Patent Description:
Arrays of sensors formed in semiconductor substrates are increasingly being used in fields such as analytical chemistry and molecular biology. For example, when analytes are captured on or near sensor pads of a sensor array, the analytes or byproducts of reactions associated with the analytes can be detected and used to elucidate information regarding the analyte. In particular, such sensor arrays have found use in genetic analysis, such as genetic sequencing or quantitative amplification.

During manufacture, various semiconductor processing techniques can alter the nature of the surface of a sensor array and the surface of well structures around the sensor array. Such processing can also leave residues on the surface or alter surface oxidation. Such altered surface chemistry can prevent or limit the capture of analytes proximate to the sensors. As such, the effectiveness of such sensor arrays is reduced and signals resulting from such sensor arrays may include erroneous data or no data.

<CIT> discloses a sensing device comprising a sensing layer have at least one functional group that binds to the semi-conducting channel layer and at least another functional group that serves as a sensor.

<CIT> discloses a method of fabricating a chemical detection device comprising forming a microwell above a CMOS device, the microwell comprising a bottom surface and sidewalls.

<CIT> discloses methods and apparatus relating to large scale FET arrays for analyte measurements.

<CIT> discloses the design and fabrication of ultrathin poly-<NUM>-hexyl thiophene (P3HT) film based amine sensors.

<CIT> discloses a system including a sensor having a sensor pad and a well wall structure defining a well operatively coupled to the sensor pad.

<CIT> discloses a process for producing a surface gate comprising a selective membrane for an integrated chemical sensor comprising a field effect transistor, wherein the surface gate is particularly sensitive to alkaline-earth species, more particularly the calcium ion.

In an example, a surface agent is deposited over surfaces adjacent to or on sensor surfaces. Such surface agents can be deposited on the sensor surfaces when the sensors are in the form of a sensor component or alternatively, when the sensors are disposed in a wafer prior to singulating the wafer into die that can be packaged into sensor components.

In a particular example, a sensor component includes an array of field effect transistor (FET) based sensors and a corresponding array of reaction sites, e.g., wells. One or more surface agents can be disposed on the surfaces of the array of FET-based sensors or the surfaces of the wells.

In an exemplary embodiment, a sensor component has a sensor and a reaction site disposed in cooperation with the sensor. The reaction site is a well. A surface agent can bind to sidewalls of the reaction site or a surface of the sensor. The surface agent includes a functional group as claimed in claim <NUM>.

In an exemplary embodiment, a sensor component includes an array of wells associated with a sensor array. The sensors of the sensor array can include field effect transistor (FET) sensors, such as ion sensitive field effect transistors (ISFET). In an example, the wells have a depth or thickness in a range of <NUM> to <NUM> micrometers. In another example, the wells can have a characteristic diameter in a range of <NUM> micrometers to <NUM> micrometers. The sensor component can form part of a sequencing system.

In a particular example, a sequencing system includes a flow cell in which a sensory array is disposed, includes communication circuitry in electronic communication with the sensory array, and includes containers and fluid controls in fluidic communication with the flow cell. In an example, <FIG> illustrates an expanded and cross-sectional view of a flow cell <NUM> and illustrates a portion of a flow chamber <NUM>. A reagent <NUM> flows across a surface of a well array <NUM>, in which the reagent <NUM> flows over the open ends of wells of the well array <NUM>. The well array <NUM> and a sensor array <NUM> together can form an integrated unit forming a lower wall (or floor) of the flow cell <NUM>. A reference electrode <NUM> can be fluidically coupled to the flow chamber <NUM>. Further, a flow cell cover <NUM> encapsulates the flow chamber <NUM> to contain the reagent <NUM> within a confined region.

<FIG> illustrates an expanded view of a well <NUM> and a sensor <NUM>, as illustrated at <NUM> of <FIG>. The volume, shape, aspect ratio (such as base width-to-well depth ratio), and other dimensional characteristics of the wells can 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 sensor <NUM> can be a chemical field-effect transistor (chemFET), more specifically an ion-sensitive FET (ISFET), with a floating gate <NUM> having a sensor plate <NUM> optionally separated from the well interior by a material layer <NUM>, which defines a sensor surface. In addition, a conductive layer (not illustrated) can be disposed over the sensor plate <NUM>. In an example, the material layer <NUM> includes an ion sensitive material layer. The material layer <NUM> can be a ceramic layer, such as an oxide of zirconium, hafnium, tantalum, aluminum, or titanium, among others, or a nitride of titanium. Alternatively, the material layer <NUM> can be formed of a metal, such as titanium, tungsten, gold, silver, platinum, aluminum, copper, or a combination thereof. In an example, the material layer <NUM> can have a thickness in a range of <NUM> to <NUM>, such as a range of <NUM> to <NUM>, a range of <NUM> to <NUM>, or even a range of <NUM> to <NUM>.

