Back-side illuminated sensor structures

Abstract

Back-side illumination (BSI) sensors (e.g., biosensors) and methods of manufacturing and using such sensors is disclosed. The sensors include a BSI image sensor including a plurality of light detectors, and an optical filter stack disposed over a back side of the BSI image sensor. The optical filter stack includes a light guide isolation structure, and a plurality of light guides. Each light guide is associated with at least one light detector. The light guide isolation structure comprises either overlapping layers comprising at least one metal material layer and at least one dielectric material layer, or a layer comprising a heavily doped silicon and at least one metal oxide. The light guide isolation structure extends about each light guide and between adjacent light guides, and is configured to reduce optical crosstalk between the light guides and the light detectors.

Description

BACK-SIDE ILLUMINATED SENSOR STRUCTURESCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application perfects and claims priority benefit of the U.S. Provisional Application 63 / 614,057, filed December 22, 2023, entitled BACK-SIDE ILLUMINATED SENSOR STRUCTURES, the entirety of which is hereby incorporated herein by reference.BACKGROUND

[0002] Image sensors may be utilized for biological and chemical analysis (referred to herein as “biosensors”). Various protocols in biological or chemical analysis involve performing controlled designated reactions. The designated reactions may be observed or detected, and subsequent analysis may identify or reveal properties of chemicals involved in the reaction, by biosensors. For example, in some multiplex assays, an unknown analyte having an identifiable label (e.g., fluorescent label) may be exposed to thousands of known probes under controlled conditions. Each known probe may be deposited into a corresponding flow cell channel with reaction sites (which may be within wells, such as nanowells) of a biosensor. Observing any chemical reactions that occur between the known probes and the unknown analyte at the reaction sites may help identify or reveal properties of the analyte. Other examples of such protocols include known DNA sequencing processes, such as sequencing-by-synthesis (SBS) or cyclic- array sequencing.

[0003] In some conventional fluorescent-detection protocols, an optical system is used to direct an excitation light onto fluorescently labeled analytes and to also detect the fluorescent signals that may emit from the fluorescently labeled analytes. Such optical systems may include an arrangement of lenses, filters, and light sources. In other detection systems, the controlled reactions occur over a solid-state imager e.g., charged coupled device (CCD) or a complementary metal-oxide-semiconductor (CMOS) detector) that does not require a large optical assembly to detect the fluorescent emissions.

[0004] In some sensor systems that provide fluorescent detection for chemical analysis, including in those that utilize numerous reaction sites, there may be a risk of optical crosstalk, where one or more particular light or image sensor corresponding to one or more particular reaction site undesirably receives light from one or more non-corresponding reaction site orsome other source. For example, some chemical analysis sensor systems may include a light filter and guide structure that is configured to, inter alia, prevent or reduce (filter out) light of wavelengths that differ from the fluorescent signals or other light signals that indicate whether a reaction has or has not occurred from passing from a reaction site to non-corresponding light or image sensors. These light filter and guide structures reduce optical crosstalk by physically blocking at least some light from reaching non-corresponding light or image sensors and / or light from sources of noninterest (e.g., the excitation light). Due to the desirable dimensions of sensor systems with submicron pixel back-side illuminated (BSI) image sensors, light filter and guide structures that effectively constrain optical crosstalk can be difficult and / or costly to manufacture. Light filter and guide structures of such BSI sensor systems (e.g., BSI biosensor systems) that reduce optical crosstalk without undesirably increasing the manufacturing cost and / or complexity thereof is therefore beneficial, advantageous, and desirable.SUMMARY

[0005] Shortcomings of the prior art can be overcome and benefits as described later in this disclosure can be achieved through the sensors (biosensors), methods of making such sensors, and methods of using such sensors. Various examples of the sensors and methods related thereto, including and excluding the additional examples enumerated below, in any combination (provided these combinations are not inconsistent), overcome these shortcomings.

[0006] In one aspect, the present disclosure provides for sensors. In some examples herein, the sensors comprise an image sensor structure, comprising an image stack, metal circuitry and an optical filter stack. The image stack comprises a substrate, a plurality of light detectors, a front side and a light receiving back side. The metal circuitry is disposed over the front side of the image stack, and is electrically coupled to the photodiodes and configured to transmit data signals based on photons detected by the light detectors. The optical filter stack is disposed over the back side of the image stack. The optical filter stack comprises a light guide isolation structure including: overlapping layers comprising at least one metal material layer and at least one dielectric material layer; or a layer including a heavily doped silicon and at least one metal oxide. The optical filter stack further comprises a plurality of light guides. The plurality of light guides comprise a plurality of openings in the light guide isolation structure, and an optical filter material disposed within the plurality of openings. Each light guide of the plurality of lightguides is associated with at least one light detector of the plurality of light detectors. The light guide isolation structure extends about each light guide of the plurality of light guides and between adjacent light guides of the plurality of light guides, and is configured to reduce optical crosstalk between the plurality of light guides and the plurality of light detectors.

[0007] In some implementations, the light guides define a total height within the light guide isolation structure within the range of about 2 pm to about 4 pm. In some implementations, a minimum width of light guide isolation structure extending between adjacent light guides is less than about 300 nm. In some implementations, the light guides are conical and narrow as they extend from a top portion of the optical filter stack to a bottom portion of the optical filter stack.

[0008] In some implementations, the optical filter stack further comprises an oxide liner layer disposed on sidewalls of each of the plurality light guides within the light guide isolation structure. In some such implementations, the oxide liner layers are disposed directly between a corresponding light guide sidewall and the optical filter material.

[0009] In some implementations, the metal circuitry is disposed within one or more dielectric layers. In some implementations, the plurality of light detectors are disposed within the substrate and spaced from the light receiving back side. In some such implementations, the image stack further comprises dielectric material disposed in a plurality of dielectric isolation portions within the substrate, the dielectric isolation portions extending at least partially about a corresponding light detector and at least partially through a thickness of the substrate below a corresponding light guide to further reduce crosstalk between the light detectors.

[0010] In some implementations, the image sensor structure further comprises a reaction structure disposed over the optical filter stack, the reaction structure comprising a detector surface. In some such implementations, the image sensor structure further comprises a lid extending over the detector surface, and a flow channel extending between the lid and the detector surface. The lid comprises at least one first port in communication with the flow channel. In some such implementations, the detector surface comprises a plurality of reaction sites and at least one analyte immobilized at the reaction sites. In some implementations, each reaction site of the plurality of reaction sites is positioned within a nanowell disposed in the reaction structure, each nano well being associated with at least one corresponding light guide and light detector.

[0011] In some implementations, the plurality of light guides are positioned fully within the light guide isolation structure. In some implementations, at least 75% of the height of each light guide of the plurality of light guides is positioned within the light guide isolation structure.

[0012] In some implementations, the light guide isolation structure includes the overlapping layers comprising the at least one metal material layer and the at least one dielectric material layer. In some such implementations, the light guide isolation structure includes at least two metal material layers and at least two dielectric material layers, the at least two metal material layers and the at least two dielectric material layers being arranged in an alternating overlapping arrangement such that the at least two metal material layers are not contiguous with each other and the at least two dielectric material layers are not contiguous with each other. In some implementations, the light guide isolation structure includes a first dielectric material layer disposed over the back side of the image stack, a first metal material layer disposed over the first dielectric material layer, a second dielectric material layer disposed over the first metal material layer, and a second metal material layer disposed over the second dielectric material layer. In some implementations, the light guide isolation structure consists of the at least one metal material layer and the at least one dielectric material layer.

[0013] In some implementations, the at least one metal material layer includes a metal material that substantially prevents transmission therethrough of a first range of wavelengths of light that falls within the range of about 400 nm to about 700 nm, and the optical filter material is configured to allow transmission therethrough of at least a portion of incident light within the first range of wavelengths of light. In some implementations, the at least one metal material layer comprises tantalum.

[0014] In some implementations, the at least one dielectric material layer has an electrical resistivity (p) of at least 1,000 • cm at 20° C. In some implementations, the at least one dielectric material layer comprises SiO2.

[0015] In some implementations, the light guide isolation structure includes the layer comprising a heavily doped silicon and at least one metal oxide. In some implementations, the light guide isolation structure consists of the layer comprising a heavily doped silicon and at least one metal oxide. In some implementations, the layer comprising a heavily doped silicon and at least one metal oxide comprises a heavily doped silicon and at least two metal oxides.

[0016] In some implementations, the layer comprising a heavily doped silicon and at least one metal oxide comprises heavily doped silicon and metal oxide materials that substantially prevents transmission therethrough of a first range of wavelengths of light within the range of about 400 nm to about 700 nm and has an electrical resistivity (p) of at least 1,000 £1 • cm at 20° C, and the optical filter material is configured to allow transmission therethrough of at least a portion of incident light within the first range of wavelengths of light. In some implementations, the layer comprising a heavily doped silicon and at least one metal oxide includes heavily doped silicon, chromium dioxide and titanium oxide.

[0017] In another aspect, the present disclosure provides for methods of making a sensor. In some examples herein, the methods comprise forming an optical filter stack over a light receiving back side of a back- side illuminated image sensor. The image sensor comprises an image stack comprising a substrate, a plurality of light detectors, a front side and the light receiving back side. The image sensor also comprises metal circuitry disposed over the front side of the image stack, the metal circuitry being electrically coupled to the light detectors and configured to transmit data signals based on photons detected by the light detectors. The optical filter stack comprises a light guide isolation structure including: overlapping layers comprising at least one metal material layer and at least one dielectric material layer; or a layer including a heavily doped silicon and at least one metal oxide. The optical filter stack further comprises a plurality of light guides including a plurality of openings in the light guide isolation structure, and an optical filter material disposed within the openings. Each light guide of the plurality of light guides is associated with at least one light detector of the plurality of light detectors. The light guide isolation structure extends about each light guide of the plurality of light guides and between adjacent light guides of the plurality of light guides, and is configured to reduce optical crosstalk between the plurality of light guides and the plurality of light detectors.

[0018] In some implementations, forming the optical filter stack over the light receiving back side of the image sensor comprises forming the light guide isolation structure over the light receiving back side of the image sensor. In some such implementations, forming the optical filter stack over the light receiving back side of the image sensor further comprises forming the openings in the light guide isolation structure from a top side thereof. In some such implementations, forming the optical filter stack over the light receiving back side of the image sensor further comprises depositing the optical filter material in the openings in the light guideisolation structure. In some such implementations, forming the optical filter stack over the light receiving back side of the image sensor further comprises forming an oxide liner layer on sidewalls of each of the openings prior to depositing the optical filter material in the openings.

[0019] In some implementations, forming the optical filter stack over the light receiving back side of the image sensor comprises forming the overlapping layers of the at least one metal material layer and the at least one dielectric material layer over the light receiving back side of the image sensor. In some such implementations, forming the overlapping layers of the at least one metal material layer and the at least one dielectric material layer over the light receiving back side of the image sensor comprises forming at least two metal material layers and at least two dielectric material layers over the light receiving back side of the image sensor, the at least two metal material layers and the at least two dielectric material layers being altematingly arranged such that the at least two metal material layers are not contiguous with each other and the at least two dielectric material layers are not contiguous with each other.

[0020] In some implementations, forming the overlapping layers of the at least one metal material layer and the at least one dielectric material layer over the light receiving back side of the image sensor comprises forming a first dielectric material layer over the back side of the image stack, forming a first metal material layer over the first dielectric material layer, forming a second dielectric material layer over the first metal material layer, and forming a second metal material layer over the second dielectric material layer.

[0021] In some implementations, the at least one metal material layer comprises a metal material that substantially prevents transmission therethrough of a first range of wavelengths of light within the range of about 400 nm to about 700 nm, and the optical filter material is configured to allow transmission therethrough of at least a portion of incident light within the first range of wavelengths of light. In some implementations, the at least one metal material layer comprises tantalum.

[0022] In some implementations, the at least one dielectric material layer has an electrical resistivity (p) of at least 1,000 Q ■ cm at 20° C. In some implementations, the at least one dielectric material layer comprises SiO2.

[0023] In some implementations, forming the optical filter stack over the light receiving back side of the image sensor comprises forming the layer of the heavily doped silicon and at least onemetal oxide over the light receiving back side of the image sensor. In some implementations, forming the layer of the heavily doped silicon and at least one metal oxide over the light receiving back side of the image sensor comprises forming a layer of heavily doped silicon and at least two metal oxides over the light receiving back side of the image sensor. In some implementations, forming the layer of the heavily doped silicon and at least one metal oxide over the light receiving back side of the image sensor comprises forming a layer of heavily doped silicon and metal oxide materials that substantially prevents transmission therethrough of a first range of wavelengths of light within the range of about 400 nm to about 700 nm and has an electrical resistivity (p) of at least 1,000 • cm at 20° C, and the optical filter material is configured to allow transmission therethrough of at least a portion of incident light within the first range of wavelengths of light. In some implementations, forming the layer of the heavily doped silicon and at least one metal oxide over the light receiving back side of the image sensor comprises forming a layer of a heavily doped silicon, chromium dioxide and titanium oxide over the light receiving back side of the image sensor.

[0024] In another aspect, the present disclosure provides for methods of using a sensor. In some examples herein, the methods comprise introducing a reagent solution into a flow channel of a sensor. The sensor comprises an image stack comprising a substrate, a plurality of light detectors, a front side and a light receiving back side. The sensor also comprises metal circuitry disposed over the front side of the image stack, the metal circuitry being electrically coupled to the light detectors and configured to transmit data signals based on photons detected by the light detectors. The sensor further comprises an optical filter stack disposed over the back side of the image stack. The optical filter stack comprises a light guide isolation structure including: overlapping layers comprising at least one metal material layer and at least one dielectric material layer; or a layer including a heavily doped silicon and at least one metal oxide. The optical filter stack also comprises a plurality of light guides including a plurality of openings in the light guide isolation structure, and an optical filter material disposed within the plurality of openings. Each light guide of the plurality of light guides is associated with at least one light detector of the plurality of light detectors. The light guide isolation structure extends about each light guide of the plurality of light guides and between adjacent light guides of the plurality of light guides, and is configured to reduce optical crosstalk between the plurality of light guides and the plurality of light detectors. The sensor also comprises a flow cell disposed over theoptical filter stack comprising a reaction structure that comprises a detector surface that comprises reaction sites, and a lid extending over the detector surface. A flow channel extends between the lid and the detector surface. The method further comprises illuminating the detector surface with excitation light that passes through the lid.

[0025] In some implementations, the introducing the reagent solution into the flow channel comprises passing the reagent solution through at least one inlet port that extends through at least one first portion of the lid that is in communication with the flow channel. In some implementations, the introducing the reagent solution into the flow channel effectuates chemical reactions between the reagent solution and material immobilized at the reaction sites.

[0026] In some implementations, at least one of the chemical reactions and reaction products formed thereby produces light signals in response to incident light of the excitation light. In some such implementations, the reaction solution comprises fluorophores, and at least one of the chemical reactions and the reaction products incorporate the fluorophores with the material immobilized at the reaction sites. In some such implementations, the material immobilized at the reaction sites comprises at least one analyte, and the reaction solution comprises fluorescently labeled biomolecules that bind with the at least one analyte.

[0027] In some implementations, the method further comprises forming the reaction sites on the detector surface prior to the introducing the reagent solution into the flow channel. In some such implementations, forming the reaction sites comprises immobilizing material to nanowells of the detector surface. In some other implementations, introducing the reagent solution into the flow channel effectuates chemical reactions between the reagent solution and material immobilized at the reaction sites on the detector surface, at least one of the chemical reactions and reaction products formed thereby produce light signals in response to incident light of the excitation light, and the plurality of light sensors are configured to sense the light signals. In some such implementations, the plurality of light sensors transmit data signals based on detected photons of the light signals, and the metal circuity conducts the data signals.

[0028] In some implementations, the light guide isolation structure includes the overlapping layers comprising the at least one metal material layer and the at least one dielectric material layer. In some such implementations, the light guide isolation structure comprises at least two metal material layers and at least two dielectric material layers, the at least two metal materiallayers and the at least two dielectric material layers being arranged in an alternating overlapping arrangement such that the at least two metal material layers arc not contiguous with each other and the at least two dielectric material layers are not contiguous with each other. In some implementations, the light guide isolation structure comprises a first dielectric material layer disposed over the back side of the image stack, a first metal material layer disposed over the first dielectric material layer, a second dielectric material layer disposed over the first metal material layer, and a second metal material layer disposed over the second dielectric material layer. In some implementations, the light guide isolation structure consists of the at least one metal material layer and the at least one dielectric material layer.

[0029] In some implementations, the reaction sites produce light signals within a first range of wavelengths of about 400 nm to about 700 nm in response to incident light of the excitation light, the optical filter material allows transmission therethrough of at least a portion of the light signals within a second range of wavelengths that is a subset of the first range of wavelengths, and the at least one metal material layer comprises a metal material that substantially prevents transmission therethrough of the second range of wavelengths. In some implementations, the at least one metal material layer comprises tantalum. In some such implementations, the at least one dielectric material has an electrical resistivity (p) of at least 1 ,000 • cm at 20° C. In some such implementations, the at least one dielectric material layer comprises SiO2.

