Patent Publication Number: US-2007096164-A1

Title: Sensing system

Description:
BACKGROUND  
      Chemical and biological sensing systems are important in a number of different applications, such as medical, environmental, agricultural, military and industrial applications, to name a few. ChemFET sensing systems based on chemically sensitive field effect transistors have in particular been investigated for decades and have demonstrated some commercial applicability, although mainly for pH and pH-mediated enzyme sensors (EnFETs) because of the immense technical difficulties involved in the species-specific, highly sensitive biochemical sensing that is needed for biotech and medical usage.  
      One type of ChemFET sensing system employs a nanowire sensing element that is functionalized (with a functional agent) to enable the nanowire to electrically respond to the presence of an analyte in a sample. Interaction between the functionalized nanowire and the analyte may cause, for example, the generation of an electric field that, in turn, causes a detectable change in an electrical property of the nanowire (e.g., a detectable shift in electrical conductance). This type of ChemFET sensing system may alternatively be referred to herein as a “nanowire based” sensing system. Examples of a “nanowire based” sensing system are described in the patent literature. See, for example, PCT Application WO 02/48701, having international filing date of Dec. 11, 2001, entitled “NANOSENSORS”, by inventors Lieber et. al.  
      Nanowire based sensing systems offer a number of advantages including very high sensitivity and the ability to monitor very small sample sizes. There is a need, however, to improve upon the manufacturability of these sensing systems and to expand their capabilities.  
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       FIG. 1  is a high-level schematic diagram of a nanowire based sensing system;  
       FIG. 2  is a flow diagram illustrating a process that may be followed to functionalize ananowire sensing segment according to an embodiment of the invention;  
       FIG. 3  is a flow diagram illustrating an alternative process that may be followed to functionalize the nanowire sensing segment according to an embodiment of the invention;  
       FIG. 4A  is a high level schematic diagram of a nanowire based sensing system according to an embodiment of the invention;  
       FIG. 4B  illustrates one operational mode of the sensing system according to one implementation;  
       FIG. 4C  illustrates one operational mode of the sensing system according to another implementation;  
       FIG. 5  is a flow diagram illustrating a process that may be followed, according to one embodiment, to differently functionalize nanowires in an array;  
       FIG. 6  is a top plan view illustrating an example how a sensing system that embodies the invention may be constructed;  
       FIG. 7  illustrates a cross-section along the elongate dimension of a DEMUX address electrode according to one embodiment;  
       FIG. 8  illustrates a cross-section along the elongate dimension of a gate electrode according to one embodiment;  
       FIG. 9  illustrates a cross-section along line A-A′ of  FIG. 6 ;  
       FIG. 10A  is an abstract diagram illustrating a sensing system according to one embodiment;  
       FIG. 10B  is a flow diagram illustrating an example operation of the sensing system according to one embodiment.  
    
    
     DESCRIPTION  
      In the following detailed description, numerous specific details are set forth to provide a thorough understanding of claimed subject matter. However, it will be understood by those skilled in the art that claimed subject matter may be practiced without these specific details. In other instances, well-known methods, procedures, components and/or circuits have not been described in detail so as not to obscure claimed subject matter.  
      As used herein, a “nanowire” is an elongated nanoscale structure which, along its length, includes a cross-sectional dimension that is less than 1000 nanometers. The cross-section of a nanowire, in various embodiments, may be any regular shape, such as (but not limited to) square, rectangular, elliptical, trapezoidal or some other regular shape. The cross section of a nanowire, in other embodiments, may have an irregular shape.  
      As used herein, the term “Nanowire” may also be used to refer to the elongated sidewall surfaces described in the US patent application having attorney docket # 200406184, filed Oct. 31, 2005, entitled “SENSOR”, by inventor Kevin Peters. The disclosure of that application is incorporated herein by reference.  
      A nanowire, in various embodiments, may be a semiconductor and may be formed from any number of different materials, such as Si, Si-alloys, Ge, GaAs, metals, nitrides, and/or oxides, to name a few. Also, combinations of the above materials may be employed, such as an Si core with a cladding of oxide and/or nitride.  
      In various embodiments, any number of different methods may be employed to fabricate a nanowire including examples and combinations of the following: imprinting, lithography, chemical vapor deposition (CVD), etching, laser ablation, arc discharge, and/or electrochemical methods. It should be clear that these particular examples are not intended to limit the scope of claimed subject matter. By way of one non-limiting example, nanowires in various embodiments may be fabricated utilizing the techniques described in U.S. patent application Ser. No. 10/423,063, filed Apr. 24, 2003, entitled “SENSOR PRODUCED USING IMPRINT LITHOGRAPHY”, to Kevin Peters and James Stasiak.  
