Patent Abstract:
An array of sensor devices, each sensor including a set of semiconducting nanotraces having a width less than about 100 nm is provided. Method for fabricating the arrays is disclosed, providing a top-down approach for large arrays with multiple copies of the detection device in a single processing step. Nanodimensional sensing elements with precise dimensions and spacing to avoid the influence of electrodes are provided. The arrays may be used for multiplex detection of chemical and biomolecular species. The regular arrays may be combined with parallel synthesis of anchor probe libraries to provide a multiplex diagnostic device. Applications for gas phase sensing, chemical sensing and solution phase biomolecular sensing are disclosed.

Full Description:
BACKGROUND OF THE INVENTION 
       [0001]    1. Field of the Invention 
         [0002]    The present invention relates generally to active solid state devices, specifically to apparatus and method for making and using sensors with nanodimensional features that are responsive to molecular compounds, organisms or gas molecules. 
         [0003]    2. Description of Related Art 
         [0004]    The use of nanowires and nanotubes for label-free direct real-time detection of biomolecule binding is known in the art. Nanowires and nanotubes have the potential for very high-sensitivity detection since the depletion or accumulation of charge carriers, which is caused by binding of a charged biological macromolecules at the surface, can affect the entire cross-sectional conduction pathway of these nanostructures. See, e.g., Direct Ultrasensitive Electrical Detection of DNA and DNA Sequence Variations Using Nanowire Nanosensors, by Jong-in Hahm and Charles M. Lieber,  Nano Letters,  2004 (Vol. 4, No. 1 pp. 51-54), which is incorporated by reference (hereinafter Lieber). Lieber discloses measurable conductance changes associated with hybridization of a Peptide Nucleic Acid (PNA) receptor with complimentary Deoxyribose Nucleic Acid (DNA) target molecule. A practitioner skilled in the art will appreciate that a Peptide Nucleic Acid (PNA) receptor could be substituted with a Deoxyribose Nucleic Acid (DNA) receptor or a Ribose Nucleic Acid (RNA) receptor. 
         [0005]    U.S. Pat. No. 7,301,199 discloses nanowires fabricated using laser catalytic growth (LCG), and is incorporated by reference in its entirety. In LCG, a nanoparticle catalyst is used during the growth of the nanoscale wire. Laser vaporization of a composite target composed of a desired material and a catalytic material creates a hot, dense vapor. The vapor condenses into liquid nanoclusters through collision with a buffer gas. Growth begins when the liquid nanoclusters become supersaturated with the desired phase and can continue as long as reactant is available. Growth terminates when the nanoscale wire passes out of the hot reaction zone or when the temperature is decreased. In LCG, vapor phase semiconductor reactants required for nanoscale wire growth may be produced by laser ablation of solid targets, vapor-phase molecular species, or the like. To create a single junction within a nanoscale wire, the addition of the first reactant may be stopped during growth, and then a second reactant may be introduced for the remainder of the synthesis. Repeated modulation of the reactants during growth is also contemplated, which may produce nanoscale wire superlattices. LCG also may require a nanocluster catalyst suitable for growth of the different superlattice components; for example, a gold nanocluster catalyst can be used in a wide-range of III-V and IV materials. Nearly monodisperse metal nanoclusters may be used to control the diameter, and, through growth time, the length of various semiconductor nanoscale wires. This method of fabricating nanowires is known in the art, and constitutes one method of creating nano-scale features. 
         [0006]    The use of photolithography for fabrication of micron-scale features is well known in the art. In “standard” photolithography, multiple steps are performed to pattern features on a surface. In the initial step, the surface, which may be a p- or n-doped silicon wafer, is cleaned of surface contaminants. Persons skilled in the art will appreciate that many planar surfaces can be patterned in this way, including surfaces with multiple layers, such as a substrate of p- or n-doped silicon, a middle layer of insulating silicon dioxide (SiO 2 ), with a top layer of metal. Next, adhesion promoters are added to the surface to assist in photoresist coating. Photoresist may be spin-coated onto the surface, forming a uniform thickness. The wafer containing the photoresist layer is then exposed to heat to drive off solvent present from the coating process. Next, a photomask, which may be made of glass with a chromium coating, is prepared. The features desired on the surface of the wafer are patterned on the photomask. The photomask is then carefully aligned with the wafer. The photomask is exposed to light, the transparent areas of the photomask allow light to transfer to the photoresist, the photoresist reacts to the light, and a latent image is created in the photoresist. The photoresist may be either positive or negative tone photoresist. If it is negative tone photoresist, it is photopolymerized where exposed and rendered insoluble to the developer solution. If it is positive tone photoresist, exposure decomposes a development inhibitor and developer solution only dissolves photoresist in the exposed areas. Simple organic solvents are sufficient to remove undeveloped photoresist. The techniques of “etch-back” and “lift-off” patterning are used at this stage. If the “etch-back” technique is used, the photoresist is deposited over the layer to be pattered, the photoresist is patterned, and the unpatterned areas of the layer are removed by etching. If the “lift-off” technique is used, photoresist is deposited followed by deposition of a thin film of desired material. After exposure, undeveloped photoresist is removed by the developer solvent and carries away the material above it into solution leaving behind the patterned features of the thin film on the surface. Removal of the remaining photoresist may be accomplished through oxygen plasma etching, sometimes called “ashing”, or by wet chemical means using a “piranha” (3:1 H 2 SO 4 :H 2 O 2 ) solution. 
         [0007]    Although widely used and extremely useful as a micron-scale patterning tool, “standard” photolithography is limited in the resolution of the features it can pattern. The ability to project a clear image of a small feature onto the wafer is limited by the wavelength of the light that is used, and the ability of the reduction lens system to capture enough diffraction orders from the illuminated mask. The minimum feature size that a projection system can print is given approximately by: CD=k 1 *(λ/NA); where CD is the minimum feature size (also called the critical dimension, target design rule); k 1  (commonly called k 1  factor) is a coefficient that encapsulates process-related factors, and typically equals 0.4 for production; λ is the wavelength of light used; and NA is the numerical aperture of the lens as seen from the wafer. According to this equation, minimum feature sizes can be decreased by decreasing the wavelength, and increasing the numerical aperture, i.e. making lenses larger and bringing them closer to the wafer. However, this design method runs into a competing constraint. In modern systems, the depth of focus (D F ) is also a concern: D F =k 2 *(λ/(NA) 2 ). Here, k 2  is another process-related coefficient. The depth of focus restricts the thickness of the photoresist and the depth of the topography on the wafer. One solution known in the art is utilization of light sources with shorter wavelengths (λ), and creation of lenses with higher numeric apertures (NA). The drawback to this solution is the increasingly prohibitive high cost of fabricating complex sources and optics. 
