Patent Publication Number: US-2018038830-A1

Title: Nanopore-based dna sensing device with negative capacitance for improved dna sensing signal

Description:
INTRODUCTION 
     Aspects of this disclosure relate generally to sensing devices for deoxyribonucleic acid (DNA), and more particularly to methods and apparatuses for improving the DNA sensing signal of nanopore-based DNA sensing devices. 
     DNA, sometimes referred to as the “blueprint of life”, is a molecule that stores biological information. The structure of DNA, famously discovered by James Watson and Francis Crick, consists of two strands of biopolymer, coiled around one another to form a double helix. Each strand is a polynucleotide that includes a plurality of nucleotides, for example, cytosine (“C”), guanine (“G”), adenine (“A”), and thymine (“T”). Each nucleotide in a first strand of DNA may be bonded to a paired nucleotide in the second strand, thereby forming a base pair. Generally, cytosine and guanine are paired to form a “G-C” or “C-G” base pair, and adenine and thymine are paired to form an “A-T” or “T-A” base pair. 
     Although the structure of DNA is now known, new methods for analyzing individual DNA molecules are still being developed. Generally, the analysis includes ‘reading’ the nucleotide sequence of a particular DNA strand. In one method, known as nanopore DNA sequencing, a nanopore is immersed in a conductive fluid, and a voltage is applied across the nanopore. As a result, ions are conducted through the nanopore, thereby generating a measurable electric current. A DNA strand is then transmitted through a nanopore, one nucleotide at a time. The presence of a nucleotide within the nanopore disrupts the conduction of the ions, thereby causing a change in the electric current. Moreover, the change in electrical current due to a particular nucleotide differs from the change in electrical current due to other nucleotides. Accordingly, an entire DNA strand can be transmitted through the nanopore and each nucleotide in the strand can be identified based on the change in current. Over time, the changes in electric current result in a DNA sensing signal reflecting the particular nucleotides in a particular DNA strand. 
     As nanopore DNA sequencing improves, new challenges are presented. For example, a capacitance may arise within the DNA sensing device. The capacitance may limit the bandwidth of the DNA sensing signal by reducing the maximum cutoff frequency. The capacitance may also increase a noise component of the DNA sensing signal. As a result, new technologies are needed for improving the DNA sensing signal of nanopore-based DNA sensing devices. 
     SUMMARY 
     Techniques for increasing the lifetime of nanopore-based DNA sensing devices are disclosed. 
     In one example, a DNA sensing device is disclosed. The DNA sensing device may include, for example, a first electrode, a second electrode, a hydrophobic layer having a nanopore disposed therein, and a negative capacitance layer. 
     In another example, a method of fabricating a DNA sensing device is disclosed. The method of fabricating a DNA sensing device may include, for example, providing a first electrode, providing a second electrode, providing a hydrophobic layer, disposing a nanopore in the hydrophobic layer, and providing a negative capacitance layer. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The accompanying drawings are presented to aid in the description of various aspects of the disclosure and are provided solely for illustration of the aspects and not limitation thereof. 
         FIG. 1  generally illustrates a DNA sensor array in accordance with aspects of the disclosure. 
         FIG. 2  generally illustrates a nanopore-based DNA sensing device in accordance with an aspect of the disclosure. 
         FIG. 3  generally illustrates the separation and/or combination of a double-stranded DNA molecule. 
         FIG. 4A  generally illustrates a circuitry model associated with the nanopore-based DNA sensing device of  FIG. 2 . 
         FIG. 4B  generally illustrates a circuitry model with negative capacitance in accordance with aspects of the disclosure. 
         FIG. 5  generally illustrates a DNA sensing device with a negative capacitor in accordance with aspects of the disclosure. 
         FIG. 6A  generally illustrates a negative capacitor in accordance with aspects of the disclosure. 
         FIG. 6B  generally illustrates a negative capacitor in accordance with other aspects of the disclosure. 
         FIG. 6C  generally illustrates a negative capacitor in accordance with yet other aspects of the disclosure. 
         FIG. 7  generally illustrates a method for fabricating the DNA sensing device of  FIG. 5 . 
         FIG. 8  generally illustrates another DNA sensing device with a negative capacitor in accordance with other aspects of the disclosure. 
         FIG. 9A  generally illustrates a negative capacitor in accordance with yet other aspects of the disclosure. 
         FIG. 9B  generally illustrates a negative capacitor in accordance with yet other aspects of the disclosure. 
         FIG. 9C  generally illustrates a negative capacitor in accordance with yet other aspects of the disclosure. 
         FIG. 10  generally illustrates a method for fabricating the DNA sensing device of  FIG. 8 . 
         FIG. 11A  generally illustrates the DNA sensing device of  FIG. 8  in a first stage of fabrication. 
         FIG. 11B  generally illustrates the DNA sensing device of  FIG. 8  in a second stage of fabrication. 
         FIG. 11C  generally illustrates the DNA sensing device of  FIG. 8  in a third stage of fabrication. 
         FIG. 11D  generally illustrates the DNA sensing device of  FIG. 8  in a fourth stage of fabrication. 
         FIG. 11E  generally illustrates the DNA sensing device of  FIG. 8  in a fifth stage of fabrication. 
     
    
    
     DETAILED DESCRIPTION 
     The present disclosure relates generally to a method and apparatus for increasing the lifespan of a nanopore DNA sensing device. 
     More specific aspects of the disclosure are provided in the following description and related drawings directed to various examples provided for illustration purposes. Alternate aspects may be devised without departing from the scope of the disclosure. Additionally, well-known aspects of the disclosure may not be described in detail or may be omitted so as not to obscure more relevant details. 
