US20140264466A1 - Chemical sensor with protruded sensor surface - Google Patents
Chemical sensor with protruded sensor surface Download PDFInfo
- Publication number
- US20140264466A1 US20140264466A1 US13/801,243 US201313801243A US2014264466A1 US 20140264466 A1 US20140264466 A1 US 20140264466A1 US 201313801243 A US201313801243 A US 201313801243A US 2014264466 A1 US2014264466 A1 US 2014264466A1
- Authority
- US
- United States
- Prior art keywords
- chemical sensor
- conductive element
- forming
- chemical
- floating gate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- 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
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 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 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 chemical sensor in one implementation, includes a chemically-sensitive field effect transistor including a floating gate conductor having an upper surface.
- a dielectric material defines an opening extending to the upper surface of the floating gate conductor.
- a conductive element on a sidewall of the opening and extending over an upper surface of the dielectric material.
- a method for manufacturing a chemical sensor includes forming a chemically-sensitive field effect transistor including a floating gate conductor having an upper surface.
- the method further includes forming a dielectric material defining an opening extending to the upper surface of the floating gate conductor.
- the method further includes forming a conductive element on a sidewall of the opening and extending over an upper surface of the dielectric material.
- 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.
- FIGS. 3A and 3B illustrate cross-sectional and plan views respectively of a representative chemical sensors and corresponding reaction regions according to an exemplary embodiment.
- FIGS. 4 to 9 illustrate stages in a manufacturing process for forming an array of chemical sensors and corresponding well structures according to an exemplary embodiment.
- a chemical detection device include 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
- Chemical sensors with sensing surface areas which are not limited to a two-dimensional area at the bottom of the reaction regions.
- the sensing surface of the chemical sensor includes a generally horizontal portion along the bottom surface of the reaction region, as well as a generally vertical portion on a sidewall of the reaction region.
- the chemical sensor By extending the sensing surface in a generally vertical direction, the chemical sensor can have a small footprint, while also having a sufficiently large sensing surface area to avoid the noise issues associated with small sensing surfaces.
- the footprint of a chemical sensor is determined in part by the width (e.g. diameter) of the overlying reaction region and can be made small, allowing for a high density array.
- the sensing surface extends up the sidewall, the sensing surface area can be relatively large. As a result, low noise chemical sensors can be provided in a high density array, such that the characteristics of 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 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. 3A 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 a chemically-sensitive field effect transistor (chemFET), more specifically an ion-sensitive field effect transistor (ISFET) in this example.
- chemFET chemically-sensitive field effect transistor
- ISFET ion-sensitive field effect transistor
- the chemical sensor 350 includes a floating gate structure 318 having a sensor plate 320 coupled to the reaction region 301 by an electrically conductive element 370 .
- the sensor plate 320 is the uppermost floating gate conductor in the floating gate structure 318 .
- the floating gate structure 318 includes multiple patterned layers of conductive material within layers of dielectric material 319 .
- 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 having 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 having a sidewall 303 extending through dielectric material 310 to the upper surface of the sensor plate 320 .
- the dielectric material 310 may comprise one or more layers of material, such as silicon dioxide or silicon nitride.
- the dimensions of the openings, and their pitch, can vary from implementation to implementation.
- the openings can have a characteristic diameter, defined as the square root of 4 times the plan view cross-sectional area (A) divided by Pi (e.g., sqrt(4*A/ ⁇ ), of not greater than 5 micrometers, such as not greater than 3.5 micrometers, not greater than 2.0 micrometers, not greater than 1.6 micrometers, not greater than 1.0 micrometers, not greater than 0.8 micrometers, not greater than 0.6 micrometers, not greater than 0.4 micrometers, not greater than 0.2 micrometers or even not greater than 0.1 micrometers.
- the chemical sensor 350 includes a cup-shaped electrically conductive element 370 extending up the sidewall 303 of the dielectric material 310 .
- the electrically conductive element 370 is a conformal layer of material on the upper surface of the sensor plate 320 , and extends up the sidewall 303 and over a portion of the upper surface 311 of the dielectric material 310 . As a result, the electrically conductive element 370 protrudes out of the opening in the dielectric material 310 and onto the upper surface 311 of the dielectric material 310 .
- the inner surface 371 of the electrically conductive element 370 defines the reaction region 301 for the chemical sensor 350 . That is, there is no intervening deposited material layer between the inner surface 371 of the electrically conductive element 370 and the reaction region 301 . As a result of this structure, the inner surface 371 of the electrically conductive element 370 is cup-shaped and acts as the sensing surface for the chemical sensor 350 . In addition, because the electrically conductive element 370 protrudes out of the opening in the dielectric material 310 , the sensing surface area of the chemical sensor 350 is not limited by the surface area of the opening.
- the electrically conductive element 370 may comprise one or more of a variety of different materials to facilitate sensitivity to particular ions (e.g. hydrogen ions).
- the cup-shaped electrically conductive element 370 allows the chemical sensor 350 to have a small plan view area, while also having a sufficiently large surface area to avoid the noise issues associated with small sensing surfaces.
- the plan view area of the chemical sensor is determined in part by the width (or diameter) of the reaction region 301 and can be made small, allowing for a high density array.
- the sensing surface extends up the sidewall 303 and out of the reaction region 301 , the sensing surface area depends upon the depth and the circumference of the reaction region 301 , as well as the distance that the electrically conductive element 370 extends over the upper surface 311 , and can be relatively large.
- low noise chemical sensors 350 , 351 can be provided in a high density array, such that the characteristics of reactions can be accurately detected.
- a thin oxide of the material of the electrically conductive element 370 may be grown on the inner surface 371 which acts as a sensing material (e.g. an ion-sensitive sensing material) for the chemical sensor 350 .
- the electrically conductive element 370 may be titanium nitride, and titanium oxide or titanium oxynitride may be grown on the inner surface 371 during manufacturing and/or during exposure to solutions during use. Whether an oxide is formed depends on the conductive material, the manufacturing processes performed, and the conditions under which the device is operated.
- the electrically conductive element 370 is shown as a single layer of material. More generally, the electrically conductive element 370 may comprise one or more layers of a variety of electrically conductive materials, such as metals or ceramics, depending upon the implementation.
- the conductive material can be for example a metallic material or alloy thereof, or can be a ceramic material, or a combination thereof.
- An exemplary metallic material includes one of aluminum, copper, nickel, titanium, silver, gold, platinum, hafnium, lanthanum, tantalum, tungsten, iridium, zirconium, palladium, or a combination thereof.
- An exemplary ceramic material includes one of titanium nitride, titanium aluminum nitride, titanium oxynitride, tantalum nitride, or a combination thereof.
- an additional conformal sensing material (not shown) is deposited on the inner surface 371 of the electrically conductive element 370 and on the upper surface 311 of the dielectric material 310 .
- the sensing material 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 inner surface 371 of the electrically conductive element 370 surrounds the reaction region 301 .
- the opening and the reaction region 301 have circular cross sections.
- the rim 390 of the portion of the conductive element 370 extending over the upper surface 311 of the dielectric material 310 also has a circular cross section.
- these may be non-circular.
- the cross-sections 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 proximate to the electrically conductive element 370 .
- the presence of charge 324 in an analyte solution alters the surface potential at the interface between the analyte solution and the inner surface 371 of the electrically conductive element 370 , due to the protonation or deprotonation of surface charge groups caused by the ions present in the analyte solution.
- 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 of the chemical sensor 350 .
- 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.
- the distance that the electrically conductive element 370 extends away from the opening and over the upper surface 311 of the dielectric material 310 is determined by dimensions of an etch mask used to pattern the electrically conductive element 370 . Because the charge 324 is more highly concentrated near the bottom of the reaction region 301 , in some embodiments variations in the dimensions of this extension does not have a significant effect on the amplitude of the signal detected in response to the charge 324 . In such a case, the formation of the etch mask used to define the electrically conductive element 370 may not require a critical alignment step.
- 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 electrically conductive element 370 . 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 9 illustrate stages in a manufacturing process for forming an array of chemical sensors and corresponding well structures according to an exemplary embodiment.
- FIG. 4 illustrates a first stage of forming a structure including a dielectric material 310 on the sensor plate 320 of the field effect transistor of the chemical sensor 350 .
- the structure in FIG. 4 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.
- 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 completed floating gate structure 318 shown in FIG. 4 . Alternatively, other and/or additional techniques may be performed to form the structure.
- Forming the structure in FIG. 4 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 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.
- the dielectric material 310 of the structure in FIG. 4 is etched to form openings 500 , 502 extending to the upper surfaces of the floating gate structures of the chemical sensors 350 , 351 , resulting in the structure illustrated in FIG. 5 .
- the openings 500 , 502 may for example be formed by using a lithographic process to pattern a layer of photoresist on the dielectric material 310 to define the locations of the openings 500 , 502 , and then anisotropically etching the dielectric material 310 using the patterned photoreist as an etch mask.
- the anisotropic etching of the dielectric material 310 may for example be a dry etch process, such as a fluorine based Reactive Ion Etching (RIE) process.
- RIE fluorine based Reactive Ion Etching
- the openings 500 , 502 are separated by a distance 530 that is equal to their width 520 .
- the separation distance 530 between adjacent openings may be less than the width 520 .
- the separation distance 530 may be a minimum feature size for the process (e.g. a lithographic process) used to form the openings 500 , 502 . In such a case, the distance 530 may be significantly less than the width 520 .
- the conductive material 600 comprises one or more layers of electrically conductive material.
- the conductive material 600 may be a layer of titanium nitride, or a layer of titanium.
- other and/or additional conductive materials may be used, such as those described above with reference to the electrically conductive element 370 .
- more than one layer of conductive material may be deposited.
- the conductive material 600 may be deposited using various techniques, such as sputtering, reactive sputtering, atomic layer deposition (ALD), low pressure chemical vapor deposition (LPCVD), plasma enhanced chemical vapor deposition (PECVD), metal organic chemical vapor deposition (MOCVD), etc.
- ALD atomic layer deposition
- LPCVD low pressure chemical vapor deposition
- PECVD plasma enhanced chemical vapor deposition
- MOCVD metal organic chemical vapor deposition
- mask elements 700 , 702 are formed within the openings 500 , 502 , resulting in the structure illustrated in FIG. 7 .
