US20150168345A1 - Self-aligned well structures for low-noise chemical sensors - Google Patents
Self-aligned well structures for low-noise chemical sensors Download PDFInfo
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/403—Cells and electrode assemblies
- G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
- G01N27/4145—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/403—Cells and electrode assemblies
- G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/403—Cells and electrode assemblies
- G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
- G01N27/4148—Integrated circuits therefor, e.g. fabricated by CMOS processing
Definitions
- the present disclosure relates to sensors for chemical analysis, and to methods for manufacturing such sensors.
- a variety of types of chemical sensors have been used in the detection of various chemical processes.
- One type is a chemically-sensitive field effect transistor (chemFET).
- a chemFET includes a source and a drain separated by a channel region, and a chemically sensitive area coupled to the channel region.
- the operation of the chemFET is based on the modulation of channel conductance, caused by changes in charge at the sensitive area due to a chemical reaction occurring nearby.
- the modulation of the channel conductance changes the threshold voltage of the chemFET, which can be measured to detect and/or determine characteristics of the chemical reaction.
- the threshold voltage may for example be measured by applying appropriate bias voltages to the source and drain, and measuring a resulting current flowing through the chemFET.
- the threshold voltage may be measured by driving a known current through the chemFET, and measuring a resulting voltage at the source or drain.
- ISFET ion-sensitive field effect transistor
- An ion-sensitive field effect transistor is a type of chemFET that includes an ion-sensitive layer at the sensitive area.
- the presence of ions in an analyte solution alters the surface potential at the interface between the ion-sensitive layer and the analyte solution, due to the protonation or deprotonation of surface charge groups at the sensitive area caused by the ions present in the analyte solution.
- the change in surface potential at the sensitive area of the ISFET affects the threshold voltage of the device, which can be measured to indicate the presence and/or concentration of ions within the solution.
- Arrays of ISFETs may be used for monitoring chemical reactions, such as DNA sequencing reactions, based on the detection of ions present, generated, or used during the reactions. See, for example, U.S. Pat. No. 7,948,015 to Rothberg et al., which is incorporated by reference herein. More generally, large arrays of chemFETs or other types of chemical sensors may be employed to detect and measure static and/or dynamic amounts or concentrations of a variety of analytes (e.g. hydrogen ions, other ions, compounds, etc.) in a variety of processes. The processes may for example be biological or chemical reactions, cell or tissue cultures or monitoring, neural activity, nucleic acid sequencing, etc.
- analytes e.g. hydrogen ions, other ions, compounds, etc.
- a specific issue that arises in the operation of chemical sensor arrays is the susceptibility of the sensor output signals to noise.
- the noise affects the accuracy of the downstream signal processing used to determine the characteristics of the chemical and/or biological process being detected by the sensors.
- a method for forming a chemical detection device includes forming a gate dielectric on a semiconductor substrate.
- a floating gate structure is formed on the gate dielectric.
- Forming the floating gate structure includes forming a conductive material overlying the gate dielectric, forming a sacrificial material overlying the conductive material, and patterning the conductive material and the sacrificial material.
- a fill material is formed adjacent to the patterned sacrificial material and the patterned conductive material. The patterned sacrificial material is then removed to define a reaction region substantially aligned with the patterned conductive material.
- a chemical detection device in another implementation, includes a chemically-sensitive field effect transistor including a floating gate conductor coupled to a gate dielectric and having an upper surface, and a sensing material on the upper surface.
- the device also includes a fill material defining a reaction region extending above the sensing material, the reaction region overlying and substantially aligned with the floating gate conductor.
- FIG. 1 illustrates a block diagram of components of a system for nucleic acid sequencing according to an exemplary embodiment.
- FIG. 2 illustrates a cross-sectional view of a portion of the integrated circuit device and flow cell according to an exemplary embodiment.
- FIG. 3 illustrates a cross-sectional view of representative chemical sensors and corresponding reaction regions according to an exemplary embodiment.
- FIGS. 4 to 8 illustrate stages in a manufacturing process for forming a low noise chemical sensor and corresponding well structure according to an exemplary embodiment.
- a chemical detection device includes low noise chemical sensors, such as chemically-sensitive field effect transistors (chemFETs), for detecting chemical reactions within overlying, operationally associated reaction regions.
- chemFETs chemically-sensitive field effect transistors
- an upper floating gate conductor element of the chemical sensor and an overlying sacrificial material element are patterned together to form a stack. Following the formation of a fill material adjacent to the stack, the sacrificial material element can then be selectively removed to define the reaction region, using a non-etch process that does not contribute to charge accumulation.
- the non-etching process may involve heating the device to thermally decompose and evaporate the sacrificial material element to form the reaction region, without damaging the sensing surface or removing the fill material.
- FIG. 1 illustrates a block diagram of components of a system for nucleic acid sequencing according to an exemplary embodiment.
- the components include a flow cell 101 on an integrated circuit device 100 , a reference electrode 108 , a plurality of reagents 114 for sequencing, a valve block 116 , a wash solution 110 , a valve 112 , a fluidics controller 118 , lines 120 / 122 / 126 , passages 104 / 109 / 111 , a waste container 106 , an array controller 124 , and a user interface 128 .
- the integrated circuit device 100 includes a microwell array 107 overlying a sensor array that includes chemical sensors as described herein.
- the flow cell 101 includes an inlet 102 , an outlet 103 , and a flow chamber 105 defining a flow path of reagents over the microwell array 107 .
- the reference electrode 108 may be of any suitable type or shape, including a concentric cylinder with a fluid passage or a wire inserted into a lumen of passage 111 .
- the reagents 114 may be driven through the fluid pathways, valves, and flow cell 101 by pumps, gas pressure, or other suitable methods, and may be discarded into the waste container 106 after exiting the outlet 103 of the flow cell 101 .
- the fluidics controller 118 may control driving forces for the reagents 114 and the operation of valve 112 and valve block 116 with suitable software.
- the microwell array 107 includes an array of reaction regions as described herein, also referred to herein as microwells, which are operationally associated with corresponding chemical sensors in the sensor array.
- each reaction region may be coupled to a chemical sensor suitable for detecting an analyte or reaction property of interest within that reaction region.
- the microwell array 107 may be integrated in the integrated circuit device 100 , so that the microwell array 107 and the sensor array are part of a single device or chip.
- the flow cell 101 may have a variety of configurations for controlling the path and flow rate of reagents 114 over the microwell array 107 .
- the array controller 124 provides bias voltages and timing and control signals to the integrated circuit device 100 for reading the chemical sensors of the sensor array.
- the array controller 124 also provides a reference bias voltage to the reference electrode 108 to bias the reagents 114 flowing over the microwell array 107 .
- the array controller 124 collects and processes output signals from the chemical sensors of the sensor array through output ports on the integrated circuit device 100 via bus 127 .
- the array controller 124 may be a computer or other computing means.
- the array controller 124 may include memory for storage of data and software applications, a processor for accessing data and executing applications, and components that facilitate communication with the various components of the system in FIG. 1 .
- the values of the output signals of the chemical sensors indicate physical and/or chemical parameters of one or more reactions taking place in the corresponding reaction regions in the microwell array 107 .
- the values of the output signals may be processed using the techniques disclosed in Rearick et al., U.S. patent application Ser. No. 13/339,846, filed Dec. 29, 2011, based on U.S. Prov. Pat. Appl. Nos. 61/428,743, filed Dec. 30, 2010, and 61/429,328, filed Jan. 3, 2011, and in Hubbell, U.S. patent application Ser. No. 13/339,753, filed Dec. 29, 2011, based on U.S. Prov. Pat. Appl. No 61/428,097, filed Dec. 29, 2010, which are all incorporated by reference herein in their entirety.