     Those of skill in the art will appreciate that the information and signals described below may be represented using any of a variety of different technologies and techniques. For example, data, instructions, commands, information, signals, bits, symbols, and chips that may be referenced throughout the description below may be represented by voltages, currents, electromagnetic waves, magnetic fields or particles, optical fields or particles, or any combination thereof, depending in part on the particular application, in part on the desired design, in part on the corresponding technology, etc. 
     Further, many aspects are described in terms of sequences of actions to be performed by, for example, elements of a computing device. It will be recognized that various actions described herein can be performed by specific circuits (e.g., Application Specific Integrated Circuits (ASICs)), by program instructions being executed by one or more processors, or by a combination of both. In addition, for each of the aspects described herein, the corresponding form of any such aspect may be implemented as, for example, “logic configured to” perform the described action. 
       FIG. 1  generally illustrates a DNA sensor array  100  in accordance with aspects of the disclosure. 
     The DNA sensor array  100  may include a plurality of DNA sensing cells  110 . The plurality of DNA sensing cells  110  may be arranged in rows and columns to form a grid pattern. The DNA sensor array  100  may further include a row scanner  120  and a column reader  130 . The row scanner  120  and column reader  130  may facilitate the reading of a particular DNA sensing cell  110  from among the plurality of DNA sensing cells  110 . 
     Each DNA sensing cell  110  may include a DNA sensing device  112  and an amplifier  114 . As will be described in greater detail below, the DNA sensing device  112  may dynamically generate an electric current as a DNA strand is transmitted through a nanopore in the DNA sensing device  112 . Over time, the changes in electric current result in a DNA sensing signal reflecting the particular nucleotides in a particular DNA strand. The amplifier  114  may facilitate amplification of the DNA sensing signal. 
       FIG. 2  generally illustrates a pair  200  of nanopore-based DNA sensing devices  201 ,  202  in accordance with aspects of the disclosure. The DNA sensing devices  201 ,  202  may be analogous to the DNA sensing device  112  depicted in  FIG. 1 . The DNA sensing devices  201 ,  202  may be formed on a substrate  210  and at least partially within an insulator  220 . The substrate  210  may include, for example, silicon (Si) and the insulator  220  may include, for example, silicon oxide (SiO 2 ), silicon mononitride (SiN), a hydrophilic material, any combination thereof, or any other suitable material(s). The DNA sensing devices  201 ,  202  may be disposed in adjacent DNA sensing cells analogous to the DNA sensing cells  110  depicted in  FIG. 1 . The DNA sensing devices  201 ,  202  depicted in  FIG. 2  may be substantially similar to one another. Accordingly, the particular components of only one nanopore-based DNA sensing device will be described below. 
     The DNA sensing device  202  may include a semiconductor device  212  disposed on the substrate  210 . The semiconductor device  212  may include, for example, a complementary metal oxide semiconductor (CMOS) transistor. The semiconductor device  212  may be a component of an amplifier analogous to the amplifier  114  depicted in  FIG. 1 . The insulator  220  may include a via  222  in contact with the semiconductor device  212 . The via  222  may include, for example, copper (Cu), tungsten (W), aluminum (Al), any combination thereof, or any other suitable material(s). 
     The DNA sensing device  202  further includes a first electrode  230  in contact with the via  222 . The first electrode  230  may be disposed on or within the insulator  220 . The first electrode  230  may include an adhesion/diffusion layer  234 , a conductive layer  236 , and a surface layer  238 . 
     As an example, the adhesion/diffusion layer  234  may include a chromium (Cr) adhesion layer in contact with the via  222  and a gold (Au) diffusion layer between the conductive layer  236  and the Cr adhesion layer. Additionally or alternatively, the adhesion/diffusion layer  234  may include titanium nitride (TiN) and/or any other suitable material(s). The conductive layer  236  may include silver (Ag), however, it will be understood that any suitable material may be selected. The surface layer  238  may include silver chloride (AgCl), however, it will be understood that any suitable material(s) may be selected. 
     The DNA sensing device  202  further includes a separation layer  250  having a nanopore  252  embedded therein. The separation layer  250  may include a barrier layer  254  and a hydrophobic layer  256 . The barrier layer  254  may include silicon nitride (Si 3 N 4 ), however, it will be understood that any suitable material(s) may be selected. The hydrophobic layer  256  may include a lipid bilayer, a hydrophobic membrane, or any other suitable material(s). 
     The DNA sensing device  202  further includes a chamber  260 . The chamber  260  may hold a conductive fluid therein. The conductive fluid may include, for example, one or more electrolytes, for example, chlorine electrolyte (Cr), potassium electrolyte (K+), hydrogen electrolyte (H+), or any other suitable material. The conductive fluid within the chamber  260  may be divided by the separation layer  250  or a component thereof (for example, the barrier layer  254  and the hydrophobic layer  256 ) into a first subchamber  261  and a second subchamber  262 . 
     The DNA sensing device  202  may further include a second electrode  270 . The second electrode  270  may be disposed on the separation layer  250 . The second electrode  270  may include a conductive layer  276  and a surface layer  278 . The conductive layer  276  and the surface layer  278  may be analogous to the conductive layer  236  and the surface layer  238  of the first electrode  230 . The first electrode  230  may be coupled to a voltage source  280  via a first conductor  281  and the second electrode  270  may be coupled to the voltage source  280  via a second conductor  282 . 
     Fluid in the first subchamber  261  may be in contact with the surface layer  238  of the first electrode  230 , and fluid in the second subchamber  262  may be in contact with the surface layer  278  of the second electrode  270 . In the DNA sensing device  202  of  FIG. 2 , the first subchamber  261  may be a positive chamber (i.e., associated with a trans-electrode) and the second subchamber  262  may be a negative chamber (i.e., associated with a cis-electrode), but it will be understood that the polarity of subchambers  261 ,  262  may be reversed. 
