Abstract:
A sensor for biomolecules includes a silicon fin comprising undoped silicon; a source region adjacent to the silicon fin, the source region comprising heavily doped silicon; a drain region adjacent to the silicon fin, the drain region comprising heavily doped silicon of a doping type that is the same doping type as that of the source region; and a layer of a gate dielectric covering an exterior portion of the silicon fin between the source region and the drain region, the gate dielectric comprising a plurality of antibodies, the plurality of antibodies configured to bind with the biomolecules, such that a drain current flowing between the source region and the drain region varies when the biomolecules bind with the antibodies.

Description:
FIELD OF INVENTION 
     This disclosure relates generally to the field of sensors for biomolecule detection. 
     DESCRIPTION OF RELATED ART 
     Biomolecules, which may include proteins or viruses, play an important role in many illnesses; the study of biomolecules is essential for improved, cost effective disease diagnosis and treatment. Some methods that may be used to detect biomolecules include fluorescence or radioactive labeling, and patch clamp. However, these methods may be labor intensive, costly, or have limited sensitivity. Such detection methods may also be difficult to integrate into systems that include additional functionality such as sample delivery, data acquisition, or data transmission. For example, the patch clamp method is used for sensing proteins such as ion channels that are embedded in the membrane of a cell. This method includes a pipette that punctures the cell membrane embedded with proteins. Due to the presence of the pipette, the patch clamp method has limited scope for miniaturization or integration onto a multifunctional platform. 
     A field effect transistor (FET) based sensor, such as large area planar FET or a back-gated silicon nanowire FET, may be used to detect biomolecules by measuring the drain current in the sub-threshold regime where the drain current has an exponential dependence on the gate voltage of the FET. A large area planar FET may have limited sensitivity, and may therefore detect only high concentrations of biomolecules. A back-gated silicon nanowire FET exhibits improved sensitivity in comparison to large area planar FET based sensors. In a back-gated silicon nanowire FET, silicon nanowire forms the sensing surface, buried oxide act as the gate dielectric and silicon substrate act as the gate. The sensitivity of a back-gated nanowire FET may be degraded due to two factors: a large sub-threshold slope due to the thick buried oxide that acts as the gate dielectric, and formation of the inversion layer at the silicon/oxide interface such that is located away from the sensing surface of the silicon channel. Since these factors are inherent structural features of a back-gated silicon nanowire FET, its sensitivity can only enhanced by reducing the silicon nanowire thickness. However, reduction in silicon nanowire thickness causes the sensing area to decrease, resulting in slower response times, and also making the wires relatively fragile. In summary, back-gated silicon nanowire FET sensors have an inherent structural design disadvantage for biomolecule sensing applications. 
     SUMMARY 
     In one aspect, a sensor for biomolecules includes a silicon fin comprising undoped silicon; a source region adjacent to the silicon fin, the source region comprising heavily doped silicon; a drain region adjacent to the silicon fin, the drain region comprising heavily doped silicon of a doping type that is the same doping type as that of the source region; and a layer of a gate dielectric covering an exterior portion of the silicon fin between the source region and the drain region, the gate dielectric comprising a plurality of antibodies, the plurality of antibodies configured to bind with the biomolecules, such that a drain current flowing between the source region and the drain region varies when the biomolecules bind with the antibodies. 
     In one aspect, a method for sensing biomolecules in an electrolyte includes exposing a gate dielectric surface of a silicon fin, the gate dielectric surface comprising antibodies configured to bind with the biomolecules, to an electrolyte comprising the biomolecules; applying a gate voltage to an electrode immersed in the electrolyte; and measuring a change in a drain current flowing in the silicon fin to determine whether biomolecules are present in the electrolyte. 
     In one aspect, a method for sensing biomolecules in a membrane includes bringing a gate dielectric surface of a silicon fin into contact with a membrane comprising the biomolecules, the membrane being immersed in an electrolyte; applying a gate voltage to an electrode immersed in the electrolyte; adding molecules to the electrolyte, the molecules configured to cause pores in the membrane to open; and measuring a change in a drain current flowing in the silicon fin to determine whether biomolecules are present in the membrane. 
