This disclosure, in general, relates to sensors for chemical or biological analysis, and to methods for manufacturing such sensors.
A variety of types of chemical devices 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 or determine characteristics of the chemical reaction. The threshold voltage can, 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 can 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 or concentration of ions within the solution. Arrays of ISFETs can 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 in its entirety. More generally, large arrays of chemFETs or other types of chemical devices can be employed to detect and measure static 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 can, 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 device 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 or biological process being detected by the sensors. It is therefore desirable to provide devices including low noise chemical devices, and methods for manufacturing such devices.
Chemical devices are described that include low noise chemical devices, such as chemically-sensitive field effect transistors (chemFETs), for detecting chemical reactions within overlying, operationally associated reaction regions. A sensor of a chemical device can comprise a plurality of floating gate conductors with a sensing layer deposited on an uppermost floating conductor of the plurality of floating gate conductors. Applicant found that adding an additional layer above uppermost floating conductor of the plurality of floating gate conductors that is dedicated to sensing has advantages that overcome the technical challenges and cost of the additional layer. For example, Applicant have found that advantages in the chemical devices described herein include providing enhanced lithographic process margin; (for example, prevent misalign of openings or burnout); and providing larger openings in the dielectric than would be possible were the sensing area directly on top of the uppermost floating gate conductor (for example, larger openings can accommodate more signal). Moreover, well-to-well diffusion of products produces colonies (duplicates) and increase polyclonality. Applicant found that deeper wells can mitigate well-to-well diffusion and allow more time for target DNA to immobilize and amplify.
Exemplary chemical devices described herein have sensing surface areas which can comprise a dedicated layer for sensing. In embodiments described herein, a conductive element overlies and is in communication with an uppermost floating gate conductor. Because the uppermost floating gate conductor can be used to provide array lines (e.g. word lines, bit lines, etc.) and bus lines for accessing/powering the chemical devices, the uppermost floating gate conductor should be a suitable material or mixture of materials and of sufficient thickness therefor. Since the conductive element is within a different layer on the substrate of the chemical device, the conductive element can function as a dedicated sensing surface area independent of the material and thickness of the uppermost floating gate structure. As a result, low noise chemical devices can be provided in a high density array, such that the characteristics of reactions can be accurately detected. Additionally, the uppermost floating gate conductor may not be pushed to process limits; while adjacent floating gate conductors should have a thickness (i.e. for low resistivity) suitable for carrying high currents, the space between adjacent floating gate conductors may not be the minimum space allowed by process design rules. The material(s) used for the uppermost floating gate conductor can be selected based on their suitability to carry high currents. Providing the conductive element overlying and in communication with the uppermost floating gate conductor provides greater freedom in choice of material for the conductive element since the conductive element is on a different layer than the uppermost floating gate conductor. The conductive element disposed over the uppermost floating gate conductor can at least partially extend along the well wall. For example, the conductive element can extend at least 20% along the wall surface, such as at least 30% along the wall surface, at least 40% along the wall surface, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or even 100% along the wall surface. The upper surface of the well wall structure can be free of the conductive element. In an embodiment, the conductive element can cover the entire bottom of the well such that no part of the uppermost floating gate conductor is exposed to the well opening. In an embodiment, the conductive element is disposed along the bottom of the well but does not fully extend between the sidewalls, such that the bottom of the well is only partially covered by the conductive element.
During an experiment, array controller 124 collects and processes output signals from the chemical devices of the sensor array through output ports on integrated circuit device 100 via bus 127. Array controller 124 can be a computer or other computing means. The array controller can 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
The values of the output signals of the chemical devices indicate physical or chemical parameters of one or more reactions taking place in the corresponding reaction regions in the microwell array. For example, in an exemplary embodiment, the values of the output signals can 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. No. 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.
User interface 128 can display information about flow cell 101 and the output signals received from chemical devices in the sensor array on integrated circuit device 100. User interface 128 can 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 fluidics controller 118 can control delivery of individual reagents 114 to flow cell 101 and integrated circuit device 100 in a predetermined sequence, for predetermined durations, at predetermined flow rates. Array controller 124 can collect and analyze the output signals of the chemical devices indicating chemical reactions occurring in response to the delivery of reagents 114. During the experiment, the system can also monitor and control the temperature of the integrated circuit device, so that reactions take place and measurements are made at a known predetermined temperature. The system can be configured to let a single fluid or reagent contact reference electrode 108 throughout an entire multi-step reaction during operation. Valve 112 can be shut to prevent any wash solution 110 from flowing into passage 109 as reagents 114 are flowing. Although the flow of wash solution can be stopped, there can still be uninterrupted fluid and electrical communication between reference electrode 108, passage 109, and microwell array 107. The distance between reference electrode 108 and the junction between passages 109 and 111 can be selected so that little or no amount of the reagents flowing in passage 109 and possibly diffusing into passage 111 reach reference electrode 108. In an exemplary embodiment, wash solution 110 can be selected as being in continuous contact with reference electrode 108, which can be especially useful for multi-step reactions using frequent wash steps.