     Although the chamber  260  is depicted as a closed chamber, it will be understood that this is optional. For example, the chamber  260  may be an open chamber. Moreover, as will be discussed in greater detail below, the chamber  260  may include enough conductive fluid to fill the first subchamber  261  and cover the second electrode  270 . 
       FIG. 3  generally illustrates a detail of the nanopore  252  of  FIG. 2  in accordance with an aspect of the disclosure. The nanopore  252  may be a biological nanopore. As noted above, the nanopore  252  may be embedded in the separation layer  250 , and the separation layer  250  may separate the first subchamber  261  from the second subchamber  262 . As noted previously, the separation layer  250  may include a lipid bilayer, a hydrophobic membrane, or any other suitable material(s). 
     The nanopore  252  may include, for example, a translocator  258  and an assembler  259 . The translocator  258  permits fluid communication (for example, passage of conductive fluid) between the first subchamber  261  and the second subchamber  262 . For example, if the second subchamber  262  is negatively charged and the first subchamber  261  is positively charged, then negative ions (for example, Cl − ) may pass from the second subchamber  262  to the first subchamber  261  via the translocator  258  and/or positive ions (for example, K +  and/or H + ) may pass from the first subchamber  261  to the second subchamber  262 . In some implementations, the translocator  258  may include alpha hemolysin. 
     The assembler  259  may separate a double-stranded DNA molecule  300  into a first DNA strand  301  and a second DNA strand  302  and/or combine the first DNA strand  301  and the second DNA strand  302  into the double-stranded DNA molecule  300 . In some implementations, the assembler  259  may include DNA polymerase. 
       FIG. 3  generally illustrates the separation and/or combination of a double-stranded DNA molecule  300 . For example, the double-stranded DNA molecule  300  may move from the second subchamber  262  into the assembler  259 , where it is separated by the assembler  259  into the first DNA strand  301  and the second DNA strand  302 . The first DNA strand  301  may be led into the translocator  258  and translocated across the separation layer  250 , from the second subchamber  262  to the first subchamber  261 . As another example, the first DNA strand  301  may be drawn from the first subchamber  261  through the translocator  258  and into the assembler  259 , where it is combined with the second DNA strand  302  into the double-stranded DNA molecule  300 . The double-stranded DNA molecule  300  may then be moved into the second subchamber  262 . 
     In some implementations, the following method may be used to perform DNA sequencing using the DNA sensing device  202  of  FIG. 2  and the nanopore  252  of  FIG. 3 . First, a voltage may be applied to the first electrode  230  and the second electrode  270  via the first conductor  281  and the second conductor  282 , respectively. As a result, a positive charge may appear on the first electrode  230  and a negative charge may appear on the second electrode  270 . 
     As an example, the second electrode  270  may include a surface layer  278  including AgCl and a conductive layer  276  including Ag. When the voltage V is applied (such that the second electrode  270  is negatively charged), the AgCl in the second electrode  270  may be converted into Ag and chlorine electrolytes, i.e., AgCl(s)+e − →Ag(s)+Cl − . As the second electrode  270  generates Cl −  ions, the second subchamber  262  may become negatively charged. 
     Moreover, the first electrode  230  may include a surface layer  238  including AgCl and a conductive layer  236  including Ag. When the voltage V is applied (such that the first electrode  230  is positively charged), the Ag in the first electrode  230  may combine with Cl −  ions in the first subchamber  261 , i.e., Ag(s)+Cl + →AgCl(s)+e − . As the first electrode  230  combines Cl −  ions into AgCl, the first subchamber  261  may become positively charged. 
     As a result, ions in the chamber  260  may have a tendency to flow toward either the first subchamber  261  (which is positively charged) or the second subchamber  262  (which is negatively charged). For example, Cl −  ions in the chamber  260  (including Cl −  ions generated at the second electrode  270 ) may have a tendency to flow toward the positively-charged first subchamber  261 . 
     As the first electrode  230  generates electrons e − , an electrical current i PORE  may flow through the via  222  to the semiconductor device  212 . 
     Because Cl −  ions may have a tendency to flow toward the positively-charged first subchamber  261 , the Cl −  ions may translocate across the separation layer  250  via the nanopore  252 . However, the nanopore  252  may also be configured to translocate DNA (for example, the first DNA strand  301 , as shown in  FIG. 3 ). 
     As the first DNA strand  301  shown in  FIG. 3  is being translocated, it may impede the flow of Cl −  ions through the nanopore  252 . As a result, the current i PORE  may be reduced due to the translocation of the first DNA strand  301 . Moreover, different types of nucleotide may have different effects on the flow of Cl −  ions through the nanopore  252 . 
     Accordingly, as different types of nucleotide pass through the nanopore  252 , different quantities of Cl −  ions may pass through the nanopore  252 , and a different electrical current i PORE  may be measured at the semiconductor device  212 . For example, a C nucleotide may cause a current i C , an A nucleotide may cause a current i A , a T nucleotide may cause a current i T , and a G nucleotide may cause a small current i G . As the first DNA strand  301  passes through the nanopore  252 , the DNA sensing device  202  will generate a current waveform i PORE (t) that indicates the sequence of nucleotides in the first DNA strand  301 . 
       FIG. 4A  generally illustrates a circuitry model  400 A associated with the nanopore-based DNA sensing device  202  of  FIG. 2 . 