- the user interface 128 may display information about the flow cell 101 and the output signals received from chemical sensors in the sensor array on the integrated circuit device 100 .
- the user interface 128 may also display instrument settings and controls, and allow a user to enter or set instrument settings and controls.
- the fluidics controller 118 may control delivery of the individual reagents 114 to the flow cell 101 and integrated circuit device 100 in a predetermined sequence, for predetermined durations, at predetermined flow rates.
- the array controller 124 can then collect and analyze the output signals of the chemical sensors indicating chemical reactions occurring in response to the delivery of the reagents 114 .
- the system may also monitor and control the temperature of the integrated circuit device 100 , so that reactions take place and measurements are made at a known predetermined temperature.
- the system may be configured to let a single fluid or reagent contact the reference electrode 108 throughout an entire multi-step reaction during operation.
- the valve 112 may be shut to prevent any wash solution 110 from flowing into passage 109 as the reagents 114 are flowing. Although the flow of wash solution may be stopped, there may still be uninterrupted fluid and electrical communication between the reference electrode 108 , passage 109 , and the microwell array 107 .
- the distance between the reference electrode 108 and the junction between passages 109 and 111 may be selected so that little or no amount of the reagents flowing in passage 109 and possibly diffusing into passage 111 reach the reference electrode 108 .
- the wash solution 110 may be selected as being in continuous contact with the reference electrode 108 , which may be especially useful for multi-step reactions using frequent wash steps.
- FIG. 2 illustrates cross-sectional and expanded views of a portion of the integrated circuit device 100 and flow cell 101 .
- the flow chamber 105 of the flow cell 101 confines a reagent flow 208 of delivered reagents across open ends of the reaction regions in the microwell array 107 .
- the volume, shape, aspect ratio (such as base width-to-well depth ratio), and other dimensional characteristics of the reaction regions may be selected based on the nature of the reaction taking place, as well as the reagents, byproducts, or labeling techniques (if any) that are employed.
- the chemical sensors of the sensor array 205 are responsive to (and generate output signals) chemical reactions within associated reaction regions in the microwell array 107 to detect an analyte or reaction property of interest.
- the chemical sensors of the sensor array 205 may for example be chemically sensitive field-effect transistors (chemFETs), such as ion-sensitive field effect transistors (ISFETs). Examples of chemical sensors and array configurations that may be used in embodiments are described in U.S. Patent Application Publication No. 2010/0300559, No. 2010/0197507, No. 2010/0301398, No. 2010/0300895, No. 2010/0137143, and No. 2009/0026082, and U.S. Pat. No. 7,575,865, each which are incorporated by reference herein.
- FIG. 3 illustrates a cross-sectional view of two representative chemical sensors and their corresponding reaction regions according to an exemplary embodiment.
- two chemical sensors 350 , 351 are shown, representing a small portion of a sensor array that can include millions of chemical sensors.
- Chemical sensor 350 is coupled to corresponding reaction region 301 , and chemical sensor 351 is coupled to corresponding reaction region 302 .
- Chemical sensor 350 is representative of the chemical sensors in the sensor array.
- the chemical sensor 350 is an ion-sensitive field effect transistor.
- the chemical sensor 350 includes a floating gate structure 318 having a floating gate conductor (referred to herein as the sensor plate 320 ) separated from the reaction region 301 by sensing material 316 .
- the sensor plate 320 is the uppermost patterned layer of conductive material in the floating gate structure 318 underlying the reaction region 301 .
- the floating gate structure 318 includes multiple patterned layers of conductive material within layers of dielectric material 319 .
- the upper surface of the sensing material 316 acts as the sensing surface 317 for the chemical sensor 350 .
- the sensing material 316 is an ion-sensitive material, such that the presence of ions or other charged species in a solution in the reaction region 301 alters the surface potential of the sensing surface 317 .
- the change in the surface potential is due to the protonation or deprotonation of surface charge groups at the sensing surface caused by the ions present in the solution.
- the sensing material 316 may be deposited using various techniques, or naturally formed during one or more of the manufacturing processes used to form the chemical sensor 350 .
- the sensing material 316 is a metal oxide, such as an oxide of silicon, tantalum, aluminum, lanthanum, titanium, zirconium, hafnium, tungsten, palladium, iridium, etc.
- the sensing material 316 is an oxide of the upper layer of conductive material of the sensor plate 320 .
- the upper layer of the sensor plate 320 may be titanium nitride, and the sensing material 316 may comprise titanium oxide or titanium oxynitride.
- the sensing material 316 may comprise one or more of a variety of different materials to facilitate sensitivity to particular ions.
- silicon nitride or silicon oxynitride, as well as metal oxides such as silicon oxide, aluminum or tantalum oxides generally provide sensitivity to hydrogen ions
- sensing materials comprising polyvinyl chloride containing valinomycin provide sensitivity to potassium ions.
- Materials sensitive to other ions such as sodium, silver, iron, bromine, iodine, calcium, and nitrate may also be used, depending upon the implementation.
- the chemical sensor 350 also includes a source region 321 and a drain region 322 within a semiconductor substrate 354 .
- the source region 321 and the drain region 322 comprise doped semiconductor material have a conductivity type different from the conductivity type of the substrate 354 .
- the source region 321 and the drain region 322 may comprise doped P-type semiconductor material, and the substrate may comprise doped N-type semiconductor material.
- Channel region 323 separates the source region 321 and the drain region 322 .
- the floating gate structure 318 overlies the channel region 323 , and is separated from the substrate 354 by a gate dielectric 352 .
- the gate dielectric 352 may be for example silicon dioxide. Alternatively, other dielectrics may be used for the gate dielectric 352 .
- the reaction region 301 is within an opening extending through a fill material 310 on the dielectric material 319 .
- the fill material 310 may comprise one or more layers of material.
- the opening includes a sidewall 303 extending to the bottom surface of the sensor plate 320 of the floating gate structure 318 .
- a lower portion 314 of the opening contains the sensing material 316 and the sensor plate 320 .
- An upper portion 315 of the opening extends from the lower portion 314 to the upper surface of the fill material 310 to define the reaction region 301 .
- the opening through the fill material 310 is formed using a self-aligned process which does not require directly subjecting the sensing surface 317 to a high-energy directional plasma etching process.
- This self-aligned process includes patterning the sensor plate 320 , the sensing material 316 and an overlying sacrificial material element together using a single etch mask to form a multi-layer stack.
- the sacrificial material element defines the size and location of the reaction region 301 .
- the sacrificial material element is selectively removed to expose the sensing material 316 and define the reaction region 301 .
- the reaction region 301 is self-aligned to the sensor plate 320 . In doing so, the formation of the reaction region 301 does not require an additional mask or critical alignment step, thereby reducing costs and avoiding yield problems which can arise due to misalignment.
- the microwell 301 is substantially aligned with the sensor plate 320 of the floating gate structure 318 .
- elements or features that are “substantially aligned” have sidewalls substantially flush with a plane parallel to the sidewalls, where “substantially flush” is intended to accommodate manufacturing tolerances using a single etch mask which may cause variations in the planarity of the sidewalls.
- the sidewall 303 of the opening defining the reaction region 301 is substantially vertically aligned with the sidewall of the sensor plate 320 and the sidewall of the sensing material 316 .