     Additional features are realized through the techniques of the present exemplary embodiment. Other embodiments are described in detail herein and are considered a part of what is claimed. For a better understanding of the features of the exemplary embodiment, refer to the description and to the drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS 
       Referring now to the drawings wherein like elements are numbered alike in the several FIGURES: 
         FIG. 1  illustrates a cross section of an embodiment of a fin FET based sensor for biomolecules. 
         FIG. 2  illustrates a top view of an embodiment of a fin FET based sensor for biomolecules. 
         FIG. 3  illustrates a cross section of an embodiment of a sensor for biomolecules comprising multiple fin FETs. 
         FIG. 4  illustrates a top view of an embodiment of a sensor for biomolecules comprising multiple fin FETs. 
         FIG. 5  illustrates a cross-section of an embodiment of a sensor for biomolecules comprising multiple fin FETS. 
         FIG. 6  illustrates a cross-section of an embodiment of a sensor for biomolecules comprising fin and planar FETs. 
         FIG. 7A  illustrates a cross-section of the sensor for biomolecules comprising a planar FET that is located between two adjacent fin FETs. 
         FIG. 7B  illustrates a top view of the sensor for biomolecules comprising a planar FET that is located between two adjacent fin FETs. 
         FIG. 8  illustrates a cross-section of an embodiment of a sensor for biomolecules embedded in a membrane. 
         FIG. 9  illustrates an embodiment of a method for detection of biomolecules in an electrolyte using a sensor. 
         FIG. 10  illustrates an embodiment of a method for detection of biomolecules in a membrane using a sensor. 
     
    
    
     DETAILED DESCRIPTION 
     Embodiments of systems and methods for a sensor for biomolecules are provided, with exemplary embodiments being discussed below in detail. A structure for FET based sensor is proposed which overcomes the drawbacks of back-gated silicon nanowire FET sensor as described in above. Consequently, the proposed sensor structure may have significantly improved sensitivity, larger sensing area and higher yield in comparison to a back-gated silicon nanowire FET. 
     A sensor for biomolecules, which may include, but are not limited to, proteins or viruses, may comprise a FET-type structure comprising one or more silicon fins. The silicon fin structure may have a low sub-threshold slope (SS), an inversion layer formed close to the sensing surface, and volume inversion effects, which may act to increase the sensitivity of the sensor. Response time of the sensor may also be reduced. The sensor structure may be fabricated using standard silicon process technology, allowing the sensor to be cost effectively mass produced and easily integrated into a multi-function silicon chip that performs such functions as sample delivery, data acquisition, or data transmission. 
     A FET-based sensor may detect biomolecules by measuring the drain current (I d ) of the FET structure in the sub-threshold regime, where I d  has exponential dependence on a gate voltage. The majority of biomolecules are charged, therefore, when a charged biomolecule is in the vicinity of a silicon channel of the FET structure, the biomolecule may cause the drain current to change by ΔI d , where
 
Δ I   d   =μ*C   ox   /SS,  
 
where C ox  is the gate oxide capacitance, μ is the mobility of electrons or holes in the silicon channel, and SS is the sub-threshold slope. Since ΔI d  is a measure of sensor sensitivity, the sensitivity may be maximized by utilization of a FET structure that has a relatively small sub-threshold slope and relatively large C ox  and μ values.
 
     The silicon fin width and height may be adjusted so as to obtain a SS of about 62 mV/decade. Response time of the sensor may also be reduced by increasing the surface area of a silicon fin. A reduction in response time without degradation of sensitivity may be obtained by a channel length (L g ) of a silicon fin that is greater than about 0.5 micron (μm), a silicon fin width (W si ) that is less than about 30 nanometers (nm), and a silicon fin height (H si ) that is greater than or equal to twice W si . A W si , of less than about 25 nm may result in a volume inversion effect, which may cause mobility (μ) to increase. The gate dielectric may comprise a layer of SiO2 or SiON, or a stack consisting of SiON and metal oxide insulator such as HfO2, with an equivalent oxide thickness of about 5 nm. An electrolyte may act as the top FET gate. The gate dielectric may be covered with antibodies that selectively bind with the biomolecules to be detected in some embodiments. 