     The circuitry model  400  may include a voltage source  480 , a first conductor  481 , and a second conductor  482 . The voltage source  480 , the first conductor  481 , and the second conductor  482  may be analogous to the voltage source  280 , the first conductor  281 , and the second conductor  282  depicted in  FIG. 2 . As shown in  FIG. 2 , the first conductor  281  and the second conductor  282  may be coupled to the first electrode  230  and the second electrode  270 , respectively, thereby causing a flow of ions from the first subchamber  261  to the second subchamber  262 , or vice-versa. 
     The flow of ions between the first subchamber  261  to the second subchamber  262  may be affected by resistances and/or capacitances associated with various components of the DNA sensing device  202  depicted in  FIG. 2 . For example, a first electrolyte resistance  461  and a second electrolyte resistance  462  may represent a resistance to ion flow associated with the first subchamber  261  and the second subchamber  262 , respectively. A barrier layer capacitance  454   c  and a barrier layer resistance  454   r  may represent a capacitance of and resistance to ion flow associated with the barrier layer  254 , one or more components thereof, other elements of the DNA sensing device  202 , or any combination thereof. A pore resistance  452  may represent a resistance to ion flow associated with the nanopore  252 . A membrane capacitance  456  may represent a capacitance of ion flow associated with the hydrophobic layer  256 . 
     The resistances and capacitances depicted in the circuitry model  400 A of  FIG. 4A  may limit the bandwidth of a DNA sensing signal associated with the DNA sensing device  202  by reducing the maximum cutoff frequency of the DNA sensing signal and increasing ionic current noise within the DNA sensing signal. 
     For example, the maximum cutoff frequency may be inversely proportional to 2πRC, where R is the total resistance associated with the circuitry model  400  and C is the total capacitance of the circuitry model  400 . As an example, the first electrolyte resistance  461  and the second electrolyte resistance  462  may be in the range of 0.1-1.0 kΩ, the pore resistance  452  may be equal to or on the order of 1.0 GΩ, and the membrane capacitance  456  may be in the range of 18-30 fF. The effects associated with the barrier layer capacitance  454   c  and the barrier layer resistance  454   r  may be negligible by comparison to the effects of the aforementioned resistances and capacitances, resulting in a cutoff frequency equal to or on the order of 5.5 KHz. 
     In some implementations, the optimal cutoff frequency may be equal or nearer to the cutoff frequency associated with the supporting electronics associated with, for example, the DNA sensor array  100  and/or the DNA sensing device  202 . For example, in some implementations, the cutoff frequency associated with the DNA sensor array  100  and/or the DNA sensing device  202  may be equal to or on the order of 100 KHz. In such an implementation, it may be advantageous to increase the cutoff frequency associated with the circuitry model  400 . 
       FIG. 4B  generally illustrates a circuitry model  400 B with negative capacitance in accordance with aspects of the disclosure. 
     As noted above with respect to  FIG. 4A , the DNA sensing device  202  depicted in  FIG. 2  may be associated with resistances and capacitances that decrease the maximum cutoff frequency and increase the noise associated with the DNA sensing device  202 . Accordingly, new technologies are needed for improving the DNA sensing signal of nanopore-based DNA sensing devices. 
     In accordance with aspects of the disclosure, a negative capacitance  490  may be added to the circuitry model  400 A (as depicted in  FIG. 4A ) to provide the circuitry model  400 B (as depicted in  FIG. 4B ). The negative capacitance  490  may offset the positive capacitances associated with the barrier layer capacitance  454   c,  the membrane capacitance  456 , or any combination thereof. For example, if the combined capacitance of the membrane capacitance  456  and the barrier layer capacitance  454   c  is equal to 30 fF, then a negative capacitance  490  of −30 fF may be added in parallel with the membrane capacitance  456  and the barrier layer capacitance  454   c.  The effect of the negative capacitance  490  may be to increase the maximum cutoff frequency and/or decrease noise. 
       FIG. 5  generally illustrates a DNA sensing device  500  with a negative capacitance layer  590  in accordance with aspects of the disclosure. The DNA sensing device  500  may have a number of components that are analogous to the components of the DNA sensing device  202 . For example, the DNA sensing device  500  may include a substrate  510 , a semiconductor device  512 , an insulator  520 , a via  522 , a first electrode  530 , an adhesion/diffusion layer  534 , a conductive layer  536 , a surface layer  538 , a separation layer  550 , a nanopore  552 , a barrier layer  554 , a hydrophobic layer  556 , a chamber  560 , a first subchamber  561 , a second subchamber  562 , a second electrode  570 , a conductive layer  576 , a surface layer  578 , a voltage source  580 , a first conductor  581 , and a second conductor  582 . These elements depicted in  FIG. 5  may be analogous in some respects to the substrate  210 , the semiconductor device  212 , the insulator  220 , the via  222 , the first electrode  230 , the adhesion/diffusion layer  234 , the conductive layer  236 , the surface layer  238 , the separation layer  250 , the nanopore  252 , the barrier layer  254 , the hydrophobic layer  256 , the chamber  260 , the first subchamber  261 , the second subchamber  262 , the second electrode  270 , the conductive layer  276 , the surface layer  278 , the voltage source  280 , the first conductor  281 , and the second conductor  282  depicted in  FIG. 2 . For brevity, only the differences will be described. 
