Abstract:
A nanoscale biomolecule sensor includes a nanoscale sensor element connected between a first electrical terminal and a second electrical terminal, the nanoscale sensor element coated with a capture agent. The sensor includes an electrode arrangement operable to establish a temporary electric field in the vicinity of the nanoscale sensor element, the temporary electric field oriented to move biomolecules of interest and other biomolecules having the same charge polarity as the biomolecules of interest toward the nanoscale sensor element where the biomolecules of interest specifically bind with the capture agent, the biomolecules of interest bound to the capture agent having an electric charge that changes an electrical property of the nanoscale sensor element measurable between the electrical terminals.

Description:
BACKGROUND OF THE INVENTION  
       [0001]     Micro-analytical sensors to detect extremely small concentrations of molecules in an analyte are currently being developed. These sensors are capable of detecting particular molecules in femtomolar (fM)-order concentrations, corresponding to a few thousand, or a few hundred, molecules in a sample volume of an analyte. These sensors are referred to as molecular, or biomolecular, sensors, and are being developed in nanometer (nm) scale proportions. For example, a biomolecular sensor employing a nanowire, nanotube, or other nanostructure-scale structure has been developed that can detect extremely small concentrations of DNA molecules in a sample volume. In one example in which the biomolecule sensor can be analogized to a field effect transistor (FET), a silicon nanowire doped with a dopant forms the channel of the FET. In the case of biomolecule detection, a biomolecule that carries an external charge functions as the gate, and is referred to as a “molecular gate.” The ends of the silicon nanowire have electrical connections that are connected to what can be described as the drain and source terminals of the FET. The drain and source terminals provide an electrical pathway so that the electrical properties (for example, voltage and current) of the silicon nanowire can be monitored and controlled.  
         [0002]     In one example using an antibody and antigen as the biomolecules, the silicon nanowire is functionalized on its surface with an antibody with which a particular antigen will specifically bind. In this example, the antibody coats the surface of the silicon nanowire. In such an application, the silicon nanowire is referred to as a nanosensor element. An antibody is a protein used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses. Each antibody recognizes a specific antigen and can form an antibody-antigen complex. The formation of the antibody-antigen complex or the specific binding between antibody and antigen on the surface of the silicon nanowire results in a change in the physical or chemical properties of the antibody. As an analogy, the charge on the gate of the nanosensor changes, thus the electrical properties of the nanowire FET are affected. Other molecules in which specific binding can occur, or in which a physical or chemical property can be changed due to the presence of a specific molecule, can also be used. These molecules that are used to functionalize the nanowire or nanotube are referred to as capture agents. Capture agents include, for example, proteins, peptides, and specific DNA or RNA sequences. The nanowire then functions as a biomolecule sensor.  
         [0003]     The electrical properties of a nanowire are determined by the diameter of the nanowire and the doping applied to the nanowire. A protein, e.g. an antigen, has a net electrical charge that is related to its isoelectric point. The isoelectric point is a pH value at which the net electric charge of the protein is zero. However, as the pH value increases, the net charge of the protein becomes negative and as the pH value decreases the net charge of the protein becomes positive. Therefore, by monitoring and adjusting the pH value, the net electric charge of a biomolecule can be determined and controlled. A fluid containing the biomolecule to be analyzed is then directed toward the nanowire sensor. In one example, the nanowire sensor is located in a micro-fluidic channel and the fluid flows through the channel toward the nanowire sensor. If the fluid contains the particular biomolecule of interest, an antigen in this example, the antigen molecules will specifically bind with the antibodies which are present on the surface of the nanowire sensor. Because the antigens carry electric charge, when the antigens specifically bind to the antibodies on the nanowire sensor, the current flowing through the nanowire sensor is affected. If the electrical channel formed by the nanowire sensor is sufficiently small, a small amount of charge on the surface of the nanowire sensor will be sufficient to deplete the channel and cause a significant conductance change in the channel. By knowing the charge associated with a particular antigen (or other molecule) and by monitoring the current flowing through the nanowire sensor before and after the specific binding occurs, the presence of the antigen, and its concentration in the fluid can be determined.  