       FIG. 1  illustrates a cross-section of an embodiment of a fin FET based sensor  100  for biomolecules. Silicon fin  101  comprises undoped silicon. Silicon fin  101  is coated with gate dielectric  102 . Gate dielectric layer  102  forms the biomolecule detection surface, and may comprise oxide/HfO2 stack or SiON in some embodiments. The gate dielectric layer  102  further comprises antibodies that selectively bind with the biomolecules to be detected in some embodiments. Buried oxide layer  103  and silicon back gate  104  form a base of the sensor  100 . Line  105  illustrates the silicon fin height (H si ), and line  106  illustrates the silicon fin width (W si ). 
       FIG. 2  illustrates a top view of an embodiment of a fin FET based sensor  200  for biomolecules. Silicon fin  201  comprises a channel of undoped silicon, and has a channel length (L g ) illustrated by line  208 . Gate dielectric layers  202  and  203  form the biomolecule detection surface, and comprise oxide/HfO2 stack or SiON in some embodiments. The gate dielectric layers  202  and  203  further comprise antibodies that selectively bind with the biomolecules to be detected in some embodiments. Drain  204  comprises heavily doped n+ or p+ silicon, and source  205  comprises heavily doped silicon of the same doping type as the drain. Regions  206  and  207  comprise thick oxide layers that act to isolate the drain  204  and source  205  from an electrolyte containing biomolecules that covers the gate dielectric layers  202  and  203  in operation. 
     Some embodiments may comprise multiple fin FETs, which reduce the response time of the sensor by increasing the detection surface area.  FIG. 3  illustrates an embodiment of a cross-section of a sensor  300  for biomolecules comprising multiple fin FETs. Silicon fins  301 ,  303 , and  305  comprise undoped silicon. Silicon fins  301 ,  303 , and  305  are coated with gate dielectric layers  302 ,  304 , and  306 . Gate dielectric layers  302 ,  304 , and  306  form the biomolecule detection surface, and may comprise oxide/HfO2 stack or SiON in some embodiments. The gate dielectric layers  302 ,  304 , and  306  further comprise antibodies that selectively bind with the biomolecules to be detected in some embodiments. Buried oxide layer  307  and silicon back gate  308  form the base of the sensor  300 . Line  309  illustrates the silicon fin height (H si ), line  310  illustrates the silicon fin width (W si ), and line  311  illustrates the spacing between fins. Three fin FETs are shown in the embodiment of  FIG. 3  for illustrative purposes only; any appropriate number of fin FETs may comprise a sensor for biomolecules. 
       FIG. 4  illustrates a top view of an embodiment of a sensor  400  for biomolecules comprising multiple fin FETs. Silicon fins  401 ,  404 , and  407  comprise channels of undoped silicon having a channel length (L g ) illustrated by line  414 . Gate dielectric layers  402 ,  403 ,  405 ,  406 ,  408 , and  409  form the biomolecule detection surface, and comprise oxide/HfO2 stack or SiON in some embodiments. The gate dielectric layers  402 ,  403 ,  405 ,  406 ,  408 , and  409  further comprise antibodies that selectively bind with the biomolecules to be detected in some embodiments. Drain  410  comprises heavily doped n+ or p+silicon, and source  411  comprises heavily doped silicon of the same doping type as the drain. Regions  412  and  413  comprise thick oxide layers that act to isolate the drain  410  and source  411  from an electrolyte containing biomolecules that covers the gate dielectric layers  402 ,  403 ,  405 ,  406 ,  408 , and  409  in operation. Three fin FETs with common source and drain regions  410  and  411  are shown in the embodiment of  FIG. 4  for illustrative purposes only; any appropriate number of fin FETs may comprise a sensor for biomolecules. 