     As noted above with respect to  FIG. 4B , the negative capacitance  490  may be added to the circuitry model  401  in parallel with the membrane capacitance  456  and the barrier layer capacitance  454   c.  The effect of the negative capacitance  490  may be to increase the maximum cutoff frequency and/or decrease noise. Accordingly,  FIG. 5  depicts a negative capacitance layer  590  disposed between the first electrode  530  and the second electrode  570 . The negative capacitance layer  590  may constitute means for causing a negative capacitance. For example, the DNA sensing device  500  may include a via  592  (analogous to the via  522 ) that couples at least a portion of the first electrode  530  to a first terminal of the negative capacitance layer  590  and at least a portion of the second electrode  570  to a second terminal of the negative capacitance layer  590 . The via  592  may traverse at least a portion of the insulator  520 , at least a portion of the separation layer  550 , at least a portion of the barrier layer  554 , or any combination thereof. For example, as depicted in  FIG. 5 , the via  592  may couple the negative capacitance layer  590  to the adhesion/diffusion layer  534  of the first electrode  530  and the conductive layer  576  of the second electrode  570 . 
     As will be understood from  FIG. 5 , by disposing the negative capacitance layer  590  between the first electrode  530  and the second electrode  570 , the capacitance associated with the DNA sensing device  500  may be offset, thereby increasing the maximum cutoff frequency of the DNA sensing device  500  and/or decreasing noise associated with the DNA sensing device  500 . The negative capacitance layer  590  may include any suitable material(s). For example, the negative capacitance layer  590  may include a strontium titanate layer, a strontium ruthenate layer, a barium titanate layer, a lead zirconate titanate layer, a lanthanum strontium manganite layer, or any combination thereof. 
       FIGS. 6A-6C  generally illustrate three alternative arrangements for implementing a negative capacitance layer analogous to the negative capacitance layer  590  depicted in  FIG. 5 . In each arrangement, the negative capacitance layer is disposed within the via  592  depicted in  FIG. 5 . 
       FIG. 6A  generally illustrates a negative capacitance layer  690 A in accordance with aspects of the disclosure. The negative capacitance layer  690 A may constitute means for causing a negative capacitance. The negative capacitance layer  690 A may be disposed within the via  592  depicted in  FIG. 5  and may include a plurality of sublayers, as will be described in greater detail below. Opposing surfaces of the negative capacitance layer  690 A may be coupled to the via  592  through a pair of adhesion/diffusion barriers  610 . The opposing surfaces may constitute a first terminal and a second terminal of the negative capacitance layer  690 A. The adhesion/diffusion barriers  610  may be constructed of any suitable material, for example, titanium (Ti), titanium nitride (TiN), or any combination thereof. 
     Between the pair of adhesion/diffusion barriers  610 , the negative capacitance layer  690 A may include a strontium titanate layer  630  (for example, chemical compound SrTiO 3 ) coupled to a strontium ruthenate layer  640  (for example, chemical compound SrRuO 3 ). The strontium titanate layer  630  may be coupled to a first adhesion/diffusion barrier of the pair of adhesion/diffusion barriers  610  and the strontium ruthenate layer  640  may be coupled to a second adhesion/diffusion barrier of the pair of adhesion/diffusion barriers  610 . 
       FIG. 6B  generally illustrates a negative capacitance layer  690 B in accordance with aspects of the disclosure. The negative capacitance layer  690 B may constitute means for causing a negative capacitance. The negative capacitance layer  690 B may be disposed within the via  592  depicted in  FIG. 5  and may include a plurality of sublayers, as will be described in greater detail below. Opposing surfaces of the negative capacitance layer  690 B may be coupled to the via  592  through the pair of adhesion/diffusion barriers  610  described above. The opposing surfaces may constitute a first terminal and a second terminal of the negative capacitance layer  690 B. 
     Like the negative capacitance layer  690 A, the negative capacitance layer  690 B may include a strontium titanate layer  630  coupled to a strontium ruthenate layer  640 . Moreover, the strontium ruthenate layer  640  may be coupled to a second adhesion/diffusion barrier of the pair of adhesion/diffusion barriers  610 . However, unlike the negative capacitance layer  690 A, the negative capacitance layer  690 B may include a barium titanate layer  650  (for example, chemical compound BaTiO 3 ) between the strontium titanate layer  630  and the first adhesion/diffusion barrier of the pair of adhesion/diffusion barriers  610 . 
       FIG. 6C  generally illustrates a negative capacitance layer  690 C in accordance with aspects of the disclosure. The negative capacitance layer  690 C may constitute means for causing a negative capacitance. The negative capacitance layer  690 C may be disposed within the via  592  depicted in  FIG. 5  and may include a plurality of sublayers, as will be described in greater detail below. Opposing surfaces of the negative capacitance layer  690 C may be coupled to the via  592  through the pair of adhesion/diffusion barriers  610  described above. The opposing surfaces may constitute a first terminal and a second terminal of the negative capacitance layer  690 C. 
     Like the negative capacitance layer  690 A, the negative capacitance layer  690 C may include a strontium titanate layer  630 . The negative capacitance layer  690 C may further include a lead zirconate titanate layer  660  (for example, chemical compound PbZrTiO 3 ) and a lanthanum strontium manganite layer  670  (for example, chemical compound LSMO). The lead zirconate titanate layer  660  may be coupled to a first adhesion/diffusion barrier of the pair of adhesion/diffusion barriers  610  and the strontium titanate layer  630  may be coupled to a second adhesion/diffusion barrier of the pair of adhesion/diffusion barriers  610 . The lanthanum strontium manganite layer  670  may be disposed between and in contact with the lead zirconate titanate layer  660  and the strontium titanate layer  630 . 
       FIG. 7  generally illustrates a method  700  for fabricating the DNA sensing device of  FIG. 5 . 
     At  710 , the method  700  provides the first electrode  530 . As will be understood from  FIG. 5 , the first electrode  530  may be disposed on or within the insulator  520 . Moreover, the first electrode  530  or a portion thereof (for example, the adhesion/diffusion layer  534 ) may be electrically coupled to the semiconductor device  512  through the via  522 . As depicted in  FIG. 5 , a portion of the first electrode  530  may be disposed beneath a cavity within the insulator  520  which is to form the first subchamber  561 . Moreover, another portion of the first electrode  530  (for example, the adhesion/diffusion layer  534 ) may be disposed such that it is not beneath the cavity. 