- the sacrificial material element comprises sacrificial material which can be selectively removed relative to the fill material 310 , when subjected to a chosen process which does not contribute charge accumulation on the floating gate structure 318 .
- the chosen process is a non-etch process.
- Etching is a process for removing material by using a wet etchant or reactive ionic particles that chemically react with the material.
- the sacrificial material element may comprise a thermally decomposable material, such as a polymer having a relatively low thermal decomposition temperature.
- the sacrificial material element may for example comprise a Unity® polymer from Promerus Inc., such as polypropylene carbonate (PPC), polyethylene carbonate (PEC), polycyclohexanepropylene carbonate (PCPC), polycyclohexane carbonate (PCC), polynorbornene carbonate (PNC), polybutylnorbornene (PNB), etc.
- the structure can then be heated to a temperature at or above the thermal decomposition temperature of the sacrificial material element, such that the sacrificial material element thermally decomposes and evaporates.
- the temperature and the amount the time the device is heated depends on the selected material for the sacrificial material element, as well as its thickness, and can be determined empirically.
- the sacrificial material element may comprise other materials which can be selectively removed relative to the fill material 310 , when subjected to a chosen process.
- the sacrificial material element may comprise a dielectric material that can be selectively etched using for example a wet etch process, or a low power plasma etch process that does not contribute significant charge accumulation on the floating gate structure 318 .
- the sacrificial material element is silicon dioxide
- the fill material is silicon nitride
- a wet etchant such as buffered oxide etch (BOE) is performed to selectively remove the sacrificial material element.
- the fill material 310 may for example comprise one or more layers of dielectric material, such as silicon dioxide or silicon nitride.
- the fill material 310 is a thermally decomposable material.
- the sacrificial material element comprises material having a decomposition temperature less than that of the fill material 310 .
- the structure can then be heated to a temperature at or above the thermal decomposition temperature of the sacrificial material element, but below the thermal decomposition temperature of the fill material 310 , such that the sacrificial material element thermally decomposes and evaporates without damaging or removing the fill material 310 . In doing so, the shape of the sacrificial material element becomes the shape of the reaction region 301 .
- the sacrificial material element is a Unity® polymer from Promerus Inc. which decomposes at a temperature above 200 degrees Celsius
- the fill material 310 is for example polymide, which decomposes at a temperature above 400 degrees Celsius.
- the sacrificial material element protects the upper surface of the sensing material 316 , acts as the sensing surface 317 for the chemical sensor 350 , during the patterning process used to form the stack. In doing so, damage to the sensing surface 317 can be avoided.
- the techniques described herein can be used to form low noise chemical sensors having uniform performance across an array, such that the characteristics of chemical reactions can be accurately measured.
- the sensor plate 320 and the sensing material 316 may for example have circular cross-sections, which results in the opening and the reaction region 301 having circular cross-sections. Alternatively, these may be non-circular.
- the cross-section may be square, rectangular, hexagonal, or irregularly shaped.
- reactants, wash solutions, and other reagents may move in and out of the reaction region 301 by a diffusion mechanism 340 .
- the chemical sensor 350 is responsive to (and generates an output signal related to) the amount of a charge 324 present on the sensing material 316 opposite the sensor plate 320 . Changes in the charge 324 cause changes in the voltage on the floating gate structure 318 , which in turn changes in the threshold voltage of the transistor. This change in threshold voltage can be measured by measuring the current in the channel region 323 between the source region 321 and a drain region 322 .
- the chemical sensor 350 can be used directly to provide a current-based output signal on an array line connected to the source region 321 or drain region 322 , or indirectly with additional circuitry to provide a voltage-based output signal.
- reactions carried out in the reaction region 301 can be analytical reactions to identify or determine characteristics or properties of an analyte of interest. Such reactions can generate directly or indirectly byproducts that affect the amount of charge adjacent to the sensor plate 320 . If such byproducts are produced in small amounts or rapidly decay or react with other constituents, multiple copies of the same analyte may be analyzed in the reaction region 301 at the same time in order to increase the output signal generated. In an embodiment, multiple copies of an analyte may be attached to a solid phase support 312 , either before or after deposition into the reaction region 301 .
- the solid phase support 312 may be microparticles, nanoparticles, beads, solid or porous comprising gels, or the like.
- solid phase support 312 is also referred herein as a particle.
- multiple, connected copies may be made by rolling circle amplification (RCA), exponential RCA, or like techniques, to produce an amplicon without the need of a solid support.
- RCA rolling circle amplification
- exponential RCA exponential RCA
- a nucleotide incorporation event may be determined by detecting ions (e.g., hydrogen ions) that are generated as natural by-products of polymerase-catalyzed nucleotide extension reactions. This may be used to sequence a sample or template nucleic acid, which may be a fragment of a nucleic acid sequence of interest, for example, and which may be directly or indirectly attached as a clonal population to a solid support, such as a particle, microparticle, bead, etc.
- ions e.g., hydrogen ions
- the sample or template nucleic acid may be operably associated to a primer and polymerase and may be subjected to repeated cycles or “flows” of deoxynucleoside triphosphate (“dNTP”) addition (which may be referred to herein as “nucleotide flows” from which nucleotide incorporations may result) and washing.
- dNTP deoxynucleoside triphosphate
- the primer may be annealed to the sample or template so that the primer's 3′ end can be extended by a polymerase whenever dNTPs complementary to the next base in the template are added.
- the identity of the type, sequence and number of nucleotide(s) associated with a sample nucleic acid present in a reaction region coupled to a chemical sensor can be determined.
- FIGS. 4 to 8 illustrate stages in a manufacturing process for forming a low noise chemical sensor and corresponding well structure according to an exemplary embodiment.
- FIG. 4 illustrates a structure 400 formed in a first stage.
- the structure 400 includes a partially completed floating gate structure 410 within the dielectric 319 .
- the structure 400 can be formed by depositing a layer of gate dielectric material on the semiconductor substrate 354 , and depositing a layer of polysilicon (or other electrically conductive material) on the layer of gate dielectric material.
- the layer of polysilicon and the layer gate dielectric material can then be etched using an etch mask to form the gate dielectric elements (e.g. gate dielectric 352 ) and the lowermost conductive material element of the floating gate structures (e.g. conductive material element 412 of floating gate structure 410 ).
- ion implantation can then be performed to form the source and drain regions (e.g. source region 321 and a drain region 322 ) of the chemical sensors.
- a first layer of the dielectric material 319 can then be deposited over the lowermost conductive material elements. Conductive plugs can then be formed within vias etched in the first layer of dielectric material 319 to contact the lowermost conductive material elements of the floating gate structures. A layer of conductive material can then be deposited on the first layer of the dielectric material 319 and patterned to form second conductive material elements electrically connected to the conductive plugs. This process can then be repeated multiple times to form the partially completed floating gate structures shown in FIG. 4 . Alternatively, other and/or additional techniques may be performed to form the structure 400 .
- Forming the structure 400 can also include forming additional elements such as array lines (e.g. word lines, bit lines, etc.) for accessing the chemical sensors, additional doped regions in the substrate 354 , and other circuitry (e.g. access circuitry, bias circuitry etc.) used to operate the chemical sensors, depending upon the device and array configuration in which the chemical sensors described herein are implemented.
- the elements of the structure 400 may for example be manufactured using techniques described in U.S. Patent Application Publication No. 2010/0300559, No. 2010/0197507, No. 2010/0301398, No. 2010/0300895, No. 2010/0137143, and No. 2009/0026082, and U.S. Pat. No. 7,575,865, each which are incorporated by reference herein.