- the mask elements 700 , 702 have widths greater than that of the openings 500 , 502 , so that the mask elements 700 , 702 extend over a portion of the upper surface 311 of the dielectric material 310 .
- the mask elements 700 , 702 may for example be formed by patterning a layer of photoresist using a lithographic process. Alternatively, other materials and processes may be used to form the mask elements 700 , 702 .
- the conductive material 600 is etched using the mask elements 700 , 702 as an etch mask, resulting in the structure illustrated in FIG. 8 .
- the etching process removes exposed conductive material 600 from the upper surface 311 of the dielectric material 310 to form the cup-shaped electrically conductive elements 370 , 800 .
- the mask elements 700 , 702 also protect the inner surfaces of the electrically conductive elements 370 , 800 , which subsequently act as the sensing surfaces for the chemical sensors 350 , 351 , during the etch process. In doing so, damage to the sensing surfaces can be avoided.
- the mask elements 700 , 702 are removed to expose the electrically conductive elements 370 , 800 , resulting in the structure illustrated in FIG. 9 .
- the mask elements 700 , 702 are patterned photoresist, they can be removed using a photoresist stripping process.
- the mask elements 700 , 702 comprise other materials, other techniques may be used.
Abstract
Description
- 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 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 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.
- An issue that arises in the operation of large scale 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 chemical sensor is described. The chemical sensor includes a chemically-sensitive field effect transistor including a floating gate conductor having an upper surface. A dielectric material defines an opening extending to the upper surface of the floating gate conductor. A conductive element on a sidewall of the opening and extending over an upper surface of the dielectric material.
- In another implementation, a method for manufacturing a chemical sensor is described. The method includes forming a chemically-sensitive field effect transistor including a floating gate conductor having an upper surface. The method further includes forming a dielectric material defining an opening extending to the upper surface of the floating gate conductor. The method further includes forming a conductive element on a sidewall of the opening and extending over an upper surface of the dielectric material.
- 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. -
FIGS. 3A and 3B illustrate cross-sectional and plan views respectively of a representative chemical sensors and corresponding reaction regions according to an exemplary embodiment. -
FIGS. 4 to 9 illustrate stages in a manufacturing process for forming an array of chemical sensors and corresponding well structures according to an exemplary embodiment. - A chemical detection device are described that include low noise chemical sensors, such as chemically-sensitive field effect transistors (chemFETs), for detecting chemical reactions within overlying, operationally associated reaction regions.
- Reducing the plan or top view area (or footprint) of individual chemical sensors and the overlying reaction regions allows for higher density devices. However, as the dimensions of the chemical sensors are reduced, Applicants have found that a corresponding reduction in the sensing surface area of the sensors can significantly impact performance.
- For example, for chemical sensors having sensing surfaces defined at the bottom of the reaction regions, reducing the plan view dimensions (e.g. the width or diameter) of the reaction regions results in a similar reduction in the sensing surface areas. Applicants have found that as the sensing surface area is reduced to technology limits, fluidic noise due to the random fluctuation of charge on the sensing surface contributes to an increasing proportion of the total variation in sensing surface potential. This can significantly reduce the signal-to-noise ratio (SNR) of the sensor output signal, which affects the accuracy of the downstream signal processing used to determine the characteristics of the chemical and/or biological process being detected by the sensor.
- Chemical sensors with sensing surface areas which are not limited to a two-dimensional area at the bottom of the reaction regions. In embodiments described herein, the sensing surface of the chemical sensor includes a generally horizontal portion along the bottom surface of the reaction region, as well as a generally vertical portion on a sidewall of the reaction region.
- By extending the sensing surface in a generally vertical direction, the chemical sensor can have a small footprint, while also having a sufficiently large sensing surface area to avoid the noise issues associated with small sensing surfaces. The footprint of a chemical sensor is determined in part by the width (e.g. diameter) of the overlying reaction region and can be made small, allowing for a high density array. In addition, because the sensing surface extends up the sidewall, the sensing surface area can be relatively large. As a result, low noise chemical sensors can be provided in a high density array, such that the characteristics of 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. 3A 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 a chemically-sensitive field effect transistor (chemFET), more specifically an ion-sensitive field effect transistor (ISFET) in this example. - The
chemical sensor 350 includes a floatinggate structure 318 having asensor plate 320 coupled to thereaction region 301 by an electricallyconductive element 370. As can be seen inFIG. 3A , thesensor plate 320 is the uppermost floating gate conductor in the floatinggate structure 318. In the illustrated example, the floatinggate structure 318 includes multiple patterned layers of conductive material within layers ofdielectric material 319. - 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 having 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 floatinggate 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. 3A , thereaction region 301 is within an opening having asidewall 303 extending throughdielectric material 310 to the upper surface of thesensor plate 320. Thedielectric material 310 may comprise one or more layers of material, such as silicon dioxide or silicon nitride. - The dimensions of the openings, and their pitch, can vary from implementation to implementation. In some embodiments, the openings can have a characteristic diameter, defined as the square root of 4 times the plan view cross-sectional area (A) divided by Pi (e.g., sqrt(4*A/π), of not greater than 5 micrometers, such as not greater than 3.5 micrometers, not greater than 2.0 micrometers, not greater than 1.6 micrometers, not greater than 1.0 micrometers, not greater than 0.8 micrometers, not greater than 0.6 micrometers, not greater than 0.4 micrometers, not greater than 0.2 micrometers or even not greater than 0.1 micrometers.
- The
chemical sensor 350 includes a cup-shaped electricallyconductive element 370 extending up thesidewall 303 of thedielectric material 310. The electricallyconductive element 370 is a conformal layer of material on the upper surface of thesensor plate 320, and extends up thesidewall 303 and over a portion of theupper surface 311 of thedielectric material 310. As a result, the electricallyconductive element 370 protrudes out of the opening in thedielectric material 310 and onto theupper surface 311 of thedielectric material 310. - In the illustrated embodiment, the
inner surface 371 of the electricallyconductive element 370 defines thereaction region 301 for thechemical sensor 350. That is, there is no intervening deposited material layer between theinner surface 371 of the electricallyconductive element 370 and thereaction region 301. As a result of this structure, theinner surface 371 of the electricallyconductive element 370 is cup-shaped and acts as the sensing surface for thechemical sensor 350. In addition, because the electricallyconductive element 370 protrudes out of the opening in thedielectric material 310, the sensing surface area of thechemical sensor 350 is not limited by the surface area of the opening. The electricallyconductive element 370 may comprise one or more of a variety of different materials to facilitate sensitivity to particular ions (e.g. hydrogen ions). - The cup-shaped electrically
conductive element 370 allows thechemical sensor 350 to have a small plan view area, while also having a sufficiently large surface area to avoid the noise issues associated with small sensing surfaces. The plan view area of the chemical sensor is determined in part by the width (or diameter) of thereaction region 301 and can be made small, allowing for a high density array. In addition, because the sensing surface extends up thesidewall 303 and out of thereaction region 301, the sensing surface area depends upon the depth and the circumference of thereaction region 301, as well as the distance that the electricallyconductive element 370 extends over theupper surface 311, and can be relatively large. As a result, lownoise chemical sensors - During manufacturing and/or operation of the device, a thin oxide of the material of the electrically
conductive element 370 may be grown on theinner surface 371 which acts as a sensing material (e.g. an ion-sensitive sensing material) for thechemical sensor 350. For example, in one embodiment the electricallyconductive element 370 may be titanium nitride, and titanium oxide or titanium oxynitride may be grown on theinner surface 371 during manufacturing and/or during exposure to solutions during use. Whether an oxide is formed depends on the conductive material, the manufacturing processes performed, and the conditions under which the device is operated. - In the illustrated example, the electrically