         [0004]     Generally, scaling the above-described biomolecule sensor to nanometer-scale proportions increases the signal-to-noise ratio of the sensor, thereby improving the signal transduction and the sensitivity of the sensor. However, another consideration with respect to the sensitivity of the above-described biomolecule sensor relates to what is referred to as mass transport effect. Mass transport effect is related to the ability to direct the biomolecules in the fluid toward the sensor. Without the ability to direct the biomolecules in the fluid toward the sensor, a nanoscale sensor is generally limited to picomolar (pM)-order detection limits because of inefficient mass transport toward the nanoscale sensor.  
       SUMMARY OF THE INVENTION  
       [0005]     In an embodiment, a nanoscale biomolecule sensor comprises a nanoscale sensor element connected between a first electrical terminal and a second electrical terminal, the nanoscale sensor element coated with a capture agent. The sensor includes an electrode arrangement operable to establish a temporary electric field in the vicinity of the nanoscale sensor element, the temporary electric field oriented to move biomolecules of interest and other biomolecules having the same charge polarity as the biomolecules of interest toward the nanoscale sensor element. The biomolecules of interest specifically bind with the capture agent. The biomolecules of interest bound to the capture agent have an electric charge that changes an electrical property of the nanoscale sensor element measurable between the electrical terminals.  
         [0006]     In another embodiment, the invention is a method for operating a nanoscale biomolecule sensor. The method comprises providing a nanoscale sensor element connected between a first electrical terminal and a second electrical terminal. The nanoscale sensor element is coated with a capture agent. The method also comprises temporarily establishing an electric field in the vicinity of the nanoscale sensor element. The temporary electric field is oriented to move biomolecules of interest and other biomolecules having the same charge polarity as the biomolecules of interest towards the nanoscale sensor element where the biomolecules of interest can specifically bind with the capture agent. The method also comprises measuring a change in an electrical property of the nanoscale sensor element, the change caused by electric charge carried by the biomolecules of interest specifically bound to the capture agent. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0007]     The invention can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the present invention. Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views.  
         [0008]      FIG. 1  is a schematic diagram illustrating a biomolecule sensor implemented as a field effect transistor (FET).  
         [0009]      FIG. 2  is a schematic diagram illustrating the nanowire sensor of  FIG. 1 .  
         [0010]      FIGS. 3A through 3D  are a series of schematic diagrams illustrating a nanoscale biomolecule sensor in accordance with an embodiment of the invention.  
         [0011]      FIG. 4A  is a schematic diagram illustrating a nanoscale biomolecule sensor constructed in accordance with another embodiment of the invention.  
         [0012]      FIG. 4B  is a cross-sectional view of the secondary structure of  FIG. 4A .  
         [0013]      FIG. 5  is a schematic diagram illustrating a nanoscale biomolecule sensor constructed in accordance with another embodiment of the invention.  
         [0014]      FIG. 6A  is a schematic diagram illustrating a nanoscale biomolecule sensor constructed in accordance with another embodiment of the invention.  
         [0015]      FIG. 6B  is a cross-sectional view of the secondary structure of  FIG. 6A .  
         [0016]      FIG. 7  is a flowchart illustrating a method of operating a nanoscale biomolecule sensor in accordance with an embodiment of the invention. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0017]     The nanoscale biomolecule sensor and method for operating same will be described below in the context of attracting an antigen to an antibody placed on the surface of a silicon nanowire biomolecule sensor element. However, other nanostructures can be implemented as the biomolecule sensor element. For example, a nanotube, or other nanostructure can be implemented as the biomolecule sensor element. Further, other biomolecules can be detected by placing the appropriate capture agents on the biomolecule sensor element. Further, while an antibody-antigen system is used as one example of a capture agent, other capture agents can be used.  