- conductive material 500 is formed on the structure illustrated in FIG. 4 .
- Sensing material 510 is formed on the conductive material 500
- sacrificial material 520 is formed on sensing material 510 .
- An etch mask including mask elements 530 , 532 is then formed on the layer of sacrificial material, resulting in the structure illustrated in FIG. 5 .
- the conductive material 500 comprises one or more layers of electrically conductive material.
- the conductive material 500 may include a layer of titanium nitride formed on a layer of aluminum, or a layer of titanium nitride formed on a layer of copper.
- the number of layers may be different than two, and other and/or additional conductive materials may be used.
- Examples of conductive materials that can be used in some embodiments include tantalum, aluminum, lanthanum, titanium, zirconium, hafnium, tungsten, palladium, iridium, etc., and combinations thereof.
- the sensing material 510 may comprise one or more layers of material, such as those materials discussed above with respect to the ion-sensitive layer 316 of FIG. 3 .
- the sensing material 510 is deposited on the conductive material 500 .
- the sensing material 510 may be deposited using various techniques, such as sputtering, atomic layer deposition (ALD), low pressure chemical vapor deposition (LPCVD), plasma enhanced chemical vapor deposition (PECVD), metal organic chemical vapor deposition (MOCVD), metal organic vapour phase epitaxy (MOVPE), spin coating, spray coating etc.
- the sensing material 510 may be grown as an oxide of the upper layer of conductive material 500 .
- an oxidation process may for example be performed to oxidize the conductive material 500 to create the sensing material 510 .
- the thickness of the sacrificial material 520 defines the depth of the subsequently formed reaction regions.
- the sacrificial material 520 may be deposited using various techniques, depending on the material. For example, in embodiments in which the sacrificial material 520 has a relatively low decomposition temperature, so that it can subsequently be thermally decomposed, it may be spin coated. Alternatively, other techniques may be used. For example, the sacrificial material may be formed by sputtering, ALD, LPCVD, PECVD, MOCVD, MOVPE, spray coating etc.
- the mask elements 530 , 532 define the locations of the reaction regions and the sensor plates of the corresponding chemical sensors.
- the mask elements 530 , 532 comprise photoresist material which has been patterned using a lithographic process. Alternatively, other techniques and materials may be used.
- an etching or other patterning process is performed on the structure illustrated in FIG. 5 using the mask elements 530 , 532 as a mask, resulting in the structure illustrated in FIG. 6 .
- the etching is performed through the conductive material 500 , and stops at or in the dielectric material 319 .
- the etching may for example be performed using a single etch chemistry to each all the materials 500 , 510 , 520 , using for example chlorine or fluorine based etching chemistry, or oxygen plasma. Alternatively, different etch chemistries may be used for each of the layers.
- the etching process defines multi-layer stacks 600 , 602 beneath the mask elements 530 , 532 respectively.
- the multi-layer stack 600 includes conductive material element 610 of conductive material 500 in electrical contact with the partial floating gate structure 410 (see FIG. 4 ).
- the conductive material element 610 (also referred to as the sensor plate herein) is the uppermost patterned layer of the floating gate structure 318 , and thus completes the floating gate structure 318 .
- the multi-layer stack 600 also includes a sensing material element 620 of patterned sensing material 510 on the conductive material element 610 , and a sacrificial material element 630 of patterned sacrificial material 520 on the sensing material element 620 .
- the cross-sectional shapes of the multi-layer stacks 600 , 602 depend on the cross-sectional shapes of the mask elements 530 , 532 . These cross-sections may for example be circular. Alternatively, these may be non-circular. For example, the cross-section may be square, rectangular, hexagonal, or irregularly shaped.
- the mask elements 530 , 532 are used as etch masks for the etching process.
- the mask elements 530 , 532 may be omitted, and the sacrificial material 520 comprises a material that is photosensitive (photodefinable).
- the locations of the multi-layer stacks 600 , 602 can be defined by projecting an image onto the sacrificial material 520 using a lithographic process. After exposure, the sacrificial material 520 can then be removed from the undesired locations to form the sacrificial material elements of the multi-layer stacks 600 , 602 .
- the sacrificial material elements can then be used as etch masks during etching through the conductive material 500 to complete the multi-layer stacks 600 , 602 .
- fill material 310 is deposited on the structure illustrated in FIG. 6 , and a planarization process is performed to remove the mask elements 530 , 532 and expose the patterned sacrificial material of the multi-layer stacks 600 , 602 , resulting in the structure illustrated in FIG. 7 .
- the fill material 310 may comprise one or more layers of various materials, and may be deposited using various techniques.
- the fill material 310 is a high temperature polymer such as polyimide, TEFLON, etc. and is deposited by spin coating. Alternatively, other materials and formation techniques may be used.
- the planarization process used to expose the patterned sacrificial material of the multi-layer stacks 600 , 602 is a chemical mechanical polishing (CMP) process.
- CMP chemical mechanical polishing
- other planarization processes may be used.
- the sacrificial material elements of the multi-layer stacks 600 , 602 are selectively removed to define respective reaction regions 301 , 302 for the corresponding chemical sensors, resulting in the structure illustrated in FIG. 8 .
- the sacrificial material and the fill material 310 are each thermally decomposable material, and the sacrificial material has a decomposition temperature less than that of the fill material 310 .
- the structure is then heated (e.g. in a furnace) to a temperature at or above the thermal decomposition temperature of the sacrificial material, but below the thermal decomposition temperature of the fill material 310 , such that the sacrificial material element thermally decomposes and evaporates without damaging or removing the fill material 310 .
- the fill material 310 retains the shape of the sacrificial material element as the shape of the reaction region 301 .
- the sacrificial material element protects the upper surface of the ion-sensitive layer 316 during the patterning process used to form the stack. In doing so, damage to the sensing surface of the chemical sensor can be avoided.
- the techniques described herein can be used to form low noise chemical sensors having uniform performance across an array, such that the characteristics of chemical reactions can be accurately measured.
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Abstract
In one implementation, a chemical detection device is described. The device includes a chemically-sensitive field effect transistor including a floating gate conductor coupled to a gate dielectric and having an upper surface, and a sensing material on the upper surface. The device also includes a fill material defining a reaction region extending above the sensing material, the reaction region overlying and substantially aligned with the floating gate conductor.
Description
- This application is a divisional of U.S. patent application Ser. No. 13/751,575 filed Jan. 28, 2013, the entire contents of which are incorporated by reference herein in its entirety.
- The present disclosure relates to sensors for chemical analysis, and to methods for manufacturing such sensors.
- A variety of types of chemical sensors have been used in the detection of various chemical processes. One type is a chemically-sensitive field effect transistor (chemFET). A chemFET includes a source and a drain separated by a channel region, and a chemically sensitive area coupled to the channel region. The operation of the chemFET is based on the modulation of channel conductance, caused by changes in charge at the sensitive area due to a chemical reaction occurring nearby. The modulation of the channel conductance changes the threshold voltage of the chemFET, which can be measured to detect and/or determine characteristics of the chemical reaction. The threshold voltage may for example be measured by applying appropriate bias voltages to the source and drain, and measuring a resulting current flowing through the chemFET. As another example, the threshold voltage may be measured by driving a known current through the chemFET, and measuring a resulting voltage at the source or drain.
- An ion-sensitive field effect transistor (ISFET) is a type of chemFET that includes an ion-sensitive layer at the sensitive area. The presence of ions in an analyte solution alters the surface potential at the interface between the ion-sensitive layer and the analyte solution, due to the protonation or deprotonation of surface charge groups at the sensitive area caused by the ions present in the analyte solution. The change in surface potential at the sensitive area of the ISFET affects the threshold voltage of the device, which can be measured to indicate the presence and/or concentration of ions within the solution.