conductive element 370 is shown as a single layer of material. More generally, the electricallyconductive element 370 may comprise one or more layers of a variety of electrically conductive materials, such as metals or ceramics, depending upon the implementation. The conductive material can be for example a metallic material or alloy thereof, or can be a ceramic material, or a combination thereof. An exemplary metallic material includes one of aluminum, copper, nickel, titanium, silver, gold, platinum, hafnium, lanthanum, tantalum, tungsten, iridium, zirconium, palladium, or a combination thereof. An exemplary ceramic material includes one of titanium nitride, titanium aluminum nitride, titanium oxynitride, tantalum nitride, or a combination thereof. - In some alternative embodiments, an additional conformal sensing material (not shown) is deposited on the
inner surface 371 of the electricallyconductive element 370 and on theupper surface 311 of thedielectric material 310. The sensing material 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. - As shown in the plan view of
FIG. 3B , theinner surface 371 of the electricallyconductive element 370 surrounds thereaction region 301. In the illustrated example the opening and thereaction region 301 have circular cross sections. In addition, therim 390 of the portion of theconductive element 370 extending over theupper surface 311 of thedielectric material 310 also has a circular cross section. Alternatively, these may be non-circular. For example, the cross-sections may be square, rectangular, hexagonal, or irregularly shaped. - Referring back to
FIG. 3A , in operation, reactants, wash solutions, and other reagents may move in and out of thereaction region 301 by adiffusion mechanism 340. Thechemical sensor 350 is responsive to (and generates an output signal related to) the amount of acharge 324 proximate to the electricallyconductive element 370. The presence ofcharge 324 in an analyte solution alters the surface potential at the interface between the analyte solution and theinner surface 371 of the electricallyconductive element 370, due to the protonation or deprotonation of surface charge groups caused by the ions present in the analyte solution. Changes in thecharge 324 cause changes in the voltage on the floatinggate structure 318, which in turn changes in the threshold voltage of the transistor of thechemical sensor 350. 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. - As described in more detail below with respect to
FIGS. 4-9 , the distance that the electricallyconductive element 370 extends away from the opening and over theupper surface 311 of thedielectric material 310 is determined by dimensions of an etch mask used to pattern the electricallyconductive element 370. Because thecharge 324 is more highly concentrated near the bottom of thereaction region 301, in some embodiments variations in the dimensions of this extension does not have a significant effect on the amplitude of the signal detected in response to thecharge 324. In such a case, the formation of the etch mask used to define the electricallyconductive element 370 may not require a critical alignment step. - 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 electricallyconductive element 370. 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 9 illustrate stages in a manufacturing process for forming an array of chemical sensors and corresponding well structures according to an exemplary embodiment. -
FIG. 4 illustrates a first stage of forming a structure including adielectric material 310 on thesensor plate 320 of the field effect transistor of thechemical sensor 350. The structure inFIG. 4 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. 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 completed floatinggate structure 318 shown inFIG. 4 . Alternatively, other and/or additional techniques may be performed to form the structure. - Forming the structure in
FIG. 4 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 the structure 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, the
dielectric material 310 of the structure inFIG. 4 is etched to formopenings chemical sensors FIG. 5 . - The
openings dielectric material 310 to define the locations of theopenings dielectric material 310 using the patterned photoreist as an etch mask. The anisotropic etching of thedielectric material 310 may for example be a dry etch process, such as a fluorine based Reactive Ion Etching (RIE) process. - In the illustrated embodiment, the
openings distance 530 that is equal to theirwidth 520. Alternatively, theseparation distance 530 between adjacent openings may be less than thewidth 520. For example, theseparation distance 530 may be a minimum feature size for the process (e.g. a lithographic process) used to form theopenings distance 530 may be significantly less than thewidth 520. - Next, a conformal layer of
conductive material 600 is deposited on the structure illustrated inFIG. 5 , resulting in the structure illustrated inFIG. 6 . Theconductive material 600 comprises one or more layers of electrically conductive material. For example, theconductive material 600 may be a layer of titanium nitride, or a layer of titanium. Alternatively, other and/or additional conductive materials may be used, such as those described above with reference to the electricallyconductive element 370. In addition, more than one layer of conductive material may be deposited. - The
conductive material 600 may be deposited using various techniques, such as sputtering, reactive sputtering, atomic layer deposition (ALD), low pressure chemical vapor deposition (LPCVD), plasma enhanced chemical vapor deposition (PECVD), metal organic chemical vapor deposition (MOCVD), etc. - Next,
mask elements openings FIG. 7 . As shown inFIG. 7 , themask elements openings mask elements upper surface 311 of thedielectric material 310. - The
mask elements mask elements - Next, the
conductive material 600 is etched using themask elements FIG. 8 . The etching process removes exposedconductive material 600 from theupper surface 311 of thedielectric material 310 to form the cup-shaped electricallyconductive elements - The
mask elements conductive elements chemical sensors - Next, the
mask elements conductive elements FIG. 9 . In embodiments in which themask elements mask elements - 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 (20)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13/801,243 US8841217B1 (en) | 2013-03-13 | 2013-03-13 | Chemical sensor with protruded sensor surface |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13/801,243 US8841217B1 (en) | 2013-03-13 | 2013-03-13 | Chemical sensor with protruded sensor surface |
Publications (2)
Publication Number | Publication Date |
---|---|
US20140264466A1 true US20140264466A1 (en) | 2014-09-18 |
US8841217B1 US8841217B1 (en) | 2014-09-23 |
Family
ID=51523652
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/801,243 Active US8841217B1 (en) | 2013-03-13 | 2013-03-13 | Chemical sensor with protruded sensor surface |
Country Status (1)
Country | Link |
---|---|
US (1) | US8841217B1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10890554B1 (en) * | 2019-06-20 | 2021-01-12 | Globalfoundries Singapore Pte. Ltd. | Sensors with a non-planar sensing structure |
CN113945621A (en) * | 2015-08-25 | 2022-01-18 | 生命技术公司 | Deep micro-well design and method of making same |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8262900B2 (en) | 2006-12-14 | 2012-09-11 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US11339430B2 (en) | 2007-07-10 | 2022-05-24 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
CA2672315A1 (en) | 2006-12-14 | 2008-06-26 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes using large scale fet arrays |
US8349167B2 (en) | 2006-12-14 | 2013-01-08 | Life Technologies Corporation | Methods and apparatus for detecting molecular interactions using FET arrays |
US20100301398A1 (en) | 2009-05-29 | 2010-12-02 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
US20100137143A1 (en) | 2008-10-22 | 2010-06-03 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
US20120261274A1 (en) | 2009-05-29 | 2012-10-18 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US8776573B2 (en) | 2009-05-29 | 2014-07-15 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
AU2011226767B1 (en) | 2010-06-30 | 2011-11-10 | Life Technologies Corporation | Ion-sensing charge-accumulation circuits and methods |
US8731847B2 (en) | 2010-06-30 | 2014-05-20 | Life Technologies Corporation | Array configuration and readout scheme |
JP5952813B2 (en) | 2010-06-30 | 2016-07-13 | ライフ テクノロジーズ コーポレーション | Method and apparatus for testing ISFET arrays |
US11307166B2 (en) | 2010-07-01 | 2022-04-19 | Life Technologies Corporation | Column ADC |
EP2589065B1 (en) | 2010-07-03 | 2015-08-19 | Life Technologies Corporation | Chemically sensitive sensor with lightly doped drains |
WO2012036679A1 (en) | 2010-09-15 | 2012-03-22 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
EP2619564B1 (en) | 2010-09-24 | 2016-03-16 | Life Technologies Corporation | Matched pair transistor circuits |
US9970984B2 (en) | 2011-12-01 | 2018-05-15 | Life Technologies Corporation | Method and apparatus for identifying defects in a chemical sensor array |
US8786331B2 (en) | 2012-05-29 | 2014-07-22 | Life Technologies Corporation | System for reducing noise in a chemical sensor array |