         [0008]    Nanoimprint Lithography (NIL) solves the problem of limited minimum feature sizes and high cost by patterning nano-scale features into a quartz plate, referred to as the “template” that can be applied directly to the surface of a wafer and transferring the pattern 1:1 into a photoresist layer. “Step and Flash Imprint Lithography,” by Resnick, D., et al.,  Solid State Technology , (2007), Feb., 39, which is incorporated in its entirety by reference, discloses the method to pattern nano-scale features by first imprinting the features into a photoresist layer and dry etching the imprint layer into the desired thin film layer on a wafer. The S-FIL process, now generally known in the art as Nanoimprint Lithography (NIL), requires that electron beam lithography be first used to “write” the desired imprint pattern into the template. The template may be a quartz plate substrate coated with a chromium (Cr) layer. The electron beam resist is patterned and the pattern is transferred into the Cr layer and the final three-dimensional relief structure is etched into the quartz plate or “template.” After transfer of the pattern into the quartz layer, the Cr layer is stripped, leaving an optically transparent template with the imprint pattern etched onto one surface. 
         [0009]    To create the imprint pattern into a thin film layer on a wafer substrate, a low-viscosity photocurable monomer—known as the etch barrier—is dispensed on its surface. The transparent template is brought into contact with the monomer at a slight angle, creating a monomer wavefront that spreads across the surface and fills the three dimensional relief structures of the transparent template. UV light photopolymerizes the monomer and the template is separated from the wafer, leaving a solid replica of the reverse of the template on the substrate surface. Post-processing consists of a breakthrough etch of the residual layer of the monomer, followed by a selective etch into an organic layer and finally transfer of the pattern into the desired layer; for example a semiconductor thin film. Imprint lithography has been used to create feature CDs on the order of 20 nm in high density over large areas, e.g. 4-6″ wafers during a single imprint process. 
         [0010]    In a similar fashion, the reverse process (S-FIL/R) can be accomplished. This is achieved by imprinting the surface using the template followed by spinning on an organic layer. The organic layer is etched back to expose the top surface of the silicon-containing imprint which is then selectively etched to the substrate using the organic layer as an etch stop. A final set of etching conditions is used to transfer the pattern into the substrate material. Nanoimprint Lithography has the advantage of being limited only by physical resolution of the template rather than being limited by wavelength and numeric aperture, as in standard photolithography. As new methods emerge for template fabrication, a corresponding increase in feature resolution can be expected. 
         [0011]    U.S. Pat. No. 6,426,184 discloses a method for massively parallel synthesis of DNA, RNA, and PNA molecules utilizing photogenerated reagents (PGR), and is incorporated herein by reference. The method involves a microfluidic chamber comprising a series of wells that act as reaction sites with a transparent sealed cover. Within each well, a “linker” molecule functionalized with a “reactive group” is attached to the substrate. The reactive group couples a “spacer group” which then couples the first nucleotide to the surface. The nucleotide bears a “protection group” initial. The reactive precursor to the PGR is introduced through the microfluidic chamber into the well sites. Selective wells receive light using a spatial light modulating device during a given exposure step which results in a “photogenerated reagent” within each well that was exposed. PGR is activated only in the wells that are exposed to light, thereby causing a chemical reaction with the protection group, and “de-protecting” the terminal nucleotide in the nucleic acid sequence. The PGR is flushed from the system, and a select nucleotide with a “protection group” is introduced. The nucleotide with “protection group” is covalently bonded to the end of the nucleic acid sequence in the selected wells. In all other wells that do not get exposed to light, no reaction takes place and no nucleotide coupling occurs during that exposure cycle. After proper washing, oxidation, and capping steps, the addition of the cycle is repeated in such a fashion to synthesize any combination of nucleotides onto surface-anchored nucleic acid sequences that are specific to each well. The process is continued until the oligonucleotides of interest are constructed over the entire array. The chemistry of building oligonucleotides is well known in the art. Because the sequence is known for each well in the multiplex detection array, diagnostic tests that result in a signal transduction event can be performed by first identifying if a reaction occurs for a given well, and second by determining the position, and hence identity of the “known” anchor probe sequence. 
         [0012]    “Light Directed Massively Parallel On-chip Synthesis of Peptide Arrays with t-Boc Chemistry,” by Gao, X., et al.,  Proteomics , (2003), 3, 2135 discloses PNA synthesis using t-Boc chemistry, and is incorporated by reference herein. This article is an example of chemical syntheses of anchor probe libraries known in the art. 
         [0013]    What is needed is a cost-effective, time-efficient, reproducible method for fabricating arrays of nano-scale features on a single wafer to form a sensor device or a matrix of devices for multiplex detection of selected analytes using many simultaneous detection zones, by detecting changes in electrical characteristics of the nano-scale materials for each device. Method for making such sensors and arrays is needed. 
       SUMMARY OF INVENTION 
       [0014]    The problem of reproducibly fabricating semiconducting active layers that provide the necessary nano-dimensional features for direct electrical detection in sensing applications is solved using nanoimprint lithography to define groups of semiconducting nanotraces between electrodes. Such groups may be used as a sensor or, when anchored probe molecules are covalently coupled or synthesized to the surfaces, be used for multiplex detection of analytes. Nanoimprint lithography also provides a method to fabricate arrays of semiconducting electrode “nanotraces” in a controllable and regular pattern in a single processing step. A method that provides controlled fabrication of nanophase features provides a means for detection of gases adsorbed on the semiconductor surfaces or multiplex detection of many simultaneous detection zones. Binding of complementary targets to the anchored probe molecules in the vicinity of the semiconducting active layer produces a change in electrical conductivity of the semiconducting active layer that can be monitored externally for each sensor device in the array in parallel. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0015]      FIG. 1  depicts a subset of the multiplex detection array showing six sensor devices with the imprinted semiconductor nanotraces. The inset shows the features of an individual semiconductor nanotrace in the set of nanotraces disposed between the electrodes. 