[0030] In some implementations, the light guide isolation structure comprises the layer including a heavily doped silicon and at least one metal oxide. In some such implementations, the light guide isolation structure consists of the layer including a heavily doped silicon and at least one metal oxide. In some implementations, the layer including a heavily doped silicon and at least one metal oxide comprises a heavily doped silicon and at least two metal oxides. In some such implementations, the reaction sites produce light signals within a first range of wavelengths of about 400 nm to about 700 nm in response to incident light of the excitation light, the optical filter material allows transmission therethrough of at least a portion of the light signals within a second range of wavelengths that is a subset of the first range of wavelengths, and the layer including a heavily doped silicon and at least one metal oxide includes heavily doped silicon and metal oxide materials that substantially prevents transmission therethrough of the second range of wavelengths and has an electrical resistivity (p) of at least 1,000 £2 • cm at 20° C. In someimplementations, the layer including a heavily doped silicon and at least one metal oxide comprises heavily doped silicon, chromium dioxide and titanium oxide.

[0031] In another aspect, the present disclosure provides for additional sensors. In some examples herein, the additional sensors comprise an image sensor structure. The image sensor structure comprises an image stack comprising a substrate, a plurality of light detectors, a front side and a light receiving back side. The image sensor structure also comprises a metal circuitry disposed over the front side of the image stack, the metal circuitry being electrically coupled to the photodiodes and configured to transmit data signals based on photons detected by the photodiodes. The image sensor structure further comprises an optical filter stack disposed over the back side of the image stack. The optical filter stack comprises a light guide layer. The optical filter stack comprises a plurality of light guides including a plurality of openings in the light guide layer, an optical filter material disposed within the plurality of openings, a metal liner layer disposed within the plurality of openings over side walls of the openings defined by the light guide layer, and an oxide liner layer disposed within the plurality of openings between the metal liner layer and the optical filter material. Each light guide of the plurality of light guides is associated with at least one light detector of the plurality of light detectors. The light guide layer extends about each light guide of the plurality of light guides and between adjacent light guides of the plurality of light guides, and is void of metal structures that extend about each light guide of the plurality of light guides. The metal liner layer and the oxide liner layer of each light guide of the plurality of light guides extends about the optical filter material.

[0032] In some implementations, the light guides define a total height within the light guide isolation structure within the range of about 2 pm to about 4 pm. In some implementations, a minimum width of light guide isolation structure extending between adjacent light guides is less than about 300 nm. In some implementations, the light guides are conical and narrow as they extend from a top portion of the optical filter stack to a bottom portion of the optical filter stack. In some implementations, the metal circuitry is disposed within one or more dielectric layers.

[0033] In some implementations, the plurality of light detectors are disposed within the substrate and spaced from the light receiving back side. In some such implementations, the image stack further comprises dielectric material disposed in a plurality of dielectric isolation portions within the substrate, the dielectric isolation portions extending at least partially about a correspondinglight detector and at least partially through a thickness of the substrate below a corresponding light guide to reduce crosstalk between the light detectors.

[0034] In some implementations, the sensor structure further comprises a reaction structure disposed over the optical filter stack, the reaction structure comprising a detector surface. In some such implementations, the sensor structure further comprises a lid extending over the detector surface, and a flow channel extending between the lid and the detector surface. The lid comprises at least one first port in communication with the flow channel. In some such implementations, the detector surface comprises a plurality of reaction sites and at least one analyte immobilized at the reaction sites. In some such implementations, the plurality of reaction sites are each positioned within a nanowell disposed in the reaction structure, each nanowell being associated with at least one corresponding light guide and light detector.

[0035] In some implementations, at least 75% of the height of each light guide of the plurality of light guides is positioned within the light guide layer. In some implementations, the plurality of light guides are positioned fully within the light guide layer. In some implementations, the light guide layer comprises a polymer material, a semiconductor material, a dielectric material or a combination thereof. In some implementations, the light guide layer consists of a polymer material, a semiconductor material, a dielectric material or a combination thereof. In some implementations, the light guide layer comprises dielectric material. In some implementations, the oxide liner layer comprises a dielectric oxide material. In some implementations, the oxide liner layer comprises silicon dioxide, silicon nitride or a combination thereof.

[0036] In some implementations, the metal liner layer comprises a metal material that substantially prevents transmission therethrough of a first range of wavelengths of light that falls within the range of about 400 nm to about 700 nm, and the optical filter material allows transmission therethrough of at least a portion of incident light within the first range of wavelengths of light. In some implementations, the light guide layer is void of metal structures that extend about each light guide of the plurality of light guides and along at least the majority of the height of the light guides.

[0037] In another aspect, the present disclosure provides for additional methods of making a sensor. In some examples herein, the additional methods comprise forming an optical filter stack over a light receiving back side of a back- side illuminated image sensor. The sensor comprisesan image stack comprising a substrate, a plurality of light detectors, a front side and the light receiving back side. The sensor further comprises metal circuitry disposed over the front side of the image stack, the metal circuitry being electrically coupled to the light detectors and configured to transmit data signals based on photons detected by the light detectors. The optical filter stack comprises a light guide layer. The optical filter stack further comprises a plurality of light guides including a plurality of openings in the light guide layer, an optical filter material disposed within the plurality of openings, a metal liner layer disposed within the plurality of openings over side walls of the openings that are defined by the light guide layer, and an oxide liner layer disposed between the metal liner layer and the optical filter material. Each light guide of the plurality of light guides is associated with at least one light detector of the plurality of light detectors. The light guide layer extends about each light guide of the plurality of light guides and between adjacent light guides of the plurality of light guides, and is void of metal structures that extend about each light guide of the plurality of light guides. The metal liner layer and the oxide liner layer of each light guide extends about the optical filter material.

[0038] In some implementations, forming the optical filter stack over the light receiving back side of the image sensor comprises forming the light guide layer over the light receiving back side of the image sensor. In some such implementations, forming the optical filter stack over the light receiving back side of the image sensor further comprises forming the openings in the light guide layer from a top side thereof. In some such implementations, forming the optical filter stack over the light receiving back side of the image sensor further comprises forming the metal liner layer over the side walls of the openings that are defined by the light guide layer. In some such implementations, forming the optical filter stack over the light receiving back side of the image sensor further comprises forming the oxide liner layer over the metal liner layer. In some such implementations, forming the optical filter stack over the light receiving back side of the image sensor further comprises depositing the optical filter material over the oxide liner layer to fill the openings in the light guide layer.

[0039] In some implementations, the light guide layer comprises a polymer material, a semiconductor material, a dielectric material or a combination thereof. In some implementations, the light guide layer consists of a polymer material, a semiconductor material, a dielectric material or a combination thereof. In some implementations, the light guide layer comprises dielectric material. In some implementations, the oxide liner layer comprises adielectric oxide material. In some implementations, the oxide liner layer comprises silicon dioxide, silicon nitride or a combination thereof.

[0040] In some implementations, the metal liner layer comprises a metal material that substantially prevents transmission therethrough of a first range of wavelengths of light that falls within the range of about 400 nm to about 700 nm, and the optical filter material allows transmission therethrough of at least a portion of incident light within the first range of wavelengths of light. In some implementations, the light guide layer is void of metal structures that extend about each light guide of the plurality of light guides and along at least the majority of the height of the light guides.

[0041] In another aspect, the present disclosure provides for additional methods of using a sensor. In some examples herein, the additional methods comprise introducing a reagent solution into a flow channel of a sensor that comprises an image stack comprising a substrate, a plurality of light detectors, a front side and a light receiving back side. The sensor further comprises metal circuitry disposed over the front side of the image stack, the metal circuitry being electrically coupled to the photodiodes and configured to transmit data signals based on photons detected by the photodiodes. The sensor also comprises an optical filter stack disposed over the back side of the image stack. The optical filter stack comprises a light guide layer. The optical filter stack also comprises a plurality of light guides including a plurality of openings in the light guide layer, an optical filter material disposed within the plurality of openings, a metal liner layer disposed within the plurality of openings over side walls of the openings that are defined by the light guide layer, and an oxide liner layer disposed between the metal liner layer and the optical filter material. Each light guide of the plurality of light guides is associated with at least one light detector of the plurality of light detectors. The light guide layer extends about each light guide of the plurality of light guides and between adjacent light guides of the plurality of light guides, and is void of metal structures that extend about each light guide of the plurality of light guides. The metal liner layer and the oxide liner layer of each light guide extends about the optical filter material. The sensor further comprises a flow cell disposed over the optical filter stack comprising a reaction structure that comprises a detector surface that comprises reaction sites, and a lid extending over the detector surface. A flow channel extends between the lid and the detector surface. The additional methods further comprise illuminating the detector surface with excitation light that passes through the lid.

[0042] In some implementations, introducing the reagent solution into the flow channel comprises passing the reagent solution through at least one inlet port that extends through at least one first portion of the lid that is in communication with the flow channel.

[0043] In some implementations, introducing the reagent solution into the flow channel effectuates chemical reactions between the reagent solution and material immobilized at the reaction sites. In some such implementations, at least one of the chemical reactions and reaction products formed thereby produces light signals in response to incident light of the excitation light. In some such implementations, the reaction solution comprises fluorophores, and at least one of the chemical reactions and the reaction products incorporate the fluorophores with the material immobilized at the reaction sites. In some such implementations, the material immobilized at the reaction sites comprises at least one analyte, and the reaction solution comprises fluorescently labeled biomolecules that bind with the at least one analyte.

[0044] In some implementations, the method further comprises forming the reaction sites on the detector surface prior to the introducing the reagent solution into the flow channel. In some such implementations, forming the reaction sites comprises immobilizing material to nanowells of the detector surface.

[0045] In some implementations, introducing the reagent solution into the flow channel effectuates chemical reactions between the between the reagent solution and material immobilized at the reaction sites on the detector surface, at least one of the chemical reactions and reaction products formed thereby produce light signals in response to incident light of the excitation light, and the plurality of light sensors are configured to sense the light signals. In some such implementations, the plurality of light sensors transmit data signals based on detected photons of the light signals, and the metal circuity conducts the data signals.

[0046] In some implementations, the light guide layer comprises a polymer material, a semiconductor material, a dielectric material or a combination thereof. In some implementations, the light guide layer consists of a polymer material, a semiconductor material, a dielectric material or a combination thereof.

[0047] In some implementations, the light guide layer comprises dielectric material. In some implementations, the oxide liner layer comprises a dielectric oxide material. In some implementations, the oxide liner layer comprises silicon dioxide, silicon nitride or a combinationthereof. In some implementations, the metal liner layer comprises a metal material that substantially prevents transmission therethrough of a first range of wavelengths of light that falls within the range of about 400 nm to about 700 nm, and the optical filter material allows transmission therethrough of at least a portion of incident light within the first range of wavelengths of light.

[0048] Additional features are realized through the techniques described herein. Other examples and aspects are described in detail herein and are considered a part of the claimed aspects. These and other objects, features and advantages of this disclosure will become apparent from the following detailed description of the various aspects of the disclosure taken in conjunction with the accompanying drawings.

[0049] It should be appreciated that all combinations of the foregoing aspects and additional concepts discussed in greater detail below (provided such concepts are not mutually inconsistent) are contemplated as being part of the inventive subject matter and to achieve the advantages disclosed herein.BRIEF DESCRIPTION OF THE DRAWINGS

[0050] One or more aspects are particularly pointed out and distinctly claimed as examples in the claims at the conclusion of the specification. The foregoing and objects, features, and advantages of one or more aspects are apparent from the following detailed description taken in conjunction with the accompanying drawings, which may or may not be drawn to scale, in which:

[0051] FIG. 1 illustrates a side cross-sectional view of a portion of an exemplary sensor with submicron pixels that mitigates crosstalk from light guide thereof, according to aspects described herein;

[0052] FIG. 2 illustrates a side cross-sectional view of a back-side illumination (BSI) image sensor of the sensor of FIG. 1, according to aspects described herein;

[0053] FIG. 3 illustrates a side cross-sectional view of the image sensor of the sensor of FIG. 1 at an intermediate stage of manufacture, according to aspects described herein;

[0054] FIG. 4 illustrates a side cross-sectional view of the image sensor of the sensor of FIG. 1 at an intermediate stage of manufacture, according to aspects described herein;

[0055] FIG. 5 illustrates a side cross-sectional view of a light guide portion of the sensor of FIG. 1 at an intermediate stage of manufacture, according to aspects described herein;

[0056] FIG. 6 illustrates a top view of an array of light guides of the sensor of FIG. 1, according to aspects described herein;

[0057] FIG. 7 illustrates a side cross-sectional view of the image sensor of the sensor of FIG. 1 at an intermediate stage of manufacture, according to aspects described herein;

[0058] FIG. 8 illustrates a side cross-sectional view of the image sensor of the sensor of FIG. 1 at an intermediate stage of manufacture, according to aspects described herein;

[0059] FIG. 9 illustrates a side cross-sectional view of a portion of another exemplary sensor with submicron pixels that mitigates crosstalk from light guide thereof, according to aspects described herein;

[0060] FIG. 10 illustrates a side cross-sectional view of the image sensor of the sensor of FIG. 9 at an intermediate stage of manufacture, according to aspects described herein;

[0061] FIG. 11 illustrates a side cross-sectional view of the image sensor of the sensor of FIG. 9 at an intermediate stage of manufacture, according to aspects described herein;

[0062] FIG. 12 illustrates a side cross-sectional view of the image sensor of the sensor of FIG. 9 at an intermediate stage of manufacture, according to aspects described herein;

[0063] FIG. 13 illustrates a side cross-sectional view of the image sensor of the sensor of FIG. 9 at an intermediate stage of manufacture, according to aspects described herein;

[0064] FIG. 14 illustrates a side cross-sectional view of a portion of another exemplary sensor with submicron pixels that mitigates crosstalk from light guide thereof, according to aspects described herein;

[0065] FIG. 15 illustrates a side cross-sectional view of the image sensor of the sensor of FIG. 14 at an intermediate stage of manufacture, according to aspects described herein;

[0066] FIG. 16 illustrates a side cross-sectional view of the image sensor of the sensor of FIG. 14 at an intermediate stage of manufacture, according to aspects described herein;

[0067] FIG. 17 illustrates a side cross-sectional view of the image sensor of the sensor of FIG.14 at an intermediate stage of manufacture, according to aspects described herein;

[0068] FIG. 18 illustrates a side cross-sectional view of the image sensor of the sensor of FIG. 14 at an intermediate stage of manufacture, according to aspects described herein; and

[0069] FIG. 19 illustrates a side cross-sectional view of the image sensor of the sensor of FIG. 14 at an intermediate stage of manufacture, according to aspects described herein.DETAILED DESCRIPTION

[0070] The accompanying figures, in which like reference numerals refer to identical or functionally similar elements throughout the separate views and which are incorporated in and form a pail of the specification, further illustrate the present implementation and, together with the detailed description of the implementation, explain the principles of the present implementation. As understood by one of skill in the art, the accompanying figures arc provided for ease of understanding and illustrate aspects of certain examples of the present implementation. The implementation is not limited to the examples depicted in the figures.

[0071] The terms “connect,” “connected,” “contact” “coupled” and / or the like are broadly defined herein to encompass a variety of divergent arrangements and assembly techniques. These arrangements and techniques include, but are not limited to (1) the direct joining of one component and another component with no intervening components therebetween (i.e., the components are in direct physical contact); and (2) the joining of one component and another component with one or more components therebetween, provided that the one component being “connected to” or “contacting” or “coupled to” the other component is somehow in operative communication (e.g., electrically, fluidly, physically, optically, etc.) with the other component (notwithstanding the presence of one or more additional components therebetween). It is to be understood that some components that are in direct physical contact with one another may or may not be in electrical contact and / or fluid contact with one another. Moreover, two components that are electrically connected, electrically coupled, optically connected, optically coupled, fluidly connected or fluidly coupled may or may not be in direct physical contact, and one or more other components may be positioned therebetween.

[0072] The terms “including” and “comprising”, as used herein, mean the same thing. The terms “substantially”, “approximately”, “about”, “relatively”, or other such similar terms that may be used throughout this disclosure, including the claims, are used to describe and account for small fluctuations, such as due to variations in processing, from a reference or parameter. Such smallfluctuations include a zero fluctuation from the reference or parameter as well. For example, they can refer to less than or equal to ± 10%, such as less than or equal to ± 5%, such as less than or equal to ± 2%, such as less than or equal to ± 1%, such as less than or equal to ± 0.5%, such as less than or equal to ± 0.2%, such as less than or equal to ± 0.1%, such as less than or equal to ± 0.05%. If used herein, the terms “substantially”, “approximately”, “about”, “relatively,” or other such similar terms may also refer to no fluctuations, that is, ± 0%.