      The process of coating a nanowire with a “functional agent” may be referred to herein as “functionalization”. Functional agents may, for example, bind specific chemical and/or biological species of interest, such as, for example, thiol groups, nucleic acids (deoxyribonucleic acid or “DNA”, peptide nucleic acids or “PNA”, and Ribonucleic acid or “RNA”), aptamers, hormones, carbohydrates, proteins, antibodies, antigens, molecular receptors, and/or cellular surface binding sites, to provide a few biochemical examples. Some functional agents may bind other functional agents. For example, a first electrodeposited gold functional agent may bind a thiol-terminated DNA functional agent that may, in turn, bind a complementary DNA species of interest. Another example is a first DNA functional agent that binds a second PNA functional agent that may, in turn, bind a complementary DNA species of interest.  
      It is also noted that functional agents are not limited to binding of specific species. Also, not binding non-specific species may be another function of a functional agent. As one example, without loss of generality, the use of so-called anti-fouling functional agents may inhibit the binding of a species to a nanowire surface. Another kind of functional agent may inhibit binding until such time when a condition is changed, such as (but not limited to) pH, temperature, or oxidation state, whereupon binding is no longer inhibited. Another kind of functional agent may serve to perform enzymatic activity, such as catalysis of a reaction, as with lactase dehydrogenase. These are merely examples of the functions of functional agents and are not intended to limit the scope of claimed subject matter.  
      Sensing System Embodiment  
       FIG. 1  is a high-level schematic diagram of a nanowire based (CHEMFET) sensing system  102  that incorporates one example embodiment of the invention. In general, the sensing system  102  may be used to detect the presence of an analyte in a sample. As indicated, the sensing system  102  includes a nanowire sensing element (nanowire)  104 , a first electrode  108 , a second electrode  110  and a Field Effect Transistor (FET)  112 .  
      The nanowire  104  is, in this example, a continuous structure that bridges the two contact electrodes ( 108 ,  110 ) which, in turn, respectively provide contact points for a power supply system (not shown) and a monitor (also not shown). The monitor may be capable of monitoring an electrical property of the nanowire  104 , such as electrical conductance or resistance. The nanowire  104  may be formed, for example, from a thin layer of semiconductor material and may be disposed on an insulating material. According to one embodiment, for example, the nanowire  104  may be fabricated utilizing a commercially available SOI (silicon on insulator) wafer.  
      t is noted for the following discussion, that the nanowire  104  includes, along a particular segment  104 ( a ) of its length, an exposed surface area that is intended to be functionalized in order to enable the nanowire  104  to electrically respond to the presence of an analyte in a fluid sample (not shown). For ease of discussion, we may refer to this particular segment of the nanowire  104  as the “nanowire sensing segment”  104 ( a ).  
      n one embodiment, the sensing system may include a fluid handling system (not shown) that can be used to expose the nanowire sensing segment to one or more fluids in the course of a functionalization process or during a sensing operation. The fluid may have a chemical potential and more specifically an electrochemical potential that, in the continuing embodiment, is well-established. One common way of establishing the electrochemical potential is by contacting the fluid to a reference electrode, in most cases at a remote position from the nanowire sensing segment. Suitable reference electrodes include (but are not limited to) platinum, palladium, gold, silver, silver with silver chloride, calumel, a standard hydrogen reference cell, and others that are well known to persons skilled in electrochemistry. Accordingly, an electrochemical potential difference between the fluid and the exposed surface area of the nanowire sensing segment can be established by applying an electrical potential between the reference electrode and the first electrode  108 . The (electro)chemical potential difference is well known to influence reactions including oxidation, reactivity, binding, diffusion, ionic diffusion, and electrophoresis.  
      As indicated schematically in  FIG. 1 , the FET  112  includes a gate electrode  112 ( a ) that is positioned over a region of the nanowire that is between the nanowire sensing segment  104 ( a ) and the second electrode  110 . A suitable dielectric material (not shown) may be disposed between the gate electrode  112 ( a ) and the nanowire  104 . Moreover, the FET  112  enables the sensing system  102  to generate an electric field that has the effect of preventing (or “gating”) electric current from passing (through the body of the nanowire  104 ) between the nanowire “sensing segment”  104 ( a ) and the second electrode  110 . In this manner, the FET  112  enables the sensing system  102  to electrically disconnect the nanowire sensing segment  104 ( a ) from the second electrode  110 . While, however, the nanowire sensing segment  104 ( a ) is disconnected in this manner from the second electrode  110 , it remains electrically connected (through the body of the nanowire  104 ) to the first electrode  108 . As a result, the potential of the nanowire sensing segment  104 ( a ) tends to float to a uniform potential that is equal to the potential of the first electrode  108 .  