       FIG. 5  illustrates a cross-section of an embodiment of a sensor  500  for biomolecules comprising multiple fin FETs that is immersed in an electrolyte solution  510  comprising biomolecules  509 . Fins  501 ,  503 , and  505  are coated in gate dielectric  502 ,  504 , and  506 . Buried oxide layer  507  and silicon back gate  508  form a base of sensor  500 . Electrolyte solution  510  acts as the FET top gate. Biomolecules  509  bind with antibodies located on gate dielectric  502 ,  504 , and  506 , causing a change (ΔI d ) in the drain current (I d ) of the sensor  500 , allowing the biomolecules  509  to be detected. The gate voltage is supplied by an electrode  511 , which comprises a silver wire coated with silver chloride in some embodiments. The back gate  508  may have the same polarity bias as the electrolyte  510 , or the back gate  508  may be grounded. Top gate electrolyte  510  is in the sub-threshold regime. For the case of n-type source and drain regions, a positive polarity voltage is applied at the drain, the source voltage is held at 0V and a voltage between approximately 100 mV and 3V is applied at electrode  511 , causing a drain current to flow between the source and drain of the sensor (source and drain are discussed above, see, for example, elements  204  and  250  of  FIG. 2 , and elements  410  and  411  of  FIG. 4 ). When biomolecules  509  attaches to gate dielectric layers  502 ,  504 , and  506 , the drain current changes according to the charge of the biomolecules, allowing detection of the biomolecules. Three fin FETs are shown in the embodiment of  FIG. 5  for illustrative purposes only; any appropriate number of fin FETs may comprise a sensor for biomolecules. 
     A sensor structure may comprise a single fin FET or multiple fin FETs with common source and drain depending on whether sensitivity or response time is a more important for a particular biomolecule detection application. If higher sensitivity is desired, a single fin FET structure may be used, whereas multiple fin FETs reduce the response time. The spacing between the fin FETs in a multiple fin FET embodiment may be adjusted so as to provide size selectivity for detecting biomolecules. For example, for a sensor configured to detect a virus with a diameter of approximately 100 nm, the spacing between fin FETs may be made slightly (approximately 5%-20%) larger than the diameter of the virus to be detected. Any appropriate number of fin FETs may comprise an embodiment of a sensor for biomolecules. 
       FIG. 6  illustrates a cross-sectional view of an embodiment of a sensor  600  comprising fin and planar FETs. Planar FETs  609  and  610  comprise extremely thin planar silicon layers; planar FETs  609  and  610  are located between adjacent fin FETs  601  and  603 , and  603  and  605 , respectively. Line  613  illustrates the silicon fin FET height (H si ). Planar silicon FETs  609  and  610  comprise undoped silicon of a thickness that is less than H si , and may be less than 10 nm in some embodiments. The width of planar silicon FETs  609  and  610  is illustrated by line  614 , which is of approximately the same width as the spacing between silicon fins  603  and  605 . Planar silicon FETs  609  and  610  and fin FETs  601 ,  603 , and  605  are coated with gate dielectric  602 ,  604 ,  606 ,  611 , and  612 . Gate dielectric layers form the biomolecule detection surface, and comprise oxide/HfO2 stack or SiON in some embodiments. The gate dielectric layers comprise antibodies that selectively bind with the biomolecules to be detected in some embodiments. Buried oxide layer  607  and silicon back gate  608  form a base of sensor  600 . Three fin FETs and two planar FETs are shown in the embodiment of  FIG. 6  for illustrative purposes only; any appropriate number of fin and planar FETs may comprise a sensor for biomolecules. 
       FIG. 7A  illustrates a cross-sectional view  700   a  of a sensor comprising a planar FET, and  FIG. 7B  illustrates a top view  700   b  of a sensor comprising a planar FET. Referring to  FIG. 7A , Gate dielectric layer  701  covers planar silicon  702 , which is disposed on buried oxide layer  703  and back gate  704 . Referring to  FIG. 7B , source region  707  is located at one end of planar silicon  705 , and drain region  706  is located at the opposite end of planar silicon  705 . Drain  706  comprises heavily doped n+ or p+ silicon, and source  707  comprises heavily doped silicon of the same doping type as the drain. Source region  707  and drain region  706  are insulated by thick oxide regions  708  and  709 . Planar silicon  705  is covered with a gate dielectric, and has a channel length L g  illustrated by line  710 , which is approximately equal to the channel length of a silicon fin, as illustrated by element  208  of  FIG. 2 . 