           [0016]      FIGS. 2  A-F illustrates the fabrication sequence for preparing the electrical base including the semiconductor nanotraces for the multiplex detection array. 
           [0017]      FIGS. 3  A-E illustrate the process of preparing the imprint pattern for the semiconductor nanotraces. 
           [0018]      FIGS. 4  A-E illustrate the process for etching the semiconductor nanotraces. 
           [0019]      FIG. 5  shows a high resolution SEM of the imprinted SFIL over the semiconductor active layer. 
           [0020]      FIGS. 6  A-B show a high resolution SEM of the transfer of the imprint pattern to form the semiconductor nanotraces. This image depicts nanotraces with transverse bridging segments. 
           [0021]      FIGS. 7  A-C show the multiplex detection device preparation steps for performing PGR in the preferred embodiment and packaging onto the electronics board. 
           [0022]      FIGS. 8  A-B show examples of the response generated during binding reactivity in the preferred embodiment. 
       
    
    
     DETAILED DESCRIPTION 
       [0023]      FIG. 1  illustrates an overview of a subset of the electrical detection portion of multiplex detection array  101 , which consists of six individual sensor devices  102 A-F. A single sensor device, e.g.  102 A, is defined as a region that is independently electrically addressable from neighboring devices  102 B-F in  FIG. 1 . Some of the features have been removed in this overview to enable a visual representation of the core components of multiplex detection array  101 . Each sensor device  102  consists of a set of two interdigitated electrodes including source electrode  103 , and drain electrode  104  of an individual sensor, e.g. sensor device  102 B. A third gate electrode  105  may be positioned to cross under the interdigitated portion of each column of sensor devices  102 , e.g. sensor devices  102 C and  102 F in  FIG. 1 . Gate electrode  105  is in a lower plane than source  103  and drain  104  electrodes and is separated by thin oxide dielectric layer  106  supported by a suitable substrate wafer  107 , for example a silicon wafer or polymeric film. All of the electrodes  103 - 5  have relatively large scale features (˜1-5 μm) that are patterned using standard lithography. In this example, gate electrode  105  is common to each column of sensor devices  102  and terminates at gate electrode bonding pad  108  in an area remote from the sensor devices  102 . Similarly, source electrode  103  is common to all sensor devices  102  in each column in the array and terminates at source electrode bonding pad  109  in an area remote from sensor devices  102  and parallel with gate electrode  105 . Each of the drain electrodes  104  terminates at each sensor device  102  at drain electrode stub bonding pad  110 . A secondary process enables electrical continuity of drain electrode stub bonding pad  110  to be transferred to a higher plane that is separated by oxide insulating layer  111 . Electrical continuity is transferred by metal filling of drain electrode vias  112  that are positioned over each drain electrode stub bonding pad  110  and below each drain electrode pick-up pad  113 , which is in the higher plane. The portion of drain electrode  104 B in this plane is common for each row of sensor devices  102 ; for example, sensor devices  102 A-C and sensor devices  102 D-F in  FIG. 1 , and terminates at drain electrode bonding pad  114 . Drain electrodes  104 B are perpendicular to the source  103  and gate  105  electrodes but in a different electrode plane to prevent shorting across the sensor devices  102 . 
         [0024]    In the center of each sensor device  102  is a set of parallel semiconductor “nanotraces”  115  that are perpendicular to and disposed across, the interdigitated finger region of the source  116  and drain  117  electrodes. Semiconductor nanotraces  115  can be fabricated using nanoimprint lithography. Each semiconductor nanotrace  118 ,  FIG. 1  inset, in the set of parallel nanotraces  115  provides a narrow electrical bridge between source  103  and drain  104  electrodes by making contact with the interdigitated finger region of each of the source  116  and drain  117  electroces. In the preferred embodiment ( FIG. 1  inset), the dimensions of individual nanotraces  118  range between 10 nm to about 100 nm in width  119  and depth  120  where the depth  120  is defined by the thickness of the originally deposited semiconducting active layer. More preferable, the width of each nanotrace is less than about 50 nm. Most preferable, the width of each nanotrace is less than about 20 nm. Pitch  121  between neighboring nanotraces  118  in the set of parallel nanotraces  115  can vary depending on the number of nanotraces  118  included in the set and the total surface area of the interdigitated finger region of source  116  and drain  117  electrodes. The number of nanotraces  118  can range from one to hundreds depending on the application. The length  122  of the semiconductor nanotraces  118  spans the full distance from the outside source interdigitated finger  116  to the outside drain interdigitated finger  117  of each sensor device  102 , crossing over all interdigitated fingers therebetween. 
         [0025]    When an external electric field is applied across drain electrode  103  and source electrode  104 , electrical current must travel through the set of parallel semiconductor nanotraces  115  to pass from the source electrode finger  116  to the drain electrode finger  117 . Because the width  119  of each semiconductor nanotrace  118  is on the order of the electrical diffusion pathway and the surface-to-volume ratio for each nanotrace  118  is large, the current traveling through each nanotrace  118  is highly influenced by its local environment  123  near the surface. The response is proportional to the degree in which the electrical current traversing the set of semiconductor nanotraces  115  is influenced by changes in the electric field strength near the surface of each nanotrace  118 . The local environment  123  can be a gas phase, e.g. an air plenum sampling for toxic gases, a solution environment e.g. and aqueous buffer sampling for complementary nucleic acids, or a solid environment e.g. an electrophoresis gel sampling for nucleotides on a nucleic acid sequence. The fabrication of a set of parallel nanotraces  115  serves to homogenize the total response to changes in local environment  123  since the total response is the average of the response of each nanotrace  118  connected in parallel between the interdigitated finger region of the source  116  and drain  117  electrodes. Averaging the response over a number of nanotraces  118  lowers the failure rate of sensor devices  102  during fabrication of the multiplex detection array  101 . Because each nanotrace  118  is in direct electrical contact with the interdigitated finger region of source  116  and drain  117  electrode, contact resistance  124  between the two materials must be kept low. The present embodiment depicted in  FIG. 1  shows a bottom contact approach for forming the electrical interface between semiconductor nanotrace  118  and the interdigitated finger region of source  116  and drain  117  electrodes, however, alternate methods which include top contact between the interdigitated finger region of source  116  and drain  117  electrodes can be used to make the electrodes. Because semiconductor nanotraces  118  are electrically continuous with the interdigitated finger region of the source  116  and drain  117  electrodes that work back to the source  109  and drain  114  electrode bonding pads through source  103  and drain electrode  104  and  104 B, the source-to-drain current can be measured externally through electrodes that make contact with source  109  and drain  114  electrode bonding pads, Electrical continuity from the bonding pads to an electrode is established using common techniques such as wire or bump bonding of the multiplex detection array  101  chip to an electronics board package (not shown in  FIG. 1 ). 