- Arrays of ISFETs may be used for monitoring chemical reactions, such as DNA sequencing reactions, based on the detection of ions present, generated, or used during the reactions. See, for example, U.S. Pat. No. 7,948,015 to Rothberg et al., which is incorporated by reference herein. More generally, large arrays of chemFETs or other types of chemical sensors may be employed to detect and measure static and/or dynamic amounts or concentrations of a variety of analytes (e.g. hydrogen ions, other ions, compounds, etc.) in a variety of processes. The processes may for example be biological or chemical reactions, cell or tissue cultures or monitoring, neural activity, nucleic acid sequencing, etc.
- A specific issue that arises in the operation of chemical sensor arrays is the susceptibility of the sensor output signals to noise. Specifically, the noise affects the accuracy of the downstream signal processing used to determine the characteristics of the chemical and/or biological process being detected by the sensors.
- It is therefore desirable to provide devices including low noise chemical sensors, and methods for manufacturing such devices.
- In one implementation, a method for forming a chemical detection device is described. The method includes forming a gate dielectric on a semiconductor substrate. A floating gate structure is formed on the gate dielectric. Forming the floating gate structure includes forming a conductive material overlying the gate dielectric, forming a sacrificial material overlying the conductive material, and patterning the conductive material and the sacrificial material. A fill material is formed adjacent to the patterned sacrificial material and the patterned conductive material. The patterned sacrificial material is then removed to define a reaction region substantially aligned with the patterned conductive material.
- In another implementation, a chemical detection device is described. The device includes a chemically-sensitive field effect transistor including a floating gate conductor coupled to a gate dielectric and having an upper surface, and a sensing material on the upper surface. The device also includes a fill material defining a reaction region extending above the sensing material, the reaction region overlying and substantially aligned with the floating gate conductor.
- Particular aspects of one more implementations of the subject matter described in this specification are set forth in the drawings and the description below. Other features, aspects, and advantages of the subject matter will become apparent from the description, the drawings, and the claims.
-
FIG. 1 illustrates a block diagram of components of a system for nucleic acid sequencing according to an exemplary embodiment. -
FIG. 2 illustrates a cross-sectional view of a portion of the integrated circuit device and flow cell according to an exemplary embodiment. -
FIG. 3 illustrates a cross-sectional view of representative chemical sensors and corresponding reaction regions according to an exemplary embodiment. -
FIGS. 4 to 8 illustrate stages in a manufacturing process for forming a low noise chemical sensor and corresponding well structure according to an exemplary embodiment. - A chemical detection device is described that includes low noise chemical sensors, such as chemically-sensitive field effect transistors (chemFETs), for detecting chemical reactions within overlying, operationally associated reaction regions.
- It has been found that a significant amount of the total noise in chemical sensors, such as chemFETs, can be attributed to etching processes involved in defining the overlying reaction regions. In particular, forming the reaction region through an overlying material by subjecting the sensing surface of a chemical sensor to prolonged periods of a high-energy directional etching process can cause significant noise in the sensor. For example, plasma impinging on the sensing surface can cause charge build up, to the point of causing undesirable changes or damage within the sensor. This accumulated charge can become trapped in the gate oxide and/or the gate oxide-semiconductor substrate interface of the chemFETs, thereby contributing to the noise and resulting in variations in operation and degradation in performance.
- Techniques are described herein for forming a reaction region overlying the sensing surface of a chemical sensor, using a self-aligned process that does not require the sensing surface to be subjected to an etching process. In exemplary embodiments, an upper floating gate conductor element of the chemical sensor and an overlying sacrificial material element are patterned together to form a stack. Following the formation of a fill material adjacent to the stack, the sacrificial material element can then be selectively removed to define the reaction region, using a non-etch process that does not contribute to charge accumulation. In embodiments in which the sacrificial material element comprises thermally decomposable material, the non-etching process may involve heating the device to thermally decompose and evaporate the sacrificial material element to form the reaction region, without damaging the sensing surface or removing the fill material.
- As a result of the techniques described herein, low noise chemical sensors with uniform performance across an array are provided, such that the characteristics of subsequent chemical reactions can be accurately detected.
-
FIG. 1 illustrates a block diagram of components of a system for nucleic acid sequencing according to an exemplary embodiment. The components include aflow cell 101 on anintegrated circuit device 100, areference electrode 108, a plurality ofreagents 114 for sequencing, avalve block 116, awash solution 110, avalve 112, afluidics controller 118,lines 120/122/126,passages 104/109/111, awaste container 106, anarray controller 124, and auser interface 128. Theintegrated circuit device 100 includes amicrowell array 107 overlying a sensor array that includes chemical sensors as described herein. Theflow cell 101 includes aninlet 102, anoutlet 103, and aflow chamber 105 defining a flow path of reagents over themicrowell array 107. - The
reference electrode 108 may be of any suitable type or shape, including a concentric cylinder with a fluid passage or a wire inserted into a lumen ofpassage 111. Thereagents 114 may be driven through the fluid pathways, valves, andflow cell 101 by pumps, gas pressure, or other suitable methods, and may be discarded into thewaste container 106 after exiting theoutlet 103 of theflow cell 101. Thefluidics controller 118 may control driving forces for thereagents 114 and the operation ofvalve 112 andvalve block 116 with suitable software. - The
microwell array 107 includes an array of reaction regions as described herein, also referred to herein as microwells, which are operationally associated with corresponding chemical sensors in the sensor array. For example, each reaction region may be coupled to a chemical sensor suitable for detecting an analyte or reaction property of interest within that reaction region. Themicrowell array 107 may be integrated in theintegrated circuit device 100, so that themicrowell array 107 and the sensor array are part of a single device or chip. - The
flow cell 101 may have a variety of configurations for controlling the path and flow rate ofreagents 114 over themicrowell array 107. Thearray controller 124 provides bias voltages and timing and control signals to theintegrated circuit device 100 for reading the chemical sensors of the sensor array. Thearray controller 124 also provides a reference bias voltage to thereference electrode 108 to bias thereagents 114 flowing over themicrowell array 107. - During an experiment, the
array controller 124 collects and processes output signals from the chemical sensors of the sensor array through output ports on theintegrated circuit device 100 viabus 127. Thearray controller 124 may be a computer or other computing means. Thearray controller 124 may include memory for storage of data and software applications, a processor for accessing data and executing applications, and components that facilitate communication with the various components of the system inFIG. 1 . - The values of the output signals of the chemical sensors indicate physical and/or chemical parameters of one or more reactions taking place in the corresponding reaction regions in the
microwell array 107. For example, in an exemplary embodiment, the values of the output signals may be processed using the techniques disclosed in Rearick et al., U.S. patent application Ser. No. 13/339,846, filed Dec. 29, 2011, based on U.S. Prov. Pat. Appl. Nos. 61/428,743, filed Dec. 30, 2010, and 61/429,328, filed Jan. 3, 2011, and in Hubbell, U.S. patent application Ser. No. 13/339,753, filed Dec. 29, 2011, based on U.S. Prov. Pat. Appl. No 61/428,097, filed Dec. 29, 2010, which are all incorporated by reference herein in their entirety. - The
user interface 128 may display information about theflow cell 101 and the output signals received from chemical sensors in the sensor array on theintegrated circuit device 100. Theuser interface 128 may also display instrument settings and controls, and allow a user to enter or set instrument settings and controls. - In an exemplary embodiment, during the experiment the