       FIG. 8  illustrates a side view of an embodiment of a sensor  800  configured to detect biomolecules in a membrane  811 . Membrane  811  may contain embedded biomolecules such as ion channel or ion pump proteins. Electrolyte  810  acts as the top FET gate. Fins  801 ,  803 , and  805  are coated in gate dielectric  802 ,  804 , and  806 . Buried oxide layer  807  and silicon back gate  808  form a base of sensor  800 . The gate voltage is supplied at electrode  809 , which may comprise silver wire coated with silver chloride in some embodiments. The back gate  808  may have the same polarity bias as the membrane, or be grounded. Three fins are shown in the embodiment of  FIG. 8  for illustrative purposes only; any appropriate number of fins may comprise a sensor for biomolecules. 
       FIG. 9  illustrates an embodiment of a method  900  for detection of biomolecules using a sensor. In block  901 , a gate dielectric surface of a silicon fin is coated with antibodies that selectively bind a protein or virus to be detected. In block  902 , the gate dielectric surface is brought into contact with an electrode dipped in an electrolyte. The electrolyte acts as a FET gate. In block  903 , a voltage is applied at the sensor drain, and the sensor source voltage is set to 0V. In block  904 , a gate voltage (V g ) is applied at the electrode. A voltage (V b ) may also be applied to the back gate for threshold voltage tuning in some embodiments. In block  905 , the drain current I d  in the absence of biomolecules is measured. In block  906 , the biomolecules are added to the electrolyte. In block  907 , the biomolecules bind to the antibodies on the gate dielectric surface, thereby cause the drain current I d  in the sub-threshold regime of the sensor to change by ΔI d , and the bio-molecules to be detected according to ΔI d . 
       FIG. 10  illustrates an embodiment of a method  1000  for detecting biomolecules embedded in the membrane of a cell. In block  1001 , the gate dielectric surface is brought into contact with an electrode dipped in an electrolyte. In block  1002 , a membrane embedded with biomolecules such as ion channel proteins is brought into contact with the gate dielectric surface. In block  1003 , a voltage is applied at the drain, and the source voltage is set to 0V. In block  1004 , a gate voltage (V g ) is applied at the electrode. A voltage (V b ) may also be applied to the back gate for threshold voltage tuning in some embodiments. In block  1005 , the drain current I d  is measured. In block  1006 , liagand molecules are added to the electrolyte; the liagand molecules cause the pores in the ion channels of the membrane to open, causing ions to flow in or out of the cell, causing a localized change in ion density. In block  1007 , the drain current I d  in the sub-threshold regime of the sensor is measured to determine the ΔI d  caused by the change in ion density caused by the opening of ion channel proteins. While the embodiment of  FIG. 10  has been described with reference to liagand gated ion channel proteins, a similar procedure may be used for voltage gated ion channel proteins or ion pump proteins. 
     The technical effects and benefits of exemplary embodiments include providing a biomolecule sensor with relatively low response time and high sensitivity. The sensor may be relatively cheap to manufacture, and easy to integrate into a multi-functional silicon chip. 
     The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms “a”, “an”, and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. 
     The corresponding structures, materials, acts, and equivalents of all means or step plus function elements in the claims below are intended to include any structure, material, or act for performing the function in combination with other claimed elements as specifically claimed. The description of the present invention has been presented for purposes of illustration and description, but is not intended to be exhaustive or limited to the invention in the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the invention. The embodiment was chosen and described in order to best explain the principles of the invention and the practical application, and to enable others of ordinary skill in the art to understand the invention for various embodiments with various modifications as are suited to the particular use contemplated. Specifically, while an n-type FET-sensor embodiment was chosen to explain the principles of the invention, the principles of the invention also apply to embodiments comprising p-type FET-sensors.