       Method for Patterning the Base Electrode Structures: 
       [0026]      FIGS. 2A-F  illustrate the series of fabrication steps for multiplex detection array  101  in preparation for binding of probe libraries specific to the type of test being performed. Initially, substrate  107  is used as a base for fabricating the array of sensor devices  102 ,  FIG. 2A . Suitable materials for substrate  107  include any semiconductor or insulating wafer such as glass, doped or undoped semiconductors e.g. silicon, or polymers. Substrates such as flexible polymer films or metal foils may also be used. A series of parallel, individually-addressable gate electrodes  105  are deposited on substrate  107 . If substrate  107  is semiconductor or electrically conducting, an insulating layer (not shown in  FIG. 2 ) may be deposited prior to deposition of gate electrode  105  on substrate  107  to provide a means to prevent shorting of gate electrodes  105  to the substrate. A suitable material for gate electrodes  105  is a tie layer of chromium or titanium (˜5 nm) and a gold electrode layer (˜40-100 nm). A suitable means to deposit gate electrode layer  105  is vacuum deposition and a suitable means to subsequently pattern gate electrodes  105  is standard lithography. In the embodiment illustrated in  FIG. 2A , each gate electrode  105  is common to an entire column of sensor devices that are subsequently deposited over gate electrode  105 . Each gate electrode  105  terminates at a gate electrode bonding pad  108  that are positioned in an area remote from any sensor devices  102 , depicted previously in  FIG. 1 , to enable facile connection with an external set of electrodes. 
         [0027]    After patterning of gate electrodes  105 , gate dielectric layer  106  is deposited by chemical vapor deposition. The thickness of the gate dielectric layer  106  is a balance between maximizing the field effect from gate electrode  105  and preventing electrical breakdown at too high of an electrical field. A suitable material for gate dielectric  106  is silicon dioxide and the thickness preferably ranges between 10 nm and 200 nm. The need for gate electrode  105  is dependent on the application of the multiplex detection array  101 . As an alternative to that depicted in  FIG. 2A , the gate electrode may be formed using standard ion implantation into substrate  107 , which is well known in the art. Another embodiment might include using the entire substrate  107  as a common gate electrode. This does not require deposition and patterning of the metal gate electrode  105  although gate dielectric  106  is always deposited. Similarly, in another embodiment, the need for gate electrode  105  might be removed altogether as the chemiresistive measurement of sensor devices  102  may occur without preconditioning of the electrical properties of semiconductor nanotraces  118  using the field from a gate electrode  105 . 
         [0028]    The example illustrated in  FIG. 2B  shows common gate electrode  105  positioned below the column of sensor devices  102  created by sensor devices  102 A and  102 D in multiplex detection array  101 . A continuous metallic layer is deposited over the surface of gate dielectric  106 . The electrode material is composed of a tie layer (˜5 nm of chromium or titanium) followed by a gold layer (˜40-100 nm). The electrode materials may be deposited by thermal evaporation, electron beam evaporation, or some suitable other process. After deposition, a photolithography processing step is performed using a standard photoresist layer that is exposed and developed to generate the gold features that compose segments of both the source  103  and drain  104  electrodes. As part of the pattern, the interdigitated finger region for both source  116  and drain  117  electrodes are developed in a single layer with source electrode fingers  116  contiguous with the common source electrode  103 . Source electrode  103  is also contiguous between the source side of each sensor device  102  for a given column. For example, the source electrode connects sensor devices  102 A and  102 D,  102 B and  102 E, and  102 C and  102 F in  FIG. 2B . Each source electrode  103  terminates at a source electrode bonding pad  109 . The source electrodes  103  are parallel with the gate electrodes  105  and terminate in an area remote from the sensor devices  102  in the multiplex detection array  101 . The position of the source electrode bonding pads  109  is offset from the gate electrode bonding pads  108  to accommodate the necessary steps to liberate the gate dielectric  106  above the gate electrode bonding pads  108 . Removal of a portion of the gate dielectric layer is illustrated as the gate electrode window  201  in  FIG. 2B . Grouping of the source electrode bonding pads  109  in this region provides a means for facile electrode connectivity to an external electronic board (not shown). 
         [0029]    The interdigitated fingers on the drain side  117  is contiguous with the first leg of drain electrode  104  which terminate with the drain electrode stub bonding pad  110  on each sensor device  102 . The drain electrode stub bonding pad  110  serves as a termination point for subsequent transfer of the drain electrical connection into a secondary electrode plane (described later). In addition to the deposition of the electrode structures  103  and  104 , alignment marks for aligning subsequent layers are also patterned into the gold electrode layer on the edges of multiplex detection array  101  that are not visible in  FIG. 2 . 
       Fabrication of the Semiconductor Nanotraces 
       [0030]    After fabrication of the base electrode layers, a semiconducting active layer is deposited over the entire wafer. Chemical vapor deposition, electron beam deposition or other suitable methods may be employed. Suitable materials for the semiconducting active layer are Group IV, III-V, and II-VI materials including tin oxide (SnO 2 ), indium oxide (In 2 O 3 ), and zinc oxide (ZnO) and other nitrides and chalcogenides. Using the method of nanoimprint lithography (NIL) and a series of dry etch processes, the semiconducting active layer is patterned into a set of parallel nanotraces  115  over the interdigitated finger region of the source  116  and drain  117  electrodes. A separate set of parallel nanotraces  115  are patterned over each sensor device  102 ,  FIG. 2C . Each nanotrace  118  in the set of nanotraces  115  is patterned such that the long axis of the nanotrace  122  runs parallel with the column of sensor devices  102  and perpendicular with the interdigitated finger region of the source  116  and drain  117  of the source  103  and drain  104  electrodes. 