US9080968B2 (en) | 2013-01-04 | 2015-07-14 | Life Technologies Corporation | Methods and systems for point of use removal of sacrificial material |
US9841398B2 (en) | 2013-01-08 | 2017-12-12 | Life Technologies Corporation | Methods for manufacturing well structures for low-noise chemical sensors |
US8963216B2 (en) * | 2013-03-13 | 2015-02-24 | Life Technologies Corporation | Chemical sensor with sidewall spacer sensor surface |
US9835585B2 (en) * | 2013-03-15 | 2017-12-05 | Life Technologies Corporation | Chemical sensor with protruded sensor surface |
CN105051525B (en) | 2013-03-15 | 2019-07-26 | 生命科技公司 | Chemical device with thin conducting element |
CN105264366B (en) | 2013-03-15 | 2019-04-16 | 生命科技公司 | Chemical sensor with consistent sensor surface area |
US20140336063A1 (en) | 2013-05-09 | 2014-11-13 | Life Technologies Corporation | Windowed Sequencing |
US10458942B2 (en) | 2013-06-10 | 2019-10-29 | Life Technologies Corporation | Chemical sensor array having multiple sensors per well |
US10077472B2 (en) | 2014-12-18 | 2018-09-18 | Life Technologies Corporation | High data rate integrated circuit with power management |
KR102593647B1 (en) | 2014-12-18 | 2023-10-26 | 라이프 테크놀로지스 코포레이션 | High data rate integrated circuit with transmitter configuration |
EP3234575B1 (en) | 2014-12-18 | 2023-01-25 | Life Technologies Corporation | Apparatus for measuring analytes using large scale fet arrays |
US10048220B2 (en) * | 2015-10-08 | 2018-08-14 | Taiwan Semiconductor Manufacturing Company Ltd. | Biosensor field effect transistor having specific well structure and method of forming the same |
Family Cites Families (325)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5530312B2 (en) | 1975-01-16 | 1980-08-09 | ||
DE3269784D1 (en) | 1981-05-15 | 1986-04-17 | Licentia Gmbh | Method for measuring ionic concentrations |
JPS5870155U (en) | 1981-11-06 | 1983-05-12 | ヤマハ株式会社 | Electronic equipment storage furniture |
US4411741A (en) | 1982-01-12 | 1983-10-25 | University Of Utah | Apparatus and method for measuring the concentration of components in fluids |
NL8302964A (en) | 1983-08-24 | 1985-03-18 | Cordis Europ | DEVICE FOR DETERMINING THE ACTIVITY OF AN ION (PION) IN A LIQUID. |
NL8303792A (en) | 1983-11-03 | 1985-06-03 | Cordis Europ | Apparatus provided with an measuring circuit based on an ISFET; ISFET SUITABLE FOR USE IN THE MEASURING CIRCUIT AND METHOD FOR MANUFACTURING AN ISFET TO BE USED IN THE MEASURING CIRCUIT |
JPS60128345A (en) | 1983-12-15 | 1985-07-09 | Olympus Optical Co Ltd | Measuring device for ion concentration |
DE3513168A1 (en) | 1985-04-12 | 1986-10-16 | Thomas 8000 München Dandekar | BIOSENSOR CONSISTING OF A SEMICONDUCTOR BASED ON SILICON OR CARBON-BASED (ELECTRONIC PART) AND NUCLEIN BASE (OR. OTHER BIOL. MONOMERS) |
US4743954A (en) | 1985-06-07 | 1988-05-10 | University Of Utah | Integrated circuit for a chemical-selective sensor with voltage output |
US4863849A (en) | 1985-07-18 | 1989-09-05 | New York Medical College | Automatable process for sequencing nucleotide |
EP0213825A3 (en) | 1985-08-22 | 1989-04-26 | Molecular Devices Corporation | Multiple chemically modulated capacitance |
GB8522785D0 (en) | 1985-09-14 | 1985-10-16 | Emi Plc Thorn | Chemical-sensitive semiconductor device |
US4822566A (en) | 1985-11-19 | 1989-04-18 | The Johns Hopkins University | Optimized capacitive sensor for chemical analysis and measurement |
US4864229A (en) | 1986-05-03 | 1989-09-05 | Integrated Ionics, Inc. | Method and apparatus for testing chemical and ionic sensors |
US4722830A (en) | 1986-05-05 | 1988-02-02 | General Electric Company | Automated multiple stream analysis system |
JPS6364406A (en) | 1986-09-04 | 1988-03-22 | Tamura Seisakusho Co Ltd | Variable frequency chopping system insulating amplifier |
US5113870A (en) | 1987-05-01 | 1992-05-19 | Rossenfeld Joel P | Method and apparatus for the analysis, display and classification of event related potentials by interpretation of P3 responses |
EP0400042B1 (en) | 1988-02-08 | 1997-01-08 | I-Stat Corporation | Metal oxide electrodes |
US4971903A (en) | 1988-03-25 | 1990-11-20 | Edward Hyman | Pyrophosphate-based method and apparatus for sequencing nucleic acids |
US4874499A (en) | 1988-05-23 | 1989-10-17 | Massachusetts Institute Of Technology | Electrochemical microsensors and method of making such sensors |
US5200051A (en) | 1988-11-14 | 1993-04-06 | I-Stat Corporation | Wholly microfabricated biosensors and process for the manufacture and use thereof |
US4990974A (en) | 1989-03-02 | 1991-02-05 | Thunderbird Technologies, Inc. | Fermi threshold field effect transistor |
DE68925897T2 (en) | 1989-04-28 | 1996-10-02 | Ibm | Gate array cell, consisting of FETs of various and optimized sizes |
US6919211B1 (en) | 1989-06-07 | 2005-07-19 | Affymetrix, Inc. | Polypeptide arrays |
US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
JP3001104B2 (en) | 1989-10-04 | 2000-01-24 | オリンパス光学工業株式会社 | Sensor structure and method of manufacturing the same |
US5110441A (en) | 1989-12-14 | 1992-05-05 | Monsanto Company | Solid state ph sensor |
US5317407A (en) | 1991-03-11 | 1994-05-31 | General Electric Company | Fixed-pattern noise correction circuitry for solid-state imager |
KR940010562B1 (en) | 1991-09-06 | 1994-10-24 | 손병기 | Ion-sensing fet with ta2o5 hydrogen ion-sensing film |
AU2907092A (en) | 1991-10-21 | 1993-05-21 | James W. Holm-Kennedy | Method and device for biochemical sensing |
US5846708A (en) | 1991-11-19 | 1998-12-08 | Massachusetts Institiute Of Technology | Optical and electrical methods and apparatus for molecule detection |
US5637469A (en) | 1992-05-01 | 1997-06-10 | Trustees Of The University Of Pennsylvania | Methods and apparatus for the detection of an analyte utilizing mesoscale flow systems |
JPH06138846A (en) | 1992-10-29 | 1994-05-20 | Hitachi Ltd | Liquid crystal half-tone display system |
US5284566A (en) | 1993-01-04 | 1994-02-08 | Bacharach, Inc. | Electrochemical gas sensor with wraparound reference electrode |
US5436149A (en) | 1993-02-19 | 1995-07-25 | Barnes; Wayne M. | Thermostable DNA polymerase with enhanced thermostability and enhanced length and efficiency of primer extension |
WO1994026029A1 (en) | 1993-04-26 | 1994-11-10 | Unifet Incorporated | Method and apparatus for multiplexing devices having long thermal time constants |
JP3413664B2 (en) | 1993-08-12 | 2003-06-03 | ソニー株式会社 | Charge transfer device |
US5965452A (en) | 1996-07-09 | 1999-10-12 | Nanogen, Inc. | Multiplexed active biologic array |
US5414284A (en) | 1994-01-19 | 1995-05-09 | Baxter; Ronald D. | ESD Protection of ISFET sensors |
US5439839A (en) | 1994-07-13 | 1995-08-08 | Winbond Electronics Corporation | Self-aligned source/drain MOS process |
US6654505B2 (en) | 1994-10-13 | 2003-11-25 | Lynx Therapeutics, Inc. | System and apparatus for sequential processing of analytes |
US5631704A (en) | 1994-10-14 | 1997-05-20 | Lucent Technologies, Inc. | Active pixel sensor and imaging system having differential mode |
US5490971A (en) | 1994-10-25 | 1996-02-13 | Sippican, Inc. | Chemical detector |
US5585069A (en) | 1994-11-10 | 1996-12-17 | David Sarnoff Research Center, Inc. | Partitioned microelectronic and fluidic device array for clinical diagnostics and chemical synthesis |
US5856174A (en) | 1995-06-29 | 1999-01-05 | Affymetrix, Inc. | Integrated nucleic acid diagnostic device |
US5702964A (en) | 1995-10-17 | 1997-12-30 | Lg Semicon, Co., Ltd. | Method for forming a semiconductor device having a floating gate |
GB9620209D0 (en) | 1996-09-27 | 1996-11-13 | Cemu Bioteknik Ab | Method of sequencing DNA |
US5958703A (en) | 1996-12-03 | 1999-09-28 | Glaxo Group Limited | Use of modified tethers in screening compound libraries |
CA2271717A1 (en) | 1996-12-12 | 1998-06-18 | Prolume, Ltd. | Apparatus and method for detecting and identifying infectious agents |
US6605428B2 (en) | 1996-12-20 | 2003-08-12 | Roche Diagnostics Gmbh | Method for the direct, exponential amplification and sequencing of DNA molecules and its application |
DE19653439A1 (en) | 1996-12-20 | 1998-07-02 | Svante Dr Paeaebo | Methods for the direct, exponential amplification and sequencing of DNA molecules and their application |
US20030215857A1 (en) | 1996-12-20 | 2003-11-20 | Roche Diagnostics Gmbh | Method for the direct, exponential amplification and sequencing of DNA molecules and its application |
US5912560A (en) | 1997-02-25 | 1999-06-15 | Waferscale Integration Inc. | Charge pump circuit for voltage boosting in integrated semiconductor circuits |
US5793230A (en) | 1997-02-26 | 1998-08-11 | Sandia Corporation | Sensor readout detector circuit |
US6197557B1 (en) | 1997-03-05 | 2001-03-06 | The Regents Of The University Of Michigan | Compositions and methods for analysis of nucleic acids |
US6327410B1 (en) | 1997-03-14 | 2001-12-04 | The Trustees Of Tufts College | Target analyte sensors utilizing Microspheres |
US7622294B2 (en) | 1997-03-14 | 2009-11-24 | Trustees Of Tufts College | Methods for detecting target analytes and enzymatic reactions |
US6391622B1 (en) | 1997-04-04 | 2002-05-21 | Caliper Technologies Corp. | Closed-loop biochemical analyzers |
JP3666604B2 (en) | 1997-04-16 | 2005-06-29 | アプレラ コーポレーション | Nucleic acid archiving |
US6872527B2 (en) | 1997-04-16 | 2005-03-29 | Xtrana, Inc. | Nucleic acid archiving |
US5911873A (en) | 1997-05-02 | 1999-06-15 | Rosemount Analytical Inc. | Apparatus and method for operating an ISFET at multiple drain currents and gate-source voltages allowing for diagnostics and control of isopotential points |
US7220550B2 (en) | 1997-05-14 | 2007-05-22 | Keensense, Inc. | Molecular wire injection sensors |
US6969488B2 (en) | 1998-05-22 | 2005-11-29 | Solexa, Inc. | System and apparatus for sequential processing of analytes |