      The ability (provided by the FET  112 ) to electrically disconnect the sensing segment  104 ( a ) from the second electrode  110  may be useful for a number of purposes and it is to be understood that embodiments of the sensing system are not limited to any particular purpose. By way of example, however, such ability may be useful in a process to functionalize the nanowire sensing segment  104 ( a ). This proposition is illustrated further, by way of non-limiting examples, in the next part of this discussion.  
      Exemplary Process to Functionalize Nanowire  
       FIG. 2  is a flow diagram illustrating a process that may be followed to functionalize the nanowire sensing segment  104 ( a ) according to one embodiment of the invention. With reference now to  FIG. 2 , at step  202 , a solution is prepared (step  202 ). The solution may generally be any solution capable of preferentially functionalizing a surface area when a suitable electrochemical potential difference is established with respect to the surface. Non-limiting examples of solutions that may be prepared at step  202  are provided below.  
      At step  204 , the FET  112  is operated so as to electrically disconnect the nanowire sensing segment  104 ( a ) from the second electrode  110 . While the sensing segment  104 ( a ) is electrically disconnected from the second electrode  110  in this manner, steps  206  and steps  208  are then performed.  
      At step  206 , the nanowire sensing segment  104 ( a ) (including its exposed surface area) is electrically and uniformly charged to a pre-determined polarity (i.e., positive or negative) by applying a suitable voltage potential to the first electrode  108  so as to establish a suitable electrochemical potential difference as described above.  
      At step  208 , the uniformly charged nanowire sensing segment  104 ( a ) is functionalized using the prepared solution. This final step involves placing the solution and the charged segment in contact with each other and then permitting elements (e.g., functional agents) of the solution to interact with the exposed surface area of the sensing segment  104 ( a ).  
      Non-Limiting Example  
      According to one implementation of the process just described, electroplating is used in order to functionalize the exposed surface area of the nanowire sensing segment  104 ( a ) with a thin coating of one or more metals. The metal(s) may be selected, for example, so as to enable the nanowire  104  to electrically respond to the presence of certain chemical species in a fluid. For example, the metal(s) may be selected to enable the nanowire  104  to electrically respond to the presence of certain hydrocarbons and/or oxygen, in a gas sample. In other variations, for example, the metal coating may act as an adsorption substrate for one or more chemical cross-linkers (e.g., cross-linkers with a sufhydryl functional group) by which a biochemical species can be immobilized.  
      The solution, in this non-limiting example, is an electrolyte solution of metal-containing ionic species that is prepared (at step  202 ) by dissolving the one or more selected metal-containing constituents to a suitable solvent such as an aqueous buffer solution that can be used to electroplate the metal. The metal(s) selected could be any suitable/desired metal, including nickel, copper or gold, to name a few.  
      At step  204 , the nanowire sensing segment  104 ( a ) is disconnected from the second electrode  110 . At step  206 , an appropriate voltage is applied to the first electrode  108  so as to establish a suitable electrochemical potential difference as described above between the nanowire sensing segment  104  and the electrolyte solution.  
      At step  208 , the electrolyte solution and the charged nanowire sensing segment  104 ( a ) are brought into contact with each other in order to functionalize (via electroplating) the exposed surface area of the sensing segment  104 ( a ) with a layer of the one or more selected metals.  
      Alternative Process to Functionalize Nanowire  
       FIG. 3  is a flow diagram illustrating an alternative process that may be followed to functionalize the nanowire sensing segment  104 ( a ) according to an embodiment of the invention. With reference now to  FIG. 3 , at step  302 , a first solution (binding agent solution) is prepared that includes a binding agent that is capable of binding a particular analyte (target analyte) of interest.  
      At step  304 , a second solution (coupling agent solution) is prepared that includes a coupling agent that is capable of coupling the binding agent to the exposed surface of the nanowire sensing segment  104 ( a ). The solution is configured, in this example, so that the coupling agent in the solution is electrically charged at a pre-determined polarity (i.e., positive or negative).  
      At step  306 , the FET  112  is operated so as to electrically disconnect the nanowire sensing element  104 ( a ) from the second electrode  110 . While the sensing segment  104 ( a ) is electrically disconnected from the second electrode  110  in this manner, steps  308  and steps  310  are then performed.  
      At step  308 , the sensing segment  104 ( a ) (now disconnected from the second electrode  110 ) is electrically charged to a polarity that is opposite that of the coupling agent charge polarity. This step may be accomplished by applying an appropriate voltage to the first electrode  108 .  
      At step  310 , the coupling agent and the now electrically charged sensing segment  104 ( a ) are brought into contact with each other in order to functionalize the exposed surface area of the sensing segment  104 ( a ) with a layer of the coupling agent. As a result of the electrochemical potential difference between the solution of the charged coupling agent and the oppositely charged sensing segment  104 ( a ), the coupling agent in the solution may migrate towards and condense preferentially onto the exposed surface area of the sensing segment  104 ( a ). [Note that the ionic migration and/or the binding may be the effect of the electrochemical potential difference employed here and are both chemical mechanisms that are operable within embodiments of the present invention.] 