While the material layer <NUM> is illustrated as extending beyond the bounds of the illustrated FET component, the material layer <NUM> can extend along the bottom of the well <NUM> and optionally along the walls of the well <NUM>. The sensor <NUM> can be responsive to (and generate an output signal related to) the amount of a charge <NUM> present on the material layer <NUM> opposite the sensor plate <NUM>. Changes in the charge <NUM> can cause changes in a current between a source <NUM> and a drain <NUM> of the chemFET. In turn, the chemFET can be used directly to provide a current-based output signal or indirectly with additional circuitry to provide a voltage-based output signal. Reactants, wash solutions, and other reagents can move in and out of the wells by a diffusion mechanism <NUM>.

In an embodiment, reactions carried out in the well <NUM> can be analytical reactions to identify or determine characteristics or properties of an analyte of interest. Such reactions can generate directly or indirectly byproducts that affect the amount of charge adjacent to the sensor plate <NUM>. If such byproducts are produced in small amounts or rapidly decay or react with other constituents, multiple copies of the same analyte can be analyzed in the well <NUM> at the same time in order to increase the output signal generated. In an embodiment, multiple copies of an analyte can be attached to a solid phase support <NUM>, either before or after deposition into the well <NUM>. The solid phase support <NUM> can be a polymer matrix, such as a hydrophilic polymer matrix, for example, a hydrogel matrix or the like. For simplicity and ease of explanation, solid phase support <NUM> is also referred herein as a polymer matrix.

The well <NUM> can be defined by a wall structure, which can be formed of one or more layers of material. In an example, the wall structure can have a thickness extending from the lower surface to the upper surface of the well in a range of <NUM> micrometers to <NUM> micrometers, such as a range of <NUM> micrometers to <NUM> micrometers, a range of <NUM> micrometers to <NUM> micrometers, a range of <NUM> micrometers to <NUM> micrometers, or a range of <NUM> micrometers to <NUM> micrometers. In particular, the thickness can be in a range of <NUM> micrometers to <NUM> micrometer, such as a range of <NUM> micrometers to <NUM> micrometers, or a range of <NUM> micrometers to <NUM> micrometers. The wells <NUM> can have a characteristic diameter, defined as the square root of <NUM> times the cross-sectional area (A) divided by Pi (e.g., sqrt(<NUM>*A/π)), of not greater than <NUM> micrometers, such as not greater than <NUM> micrometers, not greater than <NUM> micrometers, not greater than <NUM> micrometers, not greater than <NUM> micrometers, not greater than <NUM> micrometers or even not greater than <NUM> micrometers. In an example, the wells <NUM> can have a characteristic diameter of at least <NUM> micrometers. In a further example, the well <NUM> can define a volume in a range of <NUM> fL to <NUM> pL, such as a volume in a range of <NUM> fL to <NUM> pL, a range of <NUM> fL to <NUM> fL, a range of <NUM> fL to <NUM> fL, or even a range of <NUM> fL to <NUM> fL.

While <FIG> illustrates a single-layer wall structure and a single-layer material layer <NUM>, the system can include one or more wall structure layers, one or more conductive layers or one or more material layers. For example, the wall structure can be formed of one or more layers, including an oxide of silicon or TEOS or including a nitride of silicon.

In a particular example illustrated in <FIG>, a system <NUM> includes a well wall structure <NUM> defining an array of wells <NUM> disposed over or operatively coupled to sensor pads of a sensor array. The well wall structure <NUM> defines an upper surface <NUM>. A lower surface <NUM> associated with the well is disposed over a sensor pad of the sensor array. The well wall structure <NUM> defines a sidewall <NUM> between the upper surface <NUM> and the lower surface <NUM>. As described above, a material layer in contact with sensor pads of the sensor array can extend along the lower surface <NUM> of a well of the array of wells <NUM> or along at least a portion of the wall <NUM> defined by the well wall structure <NUM> and defines a sensor surface. The upper surface <NUM> can be free of the material layer.