As shown in
Chemical device 350 includes a conductive element 307 overlying and in communication with an uppermost floating gate conductor in the plurality of floating gate conductors. Upper surface 307a of conductive element 307 acts as the sensing surface for the chemical device 350. The conductive element as discussed throughout the disclosure can be formed in various shapes (width, height, etc.) depending on the materials/etch techniques/fabrication processes, etc. used during the manufacture process. Conductive element 307 can comprise one or more of a variety of different materials to facilitate sensitivity to particular ions (e.g. hydrogen ions). Accordingly to an exemplary embodiment, the conductive element can comprise at least one of titanium, tantalum, titanium nitrite, or aluminum, or oxides or mixtures thereof. Conductive element 307 allows chemical device 350 to have a sufficiently large surface area to avoid the noise issues associated with small sensing surfaces. The plan view area of the chemical device is determined in part by the width (or diameter) of reaction region 301 and can be made small, allowing for a high density array. In addition, because reaction region 301 is defined by upper surface 307a of conductive element 307 and an inner surface 377a of dielectric material 377, the sensing surface area can depend upon the depth and the circumference of reaction region 301, and can be relatively large. As a result, low noise chemical devices 350, 351 can be provided in a high density array, such that the characteristics of reactions can be accurately detected.
During manufacturing or operation of the device, a thin oxide of the material of conductive element 307 can be grown on upper surface 307a which acts as a sensing material (e.g. an ion-sensitive sensing material) for chemical device 350. For example, in one embodiment the electrically conductive element can be titanium or titanium nitride. Titanium oxide or titanium oxynitride can be grown on upper surface 307a during manufacturing 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, conductive element 307 is shown as a single layer of material. More generally, the electrically conductive element can comprise one or more layers of a variety of electrically conductive materials, such as metals or ceramics, or any other suitable conductive material or mixture of materials, 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 upper surface 307a of conductive element 307. The sensing material can 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 can also be used, depending upon the implementation.
Referring to
As described in more detail below with respect to
In various exemplary embodiments, the methods, systems, and computer readable media described herein can advantageously be used to process 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 can be determined by detecting ions (e.g., hydrogen ions) that are generated as natural by-products of polymerase-catalyzed nucleotide extension reactions. This can be used to sequence a sample or template nucleic acid, which can be a fragment of a nucleic acid sequence of interest, for example, and which can 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 can be operably associated to a primer and polymerase and can be subjected to repeated cycles or “flows” of deoxynucleoside triphosphate (“dNTP”) addition (which can be referred to herein as “nucleotide flows” from which nucleotide incorporations can result) and washing. The primer can 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 devices 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 device can be determined.
As illustrated in structure 500 illustrated in
A layer of conductive material 704 is deposited on structure 600 illustrated in
A layer of conductive material 805 such as tungsten, for example, is deposited on structure 700 illustrated in
Conductive material 704 and conductive material 805 are planarized using a Chemical Mechanical Planarization (CMP) process, for example, resulting in structure 900 illustrated in
A conductive material 1107 can be formed on via barrier liner 1006, resulting in structure 1100 illustrated in
A dielectric material 1416 can be formed on structure 1300 illustrated in
The well structure or dielectric material(s) is/are etched to form openings or wells 1718, 1720 extending to the upper surfaces of the floating gate structures of chemical devices 350, 351, resulting in structure 1700 illustrated in
A layer of conductive material 1801 is deposited on the well structure illustrated in
A fill material 1901 is formed on structure illustrated in
The fill material and at least a portion of the conformal conductive material extending over the interstitial surface 1717 can be removed. Removal can be through planarization or through etching. As illustrated in
Fill material elements 2002, 2004 protect the inner surfaces of electrically conductive elements 370, 2010, which subsequently act as the sensing surfaces for chemical sensors 350, 351, during the planarization process. That is, fill material elements 2002, 2004 are a protective mask during removal of conductive material 2010 from upper surface 2020 of dielectric material 2055. In doing so, damage to the sensing surfaces can be avoided. In addition, fill material elements 2002, 2004 act to protect and retain the shape of the openings by improving the mechanical stability of the structure during the planarization process, in particular for a small separation distance between adjacent openings in the dielectric. In the illustrated embodiment, the planarization process is a chemical mechanical polishing (CMP) process. Alternatively, other planarization processes can be used. In an alternative embodiment, rather than performing a planarization process, an etching process is performed to expose upper surface 2020 of dielectric material 2055. The etching process can for example be performed using a single etch chemistry to etch the fill material 1901 and conductive material 2010 overlying upper surface 2020 of dielectric material 2055. Alternatively, a first etch chemistry can be used to etch fill material 1901 and expose conductive material 2010 on upper surface 2020 of the dielectric material, and a second etch chemistry can be used to etch the exposed conductive material 2010 to expose upper surface 2020 of dielectric material 2055. For example, in one embodiment fill material 1901 is polyimide and can be removed using an oxygen plasma etch, while conductive material 2010 is titanium nitride and can be removed using a bromine based plasma etch. The etch process can use fewer steps and be faster. The etch process provides a surface that is rougher than the surface resulting from CMP. Such a rougher surface can result in surface patterns during deposition of subsequent layers.