      At step  312 , the sensing segment  104 ( a ) (now functionalized with a layer of the coupling agent) is further functionalized with the binding agent. This step involves placing the binding agent solution in contact with the sensing segment  104 ( a ) so as to permit the layer of the coupling agent (on the sensing segment) to immobilize the binding agent and thereby couple the binding agent to the nanowire sensing segment. It is noted that in various implementations, the sensing segment  104 ( a ) may be connected to the second electrode  112  when step  312  is performed and/or the voltage applied to the first electrode  110  may be modified if desired.  
      Non-Limiting Example  
      In this non-limiting example, we discuss how the functionalization process just described may be performed so as to configure the nanowire  104  to detect the presence of a target DNA molecule in a sample. In this example, the binding agent is an amine terminated aptamer that is complementary to the target DNA molecule and the coupling agent is carboxylic silane.  
      Accordingly, step  302  may performed by preparing a binding agent solution that includes a suitable concentration of the amine terminated aptamer. Step  304  may be performed by preparing a coupling agent solution comprising carboxylic silane having a suitable PH (e.g., PH&gt;7) that results in the carboxylic silane in the solution being deprotonated and thereby developing a negative charge. Such a solution may be prepared, for example, using Carboxyethylsilanetriol Sodium Salt which is commercially available (e.g., from Gelest, Inc.).  
      At step  306 , the FET  112  is operated to electrically disconnect the nanowire sensing segment  104 ( a ) from the second electrode  110 . The nanowire sensing segment  104 ( a ) remains disconnected from the second electrode  110  while steps  308 - 310  are performed.  
      At step  308 , the nanowire sensing segment  104 ( a ) is positively charged, in this example, by applying a suitable voltage to the first electrode  108 . The reader will note that the polarity of the charged sensing segment is charged opposite that of the deprotonated carboxylic silane polarity. While the sensing segment  104 ( a ) is electrically disconnected from the second electrode  110  in this manner, steps  308  and steps  310  are then performed.  
      At step  310 , the now positively charged sensing segment  104 ( a ) is placed in contact with the carboxylic silane acid (i.e., the coupling agent solution in this example). As a result of electrostatic forces between the negatively charged carboxylic silane in the solution and the positively charged sensing segment  104 ( a ), the silane in the solution migrates towards and condenses onto the exposed surface of the (positively charged) sensing segment  104 ( a ). This can result in the exposed surface of the sensing segment  104 ( a ) being coated with a layer of the silane and, in this manner, the sensing segment  104 ( a ) is functionalized.  
      At step  312 , the now functionalized sensing segment is further functionalized with the binding agent. This step includes placing the binding agent solution in contact with the sensing segment so as to permit the binding agent (i.e., the amine terminated aptamers), in the solution to become immobilized by the layer of carboxylic silane on the sensing segment. As a result, the sensing segment is further functionalized with the amine terminated aptamers.  
      In addition to the stipulated means of establishing an electrochemical potential difference by applying a voltage between the first and reference electrodes, it is further to be understood that removing an electrochemical potential difference may also be employed in various embodiments. Whereas an ionic coupling agent or functional agent may be repelled from a surface area by application of a suitable potential, the removal of that repelling potential may result in migration and binding of said ionic agent to said surface area. The two distinct operations, based on a mechanism to attract and a mechanism not to repel, are substantially interchangeable.  
      Second Embodiment of a Sensing System  
       FIG. 4A  is a high level schematic diagram of a nanowire based (ChemFET) sensing system  402  that incorporates yet another embodiment of the invention. As indicated, the sensing system  402 , in this embodiment, includes an array of “N” nanowires  404 . To simplify the following description, we will assume that the value of “N” is eight. In other implementations, however, N may be any number, including a much greater number. The pitch of the nanowire array  404  may be smaller than 10 microns, 1000 nms, 100 nms or even approximately 10 nms, for example.  
      For the following discussion, we will assume that each of the nanowires in the array  404  is formed from a semiconductor material, is disposed on an insulating substrate and includes a sensing segment (i.e., sensing segments  404 ( a )). Furthermore, each of the nanowire sensing segments  404 ( a ) includes an exposed surface area that is intended to be functionalized.  