         [0031]    Nanoimprint lithography is a special processing technique that enables nanodimension features to be patterned into the semiconducting active layer using a top down approach without the use of expensive stepper aligner tools. The dimensions of each semiconductor nanotrace  118  are critical for increasing the response sensitivity to a level that provides practical direct electrical transduction of target molecule binding. This is achieved because the surface-to-volume ratio of each semiconducting nanotrace  118  is large due to the small width  119  and depth  120  of the nanotrace  118  ( FIG. 1  Inset). Using nanoimprint lithography, nanotraces can be patterned with physical geometries that are comparable to the grain dimensions of the nanotraces  118 , making the molecular-semiconductor electronic interaction more pronounced. Nanodimension registration with the interdigitated finger regions of the source  116  and drain  117  is achieved using a nanoimprint processing tool such as Molecular Imprints Imprio 5500 (Austin, Tex.). Also noteworthy is that the distance between the gate electrode and the set of parallel nanotraces  115  is dictated by the thickness of layer  106  and is a known, regular distance for all of the nanotraces  118  in the set of parallel nanotraces  115 . This is in contrast to nanowire sensors where the distance between the active semiconductor nanowire and the electric field from gate electrode  105  can lead to background inhomogeneities in the response. The details of the method of nanoimprint lithography are defined further in the following sections of this description. 
       Developing the Electrical Architecture for Addressing Each Drain Electrode 
       [0032]    After fabrication of the set of parallel semiconducting nanotraces  115  over each sensor device  102 , the remainder of the drain electrodes  104 B is deposited,  FIG. 2D-F . Before addition of the drain electrode layer, a photoresist layer is spun over the entire surface and patterned,  FIG. 2D . The pattern includes “islands” of photoresist  202  that are designed to protect the set of parallel nanotraces  115 . Source  109  and gate  108  electrode bonding pads are also protected during the remaining fabrication steps of multiplex detection array  101  (not shown in  FIG. 2 ). Referring to  FIG. 2D , an insulating oxide layer  111  (˜50-100 nm) is first deposited over the entire wafer to insure that contiguous drain electrodes  104 B are electrically isolated from the underlying layer and do not electrically short to source electrodes  103 . Electrical continuity between drain electrode stub bonding pad  110  and the drain electrode layer  104 E is created by first patterning a series of “vias”  112  through the oxide insulating layer  111  directly over each drain electrode stub bonding pad  110 . Vias  112  are created using a dry etch process with a patterned photoresist layer as the etch stop. After complete etching of the oxide in the vias  112  is insured, a tie layer (˜5 nm) and gold layer (˜100-200 nm) are deposited over oxide insulating layer  111  to a thickness that insures complete filling of vias  112  and electrical continuity to the drain electrode continuity pad pickup  113  in the drain electrode layer  104 B. Wet etching of the gold/tie layers lead to the formation of drain electrodes  104 B that terminate at drain electrode bonding pads  114  in an area remote from the sensor devices  102 .  FIG. 2E  shows the final drain electrode pattern. Drain electrodes  104 B are perpendicular to source  103  and gate  105  electrodes in the underlying layer. Drain electrodes  104 B provide electrical continuity between all sensor devices  102  in each row.  FIG. 2E  shows an example where a drain electrode  104 B is electrically contiguous between sensor devices forming the row  102 A,  102 B,  102 C and a second drain electrode  104 B is contiguous across the row containing sensor devices  102 D,  102 E,  102 F. Each of the drain electrodes terminates at a separate drain electrode bonding pad  114  which can be connected to an external electrical monitoring device. 
       Preparing the Final Device for Microfluidic Coupling 
       [0033]    As a final measure, oxide protection layer  203  (˜100 nm) is deposited over the entire surface of multiplex detection array  101  as illustrated in  FIG. 2F . In order to recover the set of semiconductor nanotraces  115  over each sensor device  102  for further biomolecular or chemical coupling, final photoepoxy resist layer  204  is spin-coated and patterned over sensor devices  102  to provide a bonding face for a microfluidic cover plate. Photoepoxy resist layer  204  serves two purposes. First, photoepoxy resist layer  204  acts as the etch stop during the oxide dry etch which removes the oxide material back to protection islands  202  over the set of parallel nanotraces  115 . After patterning of the photoepoxy resist, a dry etch process is used to remove the silicon dioxide from the final oxide protection layer  203  and the oxide layer  111  in that order. This produces access windows  205  to the semiconducting nanotraces  115  over each sensor device  102 . 
         [0034]    Photoepoxy resist layer  204  also serves as the final bonding and interface layer that makes contact to the microfluidic cover plate (described later). After the dry etch of the oxide layers is complete over protection islands  202 , and protection islands  202  are stripped from the surface of the set of parallel semiconductor nanotraces  115 , a light piranha etch (1 part 30% H 2 O 2 : 3 parts concentrated H 2 SO 4 ) removes any residual organic residue from the surface of the set of semiconductor nanotraces  115  yielding a pristine semiconductor surface for covalent attachment of probe molecules. As a final measure, multiplex detection device  101  is treated with an oxygen ashing step 10-30 minutes at a pressure of 700 mTorr at a power of 300 W with O 2  flow of 8 sccm. Oxygen ashing leads to diffusion of O −  into the bulk lattice of the semiconducting nanotrace  118  surface and completes the stoichiometric ratios necessary to convert the nanotraces  118  into a suitable material for molecule coupling and direct electrical transduction. Oxygen ashing is carried out using an instrument such as a March Asher and is preceded by a thermal annealing step (10 min. at 200° C.) in ambient. 