A layer of dielectric material 2101 is deposited on structure 2000 illustrated in
Fill material elements 2001, 2003 are removed to expose electrically conductive elements 370, 2010, resulting in structure 2300 illustrated in
In an alternate embodiment, dielectric material 2101 of structure 2100 in
The thickness of the dielectric material 2101 can be thicker than the well structure. For example, a ratio of the thickness of the dielectric layer to the thickness of the well structure can be in a range of 1.01 to 10, such as a range of 1.05 to 3 or a range of 1.05 to 2.
Fill material elements 2001, 2003 are removed to expose electrically conductive elements 370, 2010, resulting in structure 2500 illustrated in
Using a wafer having wells defined in a well structure formed over a substrate, a conformal titanium layer is deposited over the well structure (2200A collimated Ti), and a coating of 6 micrometer HD8820 Photo-definable polyimide is deposited over the titanium. The polyimide is exposed and developed. Both an etch process and CMP process are tested for effect on well and opening formation.
In the etch process, an oxygen-containing plasma (O2: 60 to 200 sccm; power: 61-90 W; 127 seconds) is used to remove polyimide. The titanium is subsequently etched from the interstitial surface. As illustrated in
In the CMP process, two slurries are used. First, the wafer is polished using a slurry appropriate for removal of polyimide. Second, the wafer is polished using a slurry appropriate for removal of titanium. As illustrated in
A dielectric layer is deposited over the well structure. A 1.2 micrometer layer of low temperature TEOS is deposited at 175° C. A pattern is etched in the TEOS layer, stopping on the polyimide. A long ash process followed by cleaning with NMP and aqueous solutions is used to remove the polyimide.
As illustrated in
In a first aspect, an apparatus includes a substrate; a gate structure disposed over the substrate and having an upper surface; a well structure disposed over the substrate and defining a well over the upper surface of the gate structure; a conductive layer disposed on the upper surface of the gate structure and at least partially extending along a wall of the well in the well structure; and a dielectric structure disposed over the well structure and defining an opening to the well.
In an example of the first aspect, a characteristic diameter of the well at an interface between the well structure and the dielectric structure is greater than a characteristic diameter of the opening at the interface.
In another example of the first aspect, a characteristic diameter of the well at an interface between the well structure and the dielectric structure is approximately a characteristic diameter of the opening at the interface.
In a further example of the first aspect and the above examples, a ratio of a characteristic diameter of the well at an interface between the well structure and the dielectric structure relative to a characteristic diameter of the opening at the interface is in a range of 1.01 to 2. For example, the ratio is in a range of 1.01 to 1.5. In another example, the ratio is in a range of 1.01 to 1.15.
In an additional example of the first aspect and the above examples, the well structure comprises an oxide of silicon or a nitride of silicon.
In another example of the first aspect and the above examples, the well structure comprises a layer of an oxide of silicon and a layer of a nitride of silicon.
In a further example of the first aspect and the above examples, the conductive layer extends along the wall of the well to an interface between the well structure and the dielectric structure.
In an additional example of the first aspect and the above examples, the conductive layer comprises a metal. For example, the metal is selected from the group consisting of aluminum, copper, nickel, titanium, silver, gold, platinum, hafnium, lanthanum, tantalum, tungsten, iridium, zirconium, palladium, and a combination thereof.
In another example of the first aspect and the above examples, the conductive layer comprises a conductive ceramic material. For example, the conductive ceramic material is selected from the group consisting of titanium nitride, titanium aluminum nitride, titanium oxynitride, tantalum nitride, and a combination thereof.
In a further example of the first aspect and the above examples, the dielectric structure is thicker than the well structure.
In an additional example of the first aspect and the above examples, a ratio of the thickness of the dielectric layer to the thickness of the well structure is in a range of 1.01 to 10. For example, the ratio is in a range of 1.05 to 3. In a further example, the ratio is in a range of 1.05 to 2.
In another example of the first aspect and the above examples, the dielectric layer comprises a low temperature oxide of silicon.
In a further example of the first aspect and the above examples, the gate structure is a floating gate structure.