      The sensing system  402  further includes, in this example embodiment, a demultiplexer (DEMUX)  406 , a common electrode  408  and an “array switching system”  410 . As shown, each of the nanowires  404  is coupled to a different output (D 1 -D 8 ) of the Demux  406  and, at an opposite end, to the common electrode  408 . The DEMUX  406  includes an input line  406 ( a ), a set of address lines  406 ( b ) and is configured to apply, through its D 1 -D 8  outputs, an input voltage (received via the input line  406 ( a )) to one or more of the nanowires  404  as determined by the logic states of the address input lines  406 ( b ). It is noted that according to one embodiment, the DEMUX  406  may be constructed as described below with reference to  FIG. 6 . In alternative embodiments, for example, the DEMUX  406  may be implemented as a CMOS or some other type of standard integrated circuit.  
      When disabled, the switching system  410  does not affect the electrical connection between the sensing segments and the common electrode  408 . When, however, the switching system  410  is enabled, the switching system  410  operates to electrically disconnect each of the nanowire sensing segments  404 ( a ) from the common electrode  408 . The switching system  410  may be enabled or disabled, in this embodiment, through an input line  410 ( a ).  
      or the following discussion, it is noted that when the switching system  410  is enabled, the DEMUX  406  may be operated to hold the sensing segments  404 ( a ) of selected nanowires to an elevated potential relative to the sensing segments of other nanowires in the array. By way of example,  FIG. 4B  illustrates an example of how the DEMUX  406 /switching system  410  may operate to hold the sensing segments of selected nanowire  404 ( 1 ),  404 ( 5 ) and  404 ( 8 ) to a “V( 1 )” potential while the rest of the nanowires float, for example.  
      As indicated in  FIG. 4B , the switching system  410  is enabled and, therefore, the sensing segments  404 ( a ) are all electrically disconnected from the electrode  408 . The sensing segments  404 ( a ) remain connected, however, as shown to the corresponding DEMUX (D 1 - 8 ) outputs. The V ( 1 ) potential is applied to the DEMUX input  406 ( a ) and Address “A” is applied to the DEMUX address input  406 ( b ). Address “A”, in this example, logically selects nanowire  404 ( 1 )), nanowire  404 ( 5 ) and nanowire  404 ( 8 ).  
      The DEMUX  406  is responsive to this input by applying the V ( 1 ) potential, via the D 1 , D 5  and D 8  output, to the selected nanowires  404 ( 1 ), ( 5 ) and ( 8 ). This results in charging/energizing the sensing segments of the selected nanowires ( 404 ( 1 ),  404 ( 5 ) and  404 ( 8 )) to the elevated V ( 1 ) potential. The rest of the nanowires (i.e., the unselected nanowires) are allowed to float in this embodiment. In this example, elevating the sensing segments to the V ( 1 ) potential results in the sensing segments having a positive charge relative to the unselected nanowires.  
       FIG. 4C  illustrates the operation of the DEMUX  406  according to a variation of the embodiment just described. In this example, the DEMUX  406  is responsive to the same input by applying the V ( 1 ) potential, via the D 1 , D 5  and D 8  output, to the selected nanowires  404 ( 1 ), ( 5 ) and ( 8 ). In this embodiment, however, the DEMUX  406  is configured to apply a potential (V ( 2 )) to the unselected nanowires that is of opposite polarity to the V ( 1 ) input potential. This results in the sensing segments of the unselected nanowires being charged to a polarity that is opposite that of the DEMUX input potential. In example shown, the unselected nanowires are charged to a negative polarity.  
      The demux/switch system arrangement described above may be used for a number of purposes and embodiments of the invention are not limited to any particular purpose. By way of example, however, such an arrangement may be useful in a process to differently functionalize individual nanowires in the array  404 . This proposition is illustrated further, by way of non-limiting examples, in the next part of this discussion.  
      Exemplary Process to Differently Functionalize an Array of Nanowires  
       FIG. 5  is a flow diagram illustrating a process that may be followed, according to one embodiment, to differently functionalize nanowires in the nanowire array  404 . For the next part of this discussion, we will assume the following:  
      Assumption # 1 : It is desired to functionalize the sensing segments of a first subset (nanowire subset “A”) of the nanowires  404  with a first functional agent (functional agent “A”);  
      Assumption # 2 : It is desired to functionalize the sensing segments of a second subset (nanowire subset “B”) of the nanowires  404  with a second functional agent (functional agent “B”);  
      Assumption # 3 : Nanowire subset “A” and nanowire subset “B” include different nanowires; and Assumption # 4 : Functional agent “A” and functional agent “B” are two different functional agents.  
      At step  504 , the array switching system  410  is enabled so as to electrically disconnect the sensing segments  404 ( a ) from the electrode  408 . While the sensing segments are disconnected in this manner, steps  506 - 512  are performed.  