       DETAILED DESCRIPTION OF THE METHOD OF NANOIMPRINT LITHOGRAPHY 
       [0035]    Fabrication of the set of parallel semiconductor nanotraces  115  is one of the core features of multiplex detection array  101 . To fabricate the set of parallel nanotraces  115 , the method of Nanoimprint Lithography (NIL) is employed. NIL was first described in the prior art by U.S. Pat. No. 6,334,960, which is hereby incorporated by reference herein.  FIGS. 3A-E  illustrate the process for preparing the nanoimprint features into the active semiconducting layer. The first step is to fabricate imprint template  301  that is a separate component to multiplex detection array  101 . Template  301  is composed of a quartz wafer that has been previously patterned using electron beam lithography. The method for making the imprint template is described in the prior art by U.S. Pat. No. 6,334,960. Briefly, the electron beam writes individual features into an e-beam photoresist which after development appears as grooves in the resist. The pattern is transferred into a thin chromium layer ˜30 nm thick using a dry etch process. The chromium layer is then used as a hard etch stop during a dry etch of the quartz wafer. The e-beam written features appear as “grooves”  302  in quartz template  301  with the desired pattern. The chromium layer is stripped leaving a transparent, nanopatterned quartz template  301  as a free-standing wafer. Quartz template  301  is shown above multiplex detection array  101  wafer in  FIG. 3A . For reference, the fabrication step of multiplex detection array  101  captured in  FIG. 3A  is that previously illustrated in  FIG. 2B . As a final measure, self-assembled “release” monolayer  303  is applied to the surface of template  301  by immersing template  301  into solution overnight followed by rinsing of excess. The fabrication of quartz template  301  is considered the “slow” step. Once fabricated, it can be used to make many copies of the nanoimprint pattern.  FIGS. 3B-E  show a cross-sectional view of the processing steps for preparing the set of parallel semiconductor nanotraces  115  using template  301 . Template  301  is a full wafer which contains multiple copies of multiplex detection device  101 , referred herein as the “die”. The design of multiplex detection device  101  is created such that all of the sets of parallel nanotraces  115  for every sensor device  102  in a multiplex detection array  101 , and all copies, or dies of the multiplex detection array  101  are fabricated during a single NIL process. However,  FIGS. 3A-E  illustrates a cross-sectional view of the NIL process sequence that occurs over only a single sensor device  102  in one of the multiplex detection device  101  dies. 
         [0036]    Initially, quartz template  301  is positioned such that grooves  302  are registered over the interdigitated finger region of the sensor devices  102 . As illustrated previously in FIG.  2 C, the parallel set of semiconductor nanotraces  115  is perpendicular to interdigitated finger region of the source  116  and drain  117  portions of the electrodes spanning the distance therebetween. A hard mask or back anti-reflection coating (BARC) layer  304  (˜60 nm) is deposited onto the device layer stack which, in this cross-section, consists of semiconductor active layer  305  (˜20-100 nm) on gate dielectric  106  (˜20-100 nm) which is on gate electrode  105  (˜40 nm) and supported by substrate wafer  107  (˜500 um). The cross-section view in  FIGS. 3A-E  represents a view that is parallel to interdigitated finger regions of the source  116  and drain  117  electrodes, but is in the space between adjacent source  116  and drain  117  fingers so they do not appear in this cross-sectional view. 
         [0037]    After BARC layer  304  is spun cast onto the device stack, photoresist dispenser  306  places droplets of SFIL or other suitable nanoimprint photoresist  307  onto BARC layer  304  which spreads into a continuous thin layer  308  onto the surface. Referring to  FIG. 3C , template  301  is brought into contact with photoresist  308 . Template  301  is angled onto layer  304 , so as to create a wave front of photoresist  308 . This wave front expels gas pockets, resulting in complete filling of grooves  302  of template  301 . Referring to  FIG. 3D , ultraviolet light rays  309  (˜300 W/cm 2 , 20 s) expose photoresist  308  through template  301 . Photoresist  308  reacts and polymerizes into rigid imprint layer  310 . After exposure, template  301  is moved from the surface, leaving hard imprint layer  310  which have sharp imprint features  311  that are the negative of grooves  302  in template  301 . The remaining area is a thin residual layer  312  between raised imprinted features  311 . Template  301  is released from hard imprint layer  310  under the assistance of release layer  303  on template  301 ,  FIG. 3E . 
         [0038]    After hard imprint features  311  are formed, the features are “transferred” into semiconductor active layer  305  using a series of dry etch processes,  FIGS. 4A-D . As a first step ( FIG. 4A ), a plasma dry etch system such as an Oxford Plasma Lab 80 RIE operating under a CHF 3 :O 2  environment (15 sccm CHF 3 , 7.5 sccm O 2 , p=25 mTorr) and a DC bias of ˜200 V was used to remove the residual silicon-containing SFIL polymer layer  312  at an etch rate of ˜30-40 nm/min. (˜50 s). A slight over-etch is used at this stage. This etch decreases the height of hard imprint features  311  while simultaneously removing residual layer  312 . The net effect of this etch is to reveal the surface of the BARC (organic) layer  304 . The next process is transfer of the pattern into the BARC layer using an organic dry etch of 100% O 2  (8 sccm, p=5 mTorr) and a DC bias of ˜200 V at an etch rate of 20-30 nm/min. (˜2 min. 15 s). The differential etch rate of the silicon-containing hard imprint layer  311  provides a means to selectively etch the BARC (organic) layer to the surface of semiconductor active layer  305 . The BARC layer  304  is used to smooth out small surface roughness in the wafer and make the final etch into the semiconductor active layer  305  more uniform. The geometry of the etched BARC features  401  under the hard imprint layer  311  is shown in  FIG. 4C . 
         [0039]    Referring to  FIG. 4D , a final plasma etch step consisting of an Ar:Cl 2  gas mixture (24 sccm Ar, 6 sccm Cl 2 , p=80 mTorr) at a bias of ˜200 V, and an etch rate of 10-15 nm/min. (˜1-3 mins. depending on the thickness of semiconductor active layer  305 ) is used to remove semiconductor active layer  305  and yield the set of parallel nanotraces  115 . Each semiconductor nanotrace  118  has the width  119 , depth  120 , and spacing  121  defined previously in  FIG. 2C . Alternatively, a hard mask layer, for example chromium, can be used if necessary to achieve the selectively and aspect ratio desired for semiconductor nanotraces  118 . As a final step,  FIG. 4E , etched hard imprint features  311  and etched BARC features  401  are removed using a piranha wet etch process. This process cleans the surface of semiconductor nanotraces  118  and prepares them for covalent attachment of probe molecules in later steps. 