         [0018]      FIG. 1  is a schematic diagram illustrating a biomolecule sensor  100  implemented as a field effect transistor (FET). The biomolecule sensor  100  comprises a silicon substrate  102  over which a layer  104  of a dielectric is formed. The layer  104  can be, for example, silicon dioxide (SiO 2 ), or another dielectric. An electrode  107  is formed on a surface of the layer  104 . Another dielectric is applied as a layer  105  over the electrode  107  and the layer  104 . The layer  105  may be formed using, for example, silicon nitride (for example, Si 3 N 4 ), or another dielectric. Another electrode  109  is located above the surface  114 . The electrodes  107  and  109  may be referred to as an electrode arrangement. A source  106  and a drain  108  are formed on the layer  105 . A nanowire biomolecule sensor element  110 , hereafter referred to as sensor element  110 , is formed on the surface of the layer  105  and is electrically connected to the source  106  and drain  108 . In one embodiment, the sensor element  110  is formed of silicon and is doped p-type or n-type, depending on the biomolecule sought to be detected. The source  106  and drain  108  can be metallic contacts, such as gold. The sensor element  110  can be formed with a diameter of approximately 5 to 40 nanometers (nm) and with a length of approximately 2 micrometers (μm) using semiconductor fabrication techniques. The sensor element  110  rests on the surface  114  of the layer  105  or can be suspended above the surface  114  of the layer  105 . The sensor element  110  is located between the electrodes  107  and  109  so that an electric field can be induced between the electrodes  107  and  109  and be applied in the vicinity of the sensor element  110  by a voltage applied to the electrodes  107  and  109 , as will be described below. The arrow  112  indicates the direction of flow of fluid toward and past the sensor element  110 . However, the flow direction shown is arbitrary. Further, a micro-fluidic channel (not shown) may be formed on the surface  114  of the layer  105  to direct the flow of fluid toward the sensor element  110 . The sensor element  110  located between the source  106  and the drain  108  forms the channel of a field effect transistor.  
         [0019]      FIG. 2  is a schematic diagram  200  illustrating the nanowire sensor  110  of  FIG. 1 . In the example shown in  FIG. 2 , the sensor element  110  is doped to make it electrically conductive and the surface of the sensor element  110  is functionalized with a capture agent  202  using techniques that are known in the art to make biomolecules specifically bind to it. A fluid containing an analyte is indicated using reference numeral  206  and is directed toward the sensor element  110 . In an embodiment, the fluid  206  is a solution containing the analyte to be detected. However, the fluid  206  need not be a solution. The flow of the fluid can be directed toward the sensor element  110  using, for example, a micro-fluidic channel (not shown). The micro-fluidic channel through which the fluid  206  flows can be of the order of several micrometers (μm) in width and depth. The fluid  206  moves toward the sensor element  110  due to both flow as described above and due to the application of an electric field between the electrodes  107  and  109 , as will be described below. The fluid contains a variety of biomolecules, some having a positive electrical charge and some having a negative electrical charge. The biomolecules having negative electrical charge are generally illustrated using reference numeral  212  and the biomolecules having positive electrical charge are generally illustrated using reference numeral  214 . In this example, the biomolecules  212  and  214  are antigens and the capture agent  202  is an antibody to which particular antigens will bind.  
         [0020]     The fluid  206  may contain a number of different positively-charged and negatively-charged biomolecules. However, only particular biomolecules will specifically bind to the capture agent  202 . These biomolecules are shown as specifically-bound to the capture agent  202  using reference numeral  215 . However, other negatively-charged biomolecules  212  will be attracted to the surface of the sensor element  110 , and will influence the electrical properties of the sensor element  110 , thus causing errors when attempting to detect the specifically-bound biomolecules. In this example, the capture agent  202  may comprise biomolecules, such as antibodies, proteins, peptides, DNA or RNA sequences. In this example, the biomolecules of interest are chosen from an antigen, donor, protein, peptide, receptor, ligand and a nucleotide. However, other capture agents and biomolecules may be used.  
