ,  620 , and  630  at a time so that the readout module  540  may detect, sense and measure the charges retained by the sensor cells  510 ,  520 , and  530  in a serial manner. Similar to the switch  520  in  FIG. 5 , the switches  610  may be implemented by conventional CMOS pass gates or other similar electronic components having functionalities consistent with the purpose of the switches  610 ,  620 , and  630 . 
     For yet another example,  FIG. 7  shows a schematic view of several rows of sensor cells coupled to the readout module according to an embodiment of the present invention. The rows  701 ,  702 , and  703  are similar to the row configuration shown in  FIG. 6 , so that the discussion regarding  FIG. 6  may apply to each row individually. In this plane configuration, the sensor cells in rows  701 ,  702 , and  703  may share one readout module  540 . Hence, only one row of sensor cells may be coupled to the readout module  540  at a single moment of time. As such, the row select module  121  in  FIG. 1  may selectively turn on one of the switches  710 ,  720 , and  730  at a time so that the readout module  540  may detect, sense and measure the charges retained by the sensor cells in rows  701 ,  702 , and  703  in a serial manner. Similar to the switch  520  in  FIG. 5 , the switches  710 ,  720 , and  730  may be implemented by conventional CMOS pass gates or other similar electronic components having functionalities consistent with the purpose of the switches  710 ,  720 , and  730 . 
     The discussion now turns to the internal components of the readout module  140 .  FIG. 8  shows a schematic view of the readout module  140  according to an embodiment of the present invention. The readout module  140  may include a sensing device  801 , a register  802  and a processor  804 . The sensing device  801  may serve two functions. First, the sensing device  801  may receive the charge retained by one of the sensor cells. For example, the sensing device  801  may receive the pre-sensing charges retained by the sensor cells before the probe molecules are exposed to the solution containing the TBMs. For another example, the sensing device  801  may receive the sensing charges retained by the sensor cells after the probe molecules are exposed to the solution containing the TBMs. 
     Second, the sensing device  801  may generate a pre-sensing signal  811  and a sensing signal  812  based on the received pre-sensing charges and the sensing charges respectively. More specifically, the sensing device  801  may generate two analog signals with voltage levels representing the amount of charges retained by the sensor cells before and after probe molecules are exposed to the solution containing the target molecules. Alternatively, the sensing device  801  may generate two digital signals with digital values representing the amount of charges retained by the sensor cells before and after the probe molecules are exposed to the solution containing the target molecules. In any event, the sensing device  801  may include a conventional CMOS sense amplifier (not shown) that can sense and amplify either the amount of accumulated charges or the small signal current induced by a change of charge. In the event that the pre-sensing signal  811  and the sensing signal  812  are in digital form, the sensing device  801  may also include an analog-to-digital converter. Moreover, because the sensing device  801  may include several analog components, it may receive the necessary biasing voltages from the biasing module  131  as shown in  FIG. 1 . 
     Although  FIG. 8  shows that the readout module  140  only has one sensing device  801 , the readout module  140  may have more than one sensing devices  801 , such that more than one sensor cell can be sensed at a single moment of time. For example, the readout module  140  may dedicate sufficient amount of sensing devices  801  for a row of sensor cells or a column of sensor cells. 
     The register  802  may receive and store the pre-sensing signal  811  and sensing signals  812  generated by the sensing device  801  before the processor  804  may process these signals. The register  802  may be implemented either as a digital register or an analog register, depending on the form of the pre-sensing and sensing signals  811  and  812  generated by the sensing device  801 . 
     The processor  804  may implement at least two sensing modes. In a single sensing mode, the processor  804  may calculate the target charges of the TBMs coupled to a particular sensor cell by simply comparing the sensing signal  812  with the pre-sensing signal  811 . In a multiple sensing mode, the processor  804  may generate a sampling signal  814 , which carries sampling frequency ranges from about 0.5 MHz to about 10 MHz, to control the sensing operation of the sensing device  801 . Upon receiving the sampling signal  814 , the sensing device  801  may sense the sensing charges of a particular sensor cell for multiple times at the sampling frequency. Each time when a sample is sensed, the sensing device  801  may generate a sensing signal  812  and send it over to the register  802 . As such, the sensing device  801  may generate multiple sensing signals  812  for a particular sensor cell after the probe molecules are exposed to the solution containing the TBMs. After the multiple sensing is completed, the processor  804  may access the register  802  to retrieve the multiple sensing signals  812 . To minimize the uncorrelated noise, the processor  804  may average the multiple sensing signals  812  to obtain an average sensing signal. Next, the processor  804  may compare the average sensing signal to the pre-sensing signal  811  in calculating the target charges of the TBMs coupled to a particular sensor cell. Finally, the processor  804  may generate a measurement signal or a plurality of measurement signals as the read output of the readout module  140 . Generally, each read operation may take about 10 milliseconds. 
     The discussion now turns to the output display of the BCSS. As shown in  FIG. 9A , the sensor array  910  have four sensor cells  911 ,  912 ,  913 , and  914  that are coupled to at least one TBMs. After the read operation, the BCSS may output the measurement signal to an external device (not shown) to further process the measurement results. For example, the BCSS may be coupled to a personal computer, which has a processor and a display screen coupled to the processor. As shown in  FIG. 9B , the external device may display the measurement results in a grid  920 . For example, the boxes  921 ,  922 ,  923 , and  924  are filled with different colors, such that they may indicate the sensing charges of the respective sensor cells  911 ,  912 ,  913 , and  914 . 
       FIG. 10  shows a flow chart of a method for sensing a biochemical molecule by using the MEMS biochemical sensor according to an embodiment of the present invention. These method steps are related to the discussion with respect to  FIGS. 1 to 9 . Although these steps might introduce terminologies different from those in the previous discussion, these steps are consistent with the spirit and concept of the previous discussion and should not be construed otherwise. In step  1001 , a probe molecule may be coupled to a MEMS biochemical sensor. In step  1002 , the probe molecule may be pre-charged to a bias voltage level. In step  1003 , the probe molecule may be exposed to the biochemical molecule. In step  1004 , a target charge of the biochemical molecule may be detected by using the MEMS biochemical sensor. 
     Exemplary embodiments of the invention have been disclosed in an illustrative style. Accordingly, the terminology employed throughout should be read in a non-limiting manner. Although minor modifications to the teachings herein will occur to those well versed in the art, it shall be understood that what is intended to be circumscribed within the scope of the patent warranted hereon are all such embodiments that reasonably fall within the scope of the advancement to the art hereby contributed, and that that scope shall not be restricted, except in light of the appended claims and their equivalents.