EP0985142A4 (en) | 1997-05-23 | 2006-09-13 | Lynx Therapeutics Inc | System and apparaus for sequential processing of analytes |
JP4231560B2 (en) | 1997-05-29 | 2009-03-04 | 株式会社堀場製作所 | Method and apparatus for electrochemical measurement of chemical quantity distribution |
US6002299A (en) | 1997-06-10 | 1999-12-14 | Cirrus Logic, Inc. | High-order multipath operational amplifier with dynamic offset reduction, controlled saturation current limiting, and current feedback for enhanced conditional stability |
FR2764702B1 (en) | 1997-06-11 | 1999-09-03 | Lyon Ecole Centrale | METHOD FOR IDENTIFYING AND / OR DETERMINING BIOLOGICAL SUBSTANCES PRESENT IN A CONDUCTIVE LIQUID, DEVICE AND AFFINITY SENSOR USEFUL FOR THE IMPLEMENTATION OF THIS PROCESS |
US5923421A (en) | 1997-07-24 | 1999-07-13 | Lockheed Martin Energy Research Corporation | Chemical detection using calorimetric spectroscopy |
US6465178B2 (en) | 1997-09-30 | 2002-10-15 | Surmodics, Inc. | Target molecule attachment to surfaces |
CA2305449A1 (en) | 1997-10-10 | 1999-04-22 | President & Fellows Of Harvard College | Replica amplification of nucleic acid arrays |
US6511803B1 (en) | 1997-10-10 | 2003-01-28 | President And Fellows Of Harvard College | Replica amplification of nucleic acid arrays |
US6485944B1 (en) | 1997-10-10 | 2002-11-26 | President And Fellows Of Harvard College | Replica amplification of nucleic acid arrays |
KR100251528B1 (en) | 1997-10-22 | 2000-04-15 | 김덕중 | Sense field effect transistor having multi-sense source pad |
US6369737B1 (en) | 1997-10-30 | 2002-04-09 | The Board Of Trustees Of The Leland Stanford Junior University | Method and apparatus for converting a low dynamic range analog signal to a large dynamic range floating-point digital representation |
US7090975B2 (en) | 1998-03-13 | 2006-08-15 | Promega Corporation | Pyrophosphorolysis and incorporation of nucleotide method for nucleic acid detection |
CA2325886C (en) | 1998-04-09 | 2009-07-21 | California Institute Of Technology | Electronic techniques for analyte detection |
US6780591B2 (en) | 1998-05-01 | 2004-08-24 | Arizona Board Of Regents | Method of determining the nucleotide sequence of oligonucleotides and DNA molecules |
EP1082458A1 (en) | 1998-05-01 | 2001-03-14 | Arizona Board Of Regents | Method of determining the nucleotide sequence of oligonucleotides and dna molecules |
US7875440B2 (en) | 1998-05-01 | 2011-01-25 | Arizona Board Of Regents | Method of determining the nucleotide sequence of oligonucleotides and DNA molecules |
EP1090293B2 (en) | 1998-06-24 | 2019-01-23 | Illumina, Inc. | Decoding of array sensors with microspheres |
US6195585B1 (en) | 1998-06-26 | 2001-02-27 | Advanced Bionics Corporation | Remote monitoring of implantable cochlear stimulator |
JP2002532717A (en) | 1998-12-11 | 2002-10-02 | サイミックス テクノロジーズ、インク | Sensor array based system and method for rapid material characterization |
DE69930310T3 (en) | 1998-12-14 | 2009-12-17 | Pacific Biosciences of California, Inc. (n. d. Ges. d. Staates Delaware), Menlo Park | KIT AND METHOD FOR THE NUCLEIC ACID SEQUENCING OF INDIVIDUAL MOLECULES BY POLYMERASE SYNTHESIS |
DE19857953C2 (en) | 1998-12-16 | 2001-02-15 | Conducta Endress & Hauser | Device for measuring the concentration of ions in a measuring liquid |
US6429027B1 (en) | 1998-12-28 | 2002-08-06 | Illumina, Inc. | Composite arrays utilizing microspheres |
US6361671B1 (en) | 1999-01-11 | 2002-03-26 | The Regents Of The University Of California | Microfabricated capillary electrophoresis chip and method for simultaneously detecting multiple redox labels |
GB9901475D0 (en) | 1999-01-22 | 1999-03-17 | Pyrosequencing Ab | A method of DNA sequencing |
US20020150909A1 (en) | 1999-02-09 | 2002-10-17 | Stuelpnagel John R. | Automated information processing in randomly ordered arrays |
AU2823100A (en) | 1999-02-22 | 2000-09-14 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | A hybrid electrical device with biological components |
EP1163052B1 (en) | 1999-02-23 | 2010-06-02 | Caliper Life Sciences, Inc. | Manipulation of microparticles in microfluidic systems |
US6355431B1 (en) | 1999-04-20 | 2002-03-12 | Illumina, Inc. | Detection of nucleic acid amplification reactions using bead arrays |
US20050244870A1 (en) | 1999-04-20 | 2005-11-03 | Illumina, Inc. | Nucleic acid sequencing using microsphere arrays |
US20030108867A1 (en) | 1999-04-20 | 2003-06-12 | Chee Mark S | Nucleic acid sequencing using microsphere arrays |
US7097973B1 (en) | 1999-06-14 | 2006-08-29 | Alpha Mos | Method for monitoring molecular species within a medium |
US6818395B1 (en) | 1999-06-28 | 2004-11-16 | California Institute Of Technology | Methods and apparatus for analyzing polynucleotide sequences |
EP1204859B1 (en) | 1999-07-16 | 2006-11-22 | The Board Of Regents, The University Of Texas System | Method and apparatus for the delivery of samples to a chemical sensor array |
US6459398B1 (en) | 1999-07-20 | 2002-10-01 | D.S.P.C. Technologies Ltd. | Pulse modulated digital to analog converter (DAC) |
US6977145B2 (en) | 1999-07-28 | 2005-12-20 | Serono Genetics Institute S.A. | Method for carrying out a biochemical protocol in continuous flow in a microreactor |
US6423536B1 (en) | 1999-08-02 | 2002-07-23 | Molecular Dynamics, Inc. | Low volume chemical and biochemical reaction system |
US7211390B2 (en) | 1999-09-16 | 2007-05-01 | 454 Life Sciences Corporation | Method of sequencing a nucleic acid |
US6274320B1 (en) | 1999-09-16 | 2001-08-14 | Curagen Corporation | Method of sequencing a nucleic acid |
US7244559B2 (en) | 1999-09-16 | 2007-07-17 | 454 Life Sciences Corporation | Method of sequencing a nucleic acid |
US7124221B1 (en) | 1999-10-19 | 2006-10-17 | Rambus Inc. | Low latency multi-level communication interface |
GB9926956D0 (en) | 1999-11-13 | 2000-01-12 | Koninkl Philips Electronics Nv | Amplifier |
US6518024B2 (en) | 1999-12-13 | 2003-02-11 | Motorola, Inc. | Electrochemical detection of single base extension |
JP2001175340A (en) | 1999-12-14 | 2001-06-29 | Matsushita Electric Ind Co Ltd | Potential generation circuit |
KR100744857B1 (en) | 2000-02-14 | 2007-08-01 | 코닌클리즈케 필립스 일렉트로닉스 엔.브이. | Current-to-voltage converter with controllable gain, and signal processing circuit comprising such converter |
EP1198596A1 (en) | 2000-02-15 | 2002-04-24 | Lynx Therapeutics, Inc. | Data analysis and display system for ligation-based dna sequencing |
EP1257668B1 (en) | 2000-02-16 | 2008-10-29 | Illumina, Inc. | Parallel genotyping of multiple patient samples |
US6649416B1 (en) | 2000-02-18 | 2003-11-18 | Trustees Of Tufts College | Intelligent electro-optical sensor array and method for analyte detection |
FR2805826B1 (en) | 2000-03-01 | 2002-09-20 | Nucleica | NEW DNA CHIPS |
WO2001064344A2 (en) | 2000-03-02 | 2001-09-07 | Microchips, Inc. | Microfabricated devices for the storage and selective exposure of chemicals and devices |
JP3442338B2 (en) | 2000-03-17 | 2003-09-02 | 株式会社日立製作所 | DNA analyzer, DNA base sequencer, DNA base sequence determination method, and reaction module |
DE50107049D1 (en) | 2000-03-30 | 2005-09-15 | Infineon Technologies Ag | SENSOR ARRANGEMENT AND METHOD FOR DETECTING A CONDITION OF A TRANSISTOR OF A SENSOR ARRANGEMENT |
US7001792B2 (en) | 2000-04-24 | 2006-02-21 | Eagle Research & Development, Llc | Ultra-fast nucleic acid sequencing device and a method for making and using the same |
AU2001259128A1 (en) | 2000-04-24 | 2001-11-07 | Eagle Research And Development, Llc | An ultra-fast nucleic acid sequencing device and a method for making and using the same |
US8232582B2 (en) | 2000-04-24 | 2012-07-31 | Life Technologies Corporation | Ultra-fast nucleic acid sequencing device and a method for making and using the same |
US6413792B1 (en) | 2000-04-24 | 2002-07-02 | Eagle Research Development, Llc | Ultra-fast nucleic acid sequencing device and a method for making and using the same |
US20020042388A1 (en) | 2001-05-01 | 2002-04-11 | Cooper Mark J. | Lyophilizable and enhanced compacted nucleic acids |
US20020168678A1 (en) | 2000-06-07 | 2002-11-14 | Li-Cor, Inc. | Flowcell system for nucleic acid sequencing |
US6482639B2 (en) | 2000-06-23 | 2002-11-19 | The United States Of America As Represented By The Secretary Of The Navy | Microelectronic device and method for label-free detection and quantification of biological and chemical molecules |
US6611037B1 (en) | 2000-08-28 | 2003-08-26 | Micron Technology, Inc. | Multi-trench region for accumulation of photo-generated charge in a CMOS imager |
US6939451B2 (en) | 2000-09-19 | 2005-09-06 | Aclara Biosciences, Inc. | Microfluidic chip having integrated electrodes |
WO2002030561A2 (en) | 2000-10-10 | 2002-04-18 | Biotrove, Inc. | Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof |
US6537881B1 (en) | 2000-10-16 | 2003-03-25 | Advanced Micro Devices, Inc. | Process for fabricating a non-volatile memory device |
US6558626B1 (en) | 2000-10-17 | 2003-05-06 | Nomadics, Inc. | Vapor sensing instrument for ultra trace chemical detection |
AU2002241803A1 (en) | 2000-10-20 | 2002-06-18 | The Board Of Trustees Of The Leland Stanford Junior University | Transient electrical signal based methods and devices for characterizing molecular interaction and/or motion in a sample |
US6770472B2 (en) | 2000-11-17 | 2004-08-03 | The Board Of Trustees Of The Leland Stanford Junior University | Direct DNA sequencing with a transcription protein and a nanometer scale electrometer |
AU2002229046B2 (en) | 2000-12-11 | 2006-05-18 | President And Fellows Of Harvard College | Nanosensors |
GB2370410A (en) | 2000-12-22 | 2002-06-26 | Seiko Epson Corp | Thin film transistor sensor |
WO2002079514A1 (en) | 2001-01-10 | 2002-10-10 | The Trustees Of Boston College | Dna-bridged carbon nanotube arrays |
JP4809983B2 (en) | 2001-02-14 | 2011-11-09 | 明彦 谷岡 | Apparatus and method for detecting interaction between biopolymer and ligand |