         [0021]      FIGS. 3A through 3D  are a series of a schematic diagrams illustrating a nanoscale biomolecule sensor in accordance with an embodiment of the invention.  FIG. 3A  is a schematic diagram illustrating a nanoscale biomolecule sensor  300 . The nanoscale biomolecule sensor  300  includes a sensor element  110  which has been functionalized with a capture agent  202 , in this example an antibody, as discussed above. The fluid  206  comprises negatively-charged biomolecules  212  and positively-charged biomolecules  214 . In this example, the biomolecules  212  and  214  are antigens. In this example, a variety of different positively-charged and negatively-charged biomolecules are present in the fluid  206 . A voltage source  302  is connected to the electrodes  107  and  109  to enable the application of an electrical voltage that creates a temporary electric field in the fluid  206  in the vicinity of the sensor element  110 . A monitor voltage source  310  and a current monitor  308  are connected in series between the source  106  and the drain  108  to allow the electrical properties of the sensor element  110  to be monitored. The voltage source  302 , monitor voltage source  310  and current monitor  308  are examples of the circuitry that can be used to create a temporary electric field and monitor the electrical properties of the sensor element  110 . Other circuitry may be used.  
         [0022]     In accordance with an embodiment of the invention, the voltage source  302  applies an electrical pulse  304  between the electrodes  107  and  109 . This creates a temporary electric field in the fluid  206  in the vicinity of the sensor element  110 . In the example shown here, the electrical pulse  304  is a positive electrical pulse to attract negatively-charged biomolecules  212  and  215  to the sensor element  110 . To attract positively-charged biomolecules  214  to the sensor element  110 , the electrical pulse  304  would have negative polarity. The magnitude and duration of the electrical pulse  304  can be determined based on the characteristics of the fluid and the particular biomolecule sought to be attracted. For example, depending on the application and the design of the sensor element  110 , a single pulse or a pulse train may be applied to the sensor element  110 . An exemplary voltage range of 100 millivolts (mV) to several volts (V), and a pulse width of approximately 10 milliseconds (ms) to 1 second (s) are possible. However, other voltages and pulse widths may be used.  
         [0023]      FIG. 3B  is a schematic diagram illustrating the nanoscale biomolecule sensor  300  and the sensor element  110  during the application of the electrical pulse  304 . The motive force applied to the negatively-charged biomolecules by the electric field causes the negatively-charged biomolecules  212  and  215  in the fluid  206  to migrate toward the sensor element  110 . The motive force applied to the positively-charged biomolecules causes them to migrate away from the sensor element  110 . The electric field alters the mass transport characteristics of the biomolecules in the fluid  206  so that the biomolecules having one electric charge polarity are drawn towards the sensor element  110  and those having the opposite polarity are moved away from the sensor element  110 . The application of the electrical pulse  304  causes the biomolecules having a negative electric charge polarity to move toward the sensor element  110 . The movement of the biomolecules having a negative electric charge polarity toward the sensor element  110  increases the local concentration of such biomolecules within a distance on the order of nanometers (nm) from the sensor element  110 , thus greatly enhancing the probability of specific binding between the biomolecules and the capture agent  202 . However, the electric field attracts all negatively-charged biomolecules  212  toward the sensor element  110 .  
         [0024]      FIG. 3C  is a schematic diagram illustrating the nanoscale biomolecule sensor  300  and the sensor element  110  after the application of the first electrical pulse  304 . The fluid  206  typically contains a number of different negatively-charged biomolecules. However, only particular negatively-charged biomolecules, referred to as the biomolecules of interest, will specifically bind to the capture agent  202 . These biomolecules are shown as specifically-bound to the capture agent  202  using reference numeral  215 . However, due to the positive electric charge imparted to the sensor element  110 , other negatively-charged biomolecules  212  will also be attracted to the sensor element  110 . The electrical charge associated with these biomolecules  212  will influence the electrical properties of the sensor element  110 , thus causing errors when attempting to detect the change in electrical properties of the sensor element  110  due to the specifically-bound biomolecules  215 .  