     At  720 , the method  700  provides the via  592  to the first electrode  530 . As depicted in  FIG. 5 , the via  592  may be disposed through the insulator  520 , the separation layer  550 , or any combination thereof. Moreover, the via  592  may disposed such that it extends to the adhesion/diffusion layer  534  of the first electrode  530 . 
     At  730 , the method  700  provides the negative capacitance layer  590 . 
     At  732 , the method  700  optionally disposes the negative capacitance layer  590  in the via  592  such that a first terminal of negative capacitance layer  590  is configured to be in electrical contact with the first electrode  530  and a second terminal of the negative capacitance layer  590  is configured to be in electrical contact with the second electrode  570 . For example, the via  592  may be filled with conductive material including a first portion of conductive material configured to electrically couple a bottom surface of the negative capacitance layer  590  with the first electrode  530  and a second portion of conductive material configured to electrically couple a top surface of the negative capacitance layer  590  with the second electrode  570 . 
     At  740 , the method  700  provides the second electrode  570 . The second electrode  570  may be disposed on the separation layer  550  or a portion thereof (for example, the barrier layer  554 . The barrier layer  554  may itself be disposed, at least in part, on the insulator  520 . At least a portion of the second electrode  570  may be disposed above at least a portion of the first electrode  530 . Moreover, at least a portion of the second electrode  570  may be disposed above the via  592 . As noted above, the via  592  may be disposed through the separation layer  550  and the insulator  520 . Accordingly, the second electrode  570  may be in electrical contact with the negative capacitance layer  590  through the via  592 . 
     At  750 , the method  700  provides the hydrophobic layer  556 . At least a portion of the hydrophobic layer  556  may be disposed on at least a portion of the barrier layer  554 . 
     At  752 , the method  700  optionally disposes the hydrophobic layer  556  such that it is configured to separate the first subchamber  561  from the second subchamber  562 . As depicted in  FIG. 5 , the hydrophobic layer  556  may be disposed above a cavity in the insulator  520  that includes the first electrode  530 , thereby defining the first subchamber  561 . 
     At  760 , the method  700  disposes the nanopore  552  in the hydrophobic layer  556 . As depicted in  FIG. 5 , the nanopore  552  may be disposed in a portion of the hydrophobic layer  556  that is not disposed on the barrier layer  554 . Moreover, the nanopore  552  may be disposed above a cavity in the insulator  520  that includes the first electrode  530 . 
     At  762 , the method  700  optionally disposes the nanopore  552  such that the first subchamber  561  and the second subchamber  562  are in fluid communication with one another via the nanopore  552 . A depicted in  FIG. 5 , the nanopore  552  may be disposed such that fluid in the first subchamber  561  can move into or out of the first subchamber  561  through the nanopore  552 . 
     At  770 , the method  700  optionally forms the chamber  560  and fills the chamber  560  with conductive fluid. 
     Although the method  700  is depicted in  FIG. 7  as if it is to be performed in a specific order, it will be understood that the method  700  may be performed in any suitable sequence, including sequences other than the sequence depicted in  FIG. 7 . For example, the optional formation of the chamber  560  at  770  may be performed prior to the disposing of the hydrophobic layer  556  at  750 . 
       FIG. 8  generally illustrates another DNA sensing device  800  with a negative capacitance layer  890  in accordance with aspects of the disclosure. The negative capacitance layer  890  may constitute means for causing a negative capacitance. The DNA sensing device  800  may have a number of components that are analogous to the components of the DNA sensing device  202 . For example, the DNA sensing device  800  may include an insulator  820 , a nanopore  852 , a hydrophobic layer  856 , a first subchamber  861 , and a second subchamber  862 . These elements depicted in  FIG. 8  may be analogous in some respects to the insulator  220 , the nanopore  252 , the hydrophobic layer  256 , the first subchamber  261 , and the second subchamber  262  depicted in  FIG. 2 . The DNA sensing device  800  may be disposed in relation to other elements analogous to the elements depicted in  FIG. 2 , such as the substrate  210 , the semiconductor device  212 , the via  222 , the first electrode  230 , the adhesion/diffusion layer  234 , the conductive layer  236 , the surface layer  238 , the separation layer  250 , the chamber  260 , the second electrode  270 , the conductive layer  276 , the surface layer  278 , the voltage source  280 , the first conductor  281 , and the second conductor  282 . For brevity, only the differences will be described. However, the barrier layer  254  may be omitted from the DNA sensing device  800  and a negative capacitance layer  890  may be substituted for the barrier layer  254 . 
     As noted above with respect to  FIG. 4B , the negative capacitance  490  may be added to the circuitry model  401  in parallel with the membrane capacitance  456  and the barrier layer capacitance  454   c.  It will be understood that the membrane capacitance  456  and the negative capacitance  490  are circuitry models and are depicted in  FIG. 8  solely for illustrative purposes. 
       FIG. 8  depicts the negative capacitance layer  890  disposed between the first subchamber  861  (which may be in contact with an electrode analogous to the first electrode  230 ) and the second subchamber  862  (which may be in contact with an electrode analogous to the second electrode  270 ). A portion of the negative capacitance layer  890  in contact with the first subchamber  861  may constitute a first terminal of the negative capacitance layer  890  and a portion of the negative capacitance layer  890  in contact with the second subchamber  862  may constitute a second terminal of the negative capacitance layer  890 . Accordingly, the negative capacitance layer  890  may be disposed in parallel with, for example, the membrane capacitance  456  associated with the hydrophobic layer  856 , and the effect of the negative capacitance layer  890  may be to increase the maximum cutoff frequency of the DNA sensing device  800  and/or decrease noise in the DNA sensing device  800 . 