EP1236804A1 (en) | 2001-03-02 | 2002-09-04 | Boehringer Mannheim Gmbh | A method for determination of a nucleic acid using a control |
GB0105831D0 (en) | 2001-03-09 | 2001-04-25 | Toumaz Technology Ltd | Method for dna sequencing utilising enzyme linked field effect transistors |
DE10111458B4 (en) | 2001-03-09 | 2008-09-11 | Siemens Ag | analyzer |
US8114591B2 (en) | 2001-03-09 | 2012-02-14 | Dna Electronics Ltd. | Sensing apparatus and method |
CA2440754A1 (en) | 2001-03-12 | 2002-09-19 | Stephen Quake | Methods and apparatus for analyzing polynucleotide sequences by asynchronous base extension |
JP2002272463A (en) | 2001-03-22 | 2002-09-24 | Olympus Optical Co Ltd | Method for judging form of monobasic polymorphism |
US20050058990A1 (en) | 2001-03-24 | 2005-03-17 | Antonio Guia | Biochip devices for ion transport measurement, methods of manufacture, and methods of use |
US6418968B1 (en) | 2001-04-20 | 2002-07-16 | Nanostream, Inc. | Porous microfluidic valves |
KR100442838B1 (en) | 2001-12-11 | 2004-08-02 | 삼성전자주식회사 | Method for detecting immobilization of probes and method for detecting binding degree between the probes and target samples |
KR100455283B1 (en) | 2001-04-23 | 2004-11-08 | 삼성전자주식회사 | Molecular detection chip including MOSFET fabricated in the sidewall of molecular flux channel, molecular detection apparatus having the same, fabrication method for the same, and method for molecular detection using the molecular detection apparatus |
DE60230610D1 (en) | 2001-04-23 | 2009-02-12 | Samsung Electronics Co Ltd | REN PROOF |
US6571189B2 (en) | 2001-05-14 | 2003-05-27 | Hewlett-Packard Company | System and method for scanner calibration |
US20040023253A1 (en) | 2001-06-11 | 2004-02-05 | Sandeep Kunwar | Device structure for closely spaced electrodes |
US20050009022A1 (en) | 2001-07-06 | 2005-01-13 | Weiner Michael P. | Method for isolation of independent, parallel chemical micro-reactions using a porous filter |
DE10133363A1 (en) | 2001-07-10 | 2003-01-30 | Infineon Technologies Ag | Measuring cell and measuring field with such measuring cells as well as using a measuring cell and using a measuring field |
ATE471369T1 (en) | 2001-07-30 | 2010-07-15 | Meso Scale Technologies Llc | ASSAY ELECTRODES WITH LAYERS OF IMMOBILIZED LIPID/PROTEIN AND METHOD FOR THE PRODUCTION AND USE THEREOF |
US6929944B2 (en) | 2001-08-31 | 2005-08-16 | Beckman Coulter, Inc. | Analysis using a distributed sample |
US20030054396A1 (en) | 2001-09-07 | 2003-03-20 | Weiner Michael P. | Enzymatic light amplification |
DE10151021A1 (en) | 2001-10-16 | 2003-04-30 | Infineon Technologies Ag | Sensor arrangement |
DE10151020A1 (en) | 2001-10-16 | 2003-04-30 | Infineon Technologies Ag | Circuit arrangement, sensor array and biosensor array |
US6795117B2 (en) | 2001-11-06 | 2004-09-21 | Candela Microsystems, Inc. | CMOS image sensor with noise cancellation |
WO2003042697A1 (en) | 2001-11-14 | 2003-05-22 | Genospectra, Inc. | Biochemical analysis system with combinatorial chemistry applications |
WO2003042683A1 (en) | 2001-11-16 | 2003-05-22 | Bio-X Inc. | Fet type sensor, ion density detecting method comprising this sensor, and base sequence detecting method |
US20050106587A1 (en) | 2001-12-21 | 2005-05-19 | Micronas Gmbh | Method for determining of nucleic acid analytes |
US6518146B1 (en) | 2002-01-09 | 2003-02-11 | Motorola, Inc. | Semiconductor device structure and method for forming |
US7772383B2 (en) | 2002-01-25 | 2010-08-10 | The Trustees Of Princeton University | Chemical PCR: Compositions for enhancing polynucleotide amplification reactions |
KR100403637B1 (en) | 2002-01-26 | 2003-10-30 | 삼성전자주식회사 | Power amplifier clipping circuit for minimizing output distortion |
US7276749B2 (en) | 2002-02-05 | 2007-10-02 | E-Phocus, Inc. | Image sensor with microcrystalline germanium photodiode layer |
US6926865B2 (en) | 2002-02-11 | 2005-08-09 | Matsushita Electric Industrial Co., Ltd. | Method and apparatus for detecting DNA hybridization |
JP2003258128A (en) | 2002-02-27 | 2003-09-12 | Nec Electronics Corp | Non-volatile semiconductor memory device, manufacturing method and operating method of the same |
US6953958B2 (en) | 2002-03-19 | 2005-10-11 | Cornell Research Foundation, Inc. | Electronic gain cell based charge sensor |
US6828685B2 (en) | 2002-06-14 | 2004-12-07 | Hewlett-Packard Development Company, L.P. | Memory device having a semiconducting polymer film |
US6894930B2 (en) | 2002-06-19 | 2005-05-17 | Sandisk Corporation | Deep wordline trench to shield cross coupling between adjacent cells for scaled NAND |
US20040136866A1 (en) | 2002-06-27 | 2004-07-15 | Nanosys, Inc. | Planar nanowire based sensor elements, devices, systems and methods for using and making same |
US7092757B2 (en) | 2002-07-12 | 2006-08-15 | Cardiac Pacemakers, Inc. | Minute ventilation sensor with dynamically adjusted excitation current |
US6885827B2 (en) | 2002-07-30 | 2005-04-26 | Amplification Technologies, Inc. | High sensitivity, high resolution detection of signals |
EP1525470A2 (en) | 2002-07-31 | 2005-04-27 | Infineon Technologies AG | Sensor arrangement |
US7842377B2 (en) | 2003-08-08 | 2010-11-30 | Boston Scientific Scimed, Inc. | Porous polymeric particle comprising polyvinyl alcohol and having interior to surface porosity-gradient |
CN100392097C (en) | 2002-08-12 | 2008-06-04 | 株式会社日立高新技术 | Method of detecting nucleic acid by using DNA microarrays and nucleic acid detection apparatus |
US7267751B2 (en) | 2002-08-20 | 2007-09-11 | Nanogen, Inc. | Programmable multiplexed active biologic array |
GB0219541D0 (en) | 2002-08-22 | 2002-10-02 | Secr Defence | Method and apparatus for stand-off chemical detection |
US8449824B2 (en) | 2002-09-09 | 2013-05-28 | Yizhong Sun | Sensor instrument system including method for detecting analytes in fluids |
US7595883B1 (en) | 2002-09-16 | 2009-09-29 | The Board Of Trustees Of The Leland Stanford Junior University | Biological analysis arrangement and approach therefor |
SE0202867D0 (en) | 2002-09-27 | 2002-09-27 | Pyrosequencing Ab | New sequencing method |
CN1500887A (en) | 2002-10-01 | 2004-06-02 | 松下电器产业株式会社 | Method for detecting primer elongation reaction, method and apparatus for distinguishing kinds of basic groups |
WO2004034025A2 (en) | 2002-10-10 | 2004-04-22 | Nanosys, Inc. | Nano-chem-fet based biosensors |
DE10247889A1 (en) | 2002-10-14 | 2004-04-22 | Infineon Technologies Ag | Solid-state sensor assembly has a number of sensor components on or in a substrate and an electrical signal converter coupled to a sensor element |
US20040079636A1 (en) | 2002-10-25 | 2004-04-29 | Chin Hsia | Biomedical ion sensitive semiconductor sensor and sensor array |
WO2004040291A1 (en) | 2002-10-29 | 2004-05-13 | Cornell Research Foundation, Inc. | Chemical-sensitive floating gate field effect transistor |
US6700814B1 (en) | 2002-10-30 | 2004-03-02 | Motorola, Inc. | Sense amplifier bias circuit for a memory having at least two distinct resistance states |
EP1567580A4 (en) | 2002-11-01 | 2008-04-30 | Georgia Tech Res Inst | Sacrificial compositions, methods of use thereof, and methods of decomposition thereof |
DE10251757B4 (en) | 2002-11-05 | 2006-03-09 | Micronas Holding Gmbh | Device for determining the concentration of ligands contained in a sample to be examined |
US7022288B1 (en) | 2002-11-13 | 2006-04-04 | The United States Of America As Represented By The Secretary Of The Navy | Chemical detection sensor system |
DE10255755B4 (en) | 2002-11-28 | 2006-07-13 | Schneider, Christian, Dr. | Integrated electronic circuit with field effect sensors for the detection of biomolecules |
CN1720438A (en) | 2002-11-29 | 2006-01-11 | 日本电气株式会社 | Separation equipment and separation method |
US20040197803A1 (en) | 2002-12-06 | 2004-10-07 | Hidenobu Yaku | Method, primer and kit for determining base type |
AU2004254552B2 (en) | 2003-01-29 | 2008-04-24 | 454 Life Sciences Corporation | Methods of amplifying and sequencing nucleic acids |
US7575865B2 (en) | 2003-01-29 | 2009-08-18 | 454 Life Sciences Corporation | Methods of amplifying and sequencing nucleic acids |
US20050006234A1 (en) | 2003-02-13 | 2005-01-13 | Arjang Hassibi | Semiconductor electrochemical bio-sensor array |
US20070262363A1 (en) | 2003-02-28 | 2007-11-15 | Board Of Regents, University Of Texas System | Low temperature fabrication of discrete silicon-containing substrates and devices |
TWI235236B (en) | 2003-05-09 | 2005-07-01 | Univ Chung Yuan Christian | Ion-sensitive circuit |
WO2004106891A2 (en) | 2003-05-22 | 2004-12-09 | University Of Hawaii | Ultrasensitive biochemical sensor |
WO2005015156A2 (en) | 2003-08-04 | 2005-02-17 | Idaho Research Foundation, Inc. | Molecular detector |
JP2005077210A (en) | 2003-08-29 | 2005-03-24 | National Institute For Materials Science | Biomolecule detecting element and nucleic acid analyzing method using it |
GB0322010D0 (en) | 2003-09-19 | 2003-10-22 | Univ Cambridge Tech | Detection of molecular interactions using field effect transistors |
US7008550B2 (en) | 2003-09-25 | 2006-03-07 | Hitachi Global Storage Technologies Netherlands B.V. | Method for forming a read transducer by ion milling and chemical mechanical polishing to eliminate nonuniformity near the MR sensor |
GB0323224D0 (en) | 2003-10-03 | 2003-11-05 | Rolls Royce Plc | A module for a fuel cell stack |
US20070087401A1 (en) | 2003-10-17 | 2007-04-19 | Andy Neilson | Analysis of metabolic activity in cells using extracellular flux rate measurements |
WO2005043160A2 (en) | 2003-10-31 | 2005-05-12 | University Of Hawaii | Ultrasensitive biochemical sensing platform |
US7981362B2 (en) | 2003-11-04 | 2011-07-19 | Meso Scale Technologies, Llc | Modular assay plates, reader systems and methods for test measurements |