While the wall surface of <FIG> is illustrated as extending substantially vertically and outwardly, the wall surface can extend in various directions and have various shapes. Substantially vertically denotes extending in a direction having a component that is normal to the surface defined by the sensor pad. For example, as illustrated in <FIG>, a well wall <NUM> can extend vertically, being parallel to a normal component <NUM> of a surface defined by a sensor pad. In another example, the wall surface <NUM> extends substantially vertically, in an outward direction away from the sensor pad, providing a larger opening to the well than the area of the lower surface of the well. As illustrated in <FIG>, the wall surface <NUM> extends in a direction having a vertical component parallel to the normal component <NUM> of the surface <NUM>. In an alternative example, a wall surface <NUM> extends substantially vertically in an inward direction, providing an opening area that is smaller than an area of the lower surface of the well. The wall surface <NUM> extends in a direction having a component parallel to the normal component <NUM> of the surface <NUM>.

While the surfaces <NUM>, <NUM>, or <NUM> are illustrated by straight lines, some semiconductor or CMOS manufacturing processes can result in structures having nonlinear shapes. In particular, wall surfaces, such as wall surface <NUM> and upper surfaces, such as upper surface <NUM>, can be arcuate in shape or take various nonlinear forms. While the structures and devices illustrated herewith are depicted as having linear layers, surfaces, or shapes, actual layers, surfaces, or shapes resulting from semiconductor processing can differ to some degree, possibly including nonlinear and arcuate variations of the illustrated embodiment.

<FIG> includes an illustration of exemplary wells including ion sensitive material layers. For example, a well structure <NUM> can define an array of wells, such as exemplary wells <NUM>, <NUM>, or <NUM>. The wells (<NUM>, <NUM>, or <NUM>) can be operatively coupled to an underlying sensor (not illustrated) or linked to such an underlying sensor. Exemplary well <NUM> includes an ion sensitive material layer <NUM> defining the bottom of the well <NUM> and sensor surface and extending into the structure <NUM>. While not illustrated in <FIG>, a conductive layer, such as a gate, for example, a floating gate of ion sensitive field effect transistor can reside below the ion sensitive material layer <NUM>.

In another example, as illustrated by well <NUM>, an ion sensitive material layer <NUM> can define the bottom of the well <NUM> and sensor surface without extending into the structure <NUM>. In a further example, a well <NUM> can include an ion sensitive layer <NUM> that extends along at least a portion of a sidewall <NUM> of the well <NUM> defined by the structure <NUM>. As above, the ion sensitive material layers <NUM> or <NUM> can reside over conductive layers or gates of underlying electronic devices and can define sensor surfaces.

In a particular example, the sidewalls <NUM> of the wells (<NUM>, <NUM>, or <NUM>) can be formed of metals, semi-metals, oxides thereof, or nitrides thereof, or a combination thereof. Exemplary metals include gold, silver, platinum, copper, aluminum, tungsten, titanium, or a combination thereof. An exemplary semi-metal includes silicon. In an example, the sidewalls can be formed of the silicon dioxide, silicon nitride, TEOS, or a combination thereof. In particular, the sidewalls <NUM> can be formed of one or more layers of one or more of the above materials.

Surfaces of the sensors (e.g., material layers <NUM>, <NUM>, or <NUM>) can be formed of metals, semi-metals, oxides thereof, or nitrides thereof, or combinations thereof. Exemplary metals include tungsten, titanium, tantalum, hafnium, aluminum, zirconium, gold, silver, platinum, copper, or combinations thereof. Exemplary oxides or nitrides include titanium dioxide, titanium nitride, tantalum oxide, hafnium oxide, zirconia, alumina, or combinations thereof.

In a particular example, the surfaces of the sidewalls <NUM> or the surfaces of the sensors (<NUM>, <NUM>, or <NUM>) can exhibit Bronsted base functionality, such as surface hydroxyl groups or µ-oxo groups, or Lewis acid functionality at transition metal centers. Even in some nitrides, at least partial oxidation of the surface results in formation of surface hydroxyl groups or other Bronsted base structures, particularly in the presence of aqueous solutions. Such hydroxyl groups have been demonstrated to exhibit buffering, slowing the response of sensors to ionic byproducts of reactions, such as acid protons or hydronium ions, or to changes in pH. For metal ceramic surfaces, surface metal centers can behave like Lewis acid sites.