         [0040]      FIG. 5  illustrates a High-Resolution Scanning Electron Microscope (HRSEM) cross-section micrograph of the process step just after nanoimprinting of the hard imprint features  311  over an example sensor device  102  ( FIG. 1 ) in multiplex detection array  101 . The photo micrographs are illustrative of the fabrication state depicted in  FIG. 4A  where base substrate  107 , a p-doped silicon wafer (˜500 μm) for example, is serving as gate electrode  105 . A silicon dioxide layer (˜100 nm) serves as gate dielectric  106  upon which the active semiconductor, SnO 2  layer  305  in this embodiment, is deposited (˜70 nm). A back anti-reflection layer  304 , Transpin™, is deposited on semiconductor active layer  305 , upon which final SFIL layer  308  is deposited and patterned with the alternating regions of raised hard imprint features  311  (˜150-300 in) and the thin residual layer  312  (˜20-80 nm). Width  501  and spacing  502  of hard imprint features  311  are equal to the final desired width  119  and depth  120  of the individual semiconductor nanotraces  118 . 
         [0041]      FIG. 6A  illustrates a HRSEM photomicrograph after the breakthrough etch of the BARC layer  304  to semiconductor active layer  305  (example of etch state represented by  FIG. 4C ). Access of the reactant gases to the surface of semiconductor  305  is illustrated as  601  in the figure. Additionally, residual organic debris  602  can be seen and the best results occur when the dry etch of BARC layer  304  is carried out to completion to remove these features.  FIG. 6B  illustrates the process after completion of the dry etch of semiconductor active layer  305  and stripping of the etched BARC layer  304  and etched hard imprint layer  311  (example of state in  FIG. 4E ). The embodiment of semiconductor nanotraces  118  illustrated in  FIG. 6B  includes a semiconductor nanotraces design with bridging segments  603  between each semiconductor nanotrace  118  in the set of parallel semiconductor nanotraces  115 . While the semiconductor nanotrace “mesh” embodiment is slightly altered from the previous illustration, ultimately the individual nanotraces  118  possess the same width  119  and spacing  120  of original hard imprint features  312 . The pattern is simply altered by selection of a different design written into the template  301 . After the process depicted in  FIG. 6B  is completed and the set of parallel nanotraces  115  are formed and cleaned free of organics, the multiplex detection array  101  is ready for deposition of the anchor probe library. 
       Synthesis of Anchor Probe Libraries on the Surface of the Active Semiconductor Nanotraces 
       [0042]    After fabrication of the electrical architecture of the multiplex detection device  101  illustrated previously in  FIG. 2 , the set of parallel semiconductor nanotraces  115  for each sensor device  102  is functionalized with a sensitizing compound.  FIGS. 7A-C  illustrate the steps for coupling the sensitizing compounds onto the surface of the parallel set of semiconductor nanotraces  115 . Generally, each of the semiconductor nanotraces  118  within each parallel set of semiconductor nanotraces  115  receives the same sensitizing compound. In contrast, each parallel set of semiconductor nanotraces  115  on different sensor devices  102  receives a different sensitizing compound making it uniquely responsive to external targets relative to neighboring sensor devices  102  in the multiplex detection array  101 . The collection of all the sensitizing compounds for a given multiplex detection device  101  is called the library. Different sensitization compounds from the library are added to each sensor device  102  by partitioning the sensor devices  102  into different reaction wells during coupling. Methods to segregate the different sensor devices  102  on multiplex detection device  101  during coupling of the sensitization compounds is described later. 
         [0043]    Generally, the sensitizing compounds consist of “probe” molecules that are covalently attached to the surface of the semiconductor nanotraces  118 . The probes have specific affinity for different targets. Methods that provide a means for parallel deposition of each anchored probe in the library onto the respective sets of parallel semiconductor nanotraces  115  and all of the sensor devices  102  in the multiplex detection array  101  during a single process is preferred. Generally, the specific anchored probes that are selected to be in the library of a given multiplex test are chosen based on known outcomes from individual sensor device and are representative of the type of test that is being performed. This simplest case consists of a single sensor device  102  that responds to a single or a plurality of specific targets. 
         [0044]    In the preferred embodiment described in  FIG. 7 , the probe molecules in the compound library are nucleic acid sequences that are designed to respond very specifically to the binding of the complementary sequence. In other embodiments, the anchored probes could be proteins that respond differentially when the binding of different antibodies occur. Similarly, polymers or other macromolecules that exclude or specifically bind different solution analytes or gas phase analytes can be used as the sensitizing compound which makes the sensor device  102  unique. In the embodiment where the probe library consists of short nucleic acid sequences (oligonucleotides), individual oligonucleotides can be synthesized directly from the surface of the semiconductor nanotraces  118 . A plurality of oligonucleotides can be synthesized onto the parallel set of semiconductor nanotraces on each sensor device using suitable methods such as PhotoGenerated Reagent (PGR) described in the prior art in U.S. Pat. No. 6,965,040, which is hereby incorporated by reference in its entirety. The method to deposit an anchor probe library of oligonucleotides using the method of PGR is illustrated in  FIG. 7A-C  and described below. 
         [0045]    Initially, multiplex detection device  101 , illustrated previously in  FIG. 2F , is enclosed with microfluidic coverplate  701 ,  FIG. 7A . Microfluidic plate  701  consists of a series of fluidic wells  702  (˜15 um in depth) that are connected by a network of fluidic channels  703  (−90 um in depth) that work back to a single entrance and exit port (not shown) where fluidic coupling is made externally to a fluid manifold. The fluidic network consists of both parallel and serial connections of individual fluid wells  702  via fluidic network of channels  703 . Microfluidic cover plate  701  can be glass or other suitable molded plastic component that provides a leak-tight seal between fluid wells  702 . Additionally, the fluidic cover plate wafer must be transparent to support photoactivation of certain reagents during optical irradiation using the method of PGR. Each microfluidic well  702  is designed to fully enclose a single sensor device  102  in multiplex detection array  101 . Each microfluidic well  702  provides a reaction center where photogenerated acid can diffuse throughout, but cannot cross into neighboring microfluidic wells  702 . While synthesis of nucleic acid anchor probes is illustrated as the preferred embodiment in  FIGS. 7A-C , other probe-specific classes such as proteins, small metabolites, nanoparticles, polymer nanospheres and other receptors for gas phases targets can also be deposited, or synthesized, depending on the application. Additionally, some of the sensor devices  102  in multiplex detection array  101  can be employed as references and controls. These sensor devices  102  would receive special sensitization compounds that may exclude, trap, or permit only a specific entity in the environment surrounding the semiconductor nanotraces  118 . Likewise, sensor devices  102  may be designed to bind known sequences spiked into the sample solution, for example, as a positive control. 