US7067886B2 (en) | 2003-11-04 | 2006-06-27 | International Business Machines Corporation | Method of assessing potential for charging damage in SOI designs and structures for eliminating potential for damage |
DE10352917A1 (en) | 2003-11-11 | 2005-06-16 | Endress + Hauser Conducta Gesellschaft für Mess- und Regeltechnik mbH + Co. KG | Sensor arrangement with several potentiometric sensors |
US7169560B2 (en) | 2003-11-12 | 2007-01-30 | Helicos Biosciences Corporation | Short cycle methods for sequencing polynucleotides |
US20060019264A1 (en) | 2003-12-01 | 2006-01-26 | Said Attiya | Method for isolation of independent, parallel chemical micro-reactions using a porous filter |
US7279588B2 (en) | 2003-12-02 | 2007-10-09 | Seoul National University Foundation | Dinuclear metal complex and pyrophosphate assay using the same |
US7462512B2 (en) | 2004-01-12 | 2008-12-09 | Polytechnic University | Floating gate field effect transistors for chemical and/or biological sensing |
JP4065855B2 (en) | 2004-01-21 | 2008-03-26 | 株式会社日立製作所 | Biological and chemical sample inspection equipment |
WO2005073410A2 (en) | 2004-01-28 | 2005-08-11 | 454 Corporation | Nucleic acid amplification with continuous flow emulsion |
JP3903183B2 (en) | 2004-02-03 | 2007-04-11 | 独立行政法人物質・材料研究機構 | Gene detection field effect device and gene polymorphism analysis method using the same |
CA2557841A1 (en) | 2004-02-27 | 2005-09-09 | President And Fellows Of Harvard College | Polony fluorescent in situ sequencing beads |
EP2436778A3 (en) | 2004-03-03 | 2012-07-11 | The Trustees of Columbia University in the City of New York | Photocleavable fluorescent nucleotides for DNA sequencing on chip constructed by site-specific coupling chemistry |
US20060057604A1 (en) | 2004-03-15 | 2006-03-16 | Thinkfar Nanotechnology Corporation | Method for electrically detecting oligo-nucleotides with nano-particles |
JP4127679B2 (en) | 2004-03-18 | 2008-07-30 | 株式会社東芝 | Nucleic acid detection cassette and nucleic acid detection apparatus |
DE102004014537A1 (en) | 2004-03-23 | 2005-10-13 | Fujitsu Ltd., Kawasaki | Chip-integrated detector for analyzing liquids |
JP4734234B2 (en) | 2004-03-24 | 2011-07-27 | 独立行政法人科学技術振興機構 | Measuring method and system for detecting morphology and information related to biomolecules using IS-FET |
US20050221473A1 (en) | 2004-03-30 | 2005-10-06 | Intel Corporation | Sensor array integrated circuits |
WO2005095938A1 (en) | 2004-04-01 | 2005-10-13 | Nanyang Technological University | Addressable transistor chip for conducting assays |
US7117605B2 (en) | 2004-04-13 | 2006-10-10 | Gyrodata, Incorporated | System and method for using microgyros to measure the orientation of a survey tool within a borehole |
US7544979B2 (en) | 2004-04-16 | 2009-06-09 | Technion Research & Development Foundation Ltd. | Ion concentration transistor and dual-mode sensors |
US7462452B2 (en) | 2004-04-30 | 2008-12-09 | Pacific Biosciences Of California, Inc. | Field-switch sequencing |
TWI261801B (en) | 2004-05-24 | 2006-09-11 | Rohm Co Ltd | Organic EL drive circuit and organic EL display device using the same organic EL drive circuit |
US7264934B2 (en) | 2004-06-10 | 2007-09-04 | Ge Healthcare Bio-Sciences Corp. | Rapid parallel nucleic acid analysis |
US7361946B2 (en) | 2004-06-28 | 2008-04-22 | Nitronex Corporation | Semiconductor device-based sensors |
US20060024711A1 (en) | 2004-07-02 | 2006-02-02 | Helicos Biosciences Corporation | Methods for nucleic acid amplification and sequence determination |
GB2416210B (en) | 2004-07-13 | 2008-02-20 | Christofer Toumazou | Ion sensitive field effect transistors |
JP3874772B2 (en) | 2004-07-21 | 2007-01-31 | 株式会社日立製作所 | Biologically related substance measuring apparatus and measuring method |
JP4455215B2 (en) | 2004-08-06 | 2010-04-21 | キヤノン株式会社 | Imaging device |
US7276453B2 (en) | 2004-08-10 | 2007-10-02 | E.I. Du Pont De Nemours And Company | Methods for forming an undercut region and electronic devices incorporating the same |
US7190026B2 (en) | 2004-08-23 | 2007-03-13 | Enpirion, Inc. | Integrated circuit employable with a power converter |
WO2006022370A1 (en) | 2004-08-27 | 2006-03-02 | National Institute For Materials Science | Method of analyzing dna sequence using field-effect device, and base sequence analyzer |
US20070212681A1 (en) | 2004-08-30 | 2007-09-13 | Benjamin Shapiro | Cell canaries for biochemical pathogen detection |
US7609303B1 (en) | 2004-10-12 | 2009-10-27 | Melexis Tessenderlo Nv | Low noise active pixel image sensor using a modified reset value |
US7534097B2 (en) | 2004-10-15 | 2009-05-19 | Nanyang Technological University | Method and apparatus for controlling multi-fluid flow in a micro channel |
US7381936B2 (en) | 2004-10-29 | 2008-06-03 | Ess Technology, Inc. | Self-calibrating anti-blooming circuit for CMOS image sensor having a spillover protection performance in response to a spillover condition |
US7785785B2 (en) | 2004-11-12 | 2010-08-31 | The Board Of Trustees Of The Leland Stanford Junior University | Charge perturbation detection system for DNA and other molecules |
WO2006086034A2 (en) | 2004-11-18 | 2006-08-17 | Morgan Research Corporation | Miniature fourier transform spectrophotometer |
US20060205061A1 (en) | 2004-11-24 | 2006-09-14 | California Institute Of Technology | Biosensors based upon actuated desorption |
KR100623177B1 (en) | 2005-01-25 | 2006-09-13 | 삼성전자주식회사 | Dielectric structure having a high dielectric constant, method of forming the dielectric structure, non-volatile semiconductor memory device including the dielectric structure, and method of manufacturing the non-volatile semiconductor memory device |
WO2006083751A2 (en) | 2005-01-31 | 2006-08-10 | Pacific Biosciences Of California, Inc. | Use of reversible extension terminator in nucleic acid sequencing |
US20060199493A1 (en) | 2005-02-04 | 2006-09-07 | Hartmann Richard Jr | Vent assembly |
US9040237B2 (en) | 2005-03-04 | 2015-05-26 | Intel Corporation | Sensor arrays and nucleic acid sequencing applications |
KR101269508B1 (en) | 2005-03-11 | 2013-05-30 | 고꾸리쯔 다이가꾸 호우징 도요하시 기쥬쯔 가가꾸 다이가꾸 | Cumulative chemical/physical phenomenon detecting apparatus |
US20060219558A1 (en) | 2005-04-05 | 2006-10-05 | Hafeman Dean G | Improved Methods and Devices for Concentration and Fractionation of Analytes for Chemical Analysis including Matrix-Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry (MS) |
US20060228721A1 (en) | 2005-04-12 | 2006-10-12 | Leamon John H | Methods for determining sequence variants using ultra-deep sequencing |
TWI287041B (en) | 2005-04-27 | 2007-09-21 | Jung-Tang Huang | An ultra-rapid DNA sequencing method with nano-transistors array based devices |
US20060269927A1 (en) | 2005-05-25 | 2006-11-30 | Lieber Charles M | Nanoscale sensors |
CN1881457A (en) | 2005-06-14 | 2006-12-20 | 松下电器产业株式会社 | Method of controlling an actuator, and disk apparatus using the same method |
SG162795A1 (en) | 2005-06-15 | 2010-07-29 | Callida Genomics Inc | Single molecule arrays for genetic and chemical analysis |
WO2007002204A2 (en) | 2005-06-21 | 2007-01-04 | The Trustees Of Columbia University In The City Of New York | Pyrosequencing methods and related compostions |
TW200701588A (en) | 2005-06-29 | 2007-01-01 | Leadtrend Tech Corp | Dual loop voltage regulation circuit of power supply chip |
US7890891B2 (en) | 2005-07-11 | 2011-02-15 | Peregrine Semiconductor Corporation | Method and apparatus improving gate oxide reliability by controlling accumulated charge |
JP2007035726A (en) | 2005-07-22 | 2007-02-08 | Rohm Co Ltd | Semiconductor device, module, and electronic apparatus |
US7365597B2 (en) | 2005-08-19 | 2008-04-29 | Micron Technology, Inc. | Switched capacitor amplifier with higher gain and improved closed-loop gain accuracy |
JP4353958B2 (en) | 2005-09-15 | 2009-10-28 | 株式会社日立製作所 | DNA measuring apparatus and DNA measuring method |
US7466258B1 (en) | 2005-10-07 | 2008-12-16 | Cornell Research Foundation, Inc. | Asynchronous analog-to-digital converter and method |
US7794584B2 (en) | 2005-10-12 | 2010-09-14 | The Research Foundation Of State University Of New York | pH-change sensor and method |
US7335526B2 (en) | 2005-10-31 | 2008-02-26 | Hewlett-Packard Development Company, L.P. | Sensing system |
TWI295729B (en) | 2005-11-01 | 2008-04-11 | Univ Nat Yunlin Sci & Tech | Preparation of a ph sensor, the prepared ph sensor, systems comprising the same, and measurement using the systems |
US7538827B2 (en) | 2005-11-17 | 2009-05-26 | Chunghwa Picture Tubes, Ltd. | Pixel structure |
US7576037B2 (en) | 2005-11-18 | 2009-08-18 | Mei Technologies, Inc. | Process and apparatus for combinatorial synthesis |
US7566913B2 (en) | 2005-12-02 | 2009-07-28 | Nitronex Corporation | Gallium nitride material devices including conductive regions and methods associated with the same |
GB2436619B (en) | 2005-12-19 | 2010-10-06 | Toumaz Technology Ltd | Sensor circuits |
KR100718144B1 (en) | 2006-01-09 | 2007-05-14 | 삼성전자주식회사 | Fet based sensor for detecting ionic material, device for detecting ionic material comprising the same, and method for detecting ionic material using the fet based sensor |
CA2646465C (en) | 2006-03-17 | 2015-06-16 | The Government Of The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Apparatus for microarray binding sensors having biological probe materials using carbon nanotube transistors |
US20070233477A1 (en) | 2006-03-30 | 2007-10-04 | Infima Ltd. | Lossless Data Compression Using Adaptive Context Modeling |
US7923240B2 (en) | 2006-03-31 | 2011-04-12 | Intel Corporation | Photo-activated field effect transistor for bioanalyte detection |
WO2007123908A2 (en) | 2006-04-18 | 2007-11-01 | Advanced Liquid Logic, Inc. | Droplet-based multiwell operations |