In an example, a surface agent can bind to the sidewalls <NUM> and the sensor surfaces (<NUM>, <NUM>, or <NUM>). In particular, the surface agent can bind as a monolayer over one or more of the surfaces. In particular, the surface agent includes a functional group reactive with the Bronsted base or Lewis acid functionality formed on the surfaces. The surface reactive functional group consists of phospates, phosphonic acid, phosphinic acid, bisphosphonic acid, multidentate phosphates or phosphonates, polyphosphates/phosphonates, alkoxy derivatives thereof, or any combination thereof. Exemplary alkoxy groups include methoxy, ethoxy, or combinations thereof. Phosphates can be used to functionalize titania surfaces. In further examples, particular surface reactive functional groups may preferentially deposit on one or more metal or ceramic surfaces relative to other metal or ceramic surfaces.

Distal from the functional group, the surface agent can include a functional group that includes salts of quaternary ammonium ions derived from secondary amines, tertiary amines or heterocyclic groups incorporating nitrogen. Exemplary heterocyclic groups incorporating nitrogen include quaternary amines derived from pyrrolidine, pyrrole, imidazole, piperidine, pyridine, pyrimidine, purine, triazolium, or combinations thereof. In particular, the salt can include a halide salt of the quaternary ammonium ions, such as a bromide salt. The secondary, tertiary, or quaternary amines can be conjugated to alkyl groups including methyl, ethyl, propyl, butyl, or tert-butyl alkyl groups. In another example, the distal functional group can include hindered primary, secondary or tertiary amines, such as amines hindered by proximal phosphate, phosphonate, phosphinate, or combinations thereof.

In an example, the distal functional group can be bound to the surface reactive functional group by an amide, alkyl, alkoxy, aryl, or polyether or thioether moiety, or a combination thereof. For example, the distal functional group can be separated from the surface reactive functional group by an alkyl moiety having <NUM> to <NUM> carbons, such as <NUM> to <NUM> carbons. In an example, the alkyl moiety can have <NUM> to <NUM> carbons, such as <NUM> to <NUM> carbons.

In another example, the alkyl moiety can have <NUM> to <NUM> carbons, such as <NUM> to <NUM> carbons, or <NUM> to <NUM> carbons. In particular, surface agents including hindered amine distal functionality can have an alkyl moiety having <NUM> to <NUM> carbons, such as <NUM> to <NUM> carbons, or <NUM> to <NUM> carbons. In another example, the alkoxy moiety can have a number of carbons in a range similar to that of the alkyl moiety. In an additional example, a polyether moiety can have between <NUM> and <NUM> ether units, each having between <NUM> and <NUM> carbons, such as between <NUM> and <NUM> carbons. For example, the polyether moiety can have between <NUM> and <NUM> ether units, such as between <NUM> and <NUM> ether units.

In another example, the surface agent can be a phosphonic acid-based surface agent. An exemplary surface agent includes alkyl phosphonic acids, such as octadecyl phosphonic acid; chlorine or bromine salts of quaternary amino phosphonic acids, such as imidazole phosphonic acids (e.g., <NUM>-methyl-<NUM>-(dodecylphosphonic acid) imidazolium, see D of <FIG>, or <NUM>-methyl-<NUM>-(hexylphosphonic acid) imidazolium, see E of <FIG>), (<NUM>-dodecylphosphonic acid) trimethylammonium bromide, methyl ammonium phosphonic acid (B of <FIG>), ethyl ammonium phosphonic acid (C of <FIG>), (<NUM>-dodecylphosphonic acid)tripropylammonium bromide, (<NUM>-dodecylphosphonic acid)tributylammonium bromide; (<NUM>-dodecylphosphonic acid) methyltriazolium bromide (F of <FIG>); (<NUM>-hexylphosphonic acid) imidazolium; pyridine alkyl phosphonic acids (e.g., A of <FIG>); benzo alkyl phosphonic acids; (<NUM>-amino-<NUM>-phenylmethyl) phosphonic acid; fluorinated or chlorinated derivatives thereof; derivatives thereof; or any combination thereof. In another example, the surface agent can be a biotin alkyl phosphonic acid (e.g., the structure of <FIG> in which R represents oxygen, nitrogen, sulfur, a polyether, or a combination thereof). In an example, phosphates and phosphonates can preferentially bind to sensor surfaces.