         [0025]     In accordance with an embodiment of the invention, and as shown in  FIG. 3D , a second electrical pulse  306  having a polarity opposite the polarity of the electrical pulse  304  is applied to the electrodes  107  and  109  as described above. In this example, the electrical pulse  306  has a negative polarity, and is generally smaller in magnitude than the electrical pulse  304 , but the magnitude may be equal to or greater than the magnitude of the electrical pulse  304 . The temporary electric field resulting from applying the electrical pulse  306  between the electrodes  107  and  109  causes the non-specifically-bound biomolecules  212  to move away from the sensor element  110 . Because the interaction between the capture agent  202  on the sensor element  110  and the biomolecule  212  is much weaker than the specific binding between the capture agent  202  and the specifically-bound biomolecules of interest (biomolecules of interest  215 ), the specifically-bound biomolecules  215  are not repelled and remain bound to the capture agent  202 . In this manner, after the application of the electrical pulse  306 , only the biomolecules  215  that are specifically bound to the capture agent  202  affect the electrical properties of the sensor element  110 . By monitoring the current driven through the sensor element  110  by the monitor voltage source  310  before and after the specific binding of the biomolecules  215  using the current monitor  308 , it can be determined whether the biomolecules  215  (i.e., the biomolecules of interest) are present in the fluid  206 . Further, because the application of the electrical pulse  304  causes the biomolecules of interest  215  to rapidly approach and specifically bind with the capture agent  202  (e.g. an antibody), and because the subsequent application of the electrical pulse  306  repels the non-specifically binding biomolecules  212  from the sensor element  110 , a very small concentration of biomolecules of interest  215  in the fluid  206  can be detected. For example, concentrations of biomolecules  215  in the femtomolar range can be detected by the biomolecule sensor  300 . This enables the sensor element  110  to be highly selective and highly sensitive with a fast response time. The biomolecules of interest  215  that are specifically-bound to the sensor element  110  act as a “molecular gate” and change the conductance of the sensor element  110 .  
         [0026]      FIG. 4A  is a schematic diagram illustrating a nanoscale biomolecule sensor  400  constructed in accordance with another embodiment of the invention. The nanoscale biomolecule sensor  400  comprises a biomolecule sensor portion  410  and a secondary structure  420 . The biomolecule sensor portion  410  comprises a nanowire, or nanotube,  414  that is similar to the sensor element  110  described above. A monitor voltage source  310  and a current monitor  308  are connected in series between source terminal  406  and the drain terminal  408  of the sensor portion  410  via connections  416  and  418 . The secondary structure  420  comprises a nanostructure  422  that is covered by a dielectric  424 , such as silicon nitride (SiN x ) in the case of a silicon nanowire FET sensor element, to prevent binding of biomolecules to the nanostructure  422 . However, the dielectric material is chosen based on the materials used to fabricate the secondary structure  420 . An electrode  419 , which is similar to the electrode  109  described above, is located over the nanostructure  422  to subject the secondary structure  420  to an electric field when a voltage is applied between the nanostructure  422  and the electrode  419 . The nanowire  414 , the nanostructure  422  and the electrode  419  comprise a sensor element  430 .  
         [0027]     In this embodiment, the biomolecule sensor portion  410  is used as the sensor to detect the presence of a particular biomolecule and the secondary structure  420  is used to attract the biomolecules of interest toward the surface of the nanowire  414 . The voltage source  302  and the monitor voltage source  310  are independently controlled so that the current flowing through the nanowire  414  is not interrupted when the voltage pulse described above is applied in the vicinity of the sensor element  430 . Instead of being applied to electrodes associated with the nanowire  414 , the voltage pulse is applied between the nanostructure  422  and the electrode  419 .  
         [0028]     The secondary structure  420  is placed in sufficiently close proximity to the biomolecule sensor portion  410  so that when the biomolecules of interest are attracted to the nanostructure  422  as described above, the biomolecules of interest specifically bind to the nanowire  414 . By bringing the biomolecules of interest sufficiently close to the surface of the nanowire  414 , specific binding may occur between the biomolecules of interest and the capture agent  202  (not shown) on the surface of the nanowire  414 . In one example using current processing technology, the nanowire  414  and the nanostructure  422  are separated by a distance on the order of approximately 200 nm to a few micrometers (μm), and may be separated by approximately as much as four micrometers. The proximity of the nanostructure  422  to the nanowire  414  allows an increase in the local concentration of biomolecules of interest near the nanowire  414 , and therefore increases the sensitivity and selectivity of specific binding between the biomolecules of interest and the antibodies on the nanowire  414 .  