KR100723426B1 (en) | 2006-04-26 | 2007-05-30 | 삼성전자주식회사 | Field effect transistor for detecting ionic materials and method of detecting ionic materials using the same |
EP2530168B1 (en) | 2006-05-11 | 2015-09-16 | Raindance Technologies, Inc. | Microfluidic Devices |
JP4211805B2 (en) | 2006-06-01 | 2009-01-21 | エプソンイメージングデバイス株式会社 | Electro-optical device and electronic apparatus |
WO2008007716A1 (en) | 2006-07-13 | 2008-01-17 | National University Corporation Nagoya University | Material detection device |
KR100799577B1 (en) | 2006-08-31 | 2008-01-30 | 한국전자통신연구원 | Method for forming sensor for detecting gases and biochemical materials, integrated circuit including the sensor, and method for manufacturing the integrated circuit |
US7960776B2 (en) | 2006-09-27 | 2011-06-14 | Cornell Research Foundation, Inc. | Transistor with floating gate and electret |
US8231831B2 (en) | 2006-10-06 | 2012-07-31 | Sharp Laboratories Of America, Inc. | Micro-pixelated fluid-assay structure |
US20090111705A1 (en) | 2006-11-09 | 2009-04-30 | Complete Genomics, Inc. | Selection of dna adaptor orientation by hybrid capture |
US8262900B2 (en) | 2006-12-14 | 2012-09-11 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8349167B2 (en) | 2006-12-14 | 2013-01-08 | Life Technologies Corporation | Methods and apparatus for detecting molecular interactions using FET arrays |
CA2672315A1 (en) | 2006-12-14 | 2008-06-26 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes using large scale fet arrays |
US7972828B2 (en) | 2006-12-19 | 2011-07-05 | Sigma-Aldrich Co. | Stabilized compositions of thermostable DNA polymerase and anionic or zwitterionic detergent |
US7932034B2 (en) | 2006-12-20 | 2011-04-26 | The Board Of Trustees Of The Leland Stanford Junior University | Heat and pH measurement for sequencing of DNA |
WO2008089282A2 (en) | 2007-01-16 | 2008-07-24 | Silver James H | Sensors for detecting subtances indicative of stroke, ischemia, infection or inflammation |
JP4325684B2 (en) | 2007-02-20 | 2009-09-02 | 株式会社デンソー | Sensor control apparatus and applied voltage characteristic adjusting method |
ES2440572T3 (en) | 2007-03-02 | 2014-01-29 | Dna Electronics Ltd | Detection apparatus for controlling nucleic acid amplification, using an ion-sensitive field effect transistor (ISFET) to detect pH |
CA2693059A1 (en) | 2007-07-13 | 2009-01-22 | The Board Of Trustees Of The Leland Stanford Junior University | Method and apparatus using electric field for improved biological assays |
US7609093B2 (en) | 2007-08-03 | 2009-10-27 | Tower Semiconductor Ltd. | Comparator with low supply current spike and input offset cancellation |
US20090062132A1 (en) | 2007-08-29 | 2009-03-05 | Borner Scott R | Alternative nucleic acid sequencing methods |
WO2009041917A1 (en) | 2007-09-28 | 2009-04-02 | Agency For Science, Technology And Research | Method of electrically detecting a nucleic acid molecule |
KR100940415B1 (en) | 2007-12-03 | 2010-02-02 | 주식회사 동부하이텍 | On resistance test method for back-side-drain wafer |
US8124936B1 (en) | 2007-12-13 | 2012-02-28 | The United States Of America As Represented By The Secretary Of The Army | Stand-off chemical detector |
CN101896624A (en) | 2007-12-13 | 2010-11-24 | Nxp股份有限公司 | A biosensor device and a method of sequencing biological particles |
WO2009081890A1 (en) | 2007-12-20 | 2009-07-02 | National University Corporation Toyohashi University Of Technology | Combined detector |
US20090194416A1 (en) | 2008-01-31 | 2009-08-06 | Chung Yuan Christian University | Potentiometric biosensor for detection of creatinine and forming method thereof |
DE102008012899A1 (en) | 2008-03-06 | 2009-09-10 | Robert Bosch Gmbh | Method for operating a gas sensor |
US8067731B2 (en) | 2008-03-08 | 2011-11-29 | Scott Technologies, Inc. | Chemical detection method and system |
US7885490B2 (en) | 2008-03-10 | 2011-02-08 | Octrolix Bv | Optical chemical detector and method |
US7667501B2 (en) | 2008-03-19 | 2010-02-23 | Texas Instruments Incorporated | Correlated double sampling technique |
US7821806B2 (en) | 2008-06-18 | 2010-10-26 | Nscore Inc. | Nonvolatile semiconductor memory circuit utilizing a MIS transistor as a memory cell |
GB2461127B (en) | 2008-06-25 | 2010-07-14 | Ion Torrent Systems Inc | Methods and apparatus for measuring analytes using large scale FET arrays |
US8470164B2 (en) | 2008-06-25 | 2013-06-25 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
EP2304420A4 (en) | 2008-06-26 | 2013-10-30 | Life Technologies Corp | Methods and apparatus for detecting molecular interactions using fet arrays |
KR101026468B1 (en) | 2008-09-10 | 2011-04-01 | 한국전자통신연구원 | Apparatus for detecting biomolecules and detecting method the same |
US20100301398A1 (en) | 2009-05-29 | 2010-12-02 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
US20100137143A1 (en) | 2008-10-22 | 2010-06-03 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
WO2010047804A1 (en) | 2008-10-22 | 2010-04-29 | Ion Torrent Systems Incorporated | Integrated sensor arrays for biological and chemical analysis |
US7898277B2 (en) | 2008-12-24 | 2011-03-01 | Agere Systems Inc. | Hot-electronic injection testing of transistors on a wafer |
US8101479B2 (en) | 2009-03-27 | 2012-01-24 | National Semiconductor Corporation | Fabrication of asymmetric field-effect transistors using L-shaped spacers |
US20120261274A1 (en) | 2009-05-29 | 2012-10-18 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US8776573B2 (en) | 2009-05-29 | 2014-07-15 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US8673627B2 (en) | 2009-05-29 | 2014-03-18 | Life Technologies Corporation | Apparatus and methods for performing electrochemical reactions |
US20110037121A1 (en) | 2009-08-16 | 2011-02-17 | Tung-Hsing Lee | Input/output electrostatic discharge device with reduced junction breakdown voltage |
SG188863A1 (en) | 2009-09-11 | 2013-04-30 | Agency Science Tech & Res | Method of determining a sensitivity of a biosensor arrangement, and biosensor sensitivity determining system |
US9018684B2 (en) | 2009-11-23 | 2015-04-28 | California Institute Of Technology | Chemical sensing and/or measuring devices and methods |
US8545248B2 (en) | 2010-01-07 | 2013-10-01 | Life Technologies Corporation | System to control fluid flow based on a leak detected by a sensor |
US9088208B2 (en) | 2010-01-27 | 2015-07-21 | Intersil Americas LLC | System and method for high precision current sensing |
US8878257B2 (en) | 2010-06-04 | 2014-11-04 | Freescale Semiconductor, Inc. | Methods and apparatus for an ISFET |
AU2011226767B1 (en) | 2010-06-30 | 2011-11-10 | Life Technologies Corporation | Ion-sensing charge-accumulation circuits and methods |
JP5952813B2 (en) | 2010-06-30 | 2016-07-13 | ライフ テクノロジーズ コーポレーション | Method and apparatus for testing ISFET arrays |
US8731847B2 (en) | 2010-06-30 | 2014-05-20 | Life Technologies Corporation | Array configuration and readout scheme |
EP2589065B1 (en) | 2010-07-03 | 2015-08-19 | Life Technologies Corporation | Chemically sensitive sensor with lightly doped drains |
WO2012024500A1 (en) | 2010-08-18 | 2012-02-23 | Life Technologies Corporation | Chemical coating of microwell for electrochemical detection device |
EP2619564B1 (en) | 2010-09-24 | 2016-03-16 | Life Technologies Corporation | Matched pair transistor circuits |
WO2012092515A2 (en) | 2010-12-30 | 2012-07-05 | Life Technologies Corporation | Methods, systems, and computer readable media for nucleic acid sequencing |
US8786331B2 (en) * | 2012-05-29 | 2014-07-22 | Life Technologies Corporation | System for reducing noise in a chemical sensor array |
-
2013
- 2013-03-13 US US13/801,243 patent/US8841217B1/en active Active
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113945621A (en) * | 2015-08-25 | 2022-01-18 | 生命技术公司 | Deep micro-well design and method of making same |
US10890554B1 (en) * | 2019-06-20 | 2021-01-12 | Globalfoundries Singapore Pte. Ltd. | Sensors with a non-planar sensing structure |
Also Published As
Publication number | Publication date |
---|---|
US8841217B1 (en) | 2014-09-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8841217B1 (en) | Chemical sensor with protruded sensor surface | |
US9995708B2 (en) | Chemical sensor with sidewall spacer sensor surface | |
US10422767B2 (en) | Chemical sensor with consistent sensor surface areas | |
US10481124B2 (en) | Chemical device with thin conductive element | |
US8962366B2 (en) | Self-aligned well structures for low-noise chemical sensors | |
US10436742B2 (en) | Methods for manufacturing well structures for low-noise chemical sensors | |
US9128044B2 (en) | Chemical sensors with consistent sensor surface areas | |
US9116117B2 (en) | Chemical sensor with sidewall sensor surface | |
US20140364320A1 (en) | Chemical Sensor Array Having Multiple Sensors Per Well | |
US9835585B2 (en) | Chemical sensor with protruded sensor surface | |
US20220196595A1 (en) | Chemical sensor with air via | |
EP3341718B1 (en) | Deep microwell design and method of making the same | |
US20140264465A1 (en) | Chemical sensors with partially extended sensor surfaces | |
US20140273324A1 (en) | Methods for manufacturing chemical sensors with extended sensor surfaces |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: LIFE TECHNOLOGIES CORPORATION, CALIFORNIA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:FIFE, KEITH;BUSTILLO, JAMES;OWENS, JORDAN;SIGNING DATES FROM 20130501 TO 20130604;REEL/FRAME:030545/0322 |
|
STCF | Information on status: patent grant |
Free format text: PATENTED CASE |
|
MAFP | Maintenance fee payment |
Free format text: PAYMENT OF MAINTENANCE FEE, 4TH YEAR, LARGE ENTITY (ORIGINAL EVENT CODE: M1551) Year of fee payment: 4 |
|
MAFP | Maintenance fee payment |
Free format text: PAYMENT OF MAINTENANCE FEE, 8TH YEAR, LARGE ENTITY (ORIGINAL EVENT CODE: M1552); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY Year of fee payment: 8 |