In a further example, the phosphonic acid-based surface agent can include more than one phosphonic acid surface active functional group. For example, the surface agent can be a bisphosphonic acid, including two phosphonic acid surface active functional groups, such as alendronic acid or a derivative thereof. In particular, the surface agent can be a multidentate phosphonic acid-based surface agent, for example, including more than one phosphonic acid functional group coupled to a central moiety functioning as the distal group, such as a tertiary amine or alkyldiamine. For example, the surface agent can be a functionalized amino bis(alkyl phosphonic acid), such as a biotin functionalized amino bis(methylene phosphonic acid), nitrilotris (alkyl phosphonic acid), e.g. nitrilotris (methylene phosphonic acid), an ether derivative thereof, or a combination thereof. In another example, the surface agent can be alkyldiamine tetrakis (alkyl phosphonic acid), such as ethylene diamine tetrakis (methylene phosphonic acid) (see G of <FIG>). In a further example, the surface agent can be diethylenetriamine penta(methylene phosphonic acid), hexamethylenediamine tetra(methylene phosphonic acid), tetramethylenediamine tetra(methylene phosphonic acid), or any combination thereof. In an additional example, the surface agent is a phenyl diphosphonic acid, a functionalized derivative thereof, or a combination thereof.

In particular, the surface agents can be applied over a sensor device. The sensor device can include a plurality of sensor pads and optionally wells defined over the sensor pads. The surface agent can be applied to adhere to the sidewalls of the wells, can be applied to the sensor pad surfaces, or a combination thereof. In an example, the sensor device includes a lid disposed over the wells and sensor pads and defines a flow volume or flow cell above the sensor pads and wells. The surface agent or a combination of surface agents can be applied in solution through the flow cell or flow volume to contact the wells or sensor pads.

For example, as illustrated in <FIG>, a method <NUM> includes optionally warming a sensor component, as illustrated at <NUM>. The sensor component can include a set of wells disposed over sensor pads and a lid defining a flow volume or flow cell over the wells and sensor pads. The sensor component can be warmed to a temperature in the range of <NUM>° C to <NUM>° C, such as a temperature in a range of <NUM>° C to <NUM>° C, or even a range of <NUM>° C to <NUM>° C. Optionally, the temperature of the sensor component can be maintained at temperatures within the range throughout the process or fluids can be applied at temperatures within the range throughout the process.

As illustrated at <NUM>, the sensor component can be washed. Optionally, the sensor component can be washed with an acid or base wash or a combination thereof. For example, the sensor component can be washed with a base solution, for example, including a sodium hydroxide solution having a concentration in a range between <NUM> and <NUM>, such as a concentration in a range of <NUM> to <NUM>, or a range of <NUM> to <NUM>. Following application of the base solution, the sensor component can be incubated in the presence of the base solution for a period in a range of <NUM> seconds to <NUM> minutes, such as a range of <NUM> seconds to <NUM> minutes, or a range of <NUM> seconds to <NUM> seconds.

Alternatively or in addition, the sensor component can be incubated in the presence of an acid solution. The acid solution can be an aqueous solution or can be a nonaqueous solution. In particular, the sensor component can be incubated in the presence of the acid solution for a period in a range of <NUM> seconds to <NUM> minutes, such as a range of <NUM> seconds to <NUM> minutes, or a range of <NUM> seconds to <NUM> seconds.

Exemplary acids in the acid solution can include sulfonic acid, phosphonic acid, or a combination thereof. The acid solution can further include an organic solvent. An exemplary sulfonic acid includes an alkyl sulfonic acid, an alkyl aryl sulfonic acid, or a combination thereof. An exemplary alkyl sulfonic acid includes an alkyl group having <NUM> to <NUM> carbons, such as <NUM> to <NUM> carbons, <NUM> to <NUM> carbons, or <NUM> to <NUM> carbons. In another example, the alkyl group of the alkyl sulfonic acid has <NUM> to <NUM> carbons. For example, an alkyl sulfonic acid can include methanesulfonic acid, ethanesulfonic acid, propane sulfonic acid, butane sulfonic acid, or combinations thereof. In another example, the alkyl group can be functionalized, for example, with a terminal functional group opposite the sulfonic acid functional group. An exemplary functionalized alkyl sulfonic acid includes an alkyl sulfonic acid functionalized with a terminal amine group, such as taurine. In a further example, the alkyl groups of the sulfonic acid can be halogenated, such as fluorinated.