[0073] As used herein, a “flow cell” is a portion of a device, such as a sensor or sensor structure, that comprises a flow channel positioned between a lid extending over a reaction structure. The flow channel is in communication with a plurality of reaction sites (e.g., nanowells) of the reaction structure. The device associated with a flow cell can include a detection device that detects designated reactions that occur at or proximate to the reaction sites. In some implementations, a device associated with a flow cell may include a solid-state light detection or “imaging” device, such as a Charge-Coupled Device (CCD) or Complementary Metal-Oxide Semiconductor (CMOS) (light) detection device. For example, a device can include an image layer disposed over a base substrate. The image layer may be a dielectric layer, such as SiN and may contain an array of light detectors disposed therein. A light detector as used herein may be, for example, a semiconductor, such as a photodiode, a complementary metal oxide semiconductor (CMOS) material, or both. The light detectors detect light photons of emissive light that is emitted from the fluorescent tags attached to the strands supported in or on the reaction sites, for example, in nanowells. The base substrate may be glass, silicon or other like material. In some implementations, a flow cell can fluidically and electrically couple to a cartridge (having an integrated pump), which can fluidically and / or electrically couple to a bioassay system. A cartridge and / or bioassay system may deliver a reaction solution to reaction sites of a flow cell according to a predetermined protocol (e.g., sequencing-by-synthesis), and perform a plurality of imaging events. For example, a cartridge and / or bioassay system may direct one or more reaction solutions through the flow channel of the flow cell, and thereby along the reaction sites. At least one of the reaction solutions may include four types of nucleotides having the same or different fluorescent labels. In some examples, the nucleotides bind to the reaction sites of the flow cell, such as to corresponding oligonucleotides at the reaction sites. The cartridge and / or bioassay system in these examples then illuminates the reaction sites using an excitation light source (e.g., solid-state light sources, such as light-emitting photodiodes(LEDs), and lasers). In some examples, the excitation light has a predetermined wavelength or wavelengths, including a range of wavelengths. The fluorescent labels excited by the incident excitation light may provide emission signals (e.g., light of a wavelength or wavelengths that differ from the excitation light and, potentially, each other) that may be detected by the light sensors of the device.

[0074] Devices (e.g., sensors or sensor structures) with a flow cell, as described herein, can perform various biological or chemical processes. More specifically, the devices with a flow cell described herein may be used in various processes and systems where it is desired to detect an event, property, quality, or characteristic that is indicative of a designated reaction. For example, such devices may include or be integrated with light detection devices, sensors, including but not limited to, biosensors, and their components, as well as bioassay systems that operate with sensors, including biosensors.

[0075] The flow cells facilitate a plurality of designated reactions that may be detected individually or collectively. The devices associated with a flow cell may perform numerous cycles in which the plurality of designated reactions occurs in parallel. For example, the devices with a flow cell may be used to sequence a dense array of DNA features through iterative cycles of enzymatic manipulation and light or image detection / acquisition. As such, the flow cells may be in fluidic communication with one or more microfluidic channels that deliver reagents or other reaction components in a reaction solution to a reaction site of the flow cells. The reaction sites may be provided or spaced apart in a predetermined manner, such as in a uniform or repeating pattern. Alternatively, the reaction sites may be randomly distributed. Each of the reaction sites may be associated with one or more light guides and one or more light sensors of the device that detect light from the associated reaction site. In one example, light guides include one or more filters for filtering certain wavelengths of light. The light guides may comprise, for example, an absorption filter (e.g., an organic absorption filter) such that the filter material absorbs a certain wavelength (or range of wavelengths) and allows at least one predetermined wavelength (or range of wavelengths) to pass therethrough. In some flow cell implementations, the reaction sites may be located in reaction recesses or chambers, which may at least partially compartmentalize the designated reactions therein.

[0076] As used herein, a “designated reaction” includes a change in at least one of a chemical, electrical, physical, or optical property (or quality) of a chemical or biological substance of interest, such as an analyte-of-interest. In some implementations, a designated reaction is a positive binding event, such as incorporation of a fluorescently labeled biomolecule with an analyte-of-interest, for example. More generally, a designated reaction may be a chemical transformation, chemical change, or chemical interaction. A designated reaction may also be a change in electrical properties. In particular implementations, a designated reaction includes the incorporation of a fluorescently labeled molecule with an analyte. The analyte may be an oligonucleotide and the fluorescently labeled molecule may be a nucleotide. A designated reaction may be detected when an excitation light is directed toward the oligonucleotide having the labeled nucleotide, and the fluorophore emits a detectable fluorescent signal. In other implementations, the detected fluorescence is a result of chemiluminescence or bioluminescence. A designated reaction may also increase fluorescence (or Forster) resonance energy transfer (FRET), for example, by bringing a donor fluorophore in proximity to an acceptor fluorophore, decrease FRET by separating donor and acceptor fluorophores, increase fluorescence by separating a quencher from a fluorophore, or decrease fluorescence by co-locating a quencher and fluorophore.

[0077] As used herein, a “reaction solution,” “reaction component” or “reactant” includes any substance that may be used to obtain at least one designated reaction. For example, potential reaction components include reagents, enzymes, samples, other biomolecules, and buffer solutions, for example. The reaction components may be delivered to a reaction site in the flow cells disclosed herein in a solution and / or immobilized at a reaction site. The reaction components may interact directly or indirectly with another substance, such as an analyte-of- interest immobilized at a reaction site of the flow cell.

[0078] A reaction solution and / or a reaction site may include biomolecules, samples-of-interest, analytes-of-interest, and other chemical compound(s). A biological or chemical substance may be used to detect, identify, or analyze other chemical compound(s), or function as intermediaries to study or analyze other chemical compound(s). In particular examples, the biological or chemical substances include a biomolecule. As used herein, a “biomolecule” includes at least one of a biopolymer, nucleoside, nucleic acid, polynucleotide, oligonucleotide, protein, enzyme, polypeptide, antibody, antigen, ligand, receptor, polysaccharide, carbohydrate, polyphosphate,cell, tissue, organism, or fragment thereof or any other biologically active chemical compound(s) such as analogs or mimetics of the aforementioned species. In a further example, a biological or chemical substance or a biomolecule includes an enzyme or reagent used in a coupled reaction to detect the product of another reaction such as an enzyme or reagent, such as an enzyme or reagent used to detect pyrophosphate in a pyrosequencing reaction. Enzymes and reagents useful for pyrophosphate detection are described, for example, in U.S. Patent Publication No. 2005 / 0244870 Al, which is incorporated by reference in its entirety.

[0079] Biomolecules, samples, and biological or chemical substances may be naturally occurring or synthetic and may be suspended in a solution or mixture at a reaction site. Biomolecules, samples, and biological or chemical substances may also be bound to a solid phase or gel material. Biomolecules, samples, and biological or chemical substances may also include a pharmaceutical composition. In some cases, biomolecules, samples, and biological or chemical substances of interest may be referred to as targets, probes, or analytes.

[0080] As used herein, a “biosensor” includes a device that includes a reaction structure with a plurality of reaction sites that is configured to detect designated reactions that occur at or proximate to the reaction sites. A biosensor may include a solid-state light detection or “imaging” device (e.g., a CCD or CMOS light detection device) and, optionally, a flow cell mounted thereto. The flow cell may include at least one flow channel that is in fluid communication with the reaction sites, as described herein. As one specific example, the biosensor is configured to fluidically and electrically couple to a bioassay system. The bioassay system may deliver a reaction solution to the reaction sites according to a predetermined protocol (e.g., sequencing-by-synthesis) and perform a plurality of imaging events. For example, the bioassay system may direct reaction solutions to flow along the reaction sites. At least one of the reaction solutions may include types of nucleotides having the same or different fluorescent labels. The nucleotides may bind to the reaction sites, such as to corresponding oligonucleotides at the reaction sites. The bioassay system may then illuminate the reaction sites using an excitation light source (e.g., solid-state light sources, such as light-emitting diodes (LEDs)). The excitation light may have a predetermined wavelength or wavelengths, including a range of wavelengths. The fluorescent labels excited by the incident excitation light may provide emission signals (e.g., light of a wavelength or wavelengths that differ from the excitation light and, potentially, each other) that may be detected by the light sensors.

[0081] As used herein, the term “immobilized,” when used with respect to a reaction site (which may include a biomolcculc or biological or chemical substance), includes substantially attaching a biomolecule or biological or chemical substance at a molecular level to a surface, such as to a detection surface of a light detection device or reaction structure. For example, a biomolecule or biological or chemical substance may be immobilized to a surface of the reaction structure using adsorption techniques including non-covalent interactions (e.g., electrostatic forces, van der Waals, and dehydration of hydrophobic interfaces) and covalent binding techniques where functional groups or linkers facilitate attaching the biomolecules to the surface. Immobilizing biomolecules or biological or chemical substances to the surface may be based upon the properties of the surface, the liquid medium carrying the biomolecule or biological or chemical substance, and the properties of the biomolecules or biological or chemical substances themselves. In some cases, the surface may be functionalized (e.g., chemically or physically modified) to facilitate immobilizing the biomolecules (or biological or chemical substances) to the surface.

[0082] In some examples, nucleic acids can be immobilized to the reaction structure, such as to surfaces of reaction recesses thereof. In particular examples, the devices, biosensors, bioassay systems and methods described herein may include the use of natural nucleotides and also enzymes that are configured to interact with the natural nucleotides. Natural nucleotides include, for example, ribonucleotides or deoxyribonucleotides. Natural nucleotides can be in the mono-, di-, or tri-phosphate form and can have a base selected from adenine (A), Thymine (T), uracil (U), guanine (G) or cytosine (C). It will be understood, however, that non-natural nucleotides, modified nucleotides or analogs of the aforementioned nucleotides can be used.

[0083] As noted above, a biomolecule or biological or chemical substance may be immobilized at a reaction site in a reaction recess of a reaction structure. A biomolecule or biological substance may be physically held or immobilized through an interference fit, adhesion, covalent bond, or entrapment. Examples of items or solids that may be disposed at a reaction site include polymer beads, pellets, agarose gel, powders, quantum dots, or other solids that may be compressed and / or held within the reaction chamber. In certain implementations, reaction recesses may be coated or filled with a hydrogel layer capable of covalently binding DNA oligonucleotides. In particular examples, a nucleic acid superstructure, such as a DNA ball, can be disposed in or at a reaction site, for example, by attachment to a surface of the reactionstructure (e.g., in a reaction recess / nanowell) or by residence in a liquid within a reaction recess. A DNA ball or other nucleic acid superstructure can be performed and then disposed in or at a reaction site. Alternatively, a DNA ball can be synthesized in situ at a reaction site (e.g., in a reaction recess). A substance that is immobilized at a reaction site can be in a solid, liquid, or gaseous state.

[0084] As used herein, “electrically coupled” and “optically coupled” refers to a transfer of electrical energy and light waves, respectively, between any combination of a power source, an electrode, a conductive portion of a substrate, a droplet, a conductive trace, wire, waveguide, nanostructures, other circuit segment and the like. The terms electrically coupled and optically coupled may be utilized in connection with direct or indirect connections and may pass through various intermediaries, such as a fluid intermediary, an air gap and the like.

[0085] As used herein, the term “reaction site” is a localized region where at least one designated reaction may occur, such as a location or site where a substance is positioned on or coupled with a reaction structure / surface. . A reaction site may include support surfaces of the reaction structure where a substance may be immobilized thereon. For example, some reaction sites may be positioned in nanowells in a reaction structure / layer. In some implementations, a reaction site may include a surface of a reaction structure (which may be positioned in a channel of a flow cell) that has a reaction component thereon, such as a colony of nucleic acids thereon. In some implementations, the nucleic acids in the colony have the same sequence, being for example, clonal copies of a single stranded or double stranded template. However, in some implementations a reaction site may contain only a single nucleic acid molecule, for example, in a single stranded or double stranded form. A reaction site can also include a reaction chamber or recess that at least partially defines a spatial region or volume configured to compartmentalize the designated reaction. As used herein, the terms “reaction recess” and “nanowell” include a defined spatial region of the support structure (which is often in fluid communication with a flow channel). A reaction recess / nanowell may be at least partially separated from the surrounding environment or other spatial regions. For example, a plurality of reaction recesses / nano wells may be separated from each other by shared walls. As a more specific example, the reaction recesses / nanowells may be an indent, pit, well, groove, or open-sided cavity or depression defined by interior surfaces and defining an opening or aperture so that the recesses / nanowells are in fluid communication with a flow channel.

[0086] Examples described herein may be used in various biological or chemical processes and systems, for example, in academic or commercial analysis. More specifically, examples described herein may be used in various processes and systems where it is desired to detect an event, property, quality, or characteristic that is indicative of a designated reaction. For instance, examples described herein include cartridges, biosensors, and their components as well as bioassay systems that operate with cartridges and biosensors. In particular examples, the cartridges and biosensors include a flow cell and one or more image sensors that are coupled together in a substantially unitary structure.

[0087] The bioassay systems may be configured to perform a plurality of designated reactions that may be detected individually or collectively. The biosensors and bioassay systems may be configured to perform numerous cycles in which the plurality of designated reactions occurs in parallel. For example, the bioassay systems may be used to sequence a dense array of DNA features through iterative cycles of enzymatic manipulation and image acquisition. Alternatively, rather than iterative cycles, the bioassay system can also be used to sequence a dense array of DNA features utilizing continuous observation without stepwise enzymatic action. The cartridges and biosensors may include one or more microfluidic channels that deliver reagents or other reaction components to a well or reaction site. Some examples discussed herein utilize wells and / or nano- wells as reactions sites. However, as used herein, the term “reaction site” is not limited to wells or nano-wells and contemplates various structures on a surface of the examples described herein.

[0088] In some examples, the wells or reaction sites are randomly distributed across a substantially planar reaction surface. For example, the wells or reaction sites may have an uneven distribution in which some wells or reaction sites are located closer to each other than other wells or reaction sites. In other examples, the wells or reaction sites are patterned across a reaction surface in a predetermined manner. Each of the wells or reaction sites may be associated with one or more image sensors that detect light from the associated reaction site. Yet in other examples, the wells or reaction sites are located in reaction chambers that compartmentalize the designated reactions therein.

[0089] In some examples, image sensors may detect light emitted from reaction sites and the signals indicating photons emitted from the reaction sites and detected by the individual imagesensors may correspond to those sensors' illumination values. These illumination values may be combined into an image indicating photons as detected from the wells or reaction sites. Such an image may be a raw image. Similarly, when an image is composed of values which have been processed, such as to computationally correct for crosstalk, rather than being composed of the values directly detected by individual image sensors, that image may be a sharpened image.

[0090] In some examples, image sensors (e.g., photodiodes) are associated with corresponding reaction sites (and potentially corresponding reaction recesses). An image sensor that is associated with a reaction site is configured to detect light emissions from the associated reaction site when a designated reaction has occurred at the associated reaction site. In some cases, a plurality of image sensors (e.g., several pixels of a sensor / camera device) may be associated with a single reaction site. In other cases, a single image sensor (e.g., a single pixel) may be associated with a single reaction site or with a group of wells or reaction sites. The image sensor, the reaction site, and other features of the biosensor may be configured so that at least some of the light is directly detected by the image sensor without being reflected.

[0091] Depending on the context, the term “image sensor” is utilized interchangeably herein to refer to both an array of individual pixels / photodiodes and / or an individual light sensor or pixel (which the array comprises). In the context of the examples described herein, an image sensor, which may be an array, generates a signal.

[0092] The sensor structures (e.g., biosensors) discussed in the examples herein are back-side illuminated sensors (BSIs).

[0093] As used herein, the term “adjacent” when used with respect to two wells or reaction sites means no other reaction site is located between the two wells or reaction sites. The term "adjacent" may have a similar meaning when used with respect to adjacent detection paths and adjacent image sensors (e.g., adjacent image sensors have no other image sensor therebetween). In some cases, a reaction site may not be adjacent to another reaction site; but may still be within an immediate vicinity of the other reaction site. A first reaction site may be in the immediate vicinity of a second reaction site when fluorescent emission signals from the first reaction site are detected by the image sensor associated with the second reaction site. More specifically, a first reaction site may be in the immediate vicinity of a second reaction site when the image sensor associated with the second reaction site detects, for example, crosstalk from the firstreaction site. Adjacent wells or reaction sites may be contiguous, such that they abut each other, or the adjacent sites may be non-contiguous, having an intervening or interstitial space between.

[0094] As used herein, the term “crosstalk” refers to any phenomenon by which a signal transmitted on one circuit or channel of a transmission system creates an undesired effect in another circuit or channel. Crosstalk is usually caused by undesired capacitive, inductive, or conductive coupling from one circuit or channel to another. Crosstalk can be a significant issue in structured cabling, audio electronics, integrated circuit design, wireless communication, and other communications systems. In the context of certain of the examples herein, crosstalk includes a proportion of optical signals from a given reaction site reaching light sensors or pixels that do not form a sensing pair with the reaction site. In examples where each image sensor represents a single pixel, crosstalk may be understood to mean the proportion of optical signals reaching all pixels other than the center pixel. Attenuation, or signal loss, can result from crosstalk. Additionally, crosstalk increases noise in pixels within an immediate vicinity of a reaction center.

[0095] As used herein the term “filter” refers to a filter that suitably prevents / blocks transmission of excitation wavelengths while suitably allowing transmission of emission wavelengths. For example, an emission filter can be a high quality optical-glass filter commonly used in fluorescence microscopy and spectroscopic applications for selection of the excitation wavelength of light from the light source. In some examples, an excitation wavelength is a wavelength in the excitation spectrum, a range of light wavelengths that add energy to a fluorochrome, causing it to emit wavelengths of light (e.g., the emission spectrum).

[0096] The term chemical vapor deposition (CVD) refers to a vacuum deposition method used to produce high quality, and high-performance, solid materials, including, in some of the examples herein, films. In some examples, a substrate (e.g., a silicon wafer) is exposed to one or more volatile precursors, which react and / or decompose on the substrate surface to produce a desired deposit. Plasma-enhanced chemical vapor deposition (PECVD) is a chemical vapor deposition process used to deposit thin films from a gas state (vapor) to a solid state on a substrate. The term atomic layer deposition (ALD) refers to a technique for growing thin films or layers. ALD is a variant of the chemical vapor deposition (CVD) technique where gaseous reactants(precursors) are introduced into a reaction chamber for forming the desired material via chemical surface reactions.