         [0029]      FIG. 4B  is a cross-sectional view of the secondary structure of  FIG. 4A  through section A-A. The nanostructure  422  is formed over a substrate  452  as described above. In  FIG. 4B , the nanostructure  422  is shown as being in contact with the substrate  452 ; however, the nanostructure  422  need not be in contact with the substrate  452 . A dielectric  424 , such as silicon nitride (SiN x ), is applied as a film over the nanostructure  422  to prevent binding of biomolecules to the nanostructure  422 . The dielectric material is chosen based on the materials used to fabricate the secondary structure  420 . The electrode  419  is located over the nanostructure  422  to create an electric field in the vicinity of the sensor element  430  when a voltage is applied between the nanostructure  422  and the electrode  419 .  
         [0030]      FIG. 5  is a schematic diagram illustrating a nanoscale biomolecule sensor  500  constructed in accordance with another embodiment of the invention. The nanoscale biomolecule sensor  500  comprises a biomolecule sensor portion  510  and two secondary structures  520  and  530 . The biomolecule sensor portion  510  comprises a nanowire  514  that is similar to the sensor element  110  described above. The nanowire  514  is connected in series with a monitor voltage source  310  and a current monitor  308  via connection  516  and is coupled to ground via connection  518 .  
         [0031]     The secondary structure  520  comprises a nanostructure  522  that is covered by a dielectric  524  to prevent binding of biomolecules to the nanostructure  522 . The dielectric  524  is similar to the dielectric  424 , described above. An electrode  519  is located over the nanostructure  522 . The electrode  519  is connected to one output of the voltage source  302 . The nanostructure  522  is connected to the other output of the voltage source  302 . The secondary structure  530  comprises a nanostructure  532  that is covered by a dielectric  534 , which is similar to the dielectric  524  to prevent binding of biomolecules to the nanostructure  532 . An electrode  529  is located over the nanostructure  532 . The electrode  529  is connected to one output of the voltage source  302 . The nanostructure  532  is connected to the other output of the voltage source  302 . The nanowire  514 , the nanostructure  522 , the electrode  519 , the nanostructure  532  and the electrode  529  comprise a sensor element  540 . In this embodiment, the biomolecule sensor portion  510  is used as the sensor to detect the presence of a particular biomolecule and the secondary structures  520  and  530  are used to attract the desired biomolecules toward the surface of the sensor element  514 .  
         [0032]     The secondary structures  520  and  530  are placed in sufficiently close proximity to the biomolecule sensor portion  510  so that when the biomolecules of interest are attracted to the nanostructures  522  and  532 , as described above, the biomolecules of interest specifically bind to the nanowire  514 . By bringing the biomolecules of interest sufficiently close to the surface of the nanowire  514 , specific binding may occur between the biomolecules of interest and the capture agent  202  (not shown) on the surface of the nanowire  514 . In one example using current processing technology, the nanowire  514  and the nanostructures  522  and  532  are separated by a distance on the order of approximately 200 nanometers (nm) to a few micrometers (μm) and may be separated by approximately as much as four micrometers. The proximity of the nanostructures  522  and  532  to the nanowire  514  allows an increase in the local concentration of biomolecules of interest near the nanowire  514 , and therefore increases the sensitivity and selectivity of specific binding between the biomolecules of interest and the antibodies (not shown) on the nanowire  514 .  
         [0033]      FIG. 6A  is a schematic diagram illustrating a nanoscale biomolecule sensor  600  constructed in accordance with another embodiment of the invention. The nanoscale biomolecule sensor  600  is similar to the nanoscale biomolecule sensor  500  except that the nanostructures  522  and  532  are replaced by electrical conductors  607  and  608 . The nanoscale biomolecule sensor  600  comprises a biomolecule sensor portion  610  and two secondary structures  620  and  630 . The biomolecule sensor portion  610  comprises a nanowire  614  that is similar to the sensor element  110  described above. The nanowire  614  is connected in series with a monitor voltage source  310  and a current monitor  308  via connection  616  and is coupled to ground via connection  618 .  