In a further example, the sulfonic acid includes an alkyl aryl sulfonic acid. The alkyl aryl sulfonic acid, for example, alkyl benzene sulfonic acid, can include an alkyl group having between <NUM> and <NUM> carbons. For example, the alkyl group can have between <NUM> and <NUM> carbons, such as between <NUM> and <NUM> carbons. In a particular example, the alkyl aryl sulfonic acid includes dodecyl benzene sulfonic acid. The dodecyl benzene sulfonic acid can be a purified form of dodecyl benzene sulfonic acid having at least <NUM>%, such as at least <NUM>% of alkyl aryl sulfonic acid having an alkyl group with <NUM> carbons. Alternatively, the dodecyl benzene sulfonic acid can include a blend of alkyl benzene sulfonic acid having alkyl groups with an average of <NUM> carbons. The alkyl aryl sulfonic acid can be alkylated at a blend of positions along the alkyl chain. In another example, the alkyl group can have between <NUM> and <NUM> carbons. For example, the alkyl aryl sulfonic acid can include toluene sulfonic acid.

The acid solution can have a concentration between <NUM> and <NUM> acid, such as sulfonic acid. For example, the acid solution can have a concentration between <NUM> and <NUM> acid. In another example, the acid solution includes between <NUM> wt% and <NUM> wt% of the acid, such as sulfonic acid. For example, the acid solution can include between <NUM> wt% and <NUM> wt% of the acid, such as between <NUM> wt% and <NUM> wt% of the acid, such as sulfonic acid.

The organic solvent within the acid solution is a non-aqueous solvent providing solubility for the acid (e.g., sulfonic acid) to at least the concentrations above. In an example, the organic solvent can be aprotic. The organic solvent can be a non-polar organic solvent. In another example, the organic solvent can be a polar aprotic solvent. In an example, the organic solvent can have a normal boiling point in a range of <NUM> to <NUM>° C. For example, the normal boiling point can be in a range of <NUM>° C to <NUM>° C. In another example, the normal boiling point can be in a range of <NUM>° C to <NUM>° C. Alternatively, the normal boiling point is in a range of <NUM>° C to <NUM>° C.

In a particular example, the non-polar organic solvent includes an alkane solvent, an aromatic solvent, or a combination thereof. An alkane solvent can have between <NUM> and <NUM> carbons. For example, the alkane can have between <NUM> and <NUM> carbons, such as between <NUM> and <NUM> carbons. Alternatively, the alkane can have between <NUM> and <NUM> carbons. In a particular example, the alkane is a linear alkane. For example, the alkane solvent can include pentane, hexane, heptanes, octane, decane, undecane, dodecane, or combinations thereof. In another example, the alkane is halogenated. An exemplary branched alkane can include hydrogenated dimers of C11 or C12 alpha olefins.

In a further example, the organic solvent can include a polar aprotic solvent. For example, the polar aprotic solvent can include tetrahydrofuran, ethylacetate, acetone, dimethylformamide, acetonitrile, dimethyl sulfoxide, N-methyl pyrrolidone (NMP), or combinations thereof. In another example, the organic solvent can be free of ether solvents and, for example, can include dimethylformamide, acetonitrile, dimethyl sulfoxide, or combinations thereof.

Washing can also include washing using an alcohol, such as ethanol or isopropyl alcohol, or an alcohol/water mix. An alcohol wash is particularly useful when utilizing an acid solution in a nonaqueous solvent.

In a further example, washing the sensor component can include cycling through an acid solution wash, alcohol wash, or base solution wash one or more times, for example one time, two times, or three times. Alternatively, the system can utilize a single acid wash followed by an alcohol wash or a single base wash followed by an aqueous wash or alcohol/water wash.

Following the wash, the sensor component can optionally be washed with alcohol and dried, as illustrated at <NUM>. For example, the sensor component can be further flushed with alcohol and the alcohol evaporated, for example, by a vacuum aspirating air through the flow cell or by applying dry nitrogen through the flow cell.

The surface agent can be applied to the chip, as illustrated at <NUM>. For example, the surface agent can be incorporated into a solution, applied over the sensor component, and incubated on the sensor component for a period between <NUM> minute and <NUM> hours. For example, the sensor component can be incubated in the presence of the surface agent solution for a period in a range of <NUM> minute to <NUM> minutes, such as a range of <NUM> minutes to <NUM> minutes, a range of <NUM> minutes to <NUM> minutes, a range of <NUM> minutes to <NUM> minutes, or a range of <NUM> minutes to <NUM> minutes. The incubation temperature can be in a range of <NUM>° C to <NUM>° C, such as a range of <NUM>° C to <NUM>° C, or a range of <NUM>° C to <NUM>° C.