[0097] The term chemical mechanical polishing or planarization (CMP) is a process (both polishing and planarization being options under the umbrella term) applied to selectively remove materials for topography planarization and device structure formation. CMP uses chemical oxidation and mechanical abrasion to remove material and achieve planarity. In some examples, CMP includes using a chemical reaction and mechanical abrasion with slurries containing unique chemical formulations and large numbers of abrasive particles. During polishing, chemical reaction products and mechanical wear debris are generated. Slurry particles and polishing byproducts are pressed onto wafer surface. During wafer transferring from polisher to cleaner, contaminants are adhered onto wafer surface. This process can include a cleanup of the surface that is polished and / or planarized to remove particles including organic residues. Certain of the workflows disclosed herein incorporate a CMP aspect to planarize surfaces. CMP can be utilized in the examples herein, for example, after depositions into high aspect ratio topography, which may impact the topography of the deposited top film (i.e., layer). However, even when incorporated into the examples herein, in some circumstances, this aspect can be omitted.

[0098] Reference is made below to the drawings, which may or may not be drawn to scale, for ease of understanding, wherein the same reference numbers are used throughout different figures, in some cases, to designate the same or similar components. The following detailed description of certain examples will be better understood when read in conjunction with the appended drawings.

[0099] It is desirable to reduce crosstalk in sensors, including in biosensors, as crosstalk adversely affects performance. A traditional way in which crosstalk can be reduced in an apparatus with an image sensor, such as a biosensor, is by physically constraining transmission of light by embedding various light guides in the sensor, including but not limited to typically metallic curtain structures, light pipes, and / or optical waveguides and / or microlenses. These structures aim to direct light emitted from a corresponding reaction site directly downwardly toward an image sensor that forms a sensing pair with the reaction site. These structures attempt to reduce crosstalk by physically blocking light to provide tailored absorption of light that might otherwise result in crosstalk.

[0100] Because of the manufacturing complexities and structural limitations associated with sensor devices that include metal structural elements (c.g., curtain structures) that extend about light guides and between adjacent light guides to reduce crosstalk, it is desirable to provide a version of a biosensor that suitably prevents or reduces the occurrence of optical crosstalk, without presenting the manufacturing complexity and expense associated with these structures and without constraining certain parameters of the sensor, including pitch / pixel / light guide spacing and / or height, which will be discussed herein. Rather than integrate metal / metallic curtain structures into sensing devices to reduce crosstalk emanating from / between the light guides, which increase the cost and complexity of the sensor devices, examples of sensor devices, also referred to herein as biosensors, described herein instead include a light guide isolation structure, or a light guide layer and light guide liner layers, that effectively reduce / mitigate crosstalk between light guides and light detectors (e.g., photodiodes). The disclosed exemplary sensors suitably prevent or reduce the occurrence of optical crosstalk, without presenting the manufacturing complexity and expense associated with the structural elements (e.g., curtain structures, light pipes, and / or optical waveguides), and without constraining a reduction of pitch distance and / or light guide height in a sensor (e.g., biosensor).

[0101] Described herein are various examples of forming biosensors, utilizing biosensors, and descriptions of structures of various biosensors. Various examples of the methods and the apparatuses are described below.

[0102] Referring to FIGS. 1-8, an example of an image sensor structure 100 according to the present disclosure is shown (FIGS. 1-5, 7 and 8 illustrate side cross-sectional views, and FIG. 6 illustrates a top cross-sectional view, of a portion of the image sensor structure 100. The image sensor structure 100 may include or be incorporated with additional components such that it is configured as (or embodies) a sensor (e.g., a biosensor). FIGS. 2-4, 7 and 8 illustrate intermediate stages of exemplary methods of manufacturing the image sensor structure 100.

[0103] As will be discussed in greater detail herein, the image sensor structure 100 is a submicron pixel back side illuminated (BSI) image sensor structure 100 that substantially reduces / prevents cross-talk between pixels of light escaping light guides 124 of an optical filter stack 136 to a level that can be sufficiently filtered / treated electronically (or otherwise) by other aspects / components (of a sensor) such that the signals emitted by / from the image sensorstructure 100 can be used to properly identify, based on the light detected by the image sensors 114 of the sensor structure 100, particular materials and / or properties of rcction sites 154 associated with an upper reaction structure 146 of a flow cell 150 of the sensor structure 100. The optical filter stack 136 of the sensor structure 100 is configured with dimensions that enable sub-micron pixels and high aspect ratio light guides 124, and avoids difficult and / or costly manufacturing techniques. For example, as discussed further below, the optical filter stack 136 does not include (i.e., is void of) metal curtain structures that extend about and between the light guides 124, and dielectric material in which the light guides 124 are disposed / positioned / formed, along the height (e.g., the total height or at least a majority of the height) of the light guides 124. Such metal curtain structures (and potentially dielectric material) can be difficult, costly and / or time consuming to manufacture at dimensions / physical configurations that provide for submicron pixels with sufficient critical distances.

[0104] With reference to FIG. 1, the sensor structure 100 includes an image stack 102 (or image structure 102, or image portion 102), a device stack 104 (or device structure 104, or device portion 104) disposed over a front side 105 of the image stack 102, an optical filter stack 136 disposed over a back side 103 of the image stack 102, and a flow cell 150 disposed over a back side of the optical filter stack 136. The sensor structure 100 is thereby configured as a back-side illuminated (BSI) image sensor structure as the device stack 104 is not positioned / disposed at least partially between (in a thickness direction) the optical filter stack 136 (where light enters the sensor structure 100, as described further below) and the image stack 102 (which comprises a plurality of light detectors 114), but rather the image stack 102 with the plurality of light detectors 114 is positioned / disposed between (in a thickness direction) the device stack 104 and the optical filter stack 136 where light enters the sensor structure 100. The device stack 104 of the sensor structure 100 thus does not block or interfere with light from passing from / through the flow cell 150 and the optical filter stack 136 to the plurality of light detectors 114 of the image stack 102.

[0105] The device stack 104 may comprise at least one dielectric layer 111. The one or more dielectric layers 111 may comprise or be SiO2, SiN, SiON or another dielectric material, for example. The device stack 104 may further include device circuitry 112 extending within the at least one dielectric layers 111. The device circuitry 112 may comprise or be a metal material (e.g., tungsten (W), aluminum (Al) and / or copper (Cu)) or another electrically conductivematerial. As shown in FIG. 1 , the device circuitry 112 may extend through a height / thickness of the at least one dielectric layer 111 and extend from a front side of the device stack 104 to a back side of the device stack 104 at the front side 105 of the of the image stack 102. In some implementations, the device circuitry 112 may be or comprise one or more metallization layer.

[0106] The device circuitry 112 may comprise various device circuitry 112, such as, for example traces / interconnects, resistors, capacitors, diodes and / or transistors. The device circuitry 112 may be configured to transmit / pass electrical signals from the image stack, and in particular the plurality of light detectors 114, such as for example for readout of signals from the sensing light detectors 114, digitization, storage and / or signal processing. The device circuitry 112 can thus transmit data signals based on photons detected by the plurality of light detectors 114.

[0107] A carrier substrate 106 may be coupled to the front side of the device stack 104, as shown in FIG. 1. The earner substrate 106 may comprise or be silicon or another semiconductor material. In some implementations, the carrier substrate 106 may be a wafer. The carrier substrate 106 may comprise vias or other electrically conductive structures or materials (not shown) extending therethrough from the back side of the carrier substrate 106 at the front side of the device stack 104 to the front side of the carrier substrate 106. The vias or other electrically conductive structures or materials may be electrically coupled to the device circuity 112 of the device stack, and configured to transmit / pass the electrical signals of the device circuity 112 to the front side of the carrier substrate 106. For example, in some implementations, the carrier substrate 106 may include vias (e.g., through silicon vias (TSVs)) that include an electrically conductive metal material (e.g., tungsten (W), aluminum (Al) or copper (Cu)) extending from the device circuitry 112 at the front side of the device stack 104 to the front side of the carrier substrate 106. In some such implementations, the TSVs may include electrically conductive metal liners or be filled with electrically conductive metal material(s).

[0108] As shown in FIG. 1, the carrier substrate 106 may include electrically conductive pads, pins or the like 108 at the front side thereof. The conductive pads 108 can be coupled to the vias or other electrically conductive structures or materials (not shown) extending through the carrier substrate 106 from the device circuitry 112. The conductive pads 108 provide an electrical connection with, and pass / transmit the electrical signals to, other components, such as othercomponents of the sensor structure 100 or other components of a biosensor or bioassay system in which the sensor structure 100 is incorporated or forms a portion / part of.

[0109] In some implementations, the conductive pads 108 may be bonded to the front side of the carrier substrate 106 and to the vias or other electrically conductive structures or materials (not shown) extending through the carrier substrate 106. The conductive pads 108 may be configured to transmit / pass electrical signals from the device circuitry 112 (and ultimately from the plurality of light detectors 114), such as for example for readout of signals from the sensing light detectors 114, digitization, storage and / or signal processing. The device circuitry 112, vias or other electrically conductive structures or materials extending through the carrier substrate 106 and the bond pads 108 may thereby be electrical input / output connections that extend to / from the plurality of light detectors 114 to the front side of the sensor structure 100.

[0110] As shown in FIG. 1, the image stack 102 may comprise the plurality of light detectors 114, at least one substrate material layer 116 and a plurality of isolation curtain structures 118. The plurality of light detectors 114 may be positioned proximate to or at the front side 105 of the of the of the image stack 102. The light detectors 114 may define a portion of the front side 105 of the of the image stack 102 (and thereby be exposed there at). In some other implementations (not shown), the light detectors 114 may be spaced from the front side 105 of the of the image stack 102 (in the heigh t / thickness direction), and circuitry may extend therefrom to the front side 105, and be electrically coupled with the device circuitry 1 12. In some implementations, the light detectors 114 may be spaced from the back side 103 of the of the image stack 102 (in the height / thickness direction), as shown in FIG. 1. The light detectors 114 are arranged in an array such that they are spaced from each other (such as in a defined consistent pattern) in length and width directions.

[0111] The light detectors 114 are configured to sense light, such as at least one range of wavelengths of emissive / emitted light 158 (and, potentially, excitation light 156) as described further below, and emit a signal based on such sensing. In some implementations, the light detectors are photodiodes. For example, a light detector 114 may be, for example, a semiconductor. The semiconductor may comprise photodiode, a complementary metal oxide semiconductor (CMOS) material, or both. A light detector 114 may also be a photodiode junction area or implant in a semiconductor material. For example, a light detector 114 may bean n-doped region in a p-substrate, an n-doped region on a p-well on an n-doped substrate, or any other diode combination. The light detectors 114 arc associated with at least one corresponding reaction site 154 and light guide 124, as discussed further herein.

[0112] The light detectors 114 may be disposed within the at least one substrate material layer 116. For example, the light detectors 114 may be embedded within the at least one substrate material layer 116 such that the at least one substrate material layer 116 extends about the light detectors 114 and between adjacent light detectors 114. As shown in FIG. 1, the at least one substrate material layer 116 may extend over the back side of the light detectors 114, and may define / form at least a portion of the back side 103 of the image stack 102 (and, potentially, a portion of the back side 103 of the image stack 102).

[0113] The substrate material layer 116 may comprise, or be, silicon, silicon germanium, gallium arsenide or other semiconductor material. As explained in greater detail herein, the substrate material layer 116 is operative to pass (allows transmission therethrough) emissive light 158, and potentially excitation light 156, emanating from / through the flow cell 150 disposed above the image stack 102 to the light detectors 114, as shown in FIG. 7. The emissive light 158 may be, for example, in the range of wavelengths of about 500 nanometers (nm) to about 750 nm (or about 700 nm). It is noted that the reaction sites 154 may be configured to emit certain wavelengths / colors of light depending upon the particular designated reaction / material (for example, analyte) present, such as by having different fluorescent labels. The excitation light 156 may be, for example, in the range of wavelengths of about 400 nm to about 570 nm. The emissive light 159 may have a wavelength greater than the excitation light 156. More specifically, the emissive light 158 may have a wavelength that is within a range of about 40 nm to 370 nm greater, or about 40 nm to 150 nm greater, than the wavelength of the excitation light 156. In one exemplary implementation, the emissive light 158 may be red light and the excitation light 156 may be blue light and / or green light, for example.

[0114] As shown in FIG. 1, the isolation curtain structures 118 of the image stack 102 may extend within the substrate material layer 116 from or proximately from the front side of 105 of the image stack 102 towards / to the back side 103 of the image stack 102. The isolation curtain structures 118 may be relatively thick / deep, and may change in width / length along the thickness thereof. For example, the isolation curtain structures 118 may taper (evenly or unevenly) inwidth / length as they extend in a direction extending from the front side of 105 towards the back side 103. The isolation curtain structures 118 may include relatively large aspect ratios of from about from 5 to 1 to about 25 to 1. The term aspect ratio as used herein is the ratio of the height / thickness of a feature (in this case the isolation curtain structures 118) to the maximum width / length of the feature.

[0115] Each of the isolation curtain structures 118 may be disposed adjacent a light detector 114, and may extend thereabout in the width and length directions. Due to manufacturing tolerances, the isolation curtain structures 118 may not all have the same height, as shown in FIG. 1. For example, some of the isolation curtain structures 118 may not extend across the full thickness of the substrate material layer 116 (such as not extending to the back side 103), and some other isolation curtain structures 118 may extend across the entire thickness of the substrate material layer 116.

[0116] The isolation curtain structures 118 are configured to operatively electrically isolate each light the plurality of light detectors 114 from each other. The isolation curtain structures 118 are also configured to operatively significantly reduce optical crosstalk between light detectors by blocking or significantly reducing the transmission of light, or photo-generated electrons, between light detectors 114. The isolation curtain structures 118 may be configured to prevent the transmission of a least a portion (e.g., a range of wavelengths) of the emissive light 158 (and potentially the excitation light 156) from passing therethrough. The isolation curtain structures 118 may thereby be configured to electrically and optically substantially isolate the plurality of light detectors 114 from each other.

[0117] In some implementations, the isolation curtain structures 118 may comprise or be a dielectric material. For example, the isolation curtain structures 118 may comprise or be SiCh, SiN, SiON or other dielectric material. The isolation curtain structures 118 may comprise trenches that extend within the substrate material layer 116, and optical and / or electrical isolation materials, such as a dielectric isolation material, disposed therein (e.g., partially or fully filling the trenches).

[0118] As noted above and shown in FIG. 1, the optical filter stack 136 is disposed over the back side 103 of the image stack 102, and the flow cell 150 is disposed over the back side of the optical filter stack 136. The optical filter stack 136 comprises an isolation structure 160 and aplurality of light guides 124, as shown in FIGS. 1 and 4-8. Each light guide 1 4 is associated with at least one of light detector of the plurality of light detectors 114. As shown in FIGS. 1 and 4-8, The plurality of light guides 124 comprise a plurality of openings 130 in the light guide isolation structure 160, and an optical filter material 134 at least partially disposed within the plurality of openings 130. The flow cell 150 comprises a reaction structure 146 (or reaction layer, or reaction portion) that defines, at least partially, a detector surface. The detector surface comprises the plurality of reaction sites 154, and each reaction site 154 is associated with at least one of the plurality of light guides 124, and thereby at least one of the plurality of light detectors 114.

[0119] The detector surface of the reaction structure 146 may be a top / upper surface of the reaction structure 146 that is exposed to a flow channel 159 of the flow cell 150, as shown in FIG. 1. The flow channel 159 may extend between (and be partially formed / defined by) the detector surface of the reaction structure 146 and an underside surface of a lid 155 of the flow cell 150 that is affixed over the reaction structure 146.

[0120] As shown in FIG. 1, the reaction structure 146 may define or form (at least partially) a plurality of reaction recesses or open-sided wells 148 (e.g., nanowells), with the reaction sites 154 being disposed (at least partially) within a respective well 148. The wells 148 may be defined by, for example, an indent or change in depth along the detector surface. In other examples, the detector surface may be substantially planar. Each light guide 124 may be positioned under a corresponding reaction site 114, and thereby each well 148. However, the reaction structure 146 may not define the wells 148, and / or at least sone of the reaction sites 154 may not be disposed within a respective well 148. However, as the reaction sites 154 may be defined or positioned within the wells 148 in some implementations, the terms “well” (and “nanowell”) and “reaction site” may be used interchangeably herein. However, as in some variations may provide reaction sites 154 atop elevated platforms, a planar surface, or other structures that do not necessarily constitute wells 148, the terms “well” (and “nanowell”) and “reaction site” should therefore be read as including such alternative structures.

[0121] The detector surface of the reaction structure 146 that may be functionalized (e.g., chemically or physically modified in a suitable manner for conducting designated reactions) to include the reaction sites 154. For example, the detector surface may be functionalized such thatit includes the plurality of reaction sites 154 with one or more biomolecules immobilized thereto. The detector surface of the reaction structure 146 thus permits chemicals, biomolcculcs or other analytes-of-interest to be immobilized thereon. For example, each of the reaction sites 154 may include a cluster of biomolecules that are immobilized to the detector surface.