         [0034]     The secondary structure  620  comprises an electrode  607  that is covered by a dielectric  624  to prevent binding of biomolecules to the electrode  607 . The dielectric  624  is similar to the dielectric  424 , described above. An electrode  619  is located over the electrode  607 . The electrode  619  is connected to one output of the voltage source  302 . The electrode  607  is connected to the other output of the voltage source  302 . The secondary structure  630  comprises an electrode  608  that is covered by a dielectric  634 , which is similar to the dielectric  624  to prevent binding of biomolecules to the electrode  608 . An electrode  629  is located over the electrode  608 . The electrode  629  is connected to one output of the voltage source  302 . The electrode  608  is connected to the other output of the voltage source  302 . The nanowire  614 , the electrodes  607 ,  619 ,  608  and  629  comprise a sensor element  640 . In this embodiment, the biomolecule sensor portion  610  is used as the sensor to detect the presence of a particular biomolecule and the secondary structures  620  and  630  are used to attract the desired biomolecules toward the surface of the sensor element  614 .  
         [0035]     The secondary structures  620  and  630  are placed in sufficiently close proximity to the biomolecule sensor portion  610  so that when the biomolecules of interest are attracted to the secondary structures  620  and  630  as described above, the biomolecules of interest specifically bind to the nanowire  614 . By bringing the biomolecules of interest sufficiently close to the surface of the nanowire  614 , specific binding may occur between the biomolecules of interest and the capture agent  202  (not shown) on the surface of the nanowire  614 . In one example using current processing technology, the nanowire  614  and the electrodes  607 ,  619 ,  608  and  629  are separated by a distance on the order of approximately 200 nm to a few micrometers (μm) and may be separated by approximately as much as four micrometers. The proximity of the electrodes  607 ,  619 ,  608  and  629  to the nanowire  614  allows an increase in the local concentration of biomolecules of interest near the nanowire  614 , and therefore increases the sensitivity and selectivity of specific binding between the desired biomolecules and the capture agent (not shown) on the nanowire  614 .  
         [0036]      FIG. 6B  is a cross-sectional view of the secondary structure of  FIG. 6A  through section B-B. The electrode  607  is formed over a substrate  652  as described above. A dielectric  624 , such as silicon nitride (SiN x ), is applied as a film over the electrode  607  to prevent binding of biomolecules to the electrode  607 . The dielectric material is chosen based on the materials used to fabricate the secondary structure  620 . The electrode  619  is located over the electrode  607  to create an electric field in the vicinity of the sensor element  640  when a voltage is applied between the electrode  607  and the electrode  619 .  
         [0037]      FIG. 7  is a flowchart  700  illustrating a method of operating a nanoscale biomolecule sensor in accordance with an embodiment of the invention. In block  702 , a nanoscale biomolecule sensor element is provided. The surface of the nanoscale biomolecule sensor element is coated or otherwise functionalized with a capture agent comprising biomolecules, such as the antibodies, proteins, peptides, DNA or RNA sequences described above. In block  704 , an electrical pulse is delivered to electrodes associated with the nanoscale biomolecule sensor element. The electrical pulse creates a temporary electric field between the electrodes so that biomolecules in the fluid in the electric field experience a motive force. The motive force causes biomolecules having a charge that is opposite the charge in the electric field to be attracted to the sensor element. Biomolecules that specifically bind with the capture agent on the sensor element as well as biomolecules that will not specifically bind with the capture agent on the sensor element are attracted to the sensor element. In block  706 , an electrical pulse having a polarity opposite the polarity of the first electrical pulse is optionally delivered to the electrodes associated with the sensor element. The electrical pulse having a polarity opposite the polarity of the first electrical pulse creates a second temporary electric field between the electrodes so that biomolecules in the fluid in the electric field experience a motive force. The motive force repels away from the sensor element the biomolecules having the same charge polarity as the biomolecules of interest, but that do not specifically bind with the capture agent on the sensor element. In block  708 , a change in the electrical properties of the sensor element is measured to detect the presence and the concentration of the specifically-bound biomolecules.  
         [0038]     This disclosure describes the invention in detail using illustrative embodiments. However, it is to be understood that the invention defined by the appended claims is not limited to the precise embodiments described.