         [0046]      FIG. 7B  illustrates the state of the multiplex detection array  101  after completion of the method of PGR. At this point, the microfluidic cover plate  702  is removed and the net result is a multiplex detection array  101  where the set of parallel nanotraces  115  on each sensor device  102  has a unique anchor probe molecule  704  synthesized on the surface of all of the semiconductor nanotraces  118  in the set of parallel nanotraces  115 .  FIG. 7B  inset (i) illustrates that a plurality of copies of the same anchor probe oligonucleotide molecule  704  are synthesized from the surface of semiconductor nanotrace  118  and are limited only by the molecular packing density of the anchor probe molecules  704 . At the end of the PGR process, the semiconductor nanotraces  118  for each sensor device  102  possess anchor probe molecules  704  covalently coupled to the surface where, in this example, the anchor probe sequence  705  is unique to a single sensor device  102 . The unique anchor probe sequence  705 , FIG.  7 B(ii) for each sensor device  102  is dictated exclusively by the fluidic confinement of the PGR reagents within each microfluidic well  702  that enshroud the set of semiconductor nanotraces  115  on each sensor device  102 . The number of different or redundant anchor probes  704  in the multiplex detection array  101  library is limited only by the number of sensor devices  102  and corresponding microfluidic wells  702  designed in the microfluidic cover plate  701 . 
         [0047]    As a final measure, multiplex detection array  101  with anchored probes  704  is packaged onto electronics board  706 ,  FIG. 7C . Electrode bonding pads on multiplex detection device  101  are made contiguous with the electronics board  706  using a suitable technique such as wire or bump bonding. In the embodiment shown in  FIG. 7C , a wire bond  707  connection is made between gate electrode bonding pad  108  and gate electronics control lead  708 . Additionally, wire bond  709  between the source electrode bonding pad  109  and source electronics control lead  710 , and wire bond  711  between the drain electrode bonding pad  114  and drain electronics control lead  712  are made. Some level of embedded logic is also included on the electronics board  706  (not shown) that enables multiplex signal acquisition, processing and results determination. 
       Detection of the Target Molecules 
       [0048]    In the case of the preferred embodiment described above, the multiplex detection array  101  would be packaged within a common fluidic-tight vessel (not shown) that serves as the sample fluid reaction chamber which brings together the sample fluid with the multiplex detection array  101 . For example, in the case of a diagnostic test for a virulent pathogen, the target nucleic acid sequence would bind with its complementary anchored probe oligonucleotide sequence  705  on one of the sensor devices  102  in the multiplex detection array  101 . The sensor device  102  that bears the matching anchored probe oligonucleotide sequence  705  that is complementary to the target would incur a change in the source-drain electrical current which would be measured in the external circuit. A temperature controller device can be used to insure that the conditions for optimum binding affinity are achieved during reaction. A solid state cooler/heater device such as a thermoelectric cooler, for example, may be used in the instrument and pushed up against the cartridge when it is inserted into the instrument. Signal processing from the embedded control logic would then indicate to the user that the presence of the target nucleic acid sequence corresponding to a match with the known anchor probe sequence  705  was present in the sample. The result would be displayed on a digital display device that is part of the analysis instrument. The user would then determine a course of action based on the result of the diagnostic test. In the simplest case, a single sensor device  102  is used to determine the identity of an unknown target. The multiplex detection array  101  is designed to assess the presence of a single or plurality of targets during a single sample introduction onto multiplex detection array  101 . The embedded control logic makes a continuous measurement of the current in all of the sensor, reference and control devices  102  in the multiplex detection array  101 . 
         [0049]    In alternate embodiments, the anchored probe oligonucleotide would be designed to look for a specific sequence that had been expressed such as RNA, or DNA that is specific to a particular organism. In other embodiments, the anchor probes may be nucleic acid sequences that have been selected based on a specific affinity to a target molecule or entity on a surface, e.g. a cell wherein the anchored probe sequence coils into a 3D conformation that interacts with the target in the form of an aptamer. In another embodiment, the anchor probe molecule may be a protein that has a specific affinity for a target protein or antigen, or the anchor probe molecule may be a small molecule that has a specific affinity for another molecule or ion in solution. 
         [0050]      FIG. 8A-B  illustrates the chemical binding effect of targets to the anchor probe molecules  704  on multiplex detection array  101 . In this embodiment, anchor probes  704  synthesized on the surface of semiconductor nanotraces  118  display a baseline current  801  that is measured and recorded prior to introduction of target molecules  802 ,  FIG. 8B . Upon addition of target molecule  802  to the fluid space above sensor device  102  ( FIG. 8B ), and if the target sequence  802  matches the anchor probe sequence  705  on any given sensor device  102  in the multiplex detection array  101 , it will hybridize with the surface complement. Upon hybridization, the current traveling through the semiconductor nanotrace  118  will change at the point indicated by  803 . Because anchor probe sequence  705  of sensor device  102  that undergoes a change in current is known, the identity of the unknown target sequence  802  can be made. The change in the current will be a new value  804  that indicates the presence of target  802 . The magnitude and direction of the change in current is indicative of the concentration of target, nature of the surface interaction, local electric field and properties of the semiconductor nanotraces. The properties of the semiconductor nanotraces can be influenced by the doping level, external field applied by the gate electrode and other things that can affect or change the majority carrier concentration and mobility. 
         [0051]    Although the present invention has been described with reference to specific details, it is not intended that such details should be regarded as limitations of the scope of the invention, except as and to the extent that they are included in the accompanying claims.

Technology Classification (CPC): 7