      At step  506 , a pre-determined input voltage signal (potential “A”) and the address of nanowire subset “A” are applied to the DEMUX  406 . The DEMUX  406  is responsive to this input by applying potential “A” to the nanowire members of nanowire subset “A”. As a result, the sensing segments of these particular nanowires are each elevated to potential “A”. The DEMUX, in some implementations, may allow the rest of the nanowires (including their respective sensing segments) to float. In other implementations, the DEMUX may apply a different potential to the remaining (i.e., unselected) nanowires.  
      At step  508 , a solution (solution “A”) is brought in contact with the nanowire array  404 . Solution “A” is configured to interact with the array  404  so as preferentially functionalize, with functional agent “A”, those sensing segments that are presently being held to voltage potential “A” over those sensing segments that are floating and/or at a different potential. As a result of step  508  being performed, the sensing segments of nanowire subset “A” are functionalized with functional agent “A”. The rest of the sensing segments are not functionalized with this particular agent and/or are coated with a minimal quantity of agent “A”.  
      After the sensing segments of nanowire subset “A” are functionalized with functional agent “A” as just described, the process may be continued in a similar manner so as to functionalize the sensing segments of nanowire subset “B” with functional agent “B”.  
      Accordingly, at step  510 , a pre-determined input voltage signal (potential “B”) and the address of nanowire subset “B” are applied to the DEMUX  406 . The DEMUX  406  is responsive to this input by applying potential “B” to the nanowire members of nanowire subset “B”. As a result, the sensing segments of these particular nanowires are each elevated to potential “B”. The rest of the nanowires (including their respective sensing segments) may float. In other implementations, the DEMUX may apply a different potential (of opposite polarity) to the remaining nanowires.  
      At step  512 , a second solution (solution “B”) is brought in contact with the nanowire array  404 . Solution “B” is configured to interact with the array  404  so as to preferentially functionalize, with functional agent “B”, those sensing segments that are presently being held to potential “B” over those sensing segments that are floating/and or are at a different potential.  
      This results in modifying the array  404  so that the sensing segments of nanowire subset “B” are functionalized with functional agent “B”. The rest of the sensing segments are not functionalized with this agent and/or are coated with a minimal quantity of agent “B.” 
      As indicated by step  514 , the general process just described may be further used to functionalize other subsets of the nanowires in the array with any number of different functional agents.  
      Example Construction of Sensing System  
       FIG. 6  is a top plan view illustrating an example how variations of the sensing system just described may be constructed, according to one embodiment.  
      As shown, the sensing system of this example includes a cross bar arrangement  602  that includes an array of eight nanowires  604 ( 1 - 8 ) and a set of nine elongate electrodes  614 ,  610 ,  612  and  616 ( 1 - 6 ) that respectively cross each nanowire in the array  604  as shown.  
      The cross bar arrangement  602  includes, as shown, a DEMUX region  606  and a “sensing region”  608 .  
      The nanowire array  604 ( 1 - 8 ), in this example, may be disposed on a dielectric material, such as silicon oxide and may have a pitch that is smaller than 10 microns, 1000 nms, 100 nms or even approximately 10 nms, for example. The material of the nanowires  604  may be a semi-conductive material such as, for example, (N or P) doped silicon.  
      As depicted by  FIG. 6 , each of the nanowires  604  ( 1 - 8 ) respectively includes a sensing segment  608  ( 1 - 8 ) that is located within the cross bar sensing region  608 .  
      Demux Architecture  
      The DEMUX region  606  generally provides the cross bar arrangement with a 1×8 DEMUX circuit. Suitable techniques for constructing such a circuit are provided by U.S. application Ser. No. 10/835,659, filed Apr. 30, 2004, entitled “FIELD-EFFECT-TRANSISTOR MULTIPLEXING/DEMULTIPLEXING ARCHITECTURES AND METHODS OF FORMING THE SAME”, by inventors Xiofeng Yang and Pavel Kornilovich. The disclosure of that application is incorporated herein by reference.  
      As shown, the DEMUX region  606  may logically be divided into an input region  606 ( a ), an address region ( 606 ( b )) and an output region  606 ( c ). To assist in the following discussion:  
      1.) The segment of each nanowire in the array  604  that is located within the DEMUX input region  606 ( a ) may be referred to as the “input segment” of the nanowire;  
      2) The segment of each nanowire in the array  604  that is located within the DEMUX address region  606 ( b ) may be referred to as the “address segment” of the nanowire; and  
      3) The segment of each nanowire in the array  604  that is located within the DEMUX output region  606 ( c ) may be referred to as the “output segment” of the nanowire.  
      As shown, the DEMUX input region  606 ( a ) includes a DEMUX input electrode  614  which is in electrical contact with the nanowire input segment of each nanowire in the array  604 . The DEMUX input electrode  614  may provide an electrical contact point for a power supply system (not shown) and can be used to apply an input voltage (e.g., V( 1 )) to the DEMUX input region  606 ( a ).  