In an example, the surface agent solution can include a solvent such as alcohol (e.g., ethanol or isopropyl alcohol), N-methyl pyrrolidone (NMP), dimethylformamide (DMF), or a combination thereof. Optionally the solution can include water. The surface agent can be included in amounts of <NUM>% to <NUM>% by weight, such as a range of <NUM>% to <NUM>% by weight. In particular, exemplary silane-based surface agents can be included in a solution in an amount in a range of <NUM>% to <NUM>% by weight, such as a range of <NUM>% to <NUM>% by weight. Exemplary phosphonic acid surface agents can be included in a range of <NUM>% to <NUM>% by weight, such as a range of <NUM>% to <NUM>% by weight, or a range of <NUM>% to <NUM>% by weight.

Following application of the surface agent, the sensor component can be washed and dried, as illustrated at <NUM>. For example, the sensor component can be washed with alcohol, such as ethanol or isopropyl alcohol, and dried.

In another example, the surface agent can be applied at wafer level prior to singulating and forming a semiconductor chip sensor component. The wafer can include a plurality of die. Each die can include an array of sensors and a set of reaction sites defined in cooperation with the sensors. For example, wells can be formed in a surface layer to expose sensor pads of the sensors. In an example, the wafer can be treated in a manner similar to the sensor component as described in relation to <FIG> prior to singulating the wafer and subsequently packaging individual die into sensor components including a flow cell lid and substrate.

In another example, the wafer can be treated using an oxygen plasma followed by application of the surface agent. For example, <FIG> illustrates an exemplary method <NUM> that includes treating the wafer, and in particular, the wells and sensor surfaces of the wafer with an oxygen plasma, as illustrated at <NUM>. In an example, the wafer is exposed to an oxygen plasma at <NUM> mtorr to <NUM> mtorr of oxygen, such as <NUM> mtorr to <NUM> mtorr, or <NUM> mtorr to <NUM> mtorr of oxygen, and <NUM> W to <NUM> W, such as <NUM> W to <NUM> W, or <NUM> W to <NUM> W for a period in a range of <NUM> minute to <NUM> minutes, such as a range of <NUM> minutes to <NUM>.

As illustrated at <NUM>, a surface agent solution can be applied to the wafer. The wafer can be inserted into a bath including a surface agent and a solvent solution. In an example, the solvent solution can include N-methyl pyrrolidone (NMP) and water. Alternatively, the solvent solution can include alcohol or an alcohol/water mixture. The surface agent can be included in the surface agent solution in a concentration in a range of <NUM>/ml to <NUM>/ml. For example, the concentration can be in a range of <NUM>/ml to <NUM>/ml, or a range of <NUM>/ml to <NUM>/ml. The bath can be held at a temperature in a range of <NUM>° C to <NUM>° C, such as a range of <NUM>° C to <NUM>° C, a range of <NUM>° C to <NUM>° C, or a range of <NUM>° C to <NUM>° C. The wafer can be incubated in the surface agent solution for a period between <NUM> minutes and <NUM> minutes, such as a period in a range of <NUM> minutes to <NUM> minutes, or a period in a range of <NUM> minutes to <NUM> minutes.

As illustrated at <NUM>, the wafer can be washed and dried. For example, the wafer can be washed in an NMP/water solution and subsequently washed in water. The wafer can then be dried.

Optionally, the wafer can be annealed, as illustrated at <NUM>. For example, the wafer can be held at an elevated temperature for an extended period. For example, the wafer can be annealed at a temperature in a range of <NUM>° C to <NUM>° C, such as a temperature in a range of <NUM>° C to <NUM>° C, or a range of <NUM>° C to <NUM>° C. The wafer can be annealed in an air atmosphere. Alternatively, the wafer can be annealed in an inert atmosphere, such as a nitrogen atmosphere or a helium atmosphere. The wafer can be annealed for a period in a range of <NUM> minutes to <NUM> hours, such as a range of <NUM> hour to <NUM> hours.

As illustrated at <NUM>, the wafer can be singulated into individual die. Each of the die can be packaged into sensor components, as illustrated at <NUM>. For example, the die can be applied to a circuit substrate and wire bound to the substrate. A lid can be applied over the die to form a flow cell. Further, the substrate/die assembly can be encapsulated to further secure the die to the substrate and protect the wire bonds or interconnects.

Embodiments of the above described sensor components and methods provide technical advantages relating to increased key signal from the sensor component. In particular, the sensor component can exhibit higher key signal, faster response, and less buffering.

A sensor component is prepared using butyl ammonium trimethoxy silane (BATS) following the protocol below. The BATS is available from GELEST, part number SIT8422.