     The negative capacitance layer  890  may include any suitable material(s). For example, the negative capacitance layer  890  may include a strontium titanate layer, a strontium ruthenate layer, a barium titanate layer, a lead zirconate titanate layer, a lanthanum strontium manganite layer, or any combination thereof. 
     The negative capacitance layer  890  may include opposing surfaces, and at least a portion of each of the opposing surfaces may form a first terminal or a second terminal of the negative capacitance layer  890 . For example, a bottom surface of the negative capacitance layer  890  may be disposed on the insulator  820  and the portion of the bottom surface that is not disposed on the insulator  820  may be in contact with the first subchamber  861 . Moreover, the hydrophobic layer  856  may be disposed on at least a portion of the negative capacitance layer  890 . The portion of the negative capacitance layer  890  that is not in contact with the hydrophobic layer  856  may be in contact with the second subchamber  862 . As will be further understood from  FIG. 8 , the portions of the negative capacitance layer  890  that are in contact with the first subchamber  861  on one surface and in contact with the second subchamber  862  on the opposing surface will act as a negative capacitor analogous to the negative capacitance  490  depicted in  FIG. 4B . 
       FIGS. 9A-9C  generally illustrate three alternative arrangements for implementing a negative capacitance layer analogous to the negative capacitance layer  890  depicted in  FIG. 8 . In each arrangement, the negative capacitance layer is disposed between the first subchamber  861  (which may be in contact with an electrode analogous to the first electrode  230 ) and the second subchamber  862  (which may be in contact with an electrode analogous to the second electrode  270 ), as depicted in  FIG. 8 . 
       FIG. 9A  generally illustrates a negative capacitance layer  990 A in accordance with aspects of the disclosure. The negative capacitance layer  990 A may constitute means for causing a negative capacitance. The negative capacitance layer  990 A may include a hydrophobic material layer  910 . The hydrophobic material layer  910  may form a surface (for example, a first surface) of the negative capacitance layer  990 A and may be in contact with the first subchamber  861  or the second subchamber  862 . An opposing surface (for example, a second surface) of the negative capacitance layer  990 A may include an adhesion/diffusion barrier  920 . The adhesion/diffusion barrier  920  may be constructed of any suitable material, for example, titanium (Ti), titanium nitride (TiN), or any combination thereof. 
     Between the hydrophobic material layer  910  and the adhesion/diffusion barrier  920 , the negative capacitance layer  990 A may include a strontium titanate layer  930  (for example, chemical compound SrTiO 3 ) coupled to a strontium ruthenate layer  940  (for example, chemical compound SrRuO 3 ). The strontium titanate layer  930  may be coupled to the hydrophobic material layer  910  and the strontium ruthenate layer  940  may be coupled to the adhesion/diffusion barrier  920 . 
       FIG. 9B  generally illustrates a negative capacitance layer  990 B in accordance with aspects of the disclosure. The negative capacitance layer  990 B may constitute means for causing a negative capacitance. The negative capacitance layer  990 B may include the hydrophobic material layer  910  described above in relation to  FIG. 9A . The hydrophobic material layer  910  may be a surface of the negative capacitance layer  990 B and may be in contact with the first subchamber  861  or the second subchamber  862 . An opposing surface of the negative capacitance layer  990 B may include the adhesion/diffusion barrier  920  described above in relation to  FIG. 9A . The opposing surfaces may constitute a first terminal and a second terminal of the negative capacitance layer  990 B. 
     Between the hydrophobic material layer  910  and the adhesion/diffusion barrier  920 , the negative capacitance layer  990 A may include the strontium titanate layer  930  and the strontium ruthenate layer  940  described above in relation to  FIG. 9A . However, unlike the negative capacitance layer  990 A, the negative capacitance layer  990 B may include a barium titanate layer  950  between the strontium titanate layer  930  and the hydrophobic material layer  910 . 
       FIG. 9C  generally illustrates a negative capacitance layer  990 C in accordance with aspects of the disclosure. The negative capacitance layer  990 C may constitute means for causing a negative capacitance. The negative capacitance layer  990 C may include the hydrophobic material layer  910  described above in relation to  FIG. 9A . The hydrophobic material layer  910  may be a surface of the negative capacitance layer  990 C and may be in contact with the first subchamber  861  or the second subchamber  862 . An opposing surface of the negative capacitance layer  990 C may include the adhesion/diffusion barrier  920  described above in relation to  FIG. 9A . The opposing surfaces may constitute a first terminal and a second terminal of the negative capacitance layer  990 C. 
     Between the hydrophobic material layer  910  and the adhesion/diffusion barrier  920 , the negative capacitance layer  990 C may include the strontium titanate layer  930  described above in relation to  FIG. 9A . However, unlike the negative capacitance layer  990 A, the negative capacitance layer  990 C may further include a lead zirconate titanate layer  960  and a lanthanum strontium manganite layer  970 . The lead zirconate titanate layer  960  may be coupled to the hydrophobic material layer  910  and the strontium titanate layer  930  may be coupled to the adhesion/diffusion barrier  920 . The lanthanum strontium manganite layer  970  may be disposed between and in contact with the lead zirconate titanate layer  960  and the strontium titanate layer  930 . 
       FIG. 10  generally illustrates a method for fabricating the DNA sensing device of  FIG. 8 . 