      The address region  606 ( b ) of this example includes six address electrodes electrodes  616  ( 1 - 6 ) that generally provide a means for selecting one or more nanowires in the array. The address region  606 ( b ) may include additional address electrodes which are not illustrated. In this embodiment, one or more nanowires may be selected by applying address input to the address electrodes  616  ( 1 - 6 ) that is in accordance with a pre-determined protocol.  
      The address segment of each nanowire that is not selected is electrically gated (at least once) via an electric field that is generated by one or more of the address electrodes  616  ( 1 - 6 )). This results in the (unselected) nanowire input segment being electrically disconnected from the nanowire output segment. As a result, the DEMUX input voltage (e.g., V 1 ) is not routed to the (unselected) nanowire output segment and corresponding sensing segment.  
      The address segment of each nanowire that is selected, however, is not electrically gated by any of the address electrodes and, therefore, the nanowire output segment and input segment remain electrically connected (through the address segment of the nanowire). Consequently, the DEMUX input voltage (e.g., V ( 1 )) is routed to the output segment and sensing segment of each selected nanowire.  
      Referring now also to  FIG. 7 , a cross-section along the elongate dimension of a representative one of the DEMUX address electrodes (i.e., in this example address electrode  616 ( 6 )) is shown.  
      As indicated in  FIG. 7 , a dielectric structure is located between each nanowire  604 ( 1 - 8 ) and the address electrode  616  ( 6 ). The dielectric structures are generally of one of two thicknesses: thickness “A” or thickness “B”, wherein thickness “A” is greater than thickness “B”. First dielectric structure  702 , for example, corresponds to thickness “A” and is interposed between the nanowire  604 ( 1 ) and the address electrode  616 ( 6 ). The second dielectric structure  704 , for example, corresponds to thickness “B” and is interposed between the nanowire  604 ( 8 ), for example.  
      Moreover, in operation, an address input (in the form of a pre-determined voltage) may be placed on the address input electrode  608  ( 3 ) and, as a result, the electrode  608 ( 3 ) generates an electric field. The electric field is effective to electrically “gate” a nanowire through the thinner dielectric structure (i.e., thickness “B”). The electric field is not effective, however, to gate a nanowire through the thicker dielectric structure (i.e., thickness “A”). Accordingly, the thickness of the dielectric between each address electrode and each respective nanowire can be selected so as to implement the DEMUX address protocol.  
      As illustrated in  FIG. 7 , in the example shown, the electric field generated by the address electrode  608  ( 3 ) is not effective to electrically gate nanowires  604 ( 1 ), ( 3 ), ( 5 ) and ( 7 ) through the corresponding thicker dielectric structures. The electrical field is, however, effective to electrically gate nanowires  604 ( 2 ), ( 4 ) and ( 8 ) through the corresponding thinner dielectric structures.  
      Referring now also to  FIG. 8 , a cross-section along the elongate dimension of another electrode (gate electrode  610 ) is shown. As shown, located between the gate electrode  610  and each nanowire is a dielectric structure of the thinner thickness (i.e., thickness “B”). Moreover, when a suitable voltage is applied to the gate electrode  610 , the gate electrode  610  generates an electric field that electrically gates each of the nanowires  604  in the region that is overlapped/crossed by the gate electrode  610 . In this manner, the gate electrode  610  can be used to electrically disconnect the sensing segment of each nanowire  604  from the (common) electrode  612 . Accordingly, the gate electrode represents one embodiment of an array switching system as described and illustrated above in  FIG. 4A .  
      As previously noted, the DEMUX input electrode  614  may provide a contact point for an external power supply system. It is further noted that the common electrode  612  may provide a second contact point for the external power supply system as well as a monitoring system (not shown) that is capable of monitoring an electrical property of each nanowire during a sensing operation, as is described further below.  
      Referring now also to  FIG. 9 , a cross-section of the nanowire sensing segment along line A-A′ of  FIG. 6  is shown according to one embodiment. In this example, we assume the nanowire sensing segments have been differently functionalized by the methods described above and by using the DEMUX ability provided by the DEMUX region  606  along with the capability provided by the gate electrode  610  to disconnect the array of nanowires  604  from the common electrode  612 . For example, the nanowire sensing segment  604 ( 1 ) is functionalized with a coupling agent and is further functionalized with a binding agent linked to the coupling agent, the functional ensemble being indicated in  FIG. 9  as  902 ( 1 ). The nanowire sensing segment  604 ( 8 ) is functionalized with the same coupling agent and is functionalized with a different binding agent linked to the coupling agent, the ensemble of functional agents being indicated as  902 ( 8 ).  