Perform dodecyl benzene sulfonic acid (DBSA) treatment on the chip.

Repeat twice more for a total of <NUM> DBSA/NaOH cycles.

Make a <NUM> % BATS solution. To make <NUM> of solution: <NUM>µL BATS (<NUM>% in DMF) with <NUM>µL absolute ethanol and <NUM>µL NF water.

Place DBSA cleaned chip into <NUM> oz jar, equipped with a <NUM> tube filled <NUM>% EtOH. Add <NUM>µL of BATS solution to chip, making sure both the inlet and exit wells are completely filled.

Remove jar from oven and take chip from jar.

Wash top and ports of chip with <NUM> ethanol (hold chip over large mouthed container).

Push <NUM> × <NUM> ethanol through chip using <NUM> pipette tip fitted with a filterless <NUM>µL tip. Remove ethanol from chip with vacuum.

A sensor component (ION Torrent ™ Proton II available from Life Technologies Corporation) is treated with imidazole phosphoric acid (ImPA) using the following protocol. The ImPA solution includes <NUM>/mL ImPA in <NUM>% isopropanol/<NUM>% diH2O.

A sensor component (ION Torrent ™ Proton II available from Life Technologies Corporation) is treated with <NUM>-dodecylphosphonic acid trimethoxyammonium bromide (MAPA) using the following protocol. The MAPA solution includes <NUM>/mL ImPA in diH2O.

A wafer including sensor die to be converted to sensor chips (ION Torrent™ Proton II sensors from Life Technologies Corporation) is treated with ImPA prior to dicing and packaging using the following process:.

A wafer including sensor die to be converted to sensor chips (ION Torrent™ Proton II sensors from Life Technologies Corporation) is treated with ImPA prior to dicing and packaging using the following process.

Run the plasma cleaner for one cycle prior to introducing the wafer (<NUM> minutes, <NUM> watts, <NUM> mtorr oxygen). Place a wafer on center rack in the plasma cleaner. Run the plasma for <NUM> minute, <NUM> watt plasma clean with <NUM> mtorr of oxygen.

Make the following solution (<NUM>/mL ImPA in <NUM>% NMP/<NUM>% water): <NUM> gram ImPA, <NUM> NMP, and <NUM> nanopure water. Sonicate briefly to get the ImPA fully into solution.

Once the wafer is plasma cleaned, immediately place the wafer in pie dish and cover with the ImPA solution. Turn over a second pie dish to use as cover. Place in a <NUM> oven for <NUM> hour. Remove the covered pie dish from oven. Rinse the wafer by immersing in a clean pie dish containing fresh <NUM>% NMP/<NUM>% water. Swirl to aid in rinsing. Rinse the pie dish containing ImPA with <NUM>/<NUM> NMP water mixture and fill with fresh <NUM>/<NUM> NMP to use as a second rinse bath. Transfer the wafer to second bath and swirl to aid rinsing. Repeat again with a third <NUM>/<NUM> NMP water bath.

After completing the three NMP/water rinses, transfer the wafer to a pie dish containing nanopure water for first water rinse. Swirl to aid rinsing. Complete two more water bath submersions with the wafer, for a total of <NUM> NMP/water rinses and <NUM> water only rinses (alternating the wafer between the two pie dishes used for the initial treatment).

Remove the wafer and dry with a nitrogen gas stream. Store in a wafer carrier for transport for assembly.

In the foregoing specification, the concepts have been described with reference to specific embodiments. 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.

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.

Claim 1:
A sensor component comprising:
a sensor (<NUM>) including a sensor surface (<NUM>);
a reaction site in cooperation with the sensor (<NUM>) and exposing the sensor surface (<NUM>); and
a surface agent bound to the sidewall surface of the reaction site or the sensor surface (<NUM>), the surface agent including a surface active functional group reactive with the sensor surface (<NUM>) and including a distal functionality;
the surface active functional group including phosphate, phosphonic acid, phosphinic acid, a bisphosphonic acid, multidentate phosphates or phosphonates, polyphosphates/phosphonates, alkoxy derivatives thereof, or any combination thereof;
characterized in that the reaction site is a well (<NUM>, <NUM>, <NUM>, <NUM>) including a sidewall surface (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>) and an ion sensitive material layer (<NUM>, <NUM>, <NUM>, <NUM>) defining the bottom of the well and the sensor surface (<NUM>), and
further characterized in that the distal functionality includes an amine and has a positive charge.