fluidics controller 118 may control delivery of theindividual reagents 114 to theflow cell 101 andintegrated circuit device 100 in a predetermined sequence, for predetermined durations, at predetermined flow rates. Thearray controller 124 can then collect and analyze the output signals of the chemical sensors indicating chemical reactions occurring in response to the delivery of thereagents 114. - During the experiment, the system may also monitor and control the temperature of the
integrated circuit device 100, so that reactions take place and measurements are made at a known predetermined temperature. - The system may be configured to let a single fluid or reagent contact the
reference electrode 108 throughout an entire multi-step reaction during operation. Thevalve 112 may be shut to prevent anywash solution 110 from flowing intopassage 109 as thereagents 114 are flowing. Although the flow of wash solution may be stopped, there may still be uninterrupted fluid and electrical communication between thereference electrode 108,passage 109, and themicrowell array 107. The distance between thereference electrode 108 and the junction betweenpassages passage 109 and possibly diffusing intopassage 111 reach thereference electrode 108. In an exemplary embodiment, thewash solution 110 may be selected as being in continuous contact with thereference electrode 108, which may be especially useful for multi-step reactions using frequent wash steps. -
FIG. 2 illustrates cross-sectional and expanded views of a portion of theintegrated circuit device 100 and flowcell 101. During operation, theflow chamber 105 of theflow cell 101 confines areagent flow 208 of delivered reagents across open ends of the reaction regions in themicrowell array 107. The volume, shape, aspect ratio (such as base width-to-well depth ratio), and other dimensional characteristics of the reaction regions may be selected based on the nature of the reaction taking place, as well as the reagents, byproducts, or labeling techniques (if any) that are employed. - The chemical sensors of the
sensor array 205 are responsive to (and generate output signals) chemical reactions within associated reaction regions in themicrowell array 107 to detect an analyte or reaction property of interest. The chemical sensors of thesensor array 205 may for example be chemically sensitive field-effect transistors (chemFETs), such as ion-sensitive field effect transistors (ISFETs). Examples of chemical sensors and array configurations that may be used in embodiments are described in U.S. Patent Application Publication No. 2010/0300559, No. 2010/0197507, No. 2010/0301398, No. 2010/0300895, No. 2010/0137143, and No. 2009/0026082, and U.S. Pat. No. 7,575,865, each which are incorporated by reference herein. -
FIG. 3 illustrates a cross-sectional view of two representative chemical sensors and their corresponding reaction regions according to an exemplary embodiment. InFIG. 3 , twochemical sensors -
Chemical sensor 350 is coupled tocorresponding reaction region 301, andchemical sensor 351 is coupled tocorresponding reaction region 302.Chemical sensor 350 is representative of the chemical sensors in the sensor array. In the illustrated example, thechemical sensor 350 is an ion-sensitive field effect transistor. Thechemical sensor 350 includes a floating gate structure 318 having a floating gate conductor (referred to herein as the sensor plate 320) separated from thereaction region 301 by sensingmaterial 316. As shown inFIG. 3 , the sensor plate 320 is the uppermost patterned layer of conductive material in the floating gate structure 318 underlying thereaction region 301. - In the illustrated example, the floating gate structure 318 includes multiple patterned layers of conductive material within layers of
dielectric material 319. As described in more detail below, the upper surface of thesensing material 316 acts as thesensing surface 317 for thechemical sensor 350. - In the illustrated embodiment, the
sensing material 316 is an ion-sensitive material, such that the presence of ions or other charged species in a solution in thereaction region 301 alters the surface potential of thesensing surface 317. The change in the surface potential is due to the protonation or deprotonation of surface charge groups at the sensing surface caused by the ions present in the solution. Thesensing material 316 may be deposited using various techniques, or naturally formed during one or more of the manufacturing processes used to form thechemical sensor 350. In some embodiments, thesensing material 316 is a metal oxide, such as an oxide of silicon, tantalum, aluminum, lanthanum, titanium, zirconium, hafnium, tungsten, palladium, iridium, etc. - In some embodiments, the
sensing material 316 is an oxide of the upper layer of conductive material of the sensor plate 320. For example, the upper layer of the sensor plate 320 may be titanium nitride, and thesensing material 316 may comprise titanium oxide or titanium oxynitride. More generally, thesensing material 316 may comprise one or more of a variety of different materials to facilitate sensitivity to particular ions. For example, silicon nitride or silicon oxynitride, as well as metal oxides such as silicon oxide, aluminum or tantalum oxides, generally provide sensitivity to hydrogen ions, whereas sensing materials comprising polyvinyl chloride containing valinomycin provide sensitivity to potassium ions. Materials sensitive to other ions such as sodium, silver, iron, bromine, iodine, calcium, and nitrate may also be used, depending upon the implementation. - The
chemical sensor 350 also includes asource region 321 and adrain region 322 within asemiconductor substrate 354. Thesource region 321 and thedrain region 322 comprise doped semiconductor material have a conductivity type different from the conductivity type of thesubstrate 354. For example, thesource region 321 and thedrain region 322 may comprise doped P-type semiconductor material, and the substrate may comprise doped N-type semiconductor material. -
Channel region 323 separates thesource region 321 and thedrain region 322. The floating gate structure 318 overlies thechannel region 323, and is separated from thesubstrate 354 by agate dielectric 352. Thegate dielectric 352 may be for example silicon dioxide. Alternatively, other dielectrics may be used for thegate dielectric 352. - As shown in
FIG. 3 , thereaction region 301 is within an opening extending through afill material 310 on thedielectric material 319. As described in more detail below, thefill material 310 may comprise one or more layers of material. - The opening includes a
sidewall 303 extending to the bottom surface of the sensor plate 320 of the floating gate structure 318. As a result of this structure, alower portion 314 of the opening contains thesensing material 316 and the sensor plate 320. Anupper portion 315 of the opening extends from thelower portion 314 to the upper surface of thefill material 310 to define thereaction region 301. - As described in more detail below with respect to
FIGS. 4-8 , the opening through thefill material 310 is formed using a self-aligned process which does not require directly subjecting thesensing surface 317 to a high-energy directional plasma etching process. This self-aligned process includes patterning the sensor plate 320, thesensing material 316 and an overlying sacrificial material element together using a single etch mask to form a multi-layer stack. The sacrificial material element defines the size and location of thereaction region 301. Following the formation of thefill material 310 adjacent to the stack, the sacrificial material element is selectively removed to expose thesensing material 316 and define thereaction region 301. By using the same mask to pattern the sensor plate 320 and to define the location of thereaction region 301, thereaction region 301 is self-aligned to the sensor plate 320. In doing so, the formation of thereaction region 301 does not require an additional mask or critical alignment step, thereby reducing costs and avoiding yield problems which can arise due to misalignment. - As a result of the self-aligned process described herein, the
microwell 301 is substantially aligned with the sensor plate 320 of the floating gate structure 318. As used herein, elements or features that are “substantially aligned” have sidewalls substantially flush with a plane parallel to the sidewalls, where “substantially flush” is intended to accommodate manufacturing tolerances using a single etch mask which may cause variations in the planarity of the sidewalls. As a result, as shown inFIG. 3 , thesidewall 303 of the opening defining thereaction region 301 is substantially vertically aligned with the sidewall of the sensor plate 320 and the sidewall of thesensing material 316. - The sacrificial material element comprises sacrificial material which can be selectively removed relative to the
fill material 310, when subjected to a chosen process which does not contribute charge accumulation on the floating gate structure 318. In exemplary embodiments described herein, the chosen process is a non-etch process. Etching is a process for removing material by using a wet etchant or reactive ionic particles that chemically react with the material. - For example, the sacrificial material element may comprise a thermally decomposable material, such as a polymer having a relatively low thermal decomposition temperature. The sacrificial material element may for example comprise a Unity® polymer from Promerus Inc., such as polypropylene carbonate (PPC), polyethylene carbonate (PEC), polycyclohexanepropylene carbonate (PCPC), polycyclohexane carbonate (PCC), polynorbornene carbonate (PNC), polybutylnorbornene (PNB), etc.