[0122] As noted above, each reaction site 154 (and thus each well 148, if included) is associated with at least one of the plurality of light guides 124 and light detectors 114. Accordingly, the emissive light 158 from a reaction site 154 (and potentially a well 148) may travel through its associated light guide 124 and be directed onto its associated light detector 114 thereby, and not onto any unassociated light detectors 114. The reaction structure 146 may thereby be configured to allow at least some of the emissive light 158 from the reaction site 154 to pass therethrough.In some implementations, the reaction structure 146 may comprise or be a material that is at least substantially transparent the emission light 158 of the reaction sites 154. In some implementations, the reaction structure 146 may comprise or be of one or more layers of a dielectric material, such as silicon nitride SiN or a type of tantalum oxide (such as tantalum pentoxide Ta2O5). However, the reaction structure 146 may comprise differing layers ( e.g., different layers, fewer layers, and / or additional layers) and / or differing materials.

[0123] As shown in FIG. 1, the flow cell 150 may include at least one additional layer 145 disposed between the reaction structure 146 and the back side of the optical filter stack 136. In some such implementations, the at least one additional layer 145 may include a passivation stack or layer. The passivation stack may be one or more layers of a dielectric material (such as SiO2 or SiN), and / or one or more layers of a polymer (such as BCB or SU8). The passivation stack may be used to reduce the chemical reactivity of the optical filter stack 136, such as with respect to chemical reactions performed on the reaction structure 146.

[0124] In certain examples, the sensor structure 100 is configured such that each light detector 114 aligns with a single light guide 124 and a single reaction site 154 (and / or single well 148). In such configurations, a given light detector 114 may be said to form a “sensing pair” with the reaction site 154 / well 148 that is directly aligned with (e.g., positioned directly above) the light detector 114. In configurations where each light detector 114 represents a single pixel, the light detector 114 forming a sensing pair with a light guide 124 and reaction site 154 / well 148 may be a “center pixel”; while an image sensor 114 / light guide 142 / reaction site 154 / well 148 that isadjacent to the center pixel may be referred to as a “neighbor pixel.” Similarly, a light detector 114 that docs not form a sensing pair with a given reaction site 154 / wcll 148 may be referred to as a “neighbor detector” or “adjacent detector” with respect to that reaction site 154 / well 148.

[0125] While just one reaction site 154 or well 148 defines a sensing pair with a given light detector 114 or pixel in one exemplary configuration of the sensor structure 100, other variations may exist where a single light detector 114 or pixel is positioned directly under two or more reaction sites 154 or wells 148. It should be understood that the term “sensing pair” may also refer to the relationships between such reaction sites 154 or wells 148 and the corresponding light detectors 114 or pixels. In other words, the term “sensing pair” should not be read as being limited only to structural arrangements where there is only a 1 :1 pixel-to-reaction site ratio, pixel-to-well ratio, sensor-to-reaction site ratio, or sensor-to-well ratio. The term the term “sensing pair” may also apply to structural arrangements providing two or more wells 148 or reaction sites 154 per pixel or light detector 114 (or more than one light detector 114). Such a sensing pair may be defined between any of the wells 148 or reaction sites 154 that are positioned over a corresponding light detector 114 or pixel.

[0126] Turning back to the flow cell 150, although not shown, the flow cell 150 may include at least one sidewall that supports the flow cover 155 over and above the detector surface of the reaction structure 146. The sidewalls may be coupled to the detector surface and extend between the flow cover 155 and the detector surface. In some examples, the sidewalls may bond the flow cover 155 to the reaction structure 146. The flow cell 150 is sized and shaped so that the flow channel 159 extends between the flow cover 155 and the reaction structure 146, as shown in FIG. 1. In some exemplary implementations, the flow channel 159 may include a height between about 50-400 pm (microns).

[0127] The flow cover 155 may include a material that is transparent at least to the excitation light 156 propagating from an exterior of the sensor structure 100 into the flow channel 159. The excitation light 156 may be generated by one or more light sources of an illumination system (not shown), which may or may not comprise part of the sensor structure or system 100. For example, the excitation light 156 may be produced by an illumination system of a biosensor or bioassay system in which the sensor structure 100 is incorporated or utilized. By way ofexample, the flow cover 155 may comprise an optically transparent material (at least to the excitation light 156), such as glass or plastic.

[0128] Also shown, the flow cover 155 may include at least one port 157 that extends therethrough and to the flow channel 159. The at least one port 157 is thereby in communication (e.g., fluidic communication) with the flow channel 159. The at least one port 157 may be configured as an inlet port for the introduction of material, such as reaction components / reagents, cleaning agents, etc., into the flow channel 159. The at least one port 157 may be configured as an outlet port for the evacuation of material, such as reaction components / reagents, cleaning agents, etc., from the flow channel 159. In some implementations, the at least one port 157 may be in communication with a port of a cartridge or a workstation. In some the flow channel 159 may be sized and shaped to direct a fluid along the detector surface, such as in a substantially even flow.

[0129] The reaction sites 154 may be distributed in a pattern along the detector surface. For instance, the reactions sites 154 may be located in rows and columns along the detector surface in a manner that is similar to a microarray. However, it is understood that various patterns (or even no patterns, such as randomized positioning) of reaction sites 154 may be used. The reaction sites 154 may include biological or chemical substances that emit the emissive light signals 158 in response to the excitation light 156. In particular examples, the reaction sites 154 include clusters or colonies of biomolecules (e.g., oligonucleotides) that are immobilized on the detector surface, and fluorophores at the reaction sites 154 may emit light in response to the excitation light 156, with such emitted light 158 being indicative of the composition of biomolecules at the reaction sites 154.

[0130] As shown in FIG. 1 and 5, the light guides 124 are configured relative to surrounding material of the light guide isolation material 160 of the optical filter stack 136 such that they comprise a light-guiding structure that directs at least a portion of at least a subset / range of wavelengths of the emissive light signals 158 to the one or more corresponding light detectors 114. For example, the light guides 124 may have a refractive index so that at least a portion of at least a subset of wavelengths of the emissive light signals 158 are substantially reflected at an interface between the light guide 124 and the surrounding light guide isolation structure 160 of the optical filter stack 136. In certain versions, a light guide 124 is configured such that theoptical density (OD) or absorbance of the excitation light 156 is at least about 4 OD. More specifically, filter material 134 of the light guides 124 may be selected and the light guides 124 may be dimensioned to achieve at least 4 OD to the excitation light 156. The plurality of light guides 124 may include substantially the same filter material 134, or the plurality of light guides 124 may include differing filter material 124. For example, in one implementation, each of the plurality of light guides 124 may include filter material 134 that is configured to selectively allow a particular range of wavelengths, such as particular emissive light signals 158, to pass therethrough to corresponding light detectors 114. As another example, in one implementation, a first plurality of the light guides 124 may include filter material 124 that is configured to selectively allow a first subset / range of wavelengths of the emissive light signals 158 to pass to corresponding light detectors 114, and a second plurality of light detectors may include filter material 124 that is configured to selectively allow a second subset / range of wavelengths of the emissive light signals 158 that differs from the first range of wavelengths to pass to corresponding light detectors 114.

[0131] As also shown in FIGS. 1 and 5, each light guide 124 may have a tapered profile such that an upper end or region is larger than a lower end or region, such as linearly narrowing from the upper region to the lower region. For example, as shown in FIG. 5, the width / length W2 of the upper end or region of each light guide 124 may be greater than the width / length W3 of the lower end or region thereof. As also shown in FIG. 5, the side walls of the opening 130 of each light guide 124, defined by the light guide isolation structure 160, may extend inwardly at an angle 0 that is acute as it extends along a height direction from the back side of the optical filter stack 136 to the front side of the optical filter stack 136 at the back end 103 of the device stack 102. In some such implementations, light guides 114 are conical and narrow as they extend from a back side portion of the optical filter stack 136 to a front side portion of the optical filter stack 136. In some other implementations, the light guides 114 may be cylindrical.

[0132] As shown in FIG. 5, the entirety of the height Hl of the light guides 124 may be positioned in the light guide isolation structure 160. In some implementations, at least the majority of the height Hl of the light guides 124 may be positioned in the light guide isolation structure 160, such as at least 50%, or at least 60%, or at least 75%, or at least 85% or at least 95% of the height Hl. In some implementations, the total / maximum height Hl of the light guides 124 may be at least about 2 pm, such as within the range of about 2 pm to about 4 pm. Inone exemplary implementation, the total / maximum height Hl of the light guides 124 is about 3 pm.

[0133] The optical filter stack 136 (as well as the flow cell 150, the image stack 102 and the device stack 104) may be configured for sub-micron pixel pitch with sufficient critical distances that allow for manufacturing of the sensor structure 100 and cross-talk mitigation between pixels / sensing pairs. For example, with reference to FIGS. 1 and 6, adjacent light guides 124 may be spaced apart, at their closest portion(s), a minimum distance DI of less than about 300 nm, and potentially greater than about 50 nm. In some implementations, adjacent light guides 124 may be spaced apart, at their closest portion(s), a minimum distance DI of less than about 200 nm, such as about 100 nm. The minimum (and maximum) distance DI between adjacent light guides 124 may be configured such that the sensor structure 100 comprises submicron pixels, and / or the light guide isolation structure 160 between adjacent pixels is of a relatively high aspect ratio.

[0134] The light guides 124 are configured to direct at least a portion of the emissive light 158 through the optical filter stack 136 and to the corresponding light detectors 114 for the detection thereof (and, thereby, the presence (or non-presence) of a particular reaction or biological material at the corresponding reaction sites 154). For example, the light guides 124 may be configured to direct photons of the emissive light 158 from fluorescent labels on biological or chemical analytes 152 (such as clusters of DNA segments or the like) disposed at the reaction sites 154 (potentially in nanowells 148) to their associated light detectors 114.

[0135] As shown in FIG. 1, the emitted light 158 from the reaction sites 154 may emit in all directions (e.g., isotropically) such that, for example, a portion of the emitted light 158 is directed into the at least one corresponding light guide 124, and a portion of the emitted light 158 is directed into the flow channel 155 and / or a portion of the flow cell 150. For the portion that is directed into the light guide 124, the optical filter stack 136 is configured to facilitate detection of the photons thereof via the at least one corresponding light detector 114. Specifically, at least a portion of the emitted light 158 from the reaction sites 154 that passes through a back or bottom opening of a corresponding light guide 124 will propagate through filter material 134 contained within the light guide 124 to the corresponding light detector 114. As explained further below, the excitation light 156 and potentially a portion of the emitted light 158,however, will be absorbed, reflected or otherwise sufficiently prevented from propagating through the light guide 124 to the light detector 114 by the filter material 134.

[0136] As shown in FIGS. 1 and 4-8, each light guide 124 may include an opening 130 in the light guide isolation structure 160 of the optical filter stack 136, and the filter material 134 disposed within the opening 130. The filter material 134 may be a material that prevents a substantial portion of the excitation light 156 (emitted from an illumination system) from passing therethrough, but allows at least a portion of the emissive light 158 to pass therethrough and to the light detectors 114. For example, filter material 134 may be configured to prevent at least 45% (or at least 55%, or at least 65%, or at least 75%, or at least 85%, or at least 95%) of the excitation light 156 from passing therethrough to the image stack 102 (and thus the light detectors 114 thereof). In some such implementations, the excitation light 156 may have wavelengths within the range of about 300 nm (or about 400 nm) to about 700 nm, such as within the range of about 400 nm to about 575 nm. In one exemplary implementation, the excitation light 156 is within the range of about 420 nm to about 560 nm.

[0137] While the optical filter material 134 is configured to prevent a substantial portion of the excitation light 156 (e.g., light within the range of 300 nm to about 700 nm, such as light within the range of about 420 nm to about 560 nm) from passing therethrough, it is also configured to allow a substantial portion of the emissive light 158 to pass therethrough. For example, the optical filter material 134 may be configured to prevent transmission of substantially all wavelengths of excitation light 156 while permitting transmission of at least a proportion of at least some wavelengths of the emissive light 158. In some examples, the transmitted proportion of incident emissive light 158 is about 1% to about 10% of incident emissive light 158. In some examples, the transmitted proportion of incident emissive light 158 is at least about 1%, or at least about 5%, or at least about 10% of incident emissive light 158. In some implementations, the optical filter material 134 (and potentially the light guides 124 generally) is configured to allow at least 0.3% quantum efficiency of the emissive light 158 (such as emissive 158 light within the range of about 600 nm to about 690 nm).

[0138] The emissive light 158 comprises wavelengths that differ from the wavelengths of the excitation light 156. In some implementations, the emissive light 158 includes wavelengths that differ from the wavelengths of the excitation light 156 and that are within the range of 300 nm(or about 400 nm) to about 700 nm, such as within the range of about 500 nm to about 700 nm. In one exemplary implementation, the emissive light 158 is within the range of about 600 nm to about 690 nm. In some configurations, the emissive light 158 may include wavelengths that are greater than the wavelengths of the excitation light 156.

[0139] The optical filter material 134 (and the light guides 124 generally) may thereby be configured to allow transmission therethrough of at least a portion of incident light within at least a first range of wavelengths that falls within the range of about 300 nm or 400 nm to about 700 nm (corresponding to the emissive light 158), and prevent or reduce transmission therethrough of at least a portion of incident light within a second range of wavelengths that that falls within the range of about 300 nm or 400 nm to about 700 nm but that differs from the first range of wavelengths (corresponding to the excitation light 156). In one example, the optical filter material 134 (and the light guides 124 generally) may be configured to substantially filter out (i.e., prevent transmission therethrough) green and blue light (corresponding to the excitation light 156), and allow at least a portion of red light to pass / transmit therethrough (corresponding to the emissive light 158).

[0140] In some exemplary implementations, the optical filter material 134 may comprise or be an optically absorptive material, such as but not limited to an organic absorption filter material. For example, the optical filter material 134 may comprise or be an optically absorptive dye or pigment. In some implementations, the optical filter material 134 may comprise or be a substantially transparent carrier or matrix material (transparent to the excitation light 156 and / or the emissive light 158), and an absorption filter material blended or carried within the matrix material. For example, the optical filter material 134 may comprise or be dyes or pigments (e.g., organic dyes or pigments) embedded in a transparent polymer matrix. In one such example, the polymer may comprise or be, for example, a cellulose acetate butyrate. The optical filter material 134 may comprise or be, for example, a dye-polymer blend, where the dye may have low fluorescence. The carrier or matrix material of the optical filter material 134, if included, may comprise or be a high index polymer matrix. The dye or pigment of the optical filter material 134, if included, may comprise or be a member of the metallized azo dye complex class, such as an orasol orange type dye, an orasol yellow type dye, a solvent yellow type dye, a solvent orange type dye or a solvent red type dye.

[0141] As also shown in FIGS. 1 , 7 and 8, each light guide 124 may optionally include one or more liner layer 162 disposed within the openings 130 and positioned (or extending) between the side walls of the opening 130 (that are defined by the light guide isolation structure 160) and the filter material 134. In some implementations, the at least one liner layer 162 may extend continuously about the filter material 134, and along at least a substantial portion of the height H of the filter material 134 / light guide 124. In some such implementations, the at least one liner layer 162 may extend continuously along at least 95% of the height H of the filter material 134 / light guide 124. As shown in FIG. 1, the at least one liner layer 162 may be positioned directly between, and contiguous with, the filter material 134 and the light guide isolation structure 160. For example, the at least one liner layer 162 may be disposed on (e.g., directly on) the sidewall of the openings 130 of the light guides 124 defined by the light guide isolation structure 160. In some implementations, the liner layer 162 may define a substantially constant thickness.

[0142] The at least one liner layer 162 may be configured as a chemical reaction protection layer, a CMP stop layer, a light shield layer, an anti-reflective layer or a combination thereof. For example, the liner layer 162 may be configured as a chemical reaction protection layer that physically and / or chemically prevents, delays, hinders, or impedes a chemical reaction between the filter material 134 (e.g., a polymer thereof) and material of the light guide isolation structure 160 (e.g., a metal thereof), such as at elevated temperatures. The liner layer 162 may also be configured as a CMP stop layer such that, after the openings 130 are filled with the filter material 134, additional light filter material outside of the openings 130 may be removed by a CMP process which terminates upon reaching the liner layer 162. In some implementations, at an intermediate stage of manufacture of the sensor structure 100, such as at the stage shown in FIG. 7 and subsequent thereto until completion of said CMP process, the liner layer 162 may extend over the interstitial areas of the light guide isolation structure 160 (between the openings 130). As another example, the liner layer 162 may be configured as a light shield layer that attenuates at least a portion of the emissive light 158 and / or the excitation light 156 transmitted into the optical filter stack 136. As another example, the liner layer 162 may be configured as an anti- reflective layer for photolithographic patterning, for example.

[0143] In some implementations, the at least one liner layer 162 may comprise at least one layer of a dielectric material. In some implementations, the at least one liner layer 162 may compriseat least one layer including an oxide, such as silicon oxide, silicon nitride or silicon oxynitride.In some implementations, the at least one liner layer 162 may comprise at least one layer including of a metal, such as tungsten (W).