     At  1010 , the method  1000  provides a first electrode analogous to the first electrode  230 . As will be understood from the previous discussion, the first electrode may be disposed on or within the insulator  820 . Moreover, the first electrode or a portion thereof (for example, an adhesion/diffusion layer analogous to adhesion/diffusion layer  234 ) may be electrically coupled to a semiconductor device analogous to the semiconductor device  212  through a via analogous to the via  222 . A portion of the first electrode may be disposed beneath a cavity within the insulator  820  which is to form the first subchamber  861 . 
     At  1030 , the method  1000  provides the negative capacitance layer  890 . As depicted in  FIG. 8 , the negative capacitance layer  890  may be disposed on, for example, the insulator  820 . 
     At  1032 , the method  1000  optionally disposes the negative capacitance layer  890  such that a first terminal of the negative capacitance layer  890  is configured to be in electrical contact with the first subchamber  861  and a second terminal of the negative capacitance layer  890  is configured to be in electrical contact with the second subchamber  862 . For example, the negative capacitance layer  890  may be disposed on the insulator  820 . 
     At  1040 , the method  1000  provides a second electrode analogous to the second electrode  270 . The second electrode may be disposed on the negative capacitance layer  890  or a portion thereof. 
     At  1050 , the method  1000  provides the hydrophobic layer  856 . At least a portion of the hydrophobic layer  856  may be disposed on at least a portion of the negative capacitance layer  890 . The hydrophobic layer  856  may be deposited and shaped as will be discussed in greater below with respect to  FIGS. 11A-11E . 
     At  1052 , the method  1000  optionally disposes the hydrophobic layer  856  such that it is configured to separate the first subchamber  861  from the second subchamber  862 . As depicted in  FIG. 8 , the hydrophobic layer  856  may be disposed above a cavity in the insulator  820  that includes the first electrode, thereby defining the first subchamber  861 . 
     At  1060 , the method  1000  disposes the nanopore  852  in the hydrophobic layer  856 . As depicted in  FIG. 8 , the nanopore  852  may be disposed in a portion of the hydrophobic layer  856  that is not disposed on the negative capacitance layer  890 . Moreover, the nanopore  852  may be disposed above a cavity in the insulator  820  that includes the first electrode. 
     At  1062 , the method  1000  optionally disposes the nanopore  852  such that the first subchamber  861  and the second subchamber  862  are in fluid communication with one another via the nanopore  852 . A depicted in  FIG. 8 , the nanopore  852  may be disposed such that fluid in the first subchamber  861  can move into or out of the first subchamber  861  through the nanopore  852 . 
     At  1070 , the method  1000  optionally forms a chamber analogous to the chamber  260  and fills the chamber with conductive fluid. 
     Although the method  1000  is depicted in  FIG. 10  as if it is to be performed in a specific order, it will be understood that the method  1000  may be performed in any suitable sequence, including sequences other than the sequence depicted in  FIG. 10 . For example, the optional formation of the chamber at  1070  may be performed prior to the providing of the hydrophobic layer  856  at  1052 . 
       FIGS. 11A-11E  generally illustrate the DNA sensing device  800  of  FIG. 8  in various stages of fabrication, as will be described in greater detail below. 
       FIG. 11A  generally illustrates the DNA sensing device  800  of  FIG. 8  in a first stage of fabrication. In the first stage, an insulator  1120 , negative capacitance layer  1190 , and hydrophobic layer  1156  may be provided. The insulator  1120  and hydrophobic layer  1156  may be analogous to the insulator  820  and hydrophobic layer  856  depicted in  FIG. 8 . The negative capacitance layer  1190  may be analogous to the negative capacitance layer  890  depicted in  FIG. 8  and/or any of the negative capacitance layers  990 A,  990 B,  990 C depicted in  FIGS. 9A-9C . 
       FIG. 11B  generally illustrates the DNA sensing device  800  of  FIG. 8  in a second stage of fabrication. In the second stage a mask  1111  may be provided. The mask  1111  may be photoresistant to one or more frequencies of light to which the hydrophobic layer  1156  is not photoresistant. The size of the mask  1111  may be selected such that the negative capacitance layer  1190  has an optimal capacitance value. For example, by increasing the size of the mask  1111 , the effective area of the negative capacitance layer  1190  may be decreased, and by decreasing the size of the mask  1111 , the effective area of the negative capacitance layer  1190  may be increased. 
       FIG. 11C  generally illustrates the DNA sensing device  800  of  FIG. 8  in a third stage of fabrication. In the third stage, the mask  1111  and at least a portion of the hydrophobic layer  1156  not covered by the mask  1111  may be exposed to light. The light may include one or more frequencies to which the mask  1111  is photoresistant and to which the  1156  is not photoresistant. 
       FIG. 11D  generally illustrates the DNA sensing device  800  of  FIG. 8  in a fourth stage of fabrication. In the fourth stage, the portion of the hydrophobic layer  1156  not covered by the mask  1111  and the mask  1111  itself have been removed. 
       FIG. 11E  generally illustrates the DNA sensing device  800  of  FIG. 8  in a fifth stage of fabrication. In the fifth stage a nanopore  1152  is provided in the hydrophobic layer  1156 . The nanopore  1152  may be analogous to the nanopore  852  depicted in  FIG. 8 . 
     While the foregoing disclosure shows various illustrative aspects, it should be noted that various changes and modifications may be made to the illustrated examples without departing from the scope defined by the appended claims. The present disclosure is not intended to be limited to the specifically illustrated examples alone. For example, unless otherwise noted, the functions, steps, and/or actions of the method claims in accordance with the aspects of the disclosure described herein need not be performed in any particular order. Furthermore, although certain aspects may be described or claimed in the singular, the plural is contemplated unless limitation to the singular is explicitly stated.