In an additional example of the first aspect and the above examples, the gate structure includes a barrier layer at the upper surface and in contact with the conductive layer.
In a second aspect, a method of forming a sensor device includes forming a well structure over a substrate, a gate structure disposed on the substrate and having an upper surface; forming a well in the well structure to expose the upper surface of the gate structure, the well including a well wall, the well structure defining an interstitial surface between wells; depositing conformally a conductive material over the well structure; removing the conductive material from the interstitial surface; forming a dielectric layer over the well structure; and forming an opening in the dielectric layer, the opening extending to the well.
In an example of the second aspect, forming the dielectric layer over the well structure comprises depositing a fill material into the well and depositing the dielectric layer over the well structure and the fill material in the well. For example, depositing the fill material into the well includes depositing the fill material over the well structure, the fill material entering the well, and removing excess fill material from over the well structure. In an example, removing the excess fill material includes performing chemical mechanical polishing of the fill material. For example, performing chemical mechanical polishing is stopped when the conductive material is detected. In an additional example, removing the excess fill material includes etching the fill material. For example, etching includes etching until the material of the conductive material is detected.
In another example of the second aspect and the above examples, a characteristic diameter of the well at an interface between the well structure and the dielectric structure is greater than a characteristic diameter of the opening at the interface.
In a further example of the second aspect and the above examples, a characteristic diameter of the well at an interface between the well structure and the dielectric structure is approximately a characteristic diameter of the opening at the interface.
In an additional example of the second aspect and the above examples, a ratio of a characteristic diameter of the well at an interface between the well structure and the dielectric structure relative to a characteristic diameter of the opening at the interface is in a range of 1.01 to 2.
In another example of the second aspect and the above examples, the well structure comprises an oxide of silicon or a nitride of silicon.
In a further example of the second aspect and the above examples, the well structure comprises a layer of an oxide of silicon and a layer of a nitride of silicon.
In an additional example of the second aspect and the above examples, the conductive layer extends along the wall of the well to an interface between the well structure and the dielectric structure.
In another example of the second aspect and the above examples, the conductive layer comprises a metal selected from the group consisting of aluminum, copper, nickel, titanium, silver, gold, platinum, hafnium, lanthanum, tantalum, tungsten, iridium, zirconium, palladium, and a combination thereof.
In a further example of the second aspect and the above examples, the conductive layer comprises a conductive ceramic material selected from the group consisting of titanium nitride, titanium aluminum nitride, titanium oxynitride, tantalum nitride, and a combination thereof.
In an additional example of the second aspect and the above examples, the dielectric structure is thicker than the well structure.
In another example of the second aspect and the above examples, a ratio of the thickness of the dielectric layer to the thickness of the well structure is in a range of 1.01 to 10.
In a further example of the second aspect and the above examples, the dielectric layer comprises a low temperature oxide of silicon.
In an additional example of the second aspect and the above examples, the gate structure is a floating gate structure.
In another example of the second aspect and the above examples, the gate structure includes a barrier layer at the upper surface and in contact with the conductive layer.
Note that not all of the activities described above in the general description or the examples are required, that a portion of a specific activity may not be required, and that one or more further activities can be performed in addition to those described. Still further, the order in which activities are listed are not necessarily the order in which they are performed.
In the foregoing specification, the concepts have been described with reference to specific embodiments. However, one of ordinary skill in the art appreciates that various modifications and changes can be made without departing from the scope of the invention as set forth in the claims below. Accordingly, the specification and figures are to be regarded in an illustrative rather than a restrictive sense, and all such modifications are intended to be included within the scope of invention.
As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having” or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, article, or apparatus that comprises a list of features is not necessarily limited only to those features but may include other features not expressly listed or inherent to such process, method, article, or apparatus. Further, unless expressly stated to the contrary, “or” refers to an inclusive-or and not to an exclusive-or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).
Also, the use of “a” or “an” are employed to describe elements and components described herein. This is done merely for convenience and to give a general sense of the scope of the invention. This description should be read to include one or at least one and the singular also includes the plural unless it is obvious that it is meant otherwise.
Benefits, other advantages, and solutions to problems have been described above with regard to specific embodiments. However, the benefits, advantages, solutions to problems, and any feature(s) that may cause any benefit, advantage, or solution to occur or become more pronounced are not to be construed as a critical, required, or essential feature of any or all the claims.
After reading the specification, skilled artisans will appreciate that certain features are, for clarity, described herein in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features that are, for brevity, described in the context of a single embodiment, may also be provided separately or in any subcombination. Further, references to values stated in ranges include each and every value within that range.
This application claims benefit of U.S. Provisional Application No. 62/209,370, filed Aug. 25, 2015, which is incorporated herein by reference in its entirety.
Number | Date | Country | |
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62209370 | Aug 2015 | US |