[0144] As shown in FIG. 1 and discussed above, the light guides 124 are disposed in, and extend at least partially through, the thickness of the light guide isolation structure 160. The light guide isolation structure 160 is configured to reduce optical crosstalk between the plurality of light guides 124, and thereby between the pixels and the light detectors 114. The light guide isolation structure 160 is configured to reduce optical crosstalk by preventing / mitigating light emanating from a reaction site 154 of a respective pixel from passing from the corresponding light guide 124 of the pixel to a non-corresponding light guide 124 (and ultimately the light detector 114 associated therewith) of a neighboring (or otherwise differing) pixel. The light guide isolation structure 160 may also prevent / mitigate excitation light 156 that may pass through a light guide 124 of a respective pixel from passing from the corresponding light guide 124 of the pixel to a non-corresponding light guide 124 of a neighboring (or otherwise differing) pixel. The light guide isolation structure 160 effectively prevents / mitigates optical crosstalk between the plurality of light guides 124, and thereby between the pixels and the light detectors 114 thereof, without the inclusion / utilization of metal curtain structure therein that at least partially surround the light guides 124, which thereby reduces the manufacturing cost and / or complexity of such image sensor structures 100.

[0145] As shown in FIGS. 1 and 6, the light guide isolation structure 160 extends about each of the plurality of light guides 124, and fully between adjacent / neighboring light guides 124. The light guide isolation structure 160 may extend continuously (i.e., uninterrupted) between the light guides 124 in the width and length directions (i.e., at a given height or thickness). In some implementations, at a given height or thickness, the light guide isolation structure 160 may be (or be defined by) a substantially uniform light guide isolation material (i.e., is monolithic) as it extends about and fully between the light guides 124, as shown in FIG. 1. The light guide isolation material of the light guide isolation structure 160 may thereby extend continuously and fully between the light guides 124 in the width and length directions at a given height or thickness.

[0146] In some implementations, at least a substantial portion of the optical filter material 134 of the light guides 124 may be positioned in the light guide isolation structure 160, such as at least 50%, or at least 60%, or at least 75%, or at least 85% or at least 95% of the height thereof. In one exemplary implementations, as shown in FIG. 1, the entirety of the height of at least the optical filter material 134 of the light guides 124 extends within the light guide isolation structure 160. In some implementations, the total / maximum height of the light guide isolation structure 160 may be at least about 2 pm, such as within the range of about 2 pm to about 4 pm. In one exemplary implementation, the total / maximum height of the light guide isolation structure 160 is about 3 pm. In some implementations, a minimum width / length of the light guide isolation structure 160 extending between adjacent light guides 124 is within the range of about 50 nm to about 300 nm, such as within the range of about 50 nm to about 200 nm.

[0147] The light guide isolation structure 160 is configured to prevent a substantial portion of the light passing (at least partially) through a light guide 124 (e.g., through the filter material 134 thereof) from passing to a neighboring light guide 124 and, ultimately, to a neighboring light detector 114 (i.e., between neighboring pixels). In some implementations, the light guide isolation structure 160 is configured to prevent at least 45%, at least 55%, at least 65%, or at least 75% of the light passing through a light guide 124 of a pixel from passing to a neighboring pixel (e.g., to the light guide 124 thereof). As noted above, the light passing through a light guide 124 may be emissive light 158 emanating from a reaction site 154, which may be within the range of 300 nm (or about 400 nm) to about 700 nm, such as within the range of about 500 nm to about 700 nm, or within the range of about 600 nm to about 690 nm. However, it is noted that the sensor structure 100 may be configured or utilized such that light of other wavelengths may pass through the light guides 124 (and potential detected by the light detectors 114), and the light guide isolation structure 160 may be configured with respect thereto such that that the light guide isolation structure 160 prevents a substantial portion of such light from passing between neighboring pixels (e.g., via the light guides 124 thereof).

[0148] In some implementations, the light guide isolation structure 160 may be configured with a refractive index (n) and extinction coefficient (k) that prevents a substantial portion (e.g., at least 45%) of the light that passes through a light guide 124 of a pixel from passing to a light guide 124 of a neighboring pixel. In some exemplary implementations, the light guide isolation structure 160 may be configured with a refractive index (n) within the range of about 1 and about1 .5 with respect to at least a portion of the light which passes through the light guides 124 (e.g., the range of wavelengths of light that can pass through the filter material 134), such as light within the range of about 400 nm to about 700 nm. In some exemplary implementations, the light guide isolation structure 160 may be configured with an extinction coefficient (k) within the range of about 5 and about 7 with respect to at least a portion of the light which passes through the light guide 124s (e.g., the range of wavelengths of light that can pass through the filter material 134), such as light within the range of about 400 nm to about 700 nm. As noted above, the light guides 124 may be configured to pass emissive light 158 within the range of about 500 nm to about 700 nm, such as within the range of about 600 nm to about 690 nm. However, it is noted that the sensor structure 100 may be configured or utilized such that light of other wavelengths may pass through the light guides 124 (and potential detected by the light detectors 114), and the refractive index (n) and extinction coefficient (k) of the light guide isolation structure 160 may be configured with respect thereto such that that the light guide isolation structure 160 prevents a substantial portion of such light from passing between pixels (e.g., via the light guides 124 thereof).

[0149] As shown in FIGS. 1, 3, 4 and 7, in some examples, the light guide isolation structure 160 may comprise or be a plurality overlapping / overlying layers (in the height / thickness direction) having differing composition / material. The overlapping layers of the light guide isolation structure 160 are disposed directly over each other in the height / thickness direction, as shown in FIGS. 1 and 3. The light guide isolation structure 160 may include an even number or an odd number of overlapping layers. The layers of the light guide isolation structure 160 may be of the same thickness or define differing thickness. In some implementations, the light guide isolation structure 160 may be void of other materials or structures other than the overlapping / overlying layers having differing materials.

[0150] As shown in FIGS. 1 and 3, in some implementations, the light guide isolation structure 160 may comprise at least one dielectric material layer 167 and at least one metal material layer 169 that are overlapped (e.g., directly overlapped) in the height / thickness direction. In some implementations, the light guide isolation structure 160 may comprise a plurality of dielectric material layers 167, and / or a plurality of metal material layers 169. In such implementations, the dielectric material layers 167 and the metal material layers 169 may altematingly overlap (i.e., altematingly arranged) . The plurality of metal material layers 169 may thereby be arranged suchthat they are not contiguous with each other, and plurality of metal material layers 169 may thereby be arranged such that they arc not contiguous with each other. For example, as shown in FIGS. 1 and 3, in some examples the light guide isolation structure 160 may include a first dielectric material layer 167 that (e.g., directly) overlaps / is disposed over the back side 103 of the image stack 102, a first metal material layer 169 that (e.g., directly) overlaps / is disposed over a back side of the first dielectric material layer 167, a second dielectric material layer 167 that (e.g., directly) overlaps / is disposed over a back side of the first metal material layer 169, and a second metal material layer 169 that (e.g., directly) overlaps / is disposed over a back side of the second dielectric material layer 167. In some other implementations, the metal material layer 169 may (e.g., directly) overlap / be disposed over the back side 103 of the image stack 102 as opposed to the first dielectric material layer 167.

[0151] The at least one metal material layer 169 may at least predominantly provide the optical cross-talk prevention / mitigation function / effect of the light guide isolation structure 160. The at least one metal material layer 169 may comprise a metal material that substantially prevents transmission therethrough of a range of wavelengths of light of which the light guides 124 are configured to allow to pass therethrough, such as the emissive light 158 within the range of about 400 nm to about 700 nm (e.g., about 600 nm to about 690 nm). In some implementations, the at least one metal material layer 169 comprises tantalum or like metal material, for example.

[0152] The at least one dielectric material layer 167 may provide an electrical isolation or insultation function, such as but not limited to the light guides 124 and / or a plurality of the metal material layers 169. The at least one dielectric material layer 167 (and / or the dielectric material thereof) may include a dielectric material that has an electrical resistivity (p) of at least 103Q • cm at 20° C, or at least 105• cm at 20° C, or at least 107• cm at 20° C. In some implementations, the at least one dielectric material layer 167 may comprise or be SiO2, SiN, SiON or another like dielectric material, for example. In one exemplary implementation, the at least one dielectric material layer 167 is a layer of SiO2.

[0153] In some implementations, the sensor structure 100 may be utilized as a sensor, such as a biosensor. For example, one or more reagent solutions may be introduced into the flow channel 155 of the flow cell 150, such as through the lid 155 of the flow cell 150 via the at least one port 157. The reagent solution may effectuate chemical reactions between the reagent solution andthe analyte material 152 immobilized at the reaction sites 154. The analyte material 152 of the reaction sites 154 may be biological or chemical substances, such as clusters of DNA segments, oligonucleotides or the like. At least one of the reaction solutions may include types of nucleotides having the same or different fluorescent labels. The nucleotides may bind to the reaction sites, such as to corresponding oligonucleotides at the reaction sites.

[0154] As noted above, the reaction sites 154 may comprise the biological or chemical analyte material 152 immobilized on / at portions, such as open-sided wells 148 (e.g., nanowells), of the detector surface of the reaction structure 146. The analyte material 152 may be immobilized on the reaction structure 146 prior to the introduction of the reagent solution, such as by introducing the (biological or chemical) analyte material 152, potentially as part of a solution or the like, into the flow channel 155 via the at least one port 157.

[0155] In some implementations, the chemical reactions between the reagent solution and certain analyte material 152 immobilized at the reaction sites 154 (such as analyte material of interest) and / or reaction products formed thereby produces the emissive light signals 158 in response to incident excitation light 156. For example, the reaction solution may include fluorophores, and the chemical reactions and / or the reaction products of the reagent solution and the analyte material 152 incorporates the fluorophores with the analyte material 152 at the reaction sites 154. In some examples, the fluorophores may be or comprise fluorescently labeled biomolecules that bind with the at least one analyte material 152. Introducing the reagent solution into the flow channel 155 can thereby effectuate chemical reactions between the reagent solution and the analyte material 152 immobilized at the reaction sites 154 on the detector surface, which incorporates fluorescently labeled material with the analyte material 152 at the reaction sites 154. During operation of the sensor structure 100, at least some of the analytes 152 (such as clusters of DNA segments or the like) at the reaction sites 154 (potentially disposed in wells 148) may thus be tagged with a fluorescent labeled molecule.

[0156] As shown in FIG. 1, after the designated reactions have occurred such that at least some of the reaction sites 154 include fluorescently-labeled molecules (the same or different fluorescently-labeled molecules), such as fluorophores, the reaction sites 154 emit light of a predefined or predetermined wavelength or range of wavelengths when excited by the excitation light 101 (i.e., when the excitation light 156 is incident upon the reaction sites 154). Theexcitation light 156 may be emitted from an excitation light source (e.g., solid-state light sources, such as light-emitting diodes (LEDs), such as from a bioassay system, and passes through the flow cover 155 and the flow channel 159 to the detector surface. The excitation light 101 may be configured with a predetermined wavelength or range of wavelengths based, at least in part, on the fluorescently-labeled molecules of the reaction solution, or vice-versa. As shown in FIG. 1, when excited by the excitation light 101, the reaction sites 154 emit the emissive light or signals 158 of a wavelength or range of wavelengths that differs from excitation light 101.

[0157] The fluorescent labels at the reaction sites 154, excited by the incident excitation light 154, may emit the emission signals 158 (e.g., light of a wavelength or wavelengths that differ from the excitation light 156 and, potentially, each other) isotropically such that a portion of the emitted light 158 is directed through the front side portion of the flow cell 150 (e.g., the reaction structure 146 and the at least one additional layer 145) and into at least one corresponding light guide 124 (and other portions of the emission signals 158 are directed into the flow channel 155 and / or a portion of the flow cell 150). Some of the photons of the emissive light 158 may thereby enter its associate light guide 124. The light guide 124, inclusive of its optical filter material 134, may filter out at least most of any excitation light 156 that is incident thereon and direct a significant portion of the emissive light 158 to an associated light detector 114 located directly below the light guide 124. The emitted light 158 may indicate the composition of the reaction sites 154, such as based on whether the emissive light 158 is emitted / detected and / or what wavelength of light is emitted / detected. In scenarios where nucleic acids are at reaction sites 154, the emitted light 158 may indicate the composition of such nucleic acids.

[0158] As at least a portion of the emitted light 158 is allowed to pass and / or is directed through a respective light guide 124 to the light detector 114 associated with the respective light guide 124. The light guide isolation structure 160, such as the at least one metal material layer 169 and potentially the at least one dielectric material layer 167, effectively prevent optical crosstalk within the sensor structure 100 by suitably preventing the emissive light 158 (and potentially the excitation light 156) that passes at least partially though the light guides 124 from reaching a neighboring or non-associated light detector 114 (i.e., a light detector 114 that does not form a sensing pair with a respective light guide 124 that the light is passing through).

[0159] The light detectors 114 are configured to receive the non-filtered emissive light 158 emitted from a corresponding reaction site 114 via its corresponding light guide 124. For example, the light detectors 114 may detect the incident emissive light photons 158, and emit an electrical signal based thereon. The device circuitry 112 within the device stack 104 may then transmit / conduct (and potentially process) the data signals. The data signals may be analyzed to reveal properties of the analytes 152, for example.

[0160] FIGS. 2-8 illustrates intermediate stages of manufacture of the sensor structure 100 during an exemplary method of making or manufacturing the sensor structure 100. As shown in FIG. 2, a back-side illuminated image sensor or sensor structure may be obtained (such as by being formed or by being obtained pre-formed). The back-side illuminated image sensor may include the image stack 102, the device stack 104 disposed over a front side 105 of the image stack 102, and the carrier substrate 106 disposed over the front side of the device stack 104. As shown in FIG. 2, the back side 103 of the image stack 102, which may be defined at least in pail by the at least one substrate material layer 116, may be exposed at this intermediate stage of manufacture. As noted above, the light detectors 114 may be spaced from the back side 103 of the image stack 102 and positioned proximate to the front side 105 of the image stack 102, as shown in FIG. 2.

[0161] As shown in FIG. 3, to form the optical stack 136, the light guide isolation structure 160 of the optical filter stack 136 may be disposed or formed over or on the back side 103 of the image stack 102. For example, the stack of the overlapping layers of the at least one dielectric material layer 167 and the at least one metal material layer 169 may be disposed or formed over the back side 103 of the image stack 102. In some implementations, each dielectric material layer 167 and / or metal material layer 169 may be disposed or formed via atomic layer deposition (ALD) or chemical vapor deposition (CVD), for example. In some such implementations, as shown in FIG. 3, a first dielectric material layer 167 may be disposed or formed (e.g., directly) on / over the back side 103 of the image stack 102, and a first metal material layer 169 may be disposed or formed (e.g., directly) on / over a back side of the first dielectric material layer 167. As also shown in FIG. 3, in some such implementations, a second dielectric material layer 167 may be disposed or formed (e.g., directly) on / over a back side of the first metal material layer 169, and a second metal material layer 169 may be disposed or formed (e.g., directly) on / over a back side of the second dielectric material layer 167.

[0162] After the light guide isolation structure 160 is disposed or formed over or on the back side 103 of the image stack 102, the array of light guide openings 130 may be disposed or formed therein, as shown in FIG. 4. For example, in one exemplary implementation, the openings 130 may be created via LF patterning (photolithography) and trench formation (dry etching) processes. The openings 130 may extend (e.g., directly) into the thickness of the light guide isolation structure 160 from a top / back side thereof toward (and potentially to) the back side 103 of the of the image stack 102. The openings 130 may be created such that the side walls thereof, defined or formed by the exposed surfaces of the light guide isolation structure 160, are angled inwardly as they extend from the top / back side of the light guide isolation structure 160 toward the back side back side 103 of the of the image stack 102. For example, as shown in FIG. 5 and noted above, the side walls of the light guide openings 130 may define an acute angle 0 with respect to a direction extending normal to the back side 103 of the of the image stack 102 and / or the top / back side of the light guide isolation structure 160. The cross-sectional size of the openings 130 may thereby differ from the back / top end thereof to the front / bottom end thereof. For example, as shown in FIGS. 5 and 8, the back / top end of the openings 130 may define a width W2, and the front / bottom end of the openings 130 may define a width W3 that is greater than width W2. As noted above, the openings 130 of the light guides 124 (and the light guides 124 themselves) may be cylindrical or frusto-conical in shape. As also noted above and shown in FIG. 6, the openings 130 may be spaced apart in the width / length directions such that the adjacent openings 130 / light guides 124 are spaced apart, at their closest portion(s) (e.g., at the back / top end of the openings 130), a minimum distance DI of less than about 300 nm, and such that the sensor structure 100 comprises submicron pixels.

[0163] As shown in FIG. 7, after the openings 130 are disposed or formed in the light guide isolation structure 160, the at least one liner layer 162 may be disposed or formed (e.g., directly) over / on the side walls of the openings 130 defined by the light guide isolation structure 160. As noted above, the at least one liner layer 162 may be configured as a chemical reaction protection layer, a CMP stop layer, a light shield layer, an anti-reflective layer or a combination thereof. In some implementations, the at least one liner layer 162 may be disposed or formed via ALD or CVD, for example. In some implementations, the at least one liner layer 162 may comprise at least one layer including an oxide, such as silicon oxide, silicon nitride or silicon oxynitride. Although not shown in FIG. 7, it is noted that liner layer 162 may be disposed or formed suchthat it also extends on / over the interstitial areas of the light guide isolation structure 160 between the openings 130 and on / over the bottom of the openings 130 (c.g., on / over the back side 103 of the image stack 102). Such portions of the liner layer 162 may later be removed from the sensor structure 100.