- During manufacturing, the structure can then be heated to a temperature at or above the thermal decomposition temperature of the sacrificial material element, such that the sacrificial material element thermally decomposes and evaporates. The temperature and the amount the time the device is heated depends on the selected material for the sacrificial material element, as well as its thickness, and can be determined empirically.
- Alternatively, the sacrificial material element may comprise other materials which can be selectively removed relative to the
fill material 310, when subjected to a chosen process. For example, the sacrificial material element may comprise a dielectric material that can be selectively etched using for example a wet etch process, or a low power plasma etch process that does not contribute significant charge accumulation on the floating gate structure 318. In one embodiment, the sacrificial material element is silicon dioxide, the fill material is silicon nitride, and a wet etchant such as buffered oxide etch (BOE) is performed to selectively remove the sacrificial material element. - Alternatively other materials and/or wet etchants may be used.
- The
fill material 310 may for example comprise one or more layers of dielectric material, such as silicon dioxide or silicon nitride. Alternatively, in some embodiments, thefill material 310 is a thermally decomposable material. In such a case, the sacrificial material element comprises material having a decomposition temperature less than that of thefill material 310. The structure can then be heated to a temperature at or above the thermal decomposition temperature of the sacrificial material element, but below the thermal decomposition temperature of thefill material 310, such that the sacrificial material element thermally decomposes and evaporates without damaging or removing thefill material 310. In doing so, the shape of the sacrificial material element becomes the shape of thereaction region 301. In one implementation, the sacrificial material element is a Unity® polymer from Promerus Inc. which decomposes at a temperature above 200 degrees Celsius, and thefill material 310 is for example polymide, which decomposes at a temperature above 400 degrees Celsius. - The sacrificial material element protects the upper surface of the
sensing material 316, acts as thesensing surface 317 for thechemical sensor 350, during the patterning process used to form the stack. In doing so, damage to thesensing surface 317 can be avoided. In addition, by selectively removing the sacrificial material element using a non-etch process which does not accumulate charge on the floating gate structure 318 (e.g. heating to cause thermal decomposition of the material), noise induced in thechemical sensor 350 during the formation of thereaction region 301 can be eliminated. As a result, the techniques described herein can be used to form low noise chemical sensors having uniform performance across an array, such that the characteristics of chemical reactions can be accurately measured. - The sensor plate 320 and the
sensing material 316 may for example have circular cross-sections, which results in the opening and thereaction region 301 having circular cross-sections. Alternatively, these may be non-circular. For example, the cross-section may be square, rectangular, hexagonal, or irregularly shaped. - In operation, reactants, wash solutions, and other reagents may move in and out of the
reaction region 301 by adiffusion mechanism 340. Thechemical sensor 350 is responsive to (and generates an output signal related to) the amount of acharge 324 present on thesensing material 316 opposite the sensor plate 320. Changes in thecharge 324 cause changes in the voltage on the floating gate structure 318, which in turn changes in the threshold voltage of the transistor. This change in threshold voltage can be measured by measuring the current in thechannel region 323 between thesource region 321 and adrain region 322. As a result, thechemical sensor 350 can be used directly to provide a current-based output signal on an array line connected to thesource region 321 or drainregion 322, or indirectly with additional circuitry to provide a voltage-based output signal. - In an embodiment, reactions carried out in the
reaction region 301 can be analytical reactions to identify or determine characteristics or properties of an analyte of interest. Such reactions can generate directly or indirectly byproducts that affect the amount of charge adjacent to the sensor plate 320. If such byproducts are produced in small amounts or rapidly decay or react with other constituents, multiple copies of the same analyte may be analyzed in thereaction region 301 at the same time in order to increase the output signal generated. In an embodiment, multiple copies of an analyte may be attached to asolid phase support 312, either before or after deposition into thereaction region 301. Thesolid phase support 312 may be microparticles, nanoparticles, beads, solid or porous comprising gels, or the like. For simplicity and ease of explanation,solid phase support 312 is also referred herein as a particle. For a nucleic acid analyte, multiple, connected copies may be made by rolling circle amplification (RCA), exponential RCA, or like techniques, to produce an amplicon without the need of a solid support. - In various exemplary embodiments, the methods, systems, and computer readable media described herein may advantageously be used to process and/or analyze data and signals obtained from electronic or charged-based nucleic acid sequencing. In electronic or charged-based sequencing (such as, pH-based sequencing), a nucleotide incorporation event may be determined by detecting ions (e.g., hydrogen ions) that are generated as natural by-products of polymerase-catalyzed nucleotide extension reactions. This may be used to sequence a sample or template nucleic acid, which may be a fragment of a nucleic acid sequence of interest, for example, and which may be directly or indirectly attached as a clonal population to a solid support, such as a particle, microparticle, bead, etc. The sample or template nucleic acid may be operably associated to a primer and polymerase and may be subjected to repeated cycles or “flows” of deoxynucleoside triphosphate (“dNTP”) addition (which may be referred to herein as “nucleotide flows” from which nucleotide incorporations may result) and washing. The primer may be annealed to the sample or template so that the primer's 3′ end can be extended by a polymerase whenever dNTPs complementary to the next base in the template are added. Then, based on the known sequence of nucleotide flows and on measured output signals of the chemical sensors indicative of ion concentration during each nucleotide flow, the identity of the type, sequence and number of nucleotide(s) associated with a sample nucleic acid present in a reaction region coupled to a chemical sensor can be determined.