      The binding agents in this non-limiting example are single-stranded DNA oligonucleotide probe molecules that differ only in their sequence of bases (e.g., ACGTAAMCCGGTTACGTTGCA and CGAATCGGATAGCCCTATGG). In this or another sensing system, nanowire sensing segments may be functionalized differently with any number of antibodies and/or nucleic acid binding agents and/or other functional agents that are adapted for the present purposes of functionalization, coupling, binding, and/or sensing.  
      Operation of Sensing System  
       FIG. 10A  is an abstract diagram illustrating further a sensing system  1002  that may incorporate the cross bar arrangement  602  in one example. As shown, the cross-bar arrangement  602  may be integrated with a fluid handing system  1004  which is used to contact nanowire sensing segments with fluid materials (e.g., fluid materials  1006 ). During a functionalization process, the fluid materials may be configured to functionalize the sensing segment of one or more of the nanowires  604  as described above. During a sensing operation, the fluid materials  1006  may be the sample that is under analysis.  
      In the embodiment shown, the fluid handling system  1004  may include, for example, an integrated micro-fluidic channel system for controllably moving a fluid from a source to the sensing segments of the nanowires  604 . Examples of such fluidic systems are generally described in the patent literature. See, for example, the patents assigned to Caliper Technologies Corporation. In other embodiments, for example, the fluid handling system  1004  may comprise a fluid reservoir that is in fluidic communication with the sensing segments of the nanowires  604 .  
      It is further noted that the fluid handling system  1004  may be integrated with a pipetting system (not shown) for transferring fluids from storage vessels to the fluid handling system  1004 . The pipetting system may include one or more automated robotic armatures, for example, for moving pipettors from the storage vessels to the fluid handling system  1004 .  
       FIG. 10B  is a flow diagram illustrating an example operation of the sensing system  1002  to test a sample fluid. We assume in this non-limiting example that the sensing segment of each nanowire in the array  604  is functionalized to detect a different analyte so to provide the sensing system  1002  with the capability to detect the presence of eight different analytes ( 1 - 8 ) in a sample. Nanowire  604 ( 1 ), for example functionalized to detect the presence analyte ( 1 ), Nanowire  604 ( 2 ) is functionalized to detect the presence of analyte ( 2 ), etc.  
      Beginning at step  1102 , the array switching system (i.e., the gate electrode  610 ) is “disabled” so as to electrically reconnect the array of nanowires  604 ( 1 - 8 ) to the common electrode  612 . This step may be performed, for example, by configuring the gate electrode  610  so that it no longer generates an electric field that is effective to gate the nanowires  604 .  
      At step  1104 , the sensing segments  608 ( 1 - 8 ) of the nanowire array  604  is placed in contact with a desired fluid sample that is to be tested. This step may include introducing the sample into the fluid handling system  1004  and permitting the sample to pass through the fluid handling system  1004 .  
      At step  1106 , nanowire  604  ( 1 ) is selected to test by applying the address of that particular nanowire to the DEMUX  606 . The rest of the nanowires (i.e., nanowires  604 ( 2 - 8 )) remain unselected. The DEMUX  606  is responsive to this input by:  
      1) Providing a closed electrical connection, through the body of the nanowire  604 ( 1 ), between the input electrode  614  and the common electrode  612 ; and  
      2) Providing an open electrical connection, through the body of each unselected nanowire, between the input electrode  614  and the common electrode.  
      At step  1108 , an electrical property (e.g., electrical conductance and/or resistance) of the selected nanowire  604 ( 1 ) is measured in order to determine if analyte ( 1 ) is present in the sample. This step may be accomplished by applying a potential difference across the input electrode  614  and the common electrode  612  and then measuring the resulting current passing through the nanowire  604 ( 1 ).  
      At steps  1110 ,  1112  another nanowire (e.g., nanowire  604 ( 2 )) in the array is selected and measured in the same manner. Steps  1110 ,  1112  may be repeated as desired in order to determine if the sample being tested includes any of the analytes ( 1 - 8 ).  
      It is noted that although the flow charts described above show a specific order of execution, it is understood that the order of-execution may differ from that which is depicted. For example, the order of execution of two or more blocks/steps may be scrambled relative to the order shown. Also, two or more blocks/steps shown in succession in the flow charts may be executed concurrently or with partial concurrence. It is understood that all such variations are within the scope of the present invention.  
      Many variations and modifications may be made to the above-described embodiment(s) of the invention without departing substantially from the spirit and principles of the invention. For example, in the above description sensing systems that use employ one or more nanowires are described. It is to be understood, however, that sensing systems that employ microscale wires may embody the invention and the processes described above may be used to functionalize microscale wires in various embodiments of the invention. For example, a sensing system that employs a wire that has a cross section less than one millimeter may embody the invention. Moreover, all such modifications and variations are intended to be included herein within the scope of the present invention.