[0164] As shown in FIG. 8, after the at least one liner layer 162 is be disposed or formed (e.g., directly) at least over / on the side walls of the openings 130 defined by the light guide isolation structure 160, the openings 130 may be filled with the filter material 134 to form the light guides 124. It is noted that the filter material 134 may also extend over the interstitial areas of the light guide isolation structure 160 between the openings 130 and above the back side 128 of the light guide isolation structure 160 over the openings 130 (i.e., overfill the openings 130). Such additional portions of the filter material 134 outside of the opening 130 may be removed such that the back side 128 of the light guide isolation structure 160 defines the back side of the optical filter stack 136 and the back side / top of filter material 134 (and the liner layer 162) within the openings 130 is substantially even with the back side 128 of the light guide isolation structure 160. Such additional portions of the filter material 134 of the filter material 134 may be removed via etching and / or CMP processes, for example. As noted above, the filter material 134 is configured to substantially block the excitation light 156 (such as excitation light 156 within the range of about 420 nm to about 560 nm), and allow a substantial portion of the emissive light 158 from the reaction sites 154 (such as emissive 158 light within the range of about 600 nm to about 690 nm) to pass therethrough.

[0165] With reference to FIG. 1, after the optical stack 136 is disposed or formed, the flow cell 150 may be disposed or formed on / over (e.g., directly on / over) the back side 128 of the light guide isolation structure 160 and the light guides 124. In some implementations, the flow cell 150 may be formed via a plurality of processes that sequentially form portions of the flow cell 150. For example, the at least one passivation layer 145 may be disposed or formed (e.g., directly) on / over the back side of the optical filter stack 136, and the reaction structure 146 may be disposed or formed (e.g., directly) on / over the back side of the optical filter stack 136 or the at least one passivation layer 145. In some implementations, the wells 148 may be disposed or formed in the reaction structure 146, such as via an etching process, for example. As another example, the lid 155 (such as side walls thereof) may be coupled to the reaction structure 146(e.g., the detector surface thereof) such that the flow channel 159 is formed or disposed therebetween.

[0166] FIGS. 9-13 illustrate another exemplary sensor structure 200 according to the present disclosure. The image sensor structure 200 of FIGS. 9-13 is substantially similar- to the image sensor structure 100 of FIGS. 1-8 described above, and therefore like reference numerals preceded with “2” are used to indicate like components, aspects, functions, processes or functions, and the description above directed thereto equally applies, and is not repeated for brevity and clarity purposes. As shown in FIGS. 9-13, sensor structure 200 differs from sensor structure 100 in the configuration of the optical filter stack 236, and more particularly the configuration of the light guide isolation structure 260 of the optical filter stack 236.

[0167] Like the light guide isolation structure 160 of the optical filter stack 136 of the sensor structure 100, the light guide isolation structure 260 of the optical filter stack 236 of the sensor structure 200 is configured to reduce optical crosstalk by preventing / mitigating light emanating from a reaction site 254 of a respective pixel from passing from the corresponding light guide 224 of the pixel to a non-corresponding light guide 224 (and ultimately the light detector 214 associated therewith) of a neighboring (or otherwise differing) pixel. The light guide isolation structure 260 may also prevent / mitigate excitation light 256 that may pass through a light guide 224 of a respective pixel from passing from the corresponding light guide 224 of the pixel to a non-corresponding light guide 224 of a neighboring (or otherwise differing) pixel. The light guide isolation structure 260 effectively prevents / mitigates optical crosstalk between the plurality of light guides 224, and thereby between the pixels and the light detectors 214 thereof, without the inclusion / utilization of metal curtain structure therein that at least partially surround the light guides 224, which thereby reduces the manufacturing cost and / or complexity of such image sensor structures 200.

[0168] The material and physical configuration of the light guide isolation structure 260 effectively prevents optical crosstalk within the sensor structure 200 by suitably preventing the emissive light 258 (and potentially the excitation light 256) that passes at least partially though the light guides 224 from reaching a neighboring or non-associated light detector 214 (i.e., a light detector 214 that does not form a sensing pair with a respective light guide 224 that the light is passing through), as discussed above. As shown in FIGS. 9-13, the light guide isolation structure260 comprises a substantially consistent or uniform material composition along its thickness (and in width / lcngth directions as it extends about and between the light guides 224). The light guide isolation structure 260 may comprise or be a material that is substantially homogenous or monolithic in thickness between the flow cell 250 and the back side 230 of the image stack 202 (and in width / length directions as it extends about and between the light guides 224). As opposed to the light guide isolation structure 160, the light guide isolation structure 260 does not comprise stacked layers of distinct differing materials, but rather is of a consistent material in its thickness and width / length as it extends between and about the light guides 224. In some examples, the light guide isolation structure 260 may include or be a single material and / or include or be a single material layer.

[0169] In some implementations, the light guide isolation structure 260 may comprise or be a heavily doped silicon and at least one metal oxide. In some such implementations, the light guide isolation structure 260 may consist of the heavily doped silicon and at least one metal oxide. For example, in some implementations, the light guide isolation structure 260 is one or more layers of heavily doped silicon and at least two metal oxides. In one exemplary implementation, the light guide isolation structure 260 includes heavily doped silicon, chromium dioxide and titanium oxide.

[0170] As shown in FIG. 10, the light guide isolation structure 260 may be disposed or formed on / over (e.g., directly on / over) the back side 203 of the image stack 202, such as via disposing or forming one or more layers the heavily doped silicon and at least one metal oxide on / over (e.g., directly on / over) the back side 203. The light guide openings 230 can then be disposed or formed in the light guide isolation structure 260 (in the heavily doped silicon and at least one metal oxide material), as shown in FIG. 11. The openings 230 can then be filled to form the light guides 224. For example, as shown in FIG. 12, the at least one liner layer 262 may be disposed within the openings 230, such as by being disposed or formed in the openings 230 over / on (e.g., directly over / on) the side walls of the openings 230 (e.g., via ALD or CVD). The remainder of the opening 230 can then be filled (e.g., via ALD or CVD) with the filter material 334 to form the light guides 224 as shown in FIG. 13.

[0171] FIGS. 14-19 illustrate another exemplary sensor structure 300 according to the present disclosure. The image sensor structure 300 of FIGS. 14-19 is substantially similar to the imagesensor structure 100 of FIGS. 1 -8 and the image sensor structure 200 of FIGS. 9-13 described above, and therefore like reference numerals preceded with “3” arc used to indicate like components, aspects, functions, processes or functions, and the description above directed thereto equally applies, and is not repeated for brevity and clarity purposes. As shown in FIGS. 14-19, sensor structure 300 differs from sensor structure 100 and sensor structure 200 in the configuration of the optical filter stack 336, and more particularly the configuration of a light guide layer 360 and the light guides 324 of the optical filter stack 336.

[0172] Like the light guide isolation structure 160 of the optical filter stack 136 of the sensor structure 100 and the light guide isolation structure 260 of the optical filter stack 236 of the sensor structure 200, the light guide layer 360 and the light guides 324 of the optical filter stack 336 of the sensor structure 300 are configured to reduce optical crosstalk by preventing / mitigating light emanating from a reaction site 354 of a respective pixel from passing from the corresponding light guide 324 of the pixel to a non-corresponding light guide 324 (and ultimately the light detector 314 associated therewith) of a neighboring (or otherwise differing) pixel. The light guide layer 360 and the light guides 324 may also prevent / mitigate excitation light 356 that may pass through a light guide 324 of a respective pixel from passing from the corresponding light guide 324 of the pixel to a non-corresponding light guide 324 of a neighboring (or otherwise differing) pixel. The light guide layer 360 and the light guides 324 effectively prevent / mitigate optical crosstalk between the plurality of light guides 324, and thereby between the pixels and the light detectors 314 thereof, without the inclusion / utilization of metal curtain structure within the light guide layer 360 that at least partially surround the light guides 324, which thereby reduces the manufacturing cost and / or complexity of such image sensor structures 300.

[0173] The material and physical configuration of the optical filter stack 336 effectively prevents optical crosstalk within the sensor structure 300 by suitably preventing the emissive light3 (and potentially the excitation light 356) that passes at least partially though the filter material 334 of the light guides 324 from reaching a neighboring or non-associated light detector 314 (i.e., a light detector 314 that does not form a sensing pair with a respective light guide 324 that the light is passing through), as discussed above. As shown in FIGS. 14-19, the light guide layer 360 comprises a substantially consistent or uniform material composition along its thickness (and in width / length directions as it extends about and between the light guides 324). The light guidelayer 360 may comprise or be a material that is substantially homogenous or monolithic in thickness between the flow cell 350 and the back side 330 of the image stack 302 and in width / length directions as it extends about and between the light guides 324. As opposed to the light guide isolation structure 160, the light guide layer 360 does not comprise stacked layers of distinct differing materials, but rather is of a consistent material in its thickness and width / length as it extends between and about the light guides 324. In some examples, the light guide layer 360 may include or be a single material and / or include or be a single material layer.

[0174] In some implementations, the light guide layer 360 includes a polymer material, a semiconductor material, a dielectric material or a combination thereof. In some such implementations, the light guide layer 360 is only the polymer material, the semiconductor material, the dielectric material, or a combination thereof. In some such implementations, the light guide layer 360 may only comprise the polymer material, semiconductor material and / or dielectric material. For example, in some implementations, the light guide layer 360 is only one or more layers of a dielectric material. In some implementations, the light guide layer 360 may comprise or be SiO2, SiN, SiON or another like dielectric material, for example. The light guide layer 360 may provide an electrical isolation or insultation function, such as but not limited to the light guides 324. The light guide layer 360 may be include a dielectric material that has an electrical resistivity (p) of at least 103• cm at 20° C, or at least 105• cm at 20° C, or at least 107Q • cm at 20° C.

[0175] As noted above, in addition to the light guide layer 360, the light guides 324 of the optical filter stack 336 may also be configured to prevent / mitigate optical crosstalk between pixels. As shown in FIGS. 14 and 17-19, the light guides 324 include at least one metal liner layer 363 disposed within the light guide openings 330 and positioned between the light guide layer 360 and the filter material 324. The at least one metal liner layer 363 extends continuously about the filter material 334, and along at least a substantial portion of the height H of the filter material 334 / light guide 324. In some such implementations, the at least one metal liner layer 363 may extend continuously along at least 95% of the height H of the filter material 334 / light guide 324, such as the full height H of the filter material 334 / light guide 324. In some implementations, the at least one metal liner layer 363 may define a substantially constant thickness.

[0176] As shown in FIGS. 14 and 17- 19, the at least one metal liner layer 363 may be disposed between (c.g., directly between) the side walls of the openings 330 (defined by the light guide layer 360) and the at least one liner layer 362 (e.g., an oxide liner layer). For example, the at least one metal liner layer 363 may be disposed directly on the side walls of the openings 330 defined by the light guide layer 360. The at least one liner layer 362 (e.g., an oxide liner layer) may extend directly on the at least one metal liner layer 363. The at least one liner layer 362 (e.g., an oxide liner layer) may thereby be positioned directly between, and contiguous with, the filter material 334 and the at least one metal liner layer 363.

[0177] The at least one metal liner layer 363 may include a metal material that substantially prevents transmission therethrough of a range of wavelengths of light of which the light guides 324 are configured to allow to pass therethrough, such as the emissive light 358 within the range of about 400 nm to about 700 nm (e.g., about 600 nm to about 690 nm). In some implementations, the at least one metal liner layer 363 may be configured to substantially prevent the excitation light 356 (such as excitation light 356 within the range of about 420 nm to about 560 nm) from passing therethrough, and substantially prevent the emissive light 358 from the reaction sites 354 (such as emissive light 358 within the range of about 600 nm to about 690 nm) from passing therethrough. In some implementations, the at least one metal material layer 369 includes tantalum or like metal material, for example.

[0178] As shown in FIG. 15, the light guide layer 360 may extend or be disposed on / over (e.g., directly on / over) the back side 303 of the image stack 302. For example, in some exemplary implementations, one or more layers of a dielectric material may be disposed on / over (e.g., directly on / over) the back side 303 to form the light guide layer 360. The light guide openings 330 can then be disposed or formed in the light guide layer 360 (e.g., in dielectric material), as shown in FIG. 16. The openings 330 can then be filled to form the light guides 324. For example, the at least one metal liner layer 363 may be disposed withing the openings 330, such as by being disposed or formed directly over / on at least the side walls of the openings 330 (such as via ALD or CVD). The at least one liner layer 362 can then be disposed in the openings 330 over / on the formed at least one metal liner layer 363, as shown in FIG. 18. For example, the least one liner layer 362 may be disposed or formed directly over / on the at least the at least one metal liner layer 363, such as via ALD or CVD. The remainder of the opening 330 can then befilled with the filter material 334 (e.g., via ALD or CVD), as shown in FIG. 19, to form the light guides 324.

[0179] The terminology used herein is for the purpose of describing particular examples only and is not intended to be limiting. As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and / or “comprising”, when used in this specification, specify the presence of stated features, integers, steps, processes, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, processes, operations, elements, components and / or groups thereof.

[0180] The corresponding structures, materials, acts, and equivalents of all means or step plus function elements in the claims below, if any, are intended to include any structure, material, or act for performing the function in combination with other claimed elements as specifically claimed. The description of one or more examples has been presented for purposes of illustration and description but is not intended to be exhaustive or limited to in the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art. The example was chosen and described in order to best explain various aspects and the practical application, and to enable others of ordinary skill in the art to understand various examples with various modifications as are suited to the particular- use contemplated.

[0181] It should be appreciated that all combinations of the foregoing concepts and additional concepts discussed in greater detail below (provided such concepts are not mutually inconsistent) are contemplated as being part of the subject matter disclosed herein at least to achieve the benefits as described herein. In particular, all combinations of claims subject matter appearing at the end of this disclosure are contemplated as being part of the subject matter disclosed herein. It should also be appreciated that terminology explicitly employed herein that also may appear in any disclosure incorporated by reference should be accorded a meaning most consistent with the particular concepts disclosed herein.

[0182] This written description uses examples to disclose the subject matter, and also to enable any person skilled in the art to practice the subject matter, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the subject matter is defined by the claims, and may include other examples that occur to thoseskilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal languages of the claims.

[0183] It is to be understood that the above description is intended to be illustrative, and not restrictive. For example, the above-described examples (and / or aspects thereof) may be used in combination with each other. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the various examples without departing from their scope. While the dimensions and types of materials described herein are intended to define the parameters of the various examples, they are by no means limiting and are merely provided by way of example. Many other examples will be apparent to those of skill in the ait upon reviewing the above description. The scope of the various examples should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. In the appended claims, the terms “including” and “in which” are used as the plain- English equivalents of the respective terms “comprising” and “wherein.” Moreover, in the following claims, the terms “first,” “second,” and “third,” etc. are used merely as labels, and are not intended to impose numerical requirements on their objects. Forms of term “based on” herein encompass relationships where an element is partially based on as well as relationships where an element is entirely based on. Forms of the term “defined” encompass relationships where an element is partially defined as well as relationships where an element is entirely defined. Further, the limitations of the following claims are not written in means-plus-function format and are not intended to be interpreted based on 35 U.S.C. § 112, sixth paragraph, unless and until such claim limitations expressly use the phrase “means for” followed by a statement of function void of further structure. It is to be understood that not necessarily all such objects or advantages described above may be achieved in accordance with any particular example. Thus, for example, those skilled in the art will recognize that the systems and techniques described herein may be embodied or carried out in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other objects or advantages as may be taught or suggested herein.

[0184] While the subject matter has been described in detail in connection with only a limited number of examples, it should be readily understood that the subject matter is not limited to suchdisclosed examples. Rather, the subject matter can be modified to incorporate any number of variations, alterations, substitutions or equivalent arrangements not heretofore described, but which are commensurate with the spirit and scope of the subject matter. Additionally, while various examples of the subject matter have been described, it is to be understood that aspects of the disclosure may include only some of the described examples. Also, while some examples are described as having a certain number of elements it will be understood that the subject matter can be practiced with less than or greater than the certain number of elements. Accordingly, the subject matter is not to be seen as limited by the foregoing description but is only limited by the scope of the appended claims.

Claims

CLAIMSWhat is claimed is:

1. An image sensor structure, comprising: an image stack comprising a substrate, a plurality of light detectors, a front side and a light receiving back side; metal circuitry disposed over the front side of the image stack, the metal circuitry being electrically coupled to the photodiodes and configured to transmit data signals based on photons detected by the light detectors; an optical filter stack disposed over the back side of the image stack, the optical filter stack comprising: a light guide isolation structure comprising: overlapping layers comprising at least one metal material layer and at least one dielectric material layer; or a layer comprising a heavily doped silicon and at least one metal oxide; a plurality of light guides comprising a plurality of openings in the light guide isolation structure and an optical filter material disposed within the plurality of openings, wherein each light guide of the plurality of light guides is associated with at least one light detector of the plurality of light detectors, wherein the light guide isolation structure extends about each light guide of the plurality of light guides and between adjacent light guides of the plurality of light guides, and is configured to reduce optical crosstalk between the plurality of light guides and the plurality of light detectors.

2. The image sensor structure according to claim 1, wherein the light guides define a total height within the light guide isolation structure within the range of about 2 pm to about 4 pm.

3. The image sensor structure according to claim 1, wherein a minimum width of light guide isolation structure extending between adjacent light guides is less than about 300 nm.