-
FIGS. 4 to 8 illustrate stages in a manufacturing process for forming a low noise chemical sensor and corresponding well structure according to an exemplary embodiment. -
FIG. 4 illustrates astructure 400 formed in a first stage. In the illustrated embodiment, thestructure 400 includes a partially completed floatinggate structure 410 within the dielectric 319. - The
structure 400 can be formed by depositing a layer of gate dielectric material on thesemiconductor substrate 354, and depositing a layer of polysilicon (or other electrically conductive material) on the layer of gate dielectric material. The layer of polysilicon and the layer gate dielectric material can then be etched using an etch mask to form the gate dielectric elements (e.g. gate dielectric 352) and the lowermost conductive material element of the floating gate structures (e.g. conductive material element 412 of floating gate structure 410). Following formation of an ion-implantation mask, ion implantation can then be performed to form the source and drain regions (e.g. source region 321 and a drain region 322) of the chemical sensors. - A first layer of the
dielectric material 319 can then be deposited over the lowermost conductive material elements. Conductive plugs can then be formed within vias etched in the first layer ofdielectric material 319 to contact the lowermost conductive material elements of the floating gate structures. A layer of conductive material can then be deposited on the first layer of thedielectric material 319 and patterned to form second conductive material elements electrically connected to the conductive plugs. This process can then be repeated multiple times to form the partially completed floating gate structures shown inFIG. 4 . Alternatively, other and/or additional techniques may be performed to form thestructure 400. - Forming the
structure 400 can also include forming additional elements such as array lines (e.g. word lines, bit lines, etc.) for accessing the chemical sensors, additional doped regions in thesubstrate 354, and other circuitry (e.g. access circuitry, bias circuitry etc.) used to operate the chemical sensors, depending upon the device and array configuration in which the chemical sensors described herein are implemented. In some embodiments, the elements of thestructure 400 may for example be manufactured using techniques described in U.S. Patent Application Publication No. 2010/0300559, No. 2010/0197507, No. 2010/0301398, No. 2010/0300895, No. 2010/0137143, and No. 2009/0026082, and U.S. Pat. No. 7,575,865, each which are incorporated by reference herein. - Next,
conductive material 500 is formed on the structure illustrated inFIG. 4 .Sensing material 510 is formed on theconductive material 500, andsacrificial material 520 is formed onsensing material 510. An etch mask includingmask elements FIG. 5 . - The
conductive material 500 comprises one or more layers of electrically conductive material. For example, theconductive material 500 may include a layer of titanium nitride formed on a layer of aluminum, or a layer of titanium nitride formed on a layer of copper. Alternatively, the number of layers may be different than two, and other and/or additional conductive materials may be used. Examples of conductive materials that can be used in some embodiments include tantalum, aluminum, lanthanum, titanium, zirconium, hafnium, tungsten, palladium, iridium, etc., and combinations thereof. - The
sensing material 510 may comprise one or more layers of material, such as those materials discussed above with respect to the ion-sensitive layer 316 ofFIG. 3 . In the illustrated example, thesensing material 510 is deposited on theconductive material 500. Thesensing material 510 may be deposited using various techniques, such as sputtering, atomic layer deposition (ALD), low pressure chemical vapor deposition (LPCVD), plasma enhanced chemical vapor deposition (PECVD), metal organic chemical vapor deposition (MOCVD), metal organic vapour phase epitaxy (MOVPE), spin coating, spray coating etc. - Alternatively, rather than separately depositing the
sensing material 510, thesensing material 510 may be grown as an oxide of the upper layer ofconductive material 500. In such a case, after depositing the conductive material, an oxidation process may for example be performed to oxidize theconductive material 500 to create thesensing material 510. - As described in more detail below, the thickness of the
sacrificial material 520 defines the depth of the subsequently formed reaction regions. Thesacrificial material 520 may be deposited using various techniques, depending on the material. For example, in embodiments in which thesacrificial material 520 has a relatively low decomposition temperature, so that it can subsequently be thermally decomposed, it may be spin coated. Alternatively, other techniques may be used. For example, the sacrificial material may be formed by sputtering, ALD, LPCVD, PECVD, MOCVD, MOVPE, spray coating etc. - The
mask elements mask elements - Next, an etching or other patterning process is performed on the structure illustrated in
FIG. 5 using themask elements FIG. 6 . As shown inFIG. 6 , the etching is performed through theconductive material 500, and stops at or in thedielectric material 319. The etching may for example be performed using a single etch chemistry to each all thematerials - The etching process defines
multi-layer stacks mask elements multi-layer stack 600 includesconductive material element 610 ofconductive material 500 in electrical contact with the partial floating gate structure 410 (seeFIG. 4 ). The conductive material element 610 (also referred to as the sensor plate herein) is the uppermost patterned layer of the floating gate structure 318, and thus completes the floating gate structure 318. - The
multi-layer stack 600 also includes asensing material element 620 of patternedsensing material 510 on theconductive material element 610, and asacrificial material element 630 of patternedsacrificial material 520 on thesensing material element 620. - The cross-sectional shapes of the
multi-layer stacks mask elements - In the illustrated embodiment, the
mask elements mask elements sacrificial material 520 comprises a material that is photosensitive (photodefinable). In such a case, the locations of themulti-layer stacks sacrificial material 520 using a lithographic process. After exposure, thesacrificial material 520 can then be removed from the undesired locations to form the sacrificial material elements of themulti-layer stacks conductive material 500 to complete themulti-layer stacks - Next, fill
material 310 is deposited on the structure illustrated inFIG. 6 , and a planarization process is performed to remove themask elements multi-layer stacks FIG. 7 . - The
fill material 310 may comprise one or more layers of various materials, and may be deposited using various techniques. In the illustrated embodiment, thefill material 310 is a high temperature polymer such as polyimide, TEFLON, etc. and is deposited by spin coating. Alternatively, other materials and formation techniques may be used. - In the illustrated embodiment, the planarization process used to expose the patterned sacrificial material of the
multi-layer stacks - Next, the sacrificial material elements of the
multi-layer stacks respective reaction regions FIG. 8 . - In the illustrated example, the sacrificial material and the
fill material 310 are each thermally decomposable material, and the sacrificial material has a decomposition temperature less than that of thefill material 310. The structure is then heated (e.g. in a furnace) to a temperature at or above the thermal decomposition temperature of the sacrificial material, but below the thermal decomposition temperature of thefill material 310, such that the sacrificial material element thermally decomposes and evaporates without damaging or removing thefill material 310. In doing so, thefill material 310 retains the shape of the sacrificial material element as the shape of thereaction region 301. - Alternatively, as described above, other techniques may be used to selectively remove (e.g. selectively wet etch) the sacrificial material.
- The sacrificial material element protects the upper surface of the ion-
sensitive layer 316 during the patterning process used to form the stack. In doing so, damage to the sensing surface of the chemical sensor can be avoided. In addition, by selectively removing the sacrificial material element using for example a non-etch process which does not accumulate charge on the floating gate structure (e.g. heating to cause thermal decomposition of the material), noise induced in the chemical sensor during the formation of the reaction region can be eliminated. As a result, the techniques described herein can be used to form low noise chemical sensors having uniform performance across an array, such that the characteristics of chemical reactions can be accurately measured. - While the present invention is disclosed by reference to the preferred embodiments and examples detailed above, it is to be understood that these examples are intended in an illustrative rather than in a limiting sense. It is contemplated that modifications and combinations will readily occur to those skilled in the art, which modifications and combinations will be within the spirit of the invention and the scope of the following claims.
Claims (9)
1. A chemical detection device, comprising:
a chemically-sensitive field effect transistor including a floating gate conductor coupled to a gate dielectric and having an upper surface, and a sensing material on the upper surface; and
a fill material defining an reaction region extending above the sensing material, the reaction region overlying and substantially aligned with the floating gate conductor.
2. The chemical detection device of claim 1 , wherein the reaction region extends to the sensing material, and the reaction region is substantially aligned with the sensing material.
3. The chemical detection device of claim 1 , wherein the chemically-sensitive field effect transistor includes a floating gate structure comprising a plurality of conductors electrically coupled to one another and separated by dielectric layers, and the floating gate conductor is an uppermost conductor in the plurality of conductors.
4. The chemical detection device of claim 1 , wherein the reaction region is self-aligned with the floating gate conductor.
5. The chemical detection device of claim 2 , wherein the chemically-sensitive field effect transistor generates a sensor signal in response to a chemical reaction occurring within the reaction region.
6. The chemical detection device of claim 5 , wherein the chemical reaction is a sequencing reaction.
7. The chemical detection device of claim 2 , wherein the sensing material comprises a metal-oxide.
8. The chemical detection device of claim 2 , wherein the sensing material is sensitive to hydrogen ions.
9. The chemical detection device of claim 2 , further comprising a microfluidic structure in fluid flow communication with the reaction region, and arranged to deliver analytes for sequencing.
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US8962366B2 (en) | 2015-02-24 |
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