4. The image sensor structure according to claim 1 , wherein the optical filter stack further comprises an oxide liner layer disposed within the openings and on sidewalls of each of the plurality of openings of the plurality light guides, the sidewalls being defined by the light guide isolation structure.

5. The image sensor structure according to claim 4, wherein the oxide liner layers are disposed directly between a corresponding sidewall and corresponding optical filter material.

6. The image sensor structure according to claim 1, wherein the plurality of light detectors are disposed within the substrate and spaced from the light receiving back side, and wherein the image stack further comprises dielectric material disposed in a plurality of dielectric isolation portions within the substrate, the dielectric isolation portions extending at least partially about a corresponding light detector and at least partially through a thickness of the substrate below a corresponding light guide to further reduce crosstalk between the light detectors.

7. The image sensor structure according to claim 1, further comprising a reaction structure disposed over the optical filter stack, the reaction structure comprising a detector surface.

8. The image sensor structure according to claim 7, further comprising a lid extending over the detector surface, wherein a flow channel extend between the lid and the detector surface, and wherein the lid comprises at least one first port that is in communication with the flow channel.

9. The image sensor structure according to claim 8, wherein the detector surface comprises a plurality of reaction sites and at least one analyte immobilized at the reaction sites.

10. The image sensor structure according to claim 9, wherein the plurality of reaction sites are each positioned within a nanowell disposed in the reaction structure, each nanowell being associated with at least one corresponding light guide and light detector.11 . The image sensor structure according to any of the previous claims, wherein the light guide isolation structure comprises the overlapping layers comprising the at least one metal material layer and the at least one dielectric material layer.

12. The image sensor structure according to claim 11, wherein the light guide isolation structure comprises at least two metal material layers and at least two dielectric material layers, the at least two metal material layers and the at least two dielectric material layers being arranged in an alternating overlapping arrangement such that the at least two metal material layers are not contiguous with each other and the at least two dielectric material layers are not contiguous with each other.

13. The image sensor structure according to claim 11 or 12, wherein the light guide isolation structure comprises a first dielectric material layer disposed over the back side of the image stack, a first metal material layer disposed over the first dielectric material layer, a second dielectric material layer disposed over the first metal material layer, and a second metal material layer disposed over the second dielectric material layer.

14. The image sensor structure according to any of claims 11-13, wherein the light guide isolation structure consists of the at least one metal material layer and the at least one dielectric material layer.

15. The image sensor structure according to any of claims 11-14, wherein the at least one metal material layer comprises a metal material that substantially prevents transmission therethrough of a first range of wavelengths of light that falls within the range of about 400 nm to about 700 nm, and wherein the optical filter material allows transmission therethrough of at least a portion of incident light within the first range of wavelengths of light.

16. The image sensor structure according to any of claims 11-15, wherein the at least one metal material layer comprises at least one tantalum layer.

17. The image sensor structure according to any of claims 11-16, wherein the at least one dielectric material layer has an electrical resistivity (p) of at least 1,000 £1 • cm at 20° C.

18. The image sensor structure according to any of claims 11-17, wherein the at least one dielectric material layer comprises at least one SiO2 layer.

19. A method, comprising: forming an optical filter stack over a light receiving back side of a back- side illuminated image sensor, the image sensor comprising: an image stack comprising a substrate, a plurality of light detectors, a front side and the light receiving back side; and metal circuitry disposed over the front side of the image stack, the metal circuitry being electrically coupled to the light detectors and configured to transmit data signals based on photons detected by the light detectors, wherein the optical filter stack comprises: a light guide isolation structure comprising: overlapping layers comprising at least one metal material layer and at least one dielectric material layer; or a layer comprising a heavily doped silicon and at least one metal oxide; a plurality of light guides comprising a plurality of openings in the light guide isolation structure and an optical filter material disposed within the plurality of openings, wherein each light guide of the plurality of light guides is associated with at least one light detector of the plurality of light detectors, wherein the light guide isolation structure extends about each light guide of the plurality of light guides and between adjacent light guides of the plurality of light guides, and is configured to reduce optical crosstalk between the plurality of light guides and the plurality of light detectors.

20. The method according to claim 19, wherein forming the optical filter stack over the light receiving back side of the image sensor comprises forming the light guide isolation structure over the light receiving back side of the image sensor.

21. The method according to claim 20, wherein forming the optical filter stack over the light receiving back side of the image sensor further comprises forming the openings in the light guide isolation structure from a top side thereof.

22. The method according to claim 21, wherein forming the optical filter stack over the light receiving back side of the image sensor further comprises depositing the optical filter material in the openings in the light guide isolation structure.

23. The method according to claim 22, wherein forming the optical filter stack over the light receiving back side of the image sensor further comprises forming an oxide liner layer on sidewalls of each of the openings prior to depositing the optical filter material in the openings.

24. The method according to any one of claims 19-23, wherein forming the optical filter stack over the light receiving back side of the image sensor comprises forming the overlapping layers comprising the at least one metal material layer and the at least one dielectric material layer over the light receiving back side of the image sensor.

25. The method according to claim 24, wherein forming the overlapping layers comprising the at least one metal material layer and the at least one dielectric material layer over the light receiving back side of the image sensor comprises forming at least two metal material layers and at least two dielectric material layers over the light receiving back side of the image sensor, the at least two metal material layers and the at least two dielectric material layers being altematingly arranged such that the at least two metal material layers are not contiguous with each other and the at least two dielectric material layers are not contiguous with each other.

26. The method according to claim 24 or 25, wherein forming the overlapping layers comprising the at least one metal material layer and the at least one dielectric material layer over the light receiving back side of the image sensor comprises forming a first dielectric material layer over the back side of the image stack, forming a first metal material layer over the firstdielectric material layer, forming a second dielectric material layer over the first metal material layer, and forming a second metal material layer over the second dielectric material layer.

27. The method according to any one of claims 19-23, wherein forming the optical filter stack over the light receiving back side of the image sensor comprises forming the layer comprising a heavily doped silicon and at least one metal oxide over the light receiving back side of the image sensor.

28. The method according to any one of claims 19-23 and 27, wherein forming the layer comprising a heavily doped silicon and at least one metal oxide over the light receiving back side of the image sensor comprises forming a layer of a heavily doped silicon and at least two metal oxides over the light receiving back side of the image sensor.

29. The method according to any one of claims 19-23, 27 and 28, wherein forming the layer comprising a heavily doped silicon and at least one metal oxide over the light receiving back side of the image sensor comprises forming a layer of a heavily doped silicon and metal oxide materials that substantially prevents transmission therethrough of a first range of wavelengths of light within the range of about 400 nm to about 700 nm and has an electrical resistivity (p) of at least 1,000 • cm at 20° C, and wherein the optical filter material allows transmission therethrough of at least a portion of incident light within the first range of wavelengths of light.

30. The method according to any one of claims 19-23 and 27-29, wherein forming the layer comprising a heavily doped silicon and at least one metal oxide over the light receiving back side of the image sensor comprises forming a layer of a heavily doped silicon, chromium dioxide and titanium oxide over the light receiving back side of the image sensor.

31. A method, comprisin : introducing a reagent solution into a flow channel of a sensor that comprises: an image stack comprising a substrate, a plurality of light detectors, a front side and a light receiving back side;metal circuitry disposed over the front side of the image stack, the metal circuitry being electrically coupled to the light detectors and configured to transmit data signals based on photons detected by the light detectors; an optical filter stack disposed over the back side of the image stack, the optical filter stack comprising: a light guide isolation structure comprising: overlapping layers comprising at least one metal material layer and at least one dielectric material layer; or a layer comprising a heavily doped silicon and at least one metal oxide; and a plurality of light guides comprising a plurality of openings in the light guide isolation structure and an optical filter material disposed within the plurality of openings, wherein each light guide of the plurality of light guides is associated with at least one light detector of the plurality of light detectors, wherein the light guide isolation structure extends about each light guide of the plurality of light guides and between adjacent light guides of the plurality of light guides, and is configured to reduce optical crosstalk between the plurality of light guides and the plurality of light detectors; and a flow cell disposed over the optical filter stack comprising a reaction structure that comprises a detector surface that comprises reaction sites, and a lid extending over the detector surface, wherein a flow channel extends between the lid and the detector surface; and illuminating the detector surface with excitation light that passes through the lid.

32. The method according to claim 31, wherein the introducing the reagent solution into the flow channel effectuates chemical reactions between the reagent solution and material immobilized at the reaction site, and wherein at least one of the chemical reactions and reaction products formed thereby produces light signals in response to incident light of the excitation light.

33. The method according to claim 32, wherein the reaction solution comprises fluorophores, and wherein at least one of the chemical reactions and the reaction products incorporate the fluorophores with the material immobilized at the reaction sites.

34. The method according to claim 33, wherein the material immobilized at the reaction sites comprises at least one analyte, and wherein the reaction solution comprises fluorescently labeled biomolecules that bind with the at least one analyte.

35. The method according to claim 45, wherein the plurality of light sensors transmit data signals based on detected photons of light signals, and wherein the metal circuity conducts the data signals.

36. The method according to any one of claims 31-35, wherein the light guide isolation structure comprises the overlapping layers comprising the at least one metal material layer and the at least one dielectric material layer.

37. The method according to claim 36, wherein the light guide isolation structure comprises at least two metal material layers and at least two dielectric material layers, the at least two metal material layers and the at least two dielectric material layers being arranged in an alternating overlapping arrangement such that the at least two metal material layers are not contiguous with each other and the at least two dielectric material layers are not contiguous with each other.

38. The method according to claim 36 or 37, wherein the light guide isolation structure comprises a first dielectric material layer disposed over the back side of the image stack, a first metal material layer disposed over the first dielectric material layer, a second dielectric material layer disposed over the first metal material layer, and a second metal material layer disposed over the second dielectric material layer.

39. The method according to any of claims 36-38, wherein the light guide isolation structure consists of the at least one metal material layer and the at least one dielectric material layer.

40. The method according to any of claims 36-39, wherein the reaction sites produce light signals within a first range of wavelengths of about 400 nm to about 700 nm in response to incident light of the excitation light, wherein the optical filter material allows transmission therethrough of at least a portion of the light signals within a second range of wavelengths that is a subset of the first range of wavelengths, and wherein the at least one metal material layer comprises a metal material that substantially prevents transmission therethrough of the second range of wavelengths.

41. The method according to any of claims 36-40, wherein the at least one metal material layer comprises at least one tantalum layer.

42. An image sensor structure, comprising: an image stack comprising a substrate, a plurality of light detectors, a front side and a light receiving back side; metal circuitry disposed over the front side of the image stack, the metal circuitry being electrically coupled to the photodiodes and configured to transmit data signals based on photons detected by the photodiodes; and an optical filter stack disposed over the back side of the image stack, the optical filter stack comprising: a light guide layer; and a plurality of light guides comprising a plurality of openings in the light guide layer, an optical filter material disposed within the plurality of openings, a metal liner layer disposed within the plurality of openings and over side walls of the openings defined by the light guide layer, and an oxide liner layer disposed within the plurality of openings between the metal liner layer and the optical filter material, wherein each light guide of the plurality of light guides is associated with at least one light detector of the plurality of light detectors, wherein the light guide layer extends about each light guide of the plurality of light guides and between adjacent light guides of the plurality of light guides, and is void of metal structures that extend about each of the plurality of light guides, and wherein the metal liner layer and the oxide liner layer of each light guide of the plurality of light guides extends about the optical filter material.

43. The image sensor structure according to claim 42, wherein the plurality of light detectors are disposed within the substrate and spaced from the light receiving back side.

44. The image sensor structure according to claim 43, wherein the image stack further comprises dielectric material disposed in a plurality of dielectric isolation portions within the substrate, the dielectric isolation portions extending at least partially about a corresponding light detector and at least partially through a thickness of the substrate below a conesponding light guide to reduce crosstalk between the light detectors.

45. The image sensor structure according to any one of claims 42-44, further comprising a reaction structure disposed over the optical filter stack, the reaction structure comprising a detector surface.

46. The image sensor structure according to claim 45, further comprising a lid extending over the detector surface, and a flow channel extending between the lid and the detector surface, and wherein the lid comprises at least one first port that is in communication with the flow channel.

47. The image sensor structure according to claim 46, wherein the detector surface comprises a plurality of reaction sites and at least one analyte immobilized at the reaction sites.

48. The image sensor structure according to claim 47, wherein the plurality of reaction sites are each positioned within a nanowell disposed in the reaction structure, each nanowell being associated with at least one corresponding light guide and light detector.

49. The image sensor structure according to any of claims 42-48, wherein the oxide liner layer comprises silicon dioxide, silicon nitride or a combination thereof.

50. The image sensor structure according to any of claims 42-49, wherein the metal liner layer comprises a metal material that substantially prevents transmission therethrough of a first range of wavelengths of light that falls within the range of about 400 nm to about 700 nm, andwherein the optical filter material allows transmission therethrough of at least a portion of incident light within the first range of wavelengths of light.

51. A method, comprising: forming an optical filter stack over a light receiving back side of a back- side illuminated image sensor, the image sensor comprising: an image stack comprising a substrate, a plurality of light detectors, a front side and the light receiving back side; and metal circuitry disposed over the front side of the image stack, the metal circuitry being electrically coupled to the light detectors and configured to transmit data signals based on photons detected by the light detectors, wherein the optical filter stack comprises: a light guide layer; and a plurality of light guides comprising a plurality of openings in the light guide layer, an optical filter material disposed within the plurality of openings, a metal liner layer disposed within the plurality of openings and over side walls of the openings defined by the light guide layer, and an oxide liner layer disposed within the plurality of openings between the metal liner layer and the optical filter material, wherein each light guide of the plurality of light guides is associated with at least one light detector of the plurality of light detectors, wherein the light guide layer extends about each light guide of the plurality of light guides and between adjacent light guides of the plurality of light guides, and is void of metal structures that extend about each light guide of the plurality of light guides, and wherein the metal liner layer and the oxide liner layer of each light guide of the plurality of light guides extends about the optical filter material.

52. The method according to claim 51, wherein forming the optical filter stack over the light receiving back side of the image sensor comprises: forming the light guide layer over the light receiving back side of the image sensor; forming the openings in the light guide layer from a top side thereof;forming the metal liner layer over the side walls of the openings defined by the light guide layer; forming the oxide liner layer over the metal liner layer; and depositing the optical filter material over the oxide liner layer to fill the openings in the light guide layer.

53. The method according to claim 51 or 52, wherein the oxide liner layer comprises silicon dioxide, silicon nitride or a combination thereof54. The method according to any one of claims 51-53, wherein the metal liner layer is comprises a metal material that substantially prevents transmission therethrough of a first range of wavelengths of light that falls within the range of about 400 nm to about 700 nm, and wherein the optical filter material allows transmission therethrough of at least a portion of incident light within the first range of wavelengths of light.

55. The method according to any one of claims 51-54, wherein the light guide layer is void of metal structures that extend about each light guide of the plurality of light guides and along at least the majority of the height of the light guides.

56. A method, comprising: introducing a reagent solution into a flow channel of a sensor that comprises: an image stack comprising a substrate, a plurality of light detectors, a front side and a light receiving back side; metal circuitry disposed over the front side of the image stack, the metal circuitry being electrically coupled to the photodiodes and configured to transmit data signals based on photons detected by the photodiodes; and an optical filter stack disposed over the back side of the image stack, the optical filter stack comprising: a light guide layer; and a plurality of light guides comprising a plurality of openings in the light guide layer, an optical filter material disposed within the plurality of openings, ametal liner layer disposed within the plurality of openings and over side walls of the openings that arc defined by the light guide layer, and an oxide liner layer disposed within the plurality of openings between the metal liner layer and the optical filter material, wherein each light guide of the plurality of light guides is associated with at least one light detector of the plurality of light detectors, wherein the light guide layer extends about each light guide of the plurality of light guides and between adjacent light guides of the plurality of light guides, and is void of metal structures that extend about each light guide of the plurality of light guides, and wherein the metal liner layer and the oxide liner layer of each light guide of the plurality of light guides extends about the optical filter material; and a flow cell disposed over the optical filter stack comprising a reaction structure that comprises a detector surface that comprises reaction sites, and a lid extending over the detector surface, wherein a flow channel extend between the lid and the detector surface; and illuminating the detector surface with excitation light that passes through the lid.

57. The method according to claim 55, wherein the introducing the reagent solution into the flow channel effectuates chemical reactions between the reagent solution and material immobilized at the reaction sites, wherein the reaction solution comprises fluorescently labeled biomolecules, and the material immobilized at the reaction sites comprises at least one analyte, and wherein at least one of the chemical reactions and the reaction products binds the fluorescently labeled biomolecules an the at least one analyte at the reaction sites.

58. The method according to claim 56, wherein the introducing the reagent solution into the flow channel effectuates chemical reactions between the between the reagent solution and material immobilized at the reaction sites on the detector surface, wherein at least one of the chemical reactions and reaction products formed thereby produce light signals in response to incident light of the excitation light, and wherein the plurality of light sensors are configured to sense the light signals.

59. The method according to any of claims 56-58, wherein the metal liner layer comprises a metal material that substantially prevents transmission therethrough of a first range of wavelengths of light that falls within the range of about 400 nm to about 700 nm, and wherein the optical filter material allows transmission therethrough of at least a portion of incident light within the first range of